How to Optimize Fertility in Males & Females

00:00:00.320 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.080 | and I'm a professor of neurobiology and ophthalmology

00:00:12.860 | at Stanford School of Medicine.

00:00:14.520 | Today, we are discussing fertility.

00:00:16.680 | We will discuss male fertility and female fertility.

00:00:20.040 | And I should mention that today's discussion

00:00:22.320 | is not just for people who are seeking to conceive children

00:00:25.400 | or who want to know how their children were conceived,

00:00:27.920 | but it's really for everybody.

00:00:29.480 | And I say that because it is the story of all of us.

00:00:33.040 | All of us are here because a specialized set of cells

00:00:36.460 | called germ cells, that is the sperm and the egg,

00:00:40.240 | and I'll make it very clear why they're called germ cells

00:00:42.320 | a little bit later, it has nothing to do with infection,

00:00:44.740 | but it's because a sperm cell and an egg cell

00:00:49.340 | arrived at one another,

00:00:50.880 | either in vivo inside of our mother or in vitro,

00:00:54.280 | so-called in vitro fertilization,

00:00:55.640 | and then were implanted into our mother and became us.

00:00:59.680 | And so understanding the process of how the egg cell

00:01:03.880 | and the sperm cell came to be is really the key

00:01:07.080 | to understanding how that fertilization process came to be.

00:01:10.680 | I know everyone's thinking,

00:01:11.520 | I know how fertilization occurs.

00:01:13.180 | It occurs through sexual intercourse and so on.

00:01:15.120 | And we'll talk a little bit about that,

00:01:17.220 | but I promise you that if you understand the menstrual cycle

00:01:21.380 | and the menstrual cycle in today's conversation

00:01:23.760 | can best be thought of as a biological cycle

00:01:26.760 | that occurs in females that allows the potential

00:01:30.000 | for fertilization by the sperm,

00:01:31.860 | because that's really what it is.

00:01:32.980 | And it's a beautifully orchestrated process

00:01:35.040 | that I'll describe to you.

00:01:36.400 | And I should say all people, males and females,

00:01:39.520 | should really understand how the menstrual cycle works,

00:01:42.000 | how it impacts fertilization,

00:01:44.860 | but also how it impacts the brain and body,

00:01:47.320 | behavior, psychology, et cetera.

00:01:49.280 | And we will also talk about spermatogenesis,

00:01:52.500 | how sperm cells come to be and how they arrive,

00:01:56.700 | that is how they swim to the egg

00:01:58.580 | and the incredible interplay between the biology

00:02:01.780 | of the sperm and the biology of the egg

00:02:05.580 | leads to this incredible thing that we call embryogenesis

00:02:08.900 | and the birth of the child.

00:02:11.060 | And of course, the development of that child

00:02:13.300 | into an infant, a toddler, an adolescent,

00:02:17.260 | a teen and an adult.

00:02:18.760 | Today's discussion again is not just for those of you

00:02:22.220 | that are seeking to have children.

00:02:24.620 | And I say that because when you look at the data,

00:02:28.420 | you look at the literature on longevity and vitality,

00:02:31.920 | two themes in biology that oftentimes people lump together,

00:02:35.600 | but aren't always the same.

00:02:36.860 | For instance, there are a lot of things that we can do

00:02:39.020 | to increase our vitality

00:02:40.700 | that actually can harm our longevity.

00:02:43.620 | But there are a subset of biological rules and mechanisms

00:02:47.980 | that when aligned, allow us to maximize

00:02:50.680 | both our vitality and our longevity.

00:02:54.200 | And I think it's fair to say

00:02:55.800 | that all of those mechanisms and tools

00:02:57.980 | are housed in the discussion around maximizing fertility.

00:03:02.320 | And that's true whether or not you're male or female.

00:03:04.080 | In other words, if you want children or if you don't,

00:03:06.860 | if you already have children or if you don't,

00:03:09.260 | understanding how fertility and fertilization occurs

00:03:13.940 | in the brain and body

00:03:15.340 | will allow you to maximize your vitality and longevity.

00:03:18.720 | And of course, today's discussion will provide

00:03:21.260 | an understanding of the biology and many actionable tools

00:03:24.160 | that will also help you conceive children

00:03:25.960 | if that's your wish.

00:03:27.040 | So of course, as is characteristic of this podcast,

00:03:29.880 | we will discuss science-based tools,

00:03:32.040 | including behavioral tools, both the dos and the don'ts.

00:03:35.500 | And we will discuss nutrition-based tools

00:03:37.540 | and supplementation-based tools and some other practices,

00:03:41.260 | including things like acupuncture,

00:03:43.220 | which have quite good data to support them

00:03:46.040 | in terms of improving fertility.

00:03:47.740 | And we will discuss why those certain practices can work.

00:03:51.860 | And we will discuss prescription drugs

00:03:53.920 | that your doctor can prescribe to you.

00:03:56.580 | If, for instance, you have a deficit

00:03:58.680 | at the level of hormone production

00:04:00.260 | or neurotransmitter production at the level of the brain

00:04:02.400 | or the pituitary gland,

00:04:03.480 | I'll explain what all of those things are soon,

00:04:05.860 | or the gonads, the ovary and the testes

00:04:08.700 | in females and males respectively.

00:04:10.820 | Again, by the end of today's episode,

00:04:13.520 | you will have a lot of knowledge and actionable tools

00:04:16.000 | related to maximizing fertility,

00:04:17.940 | and you will have a lot of knowledge and actionable tools

00:04:20.980 | related to maximizing vitality and longevity.

00:04:24.820 | Before we begin, I'd like to emphasize that this podcast

00:04:27.440 | is separate from my teaching and research roles at Stanford.

00:04:30.180 | It is, however, part of my desire and effort

00:04:32.300 | to bring zero cost to consumer information

00:04:34.220 | about science and science-related tools

00:04:36.140 | to the general public.

00:04:37.540 | In keeping with that theme,

00:04:38.620 | I'd like to thank the sponsors of today's podcast.

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00:08:20.540 | Let's talk about fertility.

00:08:21.780 | And in doing so, let's take a step back

00:08:23.500 | from this word fertility and ask,

00:08:25.580 | what is fertility and fertilization really all about?

00:08:28.740 | Well, the obvious answer

00:08:29.700 | is that it's about producing offspring.

00:08:31.920 | But more importantly, it's about producing offspring

00:08:34.940 | that contain the genetic components of both parents

00:08:38.780 | and indeed contain half of the genes from one parent

00:08:41.780 | and half of the genes from another parent.

00:08:43.920 | Now, there are two general types of cells in the body.

00:08:46.960 | The most common types of cells in the body

00:08:48.440 | are called somatic cells.

00:08:49.440 | So this would be all the cells in your body

00:08:51.200 | except the egg in females and the sperm in males.

00:08:54.980 | The egg in females and the sperm in males

00:08:57.300 | are part of what's called the germ line.

00:08:59.020 | And again, it has nothing to do with infection.

00:09:00.980 | It's just that the cells of the germ line

00:09:03.660 | have genes that cannot be modified by the behavior

00:09:07.780 | of the individual that houses those genes.

00:09:10.260 | What do I mean by that?

00:09:11.140 | Well, if I were to tell you that by exercising,

00:09:13.700 | you can improve mitochondrial function,

00:09:15.780 | you can change hormones.

00:09:18.600 | By reducing stress, you can reduce cortisol.

00:09:20.980 | By hitting puberty, for instance,

00:09:24.100 | you will have the secretion of hormones

00:09:26.260 | that then change gene expression in other cells

00:09:28.140 | leading to development of body hair, facial hair,

00:09:31.160 | deepening the voice, breast growth, et cetera.

00:09:33.920 | You'd say, okay, great, that all makes perfect sense.

00:09:36.940 | But that's all occurring in the so-called somatic cells.

00:09:39.720 | The germ cells or the germline cells,

00:09:41.960 | that is the egg and the sperm,

00:09:44.080 | are a very unique and protected set of cells

00:09:47.040 | that are generated in a particular way

00:09:49.600 | and whose genetic components

00:09:52.320 | are not modifiable by experience.

00:09:56.040 | And when you take a step back and you think about it,

00:09:57.440 | you say, oh, that's right.

00:09:58.480 | There's no reason to think that exercising

00:10:01.120 | will make the children that you have not yet had stronger.

00:10:05.440 | Of course not.

00:10:06.280 | Well, why is that?

00:10:07.100 | Well, that's because there is a barrier

00:10:09.360 | between the genes of the germline cells and behaviors.

00:10:14.080 | They cannot be modified by behaviors

00:10:16.120 | and the various things that you do in your lifetime.

00:10:18.460 | Now, I suppose there's an exception

00:10:19.860 | in the negative direction.

00:10:21.960 | And what I'm referring to here is

00:10:23.280 | if you were to say be exposed to a chemical

00:10:25.240 | that could mutate the DNA of your egg or sperm,

00:10:29.180 | or if you were to fertilize an embryo in a certain way

00:10:33.360 | or at a certain stage of life

00:10:34.580 | that it got an extra chromosome, for instance,

00:10:36.700 | we'll talk about this a little bit later,

00:10:38.280 | well, then of course you could end up with offspring

00:10:40.900 | that have modified DNA

00:10:42.880 | that don't faithfully represent half of the genes from mom

00:10:46.100 | and half of the genes from dad,

00:10:48.340 | but that's not the same as specific behaviors

00:10:51.420 | modifying the genes of those cells,

00:10:53.540 | the sperm and the egg cells,

00:10:55.340 | in a way that improves the offspring.

00:10:58.700 | So the key first thing to understand today

00:11:00.920 | is that there's a distinction between somatic cells,

00:11:02.760 | which is the vast majority of cells in your body

00:11:04.420 | and the so-called germline cells,

00:11:05.580 | which are the egg and the sperm.

00:11:06.780 | The egg and the sperm

00:11:07.860 | are these highly protected populations of cells

00:11:10.660 | that in females actually come to be during embryogenesis.

00:11:15.660 | Okay, so for all females out there,

00:11:18.340 | you generate what today I'm going to refer to

00:11:21.060 | as a vault of cells.

00:11:22.420 | You have a vault of eggs that are your germline.

00:11:26.800 | Those eggs all contain all the chromosomes of your DNA.

00:11:31.800 | So it's going to be, as most of you know,

00:11:33.680 | there are 23 chromosomes

00:11:35.560 | and chromosomes exist in pairs.

00:11:37.320 | So the way to think about this is each pair is one strand

00:11:40.520 | and you have 22 so-called autosomes

00:11:42.600 | and then you have one sex chromosome.

00:11:44.360 | The sex chromosome will be either X or Y.

00:11:46.340 | So in a female, they have two X chromosomes.

00:11:48.620 | So in each one of the eggs that a woman has

00:11:51.080 | and that she's had since she was an embryo

00:11:53.740 | and that's contained in this vault,

00:11:55.620 | those eggs are of course going to be very immature

00:11:58.620 | at birth, right?

00:11:59.480 | She hasn't undergone puberty yet

00:12:00.940 | and certainly as an embryo, she hasn't undergone puberty

00:12:03.680 | and those cells are going to contain

00:12:05.980 | 23 pairs of chromosomes.

00:12:08.680 | Okay, this is very important.

00:12:09.880 | 23 pairs of chromosomes.

00:12:12.120 | The chromosomes are essentially the wrapped up DNA

00:12:16.260 | that contains all the genetic information

00:12:18.340 | to create any cell type in the body

00:12:20.140 | and actually to create an entirely new individual.

00:12:23.360 | Now there are 23 pairs of chromosomes,

00:12:25.220 | 22 of which are called autosomes.

00:12:28.540 | Okay, if that doesn't make sense to you,

00:12:29.800 | just remember autosome, okay, there's 22 of them

00:12:32.180 | and then there's one so-called sex chromosome.

00:12:34.480 | The sex chromosomes are either X or Y, but this is a female.

00:12:37.920 | So she's going to have 23 pairs of chromosomes

00:12:40.460 | and she's going to have two X chromosomes

00:12:43.020 | for the sex chromosomes.

00:12:45.020 | Okay, if this is already confusing to you, don't worry.

00:12:47.120 | I'll make it very clear how this all relates to fertility

00:12:50.220 | and how it relates to chromosomal segregation

00:12:52.940 | and a bunch of things that I think maybe you've heard of

00:12:55.700 | and that perhaps were opaque to you,

00:12:58.120 | but I promise to make them clear.

00:12:59.180 | But just understand that within each of those eggs,

00:13:01.240 | they have 23 pairs of chromosomes.

00:13:03.640 | And for those of you that like nomenclature,

00:13:06.780 | I'll tell you that those cells are considered diploid,

00:13:09.420 | they're called the diploid.

00:13:10.820 | And that means that they have 23 pairs of chromosomes.

00:13:14.180 | As distinguished from cells that are haploid,

00:13:17.820 | where there's only one set of those 23 chromosomes.

00:13:22.060 | So instead of 23 pairs, there's only 23 chromosomes.

00:13:25.160 | We'll come back to haploid cells a little bit later.

00:13:28.060 | Okay, so when a female is born,

00:13:31.020 | she has all these eggs in the reserve, in this vault

00:13:34.140 | that she'll have for her entire life.

00:13:35.580 | She's not going to make any more,

00:13:37.300 | but they are very, very immature.

00:13:39.260 | So when a woman is in embryogenesis,

00:13:41.740 | she develops these very immature eggs, okay?

00:13:45.040 | Today, we're also going to talk about follicles

00:13:46.820 | and we will be careful to distinguish follicles from eggs.

00:13:50.820 | They're often talked about interchangeably

00:13:52.740 | online and elsewhere, and even by fertility docs and OBGYNs.

00:13:56.320 | But right now we're just talking about the egg cells, okay?

00:13:59.780 | The eggs themselves, which are cells.

00:14:02.740 | Now, the goal of fertilization is to bring that egg cell

00:14:06.620 | into close enough proximity that it can be fertilized

00:14:10.360 | by a single sperm cell.

00:14:12.340 | And that sperm cell will bring 23 chromosomes as well,

00:14:16.820 | that include, just as in the female egg,

00:14:19.740 | it'll have 22 autosomes and one sex chromosome.

00:14:23.140 | And in the male, that sex chromosome

00:14:24.820 | can either be an X chromosome,

00:14:27.380 | which then would give rise to female offspring,

00:14:30.380 | or a Y chromosome, which would give rise to male offspring.

00:14:34.020 | And today we're not talking about sexual differentiation.

00:14:36.580 | That's a topic of a previous and yet another future episode.

00:14:39.560 | But just to give you a sense of how X chromosomes

00:14:42.940 | and Y chromosomes can actually accomplish

00:14:45.220 | that sexual differentiation, both of body and brain.

00:14:49.740 | I'll just mention in two sentences that, for instance,

00:14:52.700 | if there's a Y chromosome as opposed to an X chromosome,

00:14:55.560 | that Y chromosome contains genes that suppress,

00:14:59.060 | for instance, the development of female genitalia,

00:15:02.040 | and thereby give rise to male genitalia.

00:15:05.560 | So rather than the formation of a clitoris,

00:15:07.220 | it's the formation of a penis.

00:15:08.940 | And rather than the formation of ovaries,

00:15:10.580 | the formation of a testes, okay?

00:15:12.260 | So that's more directed towards sexual differentiation.

00:15:14.940 | We're not going to get into that right now.

00:15:16.080 | We'll get into that in a future episode.

00:15:18.220 | But even if you're only tracking about 10%

00:15:21.480 | of what I'm saying right now, I promise you're doing great.

00:15:24.020 | If you're tracking more than 10%,

00:15:25.620 | well, then you're doing terrifically well.

00:15:27.220 | Because the essence of fertility and fertilization

00:15:29.740 | is to bring together that haploid cell that is the sperm,

00:15:34.240 | that only has 23 chromosomes,

00:15:38.260 | but not pairs of chromosomes, right?

00:15:40.540 | 'Cause that's the DNA from dad, together with the egg,

00:15:44.540 | which is, I told you already, has 23 pairs of chromosomes.

00:15:48.000 | So part of the fertilization process has to be

00:15:51.020 | to get rid of one half of those 23 pairs in the female.

00:15:55.140 | You got to get rid of it.

00:15:56.540 | And you have to get the egg and the sperm in proximity

00:16:00.840 | so that the egg can potentially be fertilized

00:16:03.380 | by the sperm bringing the DNA,

00:16:05.780 | the 23 single strands of chromosomes from dad

00:16:11.580 | into a cell that has 23 single strands from mom, okay?

00:16:16.060 | So I realize I'm probably being

00:16:17.660 | a little bit repetitive here,

00:16:18.740 | but I want everyone to understand this

00:16:21.340 | 'cause it really frames up fertility and reproduction

00:16:24.580 | in the proper way.

00:16:26.860 | We've got a cell from mom, the egg,

00:16:29.420 | which has 23 pairs of chromosomes.

00:16:31.940 | We need to get rid of one set of those pairs

00:16:35.820 | so that there's only 23 chromosomes.

00:16:37.860 | We need to get rid of half of those chromosomes.

00:16:40.500 | And then we need to bring that cell together physically

00:16:43.660 | with the sperm cell that contains

00:16:47.180 | the 23 chromosomal strands from dad.

00:16:49.800 | And we need to bring those together

00:16:51.940 | so that you get 23 chromosomal pairs from dad

00:16:54.860 | and 23 chromosomal pairs from mom.

00:16:58.180 | And in doing so, you create a cell,

00:17:01.920 | which then becomes multiple cells.

00:17:03.580 | That's going to be the developing embryo

00:17:05.360 | that has half the genes from mom

00:17:06.600 | and half the genes from dad.

00:17:08.220 | So I hope that's clear.

00:17:09.640 | That is the biological logic,

00:17:11.920 | which I realize is a bit of a tongue twister,

00:17:13.540 | but forgive me,

00:17:14.880 | it is the most accurate way to describe this process.

00:17:17.800 | We're trying to bring together

00:17:19.400 | the 23 single strands of chromosomes from dad

00:17:22.700 | and the 23 single strands of chromosomes from mom

00:17:25.960 | into the same cell.

00:17:28.040 | Now that requires a literal physical contact

00:17:31.820 | and pairing of the two cells.

00:17:33.520 | But as I mentioned before,

00:17:35.420 | all these eggs in mom are sitting in a vault

00:17:38.740 | and they're very, very immature.

00:17:40.660 | So the ovulatory cycle and the menstrual cycle

00:17:43.460 | are really about first eliminating

00:17:46.980 | half of the chromosomal pairs

00:17:48.640 | in that 23 sets of chromosomes

00:17:50.700 | and not getting rid of, for instance,

00:17:54.180 | half just going one to 11 or 12 to 23.

00:17:59.180 | That's not the goal.

00:18:00.300 | The goal is to have chromosomes one, two, three, four,

00:18:02.780 | five, six, all the way up to 23,

00:18:04.920 | but only to have half of the chromosomes there.

00:18:07.140 | And to bring that cell together

00:18:09.240 | with the sperm cell physically,

00:18:11.340 | then allow them to fuse

00:18:12.980 | and allow the chromosomes from dad

00:18:14.940 | and the chromosomes from mom

00:18:17.060 | to fuse within a single cell

00:18:18.320 | and duplicate into cells that contain

00:18:21.060 | half of the chromosomes from dad

00:18:22.620 | and half of the chromosomes from mom.

00:18:24.340 | That's what the ovulatory and menstrual cycle

00:18:26.340 | are really all about.

00:18:27.940 | So when thinking about it that way,

00:18:29.140 | I'd like to just initiate the discussion

00:18:31.040 | by focusing first on the female component

00:18:33.960 | or the egg component of fertility and fertilization.

00:18:38.040 | As I mentioned before, a female has all the eggs,

00:18:43.400 | albeit very immature eggs that she's going to have

00:18:46.300 | at the time that she's born.

00:18:48.420 | Now, puberty will happen at some point

00:18:52.500 | and will allow the ovulatory

00:18:54.460 | and the menstrual cycle to commence.

00:18:57.260 | Now, one question that you perhaps are asking is

00:18:59.240 | what controls the onset of puberty?

00:19:01.040 | And there are a number of different results,

00:19:04.100 | each of which could be an entire episode

00:19:05.680 | of a podcast on its own.

00:19:07.180 | But I'll just highlight a few things that we know

00:19:09.460 | about the onset of menses or menstruation,

00:19:12.780 | or it's sometimes also called menarche, all right?

00:19:15.420 | One thing that you'll notice about today's discussion

00:19:17.100 | is that if you were to take any number of your notes online

00:19:19.980 | and put them into a search function,

00:19:22.340 | that you would see a lot of different language used

00:19:24.700 | for the same thing.

00:19:25.540 | So for instance, some people will talk about

00:19:26.780 | the egg and the follicle as the same thing,

00:19:28.660 | even though they are not.

00:19:29.900 | I'll explain the difference soon.

00:19:31.200 | Some people will talk about menses or menstruation

00:19:33.460 | or menarche is the exact same thing.

00:19:35.060 | And in fact, they are not the exact same thing,

00:19:37.360 | but oftentimes these words are used interchangeably.

00:19:40.280 | I'll do my best today to not overload you with nomenclature,

00:19:43.220 | but rather to use the most commonly used terms

00:19:47.000 | for the different aspects of fertility and fertilization.

00:19:49.980 | But when it comes to the onset of puberty,

00:19:52.860 | first of all, most of you have probably heard

00:19:55.320 | that the onset of puberty is happening much earlier

00:19:59.840 | in females now than it was some years ago.

00:20:02.180 | And in fact, that is the case.

00:20:04.220 | And I'll talk about some statistics related to this,

00:20:06.620 | which are pretty striking,

00:20:08.180 | but don't necessarily point to anything detrimental.

00:20:11.760 | It doesn't necessarily mean that something bad is happening.

00:20:14.380 | What do we know for sure?

00:20:15.320 | Well, we know that there are a number of signals

00:20:18.260 | that come both through the brain and through the body

00:20:22.460 | and more likely both in order to control

00:20:24.440 | the onset of puberty in females.

00:20:26.300 | A couple of examples.

00:20:27.500 | The first is a mechanistic one.

00:20:29.460 | We know for instance, that the entire process

00:20:33.340 | of the ovulatory and menstrual cycle

00:20:35.420 | is initiated from the brain.

00:20:36.780 | We're going to get into this in a lot more detail

00:20:38.340 | in a few minutes, but there's a certain number of hormones

00:20:41.760 | and neurotransmitters that are communicated from the brain,

00:20:45.140 | a structure called the hypothalamus,

00:20:46.860 | which roughly sits above the roof of your mouth.

00:20:49.780 | And that communicates with a gland, an endocrine

00:20:53.180 | or hormone releasing gland called the pituitary gland.

00:20:56.620 | The pituitary gland looks like a stalk

00:21:00.020 | that essentially extends out of the brain.

00:21:02.900 | It's also located not far from the roof of your mouth.

00:21:06.060 | And that has two sort of small marble

00:21:08.820 | or grape-sized protrusions,

00:21:12.480 | the anterior pituitary and the posterior pituitary.

00:21:14.900 | And they release different hormones into the bloodstream.

00:21:18.320 | Puberty is in part controlled by the fact

00:21:21.540 | that up until puberty, there are neurons in the hypothalamus

00:21:25.900 | that release a neurotransmitter called GABA,

00:21:27.940 | which is inhibitory.

00:21:28.940 | And that prevents the neurons in the hypothalamus

00:21:32.220 | from releasing a very important hormone

00:21:35.860 | called gonadotropin-releasing hormone or GnRH.

00:21:39.260 | So the first thing I'd really like everyone to know

00:21:41.640 | and commit to memory today is very easy.

00:21:43.540 | GnRH stands for gonadotropin-releasing hormone.

00:21:46.880 | This comes from the brain and will communicate

00:21:49.420 | to the pituitary to release certain hormones.

00:21:52.420 | Prior to puberty in both males and females,

00:21:56.140 | there are neurons in the brain

00:21:57.660 | that are actively suppressing the neurons

00:22:00.180 | that release GnRH.

00:22:01.480 | It's like no puberty, no puberty, no puberty.

00:22:04.340 | Can't have puberty, can't have puberty.

00:22:05.840 | And in fact, those cells are releasing

00:22:08.340 | this neurotransmitter called GABA because it's inhibitory,

00:22:11.300 | prevents the firing of those neurons.

00:22:13.620 | So puberty is actively suppressed up until a certain point.

00:22:17.140 | It's also actively suppressed at least in some species.

00:22:19.900 | And we think at least partially in humans,

00:22:22.380 | by the tonic release, that means the ongoing release

00:22:25.800 | around the clock of a hormone called melatonin.

00:22:29.540 | Later in life, in fact, after puberty,

00:22:32.640 | melatonin will be secreted only in the dark phase

00:22:36.300 | of each night and around the time that one goes to sleep.

00:22:39.240 | But in children and in particular in children

00:22:42.460 | prior to puberty, melatonin is released

00:22:44.960 | more or less constantly.

00:22:46.820 | Now, melatonin isn't the only source of suppression

00:22:49.260 | of puberty, it's also these neural mechanisms

00:22:51.460 | involving GABA, but it is certainly a great candidate

00:22:55.980 | for one of the reasons why puberty

00:22:57.500 | doesn't generally tend to happen at say age four, age five.

00:23:00.480 | That would be very unusual.

00:23:01.820 | Another component of suppression of puberty

00:23:07.600 | is that typically in children,

00:23:09.480 | they have relatively low body fat stores.

00:23:11.700 | Why is this important?

00:23:12.700 | Well, we know that one of the things

00:23:15.140 | that can trigger the onset of puberty,

00:23:16.780 | in particular in females,

00:23:18.820 | is that when enough body fat accumulates,

00:23:22.340 | that body fat releases a hormone called leptin.

00:23:25.780 | And that hormone leptin travels in the bloodstream

00:23:28.500 | across the blood brain barrier and goes to the hypothalamus

00:23:31.340 | and can trigger the onset of puberty

00:23:32.940 | by activating the neurons

00:23:34.980 | that release gonadotropin-releasing hormone.

00:23:37.620 | So many people believe that one of the reasons

00:23:40.300 | that puberty is happening earlier and earlier in females

00:23:43.800 | is because of the accumulation of more body fat

00:23:47.260 | at younger ages than was observed 30 or 40

00:23:51.180 | and certainly 100 years ago.

00:23:52.940 | Now I can already imagine a number of people are thinking,

00:23:55.660 | oh, this must relate to the obesity crisis.

00:23:57.900 | And indeed there is a crisis of obesity.

00:23:59.780 | Obesity is something that is causing all sorts of problems

00:24:04.780 | with people's health at various levels, brain and body.

00:24:08.060 | And that is far more frequent today

00:24:09.700 | than it was even 20 years ago.

00:24:11.760 | So it is indeed a crisis

00:24:13.120 | because it has enormous detrimental effects

00:24:15.360 | for so many aspects of brain and body health and longevity.

00:24:20.340 | But this whole process of thinking about body fat

00:24:22.840 | signaling leptin to the hypothalamus

00:24:24.380 | and the onset of puberty doesn't necessarily

00:24:26.880 | have to do with the obesity crisis.

00:24:28.440 | It might relate, but it could also relate to, for instance,

00:24:31.480 | improved nutrition, which is allowing body fat stores

00:24:34.300 | to accumulate, maybe not to the level of obesity,

00:24:36.840 | but to accumulate earlier and at younger ages in females,

00:24:40.640 | which is then causing earlier puberty in females.

00:24:44.400 | To just highlight how that might be possible,

00:24:46.680 | I want to review some data that talk about

00:24:49.380 | the onset of menses, menstruation, that is puberty,

00:24:52.780 | in females according to country and according to age

00:24:56.480 | over the last 100 or more years.

00:24:58.920 | So what are the general trends

00:25:00.400 | in terms of the onset of puberty in females?

00:25:02.180 | Well, that's an easy one to answer.

00:25:04.960 | Over the last 100 years or so,

00:25:07.100 | the onset of puberty has been occurring much earlier

00:25:12.400 | with each passing decade.

00:25:13.880 | It's really an incredible set of statistics.

00:25:16.400 | I will provide a link to these data

00:25:18.680 | since I know a number of you are listening

00:25:20.040 | and not just watching on YouTube.

00:25:21.720 | This is from a study in which the onset of puberty

00:25:25.400 | has been analyzed from as early as the 1850s, right?

00:25:29.200 | In certain countries, there are data on that.

00:25:31.580 | Out to the 1970s in another country starting at about 1900,

00:25:35.920 | extending out to about 1990.

00:25:37.480 | These are ongoing collections of data,

00:25:40.020 | but just to give you a sense how the data are falling out

00:25:43.060 | in a couple of different countries,

00:25:44.440 | just to give you a flavor.

00:25:46.160 | But for those of you listening

00:25:48.180 | and for those of you watching,

00:25:50.260 | the essence of all of these findings

00:25:52.420 | is that puberty is happening much, much earlier

00:25:54.840 | with each passing decade.

00:25:56.120 | So for instance, in the United States,

00:25:59.560 | around 1900 or 1903, the average age of men are,

00:26:04.080 | the onset of puberty in females was about 14 years old.

00:26:08.080 | Whereas in 1990, the average age is 11.

00:26:11.940 | So that's a pretty significant,

00:26:13.600 | we can say acceleration of the onset of puberty.

00:26:17.600 | Now, of course, these are averages,

00:26:18.960 | so there will be exceptions.

00:26:20.400 | There's a distribution of data.

00:26:22.600 | Today still, there will be young females

00:26:25.040 | who will undergo puberty at age 11 or 10,

00:26:27.460 | or maybe even nine and others who will undergo puberty

00:26:29.820 | at age 13, 14, maybe even 16 or 17.

00:26:33.420 | However, if we look at, for instance, the data from Norway,

00:26:36.880 | which dates back quite far,

00:26:38.400 | they have excellent record keeping to 1850.

00:26:41.680 | What we see is that the average age

00:26:43.760 | of the onset of female puberty in 1850 in Norway

00:26:47.800 | was 17 years old.

00:26:49.720 | Whereas in 1970, it's 13 years old.

00:26:53.700 | So this is a dramatic acceleration of the onset of puberty.

00:26:57.360 | And you see a similar trend in other countries as well.

00:26:59.540 | So if we were to look in, for instance, in the UK,

00:27:03.100 | they have a smaller data set,

00:27:05.000 | meaning it only extends back to about 1940,

00:27:07.760 | but the average age of the onset of puberty in the UK

00:27:11.200 | in 1940 was 13 and a half years old.

00:27:13.680 | Again, this is just for females.

00:27:15.640 | And in 1970, it was closer to 13

00:27:18.500 | with a trend towards declining even further.

00:27:20.880 | Unfortunately, they didn't continue

00:27:21.920 | to collect data out to 2022.

00:27:24.840 | And as a final point, if we were to look at,

00:27:27.040 | for instance, in Germany and Finland,

00:27:29.420 | the average onset of puberty in 1870

00:27:32.960 | was 16 and a half years old.

00:27:34.960 | By 1940, it was down to 13 and a half years old.

00:27:38.200 | So all of these data have borne out over and over again,

00:27:42.240 | regardless of location in the world,

00:27:43.940 | which is important because when you start to think

00:27:45.440 | about the obesity crisis, you can say, well,

00:27:46.920 | that's mainly in developed countries, believe it or not,

00:27:49.720 | or perhaps not surprisingly.

00:27:51.260 | And maybe it has to do with the obesity crisis.

00:27:53.500 | And yet I don't think we can conclude that at all.

00:27:56.300 | Something is happening.

00:27:57.660 | However, it could be increased body fat stores

00:28:01.140 | due to overeating and obesity.

00:28:02.640 | However, it could also be unrelated to obesity.

00:28:05.360 | It could be, for instance, improved nutrition

00:28:08.340 | and the availability of quality nutrition,

00:28:11.220 | which can signal the maturation

00:28:13.260 | of the brain and body mechanisms

00:28:14.780 | that trigger the onset of puberty,

00:28:17.000 | ovulatory cycle and menstruation.

00:28:18.880 | So we want to be very careful about leaping to conclusions

00:28:21.340 | about what these trends mean,

00:28:22.560 | but the trends themselves are very, very apparent.

00:28:25.760 | And as a final point, I should also mention

00:28:27.660 | that there are a number of different behavioral

00:28:29.920 | and psychosocial, as they're called,

00:28:32.080 | interactions that can influence puberty as well.

00:28:34.640 | This has been most strikingly observed in animals.

00:28:37.500 | And so I don't want anyone to be alarmed

00:28:39.340 | or to leap to any great conclusions

00:28:41.180 | about the onset of timing of puberty in humans,

00:28:43.680 | but I'd be remiss if I didn't tell you

00:28:45.520 | about a certain result,

00:28:46.680 | which shows that if a young female is exposed to the odor,

00:28:51.680 | not necessarily the pheromones, right?

00:28:54.140 | There's a distinction between odors that we perceive

00:28:56.740 | and pheromones, which are subconscious, right?

00:28:59.820 | We don't actively perceive, but that can impact our biology.

00:29:03.360 | And pheromone effects in humans are very controversial.

00:29:05.520 | But we know, for instance, that if you take a female animal,

00:29:08.520 | and there's some evidence from humans

00:29:10.680 | that if you take a young pre-pubertal female

00:29:13.780 | and you expose her to the scent

00:29:17.320 | of a reproductively competent male

00:29:20.780 | for a series of days,

00:29:24.060 | but maybe even as short as a few hours,

00:29:26.940 | and she is also not regularly being exposed

00:29:30.660 | to the scent of her father,

00:29:32.720 | that she can undergo puberty earlier.

00:29:35.000 | That's right.

00:29:35.840 | There is something about the odor and/or pheromones,

00:29:39.680 | or perhaps something else that occurs

00:29:42.840 | when a young pre-pubertal female has a father

00:29:47.360 | that she's in regular contact with,

00:29:48.680 | he wouldn't necessarily have to live at home,

00:29:50.160 | but that is around a lot that his smell, excuse me,

00:29:53.760 | is registered by her biological systems

00:29:56.780 | that I don't want to say protects

00:29:58.960 | because it kind of skews the valence of the conversation,

00:30:02.120 | but that offsets or buffers the otherwise observed effect,

00:30:07.120 | which is that the scent of a reproductively competent male,

00:30:11.800 | if it's present often enough or perhaps intensely enough,

00:30:15.060 | that it can trigger the onset of puberty in that female.

00:30:17.380 | In other words, the scent of a male that is not the father,

00:30:22.160 | and we think also that is not biologically related to her,

00:30:25.160 | can trigger earlier onset of puberty,

00:30:28.040 | and that effect can at least be partially buffered

00:30:32.520 | by her being in the presence of the scent

00:30:36.040 | from her biological father.

00:30:38.040 | Now, some of you are probably already leaping to conclusions

00:30:40.520 | about what this means.

00:30:41.440 | Should you not allow your daughter to be exposed

00:30:44.240 | to any males who are of reproductive age, et cetera?

00:30:46.840 | And that's certainly not what I'm saying.

00:30:48.800 | There's a huge number of considerations

00:30:50.220 | that go into that calculation for everybody

00:30:52.720 | in circumstances, et cetera.

00:30:54.600 | But the point is that the odors of individuals,

00:30:59.080 | both related, in particular closely related

00:31:02.320 | and non-related individuals,

00:31:05.520 | can shape the neural systems and the hormone systems

00:31:10.400 | that can trigger the onset of puberty

00:31:11.920 | or suppress the onset of puberty.

00:31:13.660 | So whether or not we're talking about onset of puberty

00:31:15.860 | at this age or that age,

00:31:17.020 | and whether or not biologically related male

00:31:20.100 | or non-biologically related male scents around, et cetera,

00:31:23.580 | the thing I want everyone to know

00:31:25.040 | is that at some point during development,

00:31:27.900 | typically nowadays between the ages of 11 and 15 or so,

00:31:32.900 | again, there's variability there,

00:31:34.900 | the suppression of gonadotropin-releasing hormone

00:31:39.600 | released from the hypothalamus is removed.

00:31:41.800 | And then gonadotropin-releasing hormone

00:31:44.520 | can activate cells within the pituitary.

00:31:47.240 | And if you really want to know,

00:31:48.420 | it's the anterior pituitary in particular,

00:31:50.920 | and then the anterior pituitary gland,

00:31:53.360 | which sits at and kind of bridges the brain and the body,

00:31:57.280 | because it allows the release of hormones

00:32:00.100 | into the bloodstream,

00:32:01.420 | that anterior pituitary is going to release two key hormones

00:32:04.780 | that everyone should know the name of and what they do.

00:32:07.360 | And when I say everyone, I mean,

00:32:08.560 | males and females need to know about these hormones

00:32:11.320 | because they have an active role in both males and females.

00:32:14.000 | And of course, you should want to know

00:32:16.400 | and should know about the biology

00:32:18.200 | of everyone on the planet, in my opinion,

00:32:21.000 | because it tells you a lot more about humans

00:32:22.920 | than if you just focus on your own biology.

00:32:24.960 | But those two hormones are called luteinizing hormone,

00:32:28.500 | which is abbreviated LH,

00:32:31.280 | and follicle-stimulating hormone,

00:32:33.760 | which is abbreviated FSH, okay?

00:32:35.840 | So the simple picture that you need to have in your mind

00:32:38.840 | is gonadotropin-releasing hormone from the brain,

00:32:41.200 | from the hypothalamus in particular,

00:32:43.560 | is causing the release of luteinizing hormone

00:32:46.960 | and follicle-stimulating hormone.

00:32:49.040 | GNRH stimulates LH, luteinizing hormone,

00:32:53.040 | and follicle-stimulating hormone, FSH.

00:32:55.120 | LH and FSH travel in the blood

00:32:57.920 | and can access all the cells and tissues of the body.

00:33:00.220 | This is one of the incredible things about hormones

00:33:02.520 | is that many hormones and LH and FSH

00:33:07.480 | are included in this group, can travel into cells,

00:33:11.800 | and they can actually change the genetic expression

00:33:14.480 | of those cells.

00:33:15.320 | They can change which genes are turned on

00:33:16.880 | and which genes are turned off,

00:33:17.920 | and they can also attach to the surface of those cells

00:33:21.640 | and make those cells take on different properties.

00:33:23.320 | So they can mature those cells.

00:33:24.640 | So for instance, a good example of this

00:33:26.680 | outside of the context we've been talking about

00:33:29.060 | is the hormone testosterone can travel to the hair follicle

00:33:32.460 | and can stimulate changes in the genes

00:33:34.160 | of the cells of the hair follicle that can make hair grow.

00:33:37.160 | A different hormone, estrogen,

00:33:38.880 | can travel to the cells of the breast tissue

00:33:41.840 | and activate genes that control enlargement

00:33:43.920 | of the cells of the breast tissue.

00:33:45.480 | Prolactin, a different hormone,

00:33:46.760 | can travel to the mammary ducts

00:33:48.480 | and control the production and the secretion of milk.

00:33:52.180 | And in males, that can actually happen in certain cases,

00:33:55.400 | although it's rare, but prolactin can also travel

00:33:58.240 | to areas of the brain that control libido, for instance.

00:34:01.040 | And just so you'll never forget it,

00:34:03.380 | males' elevated levels of prolactin

00:34:05.400 | are actually what set the refractory period

00:34:07.500 | after ejaculation and prevent erection

00:34:09.600 | for some period of time.

00:34:10.960 | So you'll never forget prolactin.

00:34:12.620 | The point being that different hormones

00:34:16.140 | have different effects on different cells,

00:34:17.840 | depending on what cells those are, right?

00:34:19.660 | Estrogen or estradiol is going to have different effects

00:34:21.640 | on the breast tissue than it would on skin,

00:34:24.440 | although it has effects on both.

00:34:25.940 | Similarly, when LH and FSH, luteinizing hormone

00:34:29.740 | and follicle stimulating hormone,

00:34:31.280 | travel in the blood to the gonad,

00:34:34.840 | and the gonad is an ovary,

00:34:36.840 | it will have a certain set of consequences.

00:34:39.860 | And when luteinizing hormone

00:34:41.020 | and follicle stimulating hormone travel in the blood

00:34:43.580 | to a gonad and that gonad happens to be a testy,

00:34:46.640 | then it will have a different set

00:34:47.800 | of biological implications.

00:34:49.720 | So let's focus now on what happens

00:34:51.680 | when LH and FSH arrive at the ovary.

00:34:55.000 | And let's assume now that we're talking about a female

00:34:58.980 | who has already undergone puberty,

00:35:00.920 | or perhaps we could even frame this in the context

00:35:04.500 | of a female who is about to undergo puberty.

00:35:07.600 | FSH and LH are now able to be released

00:35:10.200 | because she's undergoing puberty,

00:35:12.260 | but the same set of processes essentially would occur

00:35:15.400 | for any point from puberty onward until menopause,

00:35:19.480 | which is the depletion of that vault,

00:35:22.000 | that ovarian reserve of all those immature eggs.

00:35:25.680 | I'd like to take a brief break

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00:36:34.340 | Okay, so we're now going to talk about

00:36:35.760 | ovulation and menstruation,

00:36:37.000 | and let's just remember what this is all about.

00:36:39.000 | This is all about creating the potential

00:36:41.800 | for an egg to be fertilized,

00:36:43.240 | and that egg needs to have half of the chromosomal pair.

00:36:47.220 | So no pairs,

00:36:48.160 | but it's got to have 23 chromosomes just from mom.

00:36:51.240 | And we need to position that egg

00:36:53.540 | so that the egg can be met by the sperm,

00:36:56.760 | and that sperm can penetrate that egg

00:36:59.000 | and donate its 23 individual strands of chromosomes

00:37:04.000 | to that egg so that you can bring together

00:37:05.800 | the DNA of dad and the DNA of mom.

00:37:09.440 | So the ovulatory and menstrual cycle occurs

00:37:12.600 | when luteinizing hormone and follicle stimulating hormone

00:37:16.360 | have been released,

00:37:18.240 | and the ovulatory/menstrual cycle,

00:37:21.920 | and here I have to kind of pick what I want to call it.

00:37:24.880 | I guess to be really accurate,

00:37:26.240 | we would just call it the female reproductive cycle,

00:37:28.480 | but that includes underneath it,

00:37:30.720 | but the menstrual cycle, as it's sometimes called,

00:37:32.640 | and the ovulatory cycle.

00:37:33.840 | So you decide, I'm going to interchangeably discuss

00:37:37.100 | the ovulatory cycle and the menstrual cycle.

00:37:39.680 | The problem is when you say menstruation,

00:37:41.180 | people often think about just the period,

00:37:42.960 | the shedding of the uterine lining

00:37:44.640 | when fertilization has not occurred.

00:37:46.660 | So if I start saying ovulatory cycle,

00:37:49.480 | just keep in mind I'm referring to the entire thing.

00:37:52.480 | Now, this is probably also a good opportunity to say

00:37:55.480 | that if you heard that the ovulatory/menstrual cycle

00:37:59.320 | is 28 days long, that's true in some cases,

00:38:02.840 | but that's not always true.

00:38:04.280 | It's on average 28 days long.

00:38:07.300 | There are some females for which the ovulatory cycle

00:38:11.160 | will be shorter, can be as short as 21 days,

00:38:13.860 | and other females for which it will be 35 days long.

00:38:18.520 | Shorter than 21 days and longer than 35 days is rare,

00:38:21.560 | although it does occur.

00:38:22.760 | One of the key things when thinking about fertility

00:38:25.560 | is if you talk to OB/GYNs who are focused on fertility,

00:38:28.560 | which I have in anticipation of this episode,

00:38:30.800 | they'll tell you that whether or not your cycle

00:38:33.660 | is 21 days long or 35 days long

00:38:36.860 | is not as much of an issue necessarily

00:38:39.560 | unless it's happening to become much shorter

00:38:42.800 | or much longer in a kind of erratic way.

00:38:45.880 | So if you're somebody who's consistently had

00:38:48.280 | 23 day long cycles and all of a sudden

00:38:50.140 | you're having 30 day long cycles,

00:38:51.640 | that's not necessarily an indication of anything bad,

00:38:54.480 | but if it's 21 days, one month,

00:38:56.800 | and it's 30 days the next month,

00:38:58.200 | and that's 17 days the next month,

00:39:00.300 | or even if it's always falling

00:39:02.660 | within that 21 to 35 day long cycle,

00:39:05.060 | but it's very variable from each month

00:39:07.340 | or every other month or so,

00:39:08.760 | you probably want to talk to your OB/GYN

00:39:11.900 | because that could indicate a number of different things.

00:39:14.040 | Which things could it indicate?

00:39:15.280 | Well, that will become clear as I spell out the biology

00:39:17.860 | in a bit more detail, okay?

00:39:19.300 | But this idea that the menstrual cycle,

00:39:21.640 | ovulatory cycle is always 28 days, that's just false.

00:39:24.300 | That's just not true.

00:39:25.840 | I should also mention that there is a common misconception

00:39:29.380 | that because the average menstrual cycle is 28 days,

00:39:32.360 | indeed the average is 28 days,

00:39:34.320 | and the lunar cycle is 28 days,

00:39:36.740 | and of course there is real biology

00:39:38.140 | to support the fact that the lunar cycle

00:39:39.760 | can in fact impact certain aspects of human behavior.

00:39:43.560 | It does, and we'll talk about lunar cycles

00:39:45.520 | in a future episode,

00:39:46.940 | but there is zero data to support the idea

00:39:50.180 | that the menstrual cycle and the lunar cycle

00:39:53.100 | are linked in any kind of causal way.

00:39:55.800 | I'm sorry to break it to you,

00:39:57.580 | the lunar cycle and the tidal cycles at the ocean

00:40:01.500 | are definitely linked in ways that are super interesting

00:40:03.700 | related to the tilt of the earth

00:40:04.540 | and the pull of gravity of different planets,

00:40:06.500 | and it's an incredible story into itself,

00:40:09.160 | but the lunar cycle and the menstrual cycle,

00:40:11.240 | despite having some weak correlation

00:40:13.500 | in terms of their duration or their so-called periodicity,

00:40:18.340 | no pun intended,

00:40:19.320 | well, there's no causal relationship whatsoever

00:40:22.820 | between the lunar cycle and the menstrual cycle.

00:40:25.360 | If any of you are aware of any real data

00:40:28.880 | that conflict with what I just said,

00:40:30.600 | please put that in the comment section on YouTube,

00:40:33.540 | but this is pretty well established as far as I know.

00:40:36.440 | Okay, so we need to bring together

00:40:39.280 | the so-called haploid contents,

00:40:42.060 | the 23 individual strands of chromosomes from the egg

00:40:45.700 | to a place in a position

00:40:47.120 | where it could potentially be fertilized by the male.

00:40:49.420 | So what happens?

00:40:50.520 | Luteinizing hormone and follicle stimulating hormone

00:40:52.920 | travel to the ovary.

00:40:54.580 | These hormones are able to access the ovary.

00:40:56.340 | There's a lot of blood supply to the ovary,

00:40:59.020 | and FSH and LH arrive at the ovary.

00:41:03.640 | The ovary has this vault,

00:41:05.160 | this ovarian reserve of immature cells.

00:41:07.840 | They reside within what are called follicles.

00:41:09.500 | The follicles are little spherical packages

00:41:12.720 | that can potentially provide a nice environment

00:41:15.680 | for those eggs to mature.

00:41:17.900 | And when FSH in particular arrives at the ovary,

00:41:23.340 | a small number of those follicles

00:41:26.000 | will split off from the reserve.

00:41:28.880 | They will exit the vault and they will undergo maturation.

00:41:33.040 | And the key player here is follicle stimulating hormone.

00:41:37.640 | And the first 14 days of the menstrual ovulatory cycle

00:41:41.720 | is referred to as the follicular phase

00:41:44.360 | because of this relationship between FSH

00:41:46.520 | triggering the maturation of a subset of follicles.

00:41:49.920 | Now, typically in the context of a 28 day or so

00:41:53.740 | ovulatory menstrual cycle,

00:41:55.300 | day one is designated as the first day of the period

00:41:58.320 | of the shedding of the uterine lining

00:42:00.480 | from the previous ovulatory menstrual cycle

00:42:04.280 | in which fertilization did not occur, okay?

00:42:07.180 | So day one is when the period initiates.

00:42:10.100 | It is days one through 14 approximately, right?

00:42:14.000 | 'Cause here we're just considering

00:42:14.940 | the average of a 28 day cycle,

00:42:16.320 | but it could be longer, it could be shorter.

00:42:18.000 | But the first half of that cycle

00:42:20.120 | is the so-called follicular phase.

00:42:21.480 | FSH has triggered the departure of a subset

00:42:25.000 | of these follicles that contain immature eggs.

00:42:27.860 | And it is triggering the maturation of those eggs.

00:42:30.820 | Luteinizing hormone is also present,

00:42:33.320 | but also at relatively low levels.

00:42:35.560 | And it's during the first half

00:42:36.600 | of this ovulatory menstrual cycle

00:42:38.620 | that the main goal is to get those follicles to mature.

00:42:41.440 | So inside of those follicles, the egg is developing,

00:42:44.640 | it's growing, it's maturing.

00:42:47.480 | And in doing so, it's also making its own hormones.

00:42:51.200 | This I think is one of the most elegant aspects

00:42:54.020 | of the ovulatory menstrual cycle

00:42:56.040 | that in a few minutes you'll learn about something

00:42:58.120 | which still to this day,

00:42:59.160 | even though I've known about this stuff for decades now

00:43:01.560 | because of my training, still just blows my mind

00:43:04.360 | that you have one hormone, follicle stimulating hormone,

00:43:07.920 | triggering the maturation of some eggs

00:43:10.520 | inside of some follicles.

00:43:11.520 | And then those follicles themselves making another hormone

00:43:14.920 | that furthers the process.

00:43:17.220 | And then soon, as you'll learn,

00:43:19.880 | create a hormone to trigger the second half of the process.

00:43:22.720 | Just a beautiful symphony of expression of different genes

00:43:26.640 | and different hormones to make everything work

00:43:28.800 | as optimally as possible.

00:43:30.320 | So as these different follicles mature somehow,

00:43:33.780 | and we still don't know exactly how,

00:43:36.000 | one of those follicles containing an egg gets selected.

00:43:40.880 | It's either because it matures the fastest

00:43:42.920 | or there's something about it

00:43:45.080 | that is still not completely understood

00:43:48.420 | that allows it to be selected.

00:43:50.560 | And all the other follicles that are maturing

00:43:53.420 | degenerate and die, and they're gone.

00:43:55.560 | They don't go back into the ovarian reserve.

00:43:58.020 | They are now depleted from that bank account

00:44:01.140 | that is the ovarian reserve.

00:44:03.260 | They die off, but that single egg

00:44:07.540 | that keep in mind contains 23 pairs of chromosomes, right?

00:44:11.600 | We haven't gotten rid of one half of those 23 sets

00:44:15.360 | of chromosomes yet, but that one will continue to mature.

00:44:18.800 | And then at some point,

00:44:20.600 | that egg will start to undergo a process

00:44:26.320 | in which those chromosomes are pulled apart

00:44:29.380 | by little components within the egg called spindles.

00:44:33.580 | They literally have a physical pulling

00:44:35.420 | of the chromosomes apart.

00:44:36.440 | So now those 23 pairs are no longer attached

00:44:39.780 | to one another at the middle like they were before,

00:44:41.820 | like two beads of strings,

00:44:44.380 | or I should say 23 short strands of beads

00:44:48.440 | that were at once connected to one another

00:44:51.560 | now are pulled apart so that you have 23 chromosomes

00:44:55.220 | on each side, but they're pulled apart from one another.

00:44:58.780 | So that diploid cell is now starting to become a cell

00:45:03.780 | in which half of the chromosomes,

00:45:05.700 | half of those 23 pairs are physically pulled away

00:45:09.000 | from the others.

00:45:10.200 | And then the egg actually starts to form its own,

00:45:13.520 | what we call an involution of membrane

00:45:15.080 | around those 23 pairs, one set of them,

00:45:19.020 | and encapsulates them.

00:45:20.480 | So you've sort of got an egg with two parts

00:45:22.640 | where the two sets of chromosomes,

00:45:24.120 | two sets of 23 chromosomes are now separate

00:45:26.040 | from one another inside of the egg.

00:45:28.020 | And then one of those actually gets ejected from the egg.

00:45:31.960 | And the name of that thing that gets ejected,

00:45:34.320 | it's sort of like a little Hubble pod is how I imagine it,

00:45:37.600 | from "Star Wars" or from any kind of "Space Odyssey" movie

00:45:41.200 | where something is ready to happen,

00:45:43.280 | a little Hubble pod shoots out of the ship.

00:45:45.120 | Well, that 23 pairs is now ejected from the egg,

00:45:49.680 | it's called the polar body, and that's going to degenerate.

00:45:52.400 | It's going to go away.

00:45:53.840 | And in doing so, take the egg cell, which was once diploid,

00:45:57.080 | it had 23 pairs of chromosomes and making it haploid.

00:46:01.120 | And now what you've got in ideal circumstances

00:46:04.340 | is a beautifully pristine egg that was selected for

00:46:07.460 | and has 23 single strands of chromosomes,

00:46:10.900 | 22 autosomes and one sex chromosome.

00:46:12.640 | And that sex chromosome is going to be an X chromosome

00:46:15.500 | almost with certainty because female mother

00:46:19.860 | is creating that egg.

00:46:22.560 | So then the egg that contains just the appropriate

00:46:25.940 | 23 single stranded chromosomes

00:46:28.840 | is going to fuse with the wall of the ovary

00:46:30.780 | and that egg will be released

00:46:33.180 | and will travel into the fallopian tube.

00:46:36.140 | Now we'll get back to that egg in a few moments,

00:46:38.200 | but that process, which represents the first half

00:46:40.600 | of the ovulatory menstrual cycle,

00:46:42.140 | again, was triggered by FSH

00:46:43.600 | and to some extent luteinizing hormone,

00:46:45.920 | but it is the ongoing maturation of that egg,

00:46:49.900 | which also causes the production of estrogen,

00:46:53.840 | which allows that whole process to occur.

00:46:55.940 | And you could say, why?

00:46:57.080 | Well, the answer to the why

00:46:58.920 | is a very important biological principle

00:47:00.780 | that we are going to return to

00:47:01.860 | in a number of different contexts today,

00:47:03.280 | both as reference to female and male fertility.

00:47:08.140 | And the principle is a so-called negative feedback.

00:47:12.580 | So when estrogen is present

00:47:14.220 | at relatively low levels in females,

00:47:17.300 | in the ovary as it is during the development of these eggs,

00:47:21.460 | some of that estrogen of course is going to exit the ovary.

00:47:25.140 | It's going to go into the bloodstream

00:47:26.380 | and it's going to travel back to the pituitary.

00:47:29.820 | Now the pituitary can release things

00:47:32.220 | like follicle stimulating hormone and luteinizing hormone.

00:47:34.880 | But the way I'd like you to think about the pituitary

00:47:37.180 | for sake of feedback loops

00:47:38.840 | is that it's sort of like a thermometer

00:47:40.980 | that you would put into a pool,

00:47:43.180 | like a backyard pool that is attached to the heater.

00:47:46.540 | And for instance,

00:47:47.780 | if you were to put a thermometer into a pool

00:47:50.460 | that you would like to keep at 70 degrees

00:47:52.900 | and the temperature of that pool is 60 degrees,

00:47:55.700 | well, then that thermometer ought to trigger

00:47:58.220 | some sort of mechanism where the pool would heat up

00:48:01.020 | until the temperature of the pool hit 70 degrees

00:48:03.220 | and then it should trigger that thermometer

00:48:05.300 | to turn off the heating system, okay?

00:48:06.940 | That's kind of a negative feedback system

00:48:08.580 | that would keep the temperature more or less correct.

00:48:11.740 | That's a lot of the way that the system's related to estrogen

00:48:14.820 | and also testosterone and these different things

00:48:16.740 | like luteinizing hormone

00:48:17.580 | and follicle stimulating hormone work as well.

00:48:20.060 | Typically, when the level of a hormone is too high,

00:48:24.360 | then it shuts down the production of the hormones

00:48:26.780 | that would trigger further production of that hormone.

00:48:28.800 | I know that's a mouthful, it's a lot to think about

00:48:30.620 | and some of you are probably thinking,

00:48:31.460 | well, I'm getting dizzy now with biology,

00:48:33.540 | but I promise you can understand this.

00:48:35.420 | In females, when estrogen is relatively low,

00:48:38.340 | but not zero, but is relatively low

00:48:40.020 | during that first follicular half of the ovulatory cycle,

00:48:43.920 | it actually triggers negative feedback on LH and FSH

00:48:47.180 | so that not too much is produced.

00:48:49.220 | But then just prior to ovulation,

00:48:51.700 | the levels of estrogen

00:48:53.060 | and the levels of some other hormones from those eggs,

00:48:56.620 | you have the eggs producing estrogen themselves,

00:48:59.400 | gets high enough that it actually triggers

00:49:01.560 | a positive feedback loop on the pituitary.

00:49:04.640 | So the pituitary is essentially observing

00:49:07.740 | the amount of estrogen in the bloodstream

00:49:09.280 | produced by the ovary and the amount of estrogen

00:49:11.680 | towards the end of the second half of the menstrual cycle

00:49:14.280 | has increased and triggers a positive feedback loop.

00:49:18.080 | It triggers the pituitary to release more FSH and LH

00:49:22.080 | and that helps trigger ovulation, okay?

00:49:25.240 | That deployment or the release

00:49:27.500 | of that one mature proper selected egg

00:49:30.160 | that's haploid with the 23 individual pairs of chromosomes

00:49:33.500 | into the fallopian tube.

00:49:35.740 | So let's just back up really quickly

00:49:37.260 | and just kind of summarize what's happened.

00:49:38.740 | Gonadotropin-releasing hormone from the hypothalamus

00:49:41.600 | triggers the release of follicle-stimulating hormone

00:49:43.620 | and luteinizing hormone.

00:49:44.900 | That travels to the ovary,

00:49:46.120 | triggers the release of a subset of immature follicles

00:49:50.220 | with immature eggs.

00:49:51.880 | Those immature follicles and immature eggs

00:49:55.100 | start to mature, start to grow

00:49:57.780 | because of the presence of follicle-stimulating hormone.

00:50:00.740 | The growth of those eggs themselves increases estrogen.

00:50:04.420 | As the estrogen starts to accumulate in the environment,

00:50:06.760 | some of that travels back to the pituitary

00:50:09.080 | and when levels of estrogen arriving at the pituitary

00:50:12.640 | are relatively low, the pituitary says,

00:50:15.740 | "Oh, we don't need to release any more

00:50:17.360 | follicle-stimulating and luteinizing hormone."

00:50:19.220 | However, at some point, just prior to ovulation,

00:50:21.680 | enough estrogen has been produced

00:50:23.240 | by that one single selected mature egg

00:50:26.120 | and some of the other follicles around it

00:50:28.140 | that were maturing but then since died off,

00:50:31.360 | that the estrogen triggers a positive feedback loop.

00:50:34.340 | The pituitary says, "Okay,"

00:50:36.520 | and releases more follicle-stimulating hormone

00:50:38.620 | and luteinizing hormone and bam,

00:50:40.700 | the egg, which has the proper genetic components,

00:50:44.520 | sets off out of the ovary and into the fallopian tube.

00:50:48.400 | So-called ovulation has begun, okay?

00:50:51.880 | That itself, what I just described,

00:50:53.660 | constitutes the first half of the ovulatory menstrual cycle,

00:50:56.800 | which we call the follicular phase

00:50:58.320 | and it's marked by the presence of FSH

00:51:00.480 | and some other things but we can really think about it

00:51:02.840 | as marked by FSH from the pituitary

00:51:05.680 | and by estrogen or estradiol made within the ovary.

00:51:09.880 | Okay, then comes the second half

00:51:11.640 | of the ovulatory menstrual cycle,

00:51:13.560 | which I personally think is one of the coolest mechanisms

00:51:16.440 | in all of biology, which is that,

00:51:19.220 | remember the follicle that housed that one egg

00:51:22.300 | that was the selected egg that became the mature egg?

00:51:24.980 | And that follicle, which no longer contains the egg

00:51:27.760 | because the egg took off and ovulated,

00:51:29.620 | is called the corpus luteum

00:51:30.820 | and the corpus luteum starts making three hormones,

00:51:34.500 | which include estradiol, a thing called inhibin,

00:51:36.900 | but the most important hormone,

00:51:38.220 | the one that you really need to know about,

00:51:39.720 | is that it starts producing very high levels of progesterone.

00:51:44.620 | Progesterone levels start to increase

00:51:47.820 | about the time of ovulation,

00:51:49.840 | although just prior to ovulation

00:51:51.600 | and over the next second half of the ovulatory cycle,

00:51:56.200 | so about 14 days if it's a 28 day cycle,

00:51:58.640 | a little bit longer, a little bit shorter,

00:51:59.660 | depending on the length of the cycle,

00:52:01.080 | levels of progesterone in the second half

00:52:03.000 | of the ovulatory cycle are going to increase by 1400 fold

00:52:08.000 | compared to what they were in the first half

00:52:10.920 | of the ovulatory cycle.

00:52:12.760 | So again, if we were to characterize

00:52:14.240 | the menstrual ovulatory cycle in broad strokes,

00:52:18.480 | what we would say is that FSH and estrogen

00:52:22.260 | mark the initial part, the first half,

00:52:25.400 | so-called follicular phase,

00:52:26.640 | and that the estrogen and FSH set in motion ovulation

00:52:30.940 | and they prime the system

00:52:32.960 | for the production of a corpus luteum,

00:52:34.500 | which produces progesterone,

00:52:36.580 | and the second half of all of this

00:52:38.700 | is called the luteal phase.

00:52:41.000 | The second half of the ovulatory menstrual cycle

00:52:43.140 | is the luteal phase because of corpus luteum,

00:52:46.620 | this otherwise discarded tissue that produces progesterone.

00:52:50.540 | What does progesterone do?

00:52:52.320 | Well, progesterone impacts the uterine lining,

00:52:56.680 | so-called endometrium, or the lining,

00:52:58.740 | the mucus lining of the uterus,

00:53:01.060 | where that egg that's ovulated

00:53:03.180 | is potentially going to implant if it's fertilized.

00:53:06.760 | And so in a kind of perfect way,

00:53:09.280 | or I should say in a seemingly perfect way,

00:53:12.440 | the egg is off on its way, it might get fertilized.

00:53:15.980 | The remnants of the compartment that let go of that egg

00:53:19.860 | produce a hormone that then prepares

00:53:22.860 | the endometrial lining of the uterus

00:53:25.200 | for the potential implantation of that egg.

00:53:27.280 | It's basically making the bed for the fertilized egg

00:53:30.120 | to potentially embed in, to implant in,

00:53:33.260 | and then achieve all the nourishment that it needs

00:53:35.680 | to grow eventually into a healthy embryo and child.

00:53:39.360 | Just an amazing set of biological mechanisms

00:53:42.200 | if you ask me, because what you're observing here

00:53:45.840 | is an incredible economy of function,

00:53:48.320 | whereby the same cellular components

00:53:50.520 | that are producing the egg,

00:53:52.340 | well, some of them are being discarded,

00:53:53.600 | but they're not being discarded without purpose.

00:53:56.200 | They're being discarded in a way that triggers

00:53:58.440 | the onset of hormonal expression

00:54:01.000 | that then prepares the fertilized egg

00:54:02.840 | to be in an enriched environment in which it can thrive.

00:54:05.920 | Now, I realize that was a lot of detail,

00:54:07.680 | but we have a couple of key themes.

00:54:09.560 | We've got the hypothalamus, GnRH.

00:54:11.520 | We've got the pituitary with LH and FSH,

00:54:14.240 | and those hormones travel to the ovary.

00:54:16.480 | The ovary has eggs in a vault,

00:54:20.080 | basically immature eggs in a vault.

00:54:21.920 | Some of those are activated by the presence

00:54:24.000 | of FSH and LH each month,

00:54:26.280 | and one of those eggs will be selected

00:54:29.080 | and will ovulate.

00:54:30.240 | The remnants of the follicle and egg that are not selected,

00:54:33.160 | the chromosomes that you don't need

00:54:34.760 | or disappear in the polar body,

00:54:36.920 | and the corpus luteum gives rise to progesterone

00:54:40.000 | and sets in motion the second half

00:54:41.680 | of the ovulatory menstrual cycle,

00:54:43.920 | which is the luteal phase,

00:54:45.360 | which is essentially the potential for that fertilized egg

00:54:48.480 | to embed in a nice nourishing environment.

00:54:51.140 | And of course, we should all be thinking

00:54:52.280 | if the egg is fertilized,

00:54:53.600 | and then it lays down in the nice comfy uterine lining

00:54:56.680 | that's been prepared by progesterone in the corpus luteum,

00:55:00.720 | well, then everything's fine and good.

00:55:02.940 | But what if fertilization doesn't occur?

00:55:04.880 | Well, we all know what happens

00:55:05.960 | if fertilization doesn't occur.

00:55:07.080 | If fertilization does not occur for whatever reason,

00:55:10.000 | that uterine lining is going to shed,

00:55:12.880 | and that's actually what's referred to as the period.

00:55:14.920 | It's the actual removal or the departure, rather,

00:55:19.160 | of the thickened endometrium lining of the uterus

00:55:24.080 | when fertilization has not occurred.

00:55:27.100 | And of course, if that happens,

00:55:29.920 | we need another ovulatory menstrual cycle.

00:55:32.440 | So how does that happen?

00:55:33.280 | Well, the hormone inhibin is also made

00:55:35.800 | by the corpus luteum and doesn't go quite as high

00:55:39.480 | as the hormone progesterone,

00:55:41.280 | but it kind of tracks that increase in progesterone

00:55:44.860 | that occurs in the second half of the ovulatory cycle.

00:55:47.960 | But then if fertilization does not occur,

00:55:50.960 | inhibin levels start to drop.

00:55:53.440 | And what I haven't told you is what inhibin does.

00:55:55.960 | Inhibin, in concert with other hormones like estrogen,

00:55:59.800 | feed back to the hypothalamus

00:56:01.600 | and prevent the further release

00:56:03.400 | of follicle stimulating hormone and luteinizing hormone.

00:56:05.880 | If you have an egg that gets fertilized and can implant,

00:56:09.920 | well, then you don't want more eggs to mature.

00:56:13.380 | You want to hold onto the ones in the vault.

00:56:15.660 | You don't want them to mature.

00:56:17.700 | And hormones like inhibin and, again,

00:56:20.100 | working with other hormones are going to prevent

00:56:22.140 | the secretion of things like FSH and LH.

00:56:24.600 | Now, typically, people are not getting pregnant every month.

00:56:27.800 | In fact, that's not possible.

00:56:29.560 | And part of the reason it's not possible

00:56:31.240 | is that if the fertilized egg implants,

00:56:33.600 | there are a number of different hormone cascades

00:56:35.080 | that shut down the production of things like GnRH, FSH,

00:56:38.080 | and LH in ways that prevent further maturation of follicles

00:56:42.720 | in a follicular phase.

00:56:44.080 | But in the instance where fertilization does occur

00:56:47.120 | and menstruation occurs,

00:56:49.260 | and I should mention that the duration of menstruation,

00:56:52.040 | the actual bleeding,

00:56:52.880 | typically is anywhere from one to five days.

00:56:55.860 | The "heaviness," the lightness or heaviness of that bleeding

00:56:59.920 | will depend on, you guessed it,

00:57:02.080 | the amount of progesterone

00:57:04.100 | that is secreted from the corpus luteum.

00:57:05.940 | That's one of the key players there.

00:57:08.320 | And if menstruation occurs,

00:57:11.580 | well, then inhibin levels also drop,

00:57:14.600 | progesterone levels also drop.

00:57:16.120 | And when that occurs, there's a positive feedback signal

00:57:20.640 | up at the level of the pituitary.

00:57:23.080 | The pituitary literally can register

00:57:25.240 | how much inhibin and progesterone and estrogen

00:57:27.960 | is present in the bloodstream.

00:57:29.640 | And if those levels are sufficiently low,

00:57:32.440 | well, then GnRH gets secreted again,

00:57:35.400 | FSH gets secreted again, and LH gets secreted again.

00:57:39.040 | And the first half, the follicular phase

00:57:41.240 | of the menstrual cycle initiates all over again.

00:57:44.480 | It's hard to overstate how beautifully orchestrated

00:57:46.960 | this entire system is,

00:57:48.800 | the number of feedback loops and feedforward loops.

00:57:51.500 | I think if you can just generally understand

00:57:53.360 | that the first half of the menstrual ovulatory cycle

00:57:56.000 | is marked by the maturation of the follicles and FSH,

00:57:58.920 | and that the second half is marked by the accumulation

00:58:01.720 | of progesterone and the thickening of the uterine lining

00:58:04.820 | should fertilization and implantation occur,

00:58:07.780 | I think that you will certainly understand

00:58:09.760 | the female reproductive cycle better

00:58:11.760 | than most people out there.

00:58:13.560 | It will also help you understand a number of things

00:58:15.200 | that are sometimes associated

00:58:16.720 | with the female reproductive cycle.

00:58:18.200 | For instance, there are data showing that in many,

00:58:20.560 | not all, but in many women,

00:58:22.920 | in the four to five days prior to ovulation,

00:58:26.660 | there is a dramatic increase in libido.

00:58:28.880 | That dramatic increase in libido

00:58:30.520 | is triggered by a number of things,

00:58:31.960 | but some of those things include the spike in FSH

00:58:35.400 | that occurs, the spike in LH that occurs,

00:58:38.520 | and some associated increases in androgens,

00:58:41.660 | things like DHEA and testosterone,

00:58:44.000 | which just as in males can be related to libido,

00:58:47.680 | in females, trigger libido.

00:58:49.360 | You can imagine why this would be an effective mechanism

00:58:51.880 | to have in place in females,

00:58:54.240 | if the goal, as it were, certainly of the egg,

00:58:58.560 | perhaps not of the woman as a whole,

00:59:00.680 | but if the goal is to fertilize the egg.

00:59:04.080 | So increases in libido just prior to the onset of ovulation.

00:59:08.480 | There's also been a lot of discussion and interest,

00:59:11.600 | and frankly, data exploring the malaise that can occur

00:59:15.740 | at certain portions of the menstrual cycle.

00:59:18.900 | And there's a lot of misconception about this.

00:59:21.200 | A lot of people have focused on the malaise

00:59:25.000 | that can occur around the time of bleeding,

00:59:27.800 | but there are actually stronger data to support

00:59:31.240 | the fact that some, again, some, not all women,

00:59:34.140 | experience a kind of malaise,

00:59:35.800 | sometimes associated with anxiety, sometimes not,

00:59:38.480 | that's associated with the mid to second half

00:59:41.640 | of the luteal phase of the ovulatory menstrual cycle.

00:59:46.640 | And that, despite what people commonly think,

00:59:51.080 | is not associated with elevated levels of estrogen,

00:59:53.720 | it's actually associated with the depletion

00:59:55.800 | in estrogen levels that can occur during certain portions

00:59:59.280 | of that second half of the luteal phase

01:00:01.980 | of the menstrual cycle.

01:00:03.400 | So again, this is highly variable.

01:00:06.760 | For some people, they might not experience any malaise

01:00:09.360 | at any point during their menstrual cycle.

01:00:11.500 | Other individuals also, for instance,

01:00:12.880 | might not experience any variation in their libido

01:00:15.480 | at any point during their menstrual cycle.

01:00:17.120 | Again, highly variable,

01:00:18.240 | and yet there are some statistically significant trends

01:00:21.020 | that have been observed that track

01:00:22.640 | to very specific hormonal components

01:00:24.380 | within the menstrual cycle.

01:00:25.760 | Again, this will all be very contextual.

01:00:28.740 | And of course, this can play out

01:00:30.740 | in a number of different ways.

01:00:31.640 | So for instance, some women experience very heightened levels

01:00:34.160 | of sensitivity to caffeine at certain portions

01:00:36.440 | of their menstrual cycle.

01:00:37.720 | Other women experience more cramping than others,

01:00:41.200 | different portions of their menstrual cycle.

01:00:43.000 | Tremendous variation from individual to individual.

01:00:46.280 | One of the, I view it as an advantage,

01:00:48.740 | but one of the things that many females

01:00:51.800 | can really do and experience,

01:00:53.920 | because they have cycles that occur every month

01:00:56.200 | that are fairly dramatic in terms of their levels of hormone.

01:00:59.280 | So for instance, a more than thousand-fold increase

01:01:02.700 | in progesterone during the luteal phase

01:01:04.640 | of the menstrual cycle.

01:01:05.740 | And I should also mention a 200-fold increase in estrogen

01:01:09.200 | during the period just prior to ovulation.

01:01:11.160 | That's why they always say estrogen primes progesterone.

01:01:14.440 | That's what you learn in kind of basic endocrinology

01:01:16.520 | when you're learning the menstrual cycle.

01:01:17.740 | Estrogen in the first half of the menstrual cycle

01:01:19.800 | primes progesterone in the second half

01:01:21.960 | of the ovulatory menstrual cycle.

01:01:24.220 | Well, those estrogen increases just prior to ovulation

01:01:28.000 | are in part responsible for the increases in libido,

01:01:32.300 | but it's also the presence of increased androgen

01:01:35.020 | just prior to ovulation.

01:01:36.080 | So there's a lot of complex interplay.

01:01:38.300 | I think what we will do is we will reserve the discussion

01:01:41.220 | about libido per se and some of the other aspects

01:01:44.680 | related to sexual differentiation

01:01:45.960 | that we were talking about earlier for a future episode.

01:01:48.040 | But hopefully now you have in mind

01:01:49.680 | what the ovulatory menstrual cycle is.

01:01:51.920 | It is a signal from the brain, from the hypothalamus,

01:01:55.400 | which then triggers a signal from the pituitary,

01:01:57.640 | an endocrine gland,

01:01:58.720 | which then signals the release of hormones

01:02:02.120 | that travel to the ovary and that control two things,

01:02:05.140 | maturation of eggs

01:02:06.680 | and the identification of one egg in particular,

01:02:09.240 | and then preparation of the milieu,

01:02:13.600 | the environment in which that fertilized egg

01:02:15.820 | could potentially land and mature

01:02:18.200 | into a healthy embryo and child.

01:02:21.160 | So if you have that framed up in your mind,

01:02:23.080 | and even if you just extracted maybe 10 to 15%

01:02:26.240 | of the hormones and different aspects that I described

01:02:29.000 | up until now,

01:02:30.080 | I would consider you far more knowledgeable

01:02:32.880 | about this entire process than 99% of people out there,

01:02:37.240 | certainly not the OBGYNs and urologists,

01:02:39.240 | but the 99% of individuals out there.

01:02:42.440 | It also frames up for us the second half of this whole story

01:02:46.160 | about fertility and fertilization,

01:02:48.000 | which is the generation of sperm

01:02:50.200 | and how the sperm eventually arrive at the egg

01:02:53.580 | and how certain sperm are selected

01:02:56.020 | to potentially fertilize that egg,

01:02:58.800 | whereas others never really stand a chance.

01:03:01.160 | So next, we're going to talk about sperm.

01:03:03.060 | We're going to talk about what sperm are,

01:03:04.720 | where they are generated and how they are generated

01:03:06.800 | and how they need to travel both within the male

01:03:09.360 | and within the female in order to allow fertilization

01:03:12.800 | to potentially occur.

01:03:14.000 | I'd like to take a brief break

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01:04:18.680 | So we've covered the ovulatory cycle in females.

01:04:21.760 | And I confess it was a lot of information

01:04:24.180 | with a lot of biological nomenclature,

01:04:26.520 | but I promise you that many of those same themes

01:04:29.080 | and indeed the same names and nomenclature

01:04:32.060 | will show up in the discussion that we're going to have now,

01:04:34.200 | which is about the generation of sperm.

01:04:36.600 | Now, sperm are similar to eggs

01:04:40.020 | in the sense that they are part of the germline.

01:04:41.880 | They're these protected cells,

01:04:43.720 | protect in the sense that the activities of an individual

01:04:47.640 | are not going to change the genetic makeup of those cells.

01:04:52.040 | Now, again, there are instances in which mutagens,

01:04:55.140 | such as chemicals could disrupt the genomes

01:04:59.360 | of the germ cells in males, just as it could in females.

01:05:01.960 | But in general, the activities, the things that we do,

01:05:05.160 | the experiences we have,

01:05:06.640 | doesn't tend to change the genome of those cells.

01:05:09.440 | However, there are a lot of lifestyle factors,

01:05:11.460 | dos and don'ts, nutrition and supplements

01:05:13.320 | and prescription drugs, et cetera,

01:05:14.800 | that can indeed modify the quality of the sperm.

01:05:18.940 | And we'll talk about what sperm quality means.

01:05:20.880 | But the point is that the sperm cell,

01:05:25.200 | much like the egg cell, are both germline cells.

01:05:29.000 | They're not like somatic cells, they are unique populations.

01:05:31.560 | And let's just remember what the job of the sperm cell is.

01:05:34.440 | The job of the sperm cell is to deliver the genetic material

01:05:38.220 | from the father and to do that

01:05:40.460 | in the form of a haploid cell.

01:05:42.940 | So that means 23 chromosomes, 22 autosomes,

01:05:47.680 | one so-called sex chromosome.

01:05:50.620 | Again, not sex the verb, at least not in this case.

01:05:52.520 | Sex the verb is a discussion

01:05:54.040 | we're going to have in a few minutes.

01:05:55.680 | But sex the noun, the sex chromosome

01:05:58.080 | can either be an X chromosome or a Y chromosome.

01:06:01.640 | Okay, so 22 autosomes and then one sex chromosome

01:06:04.600 | is going to be contained within the sperm

01:06:06.960 | because it's a haploid cell, not a diploid cell.

01:06:09.480 | Remember the egg was diploid, then it became haploid.

01:06:11.300 | The sperm cells are cells that are created

01:06:15.100 | through the division of other cells.

01:06:16.420 | But after that division occurs

01:06:18.100 | through a process called meiosis,

01:06:19.820 | the sperm cell is going to contain 23 chromosomes

01:06:24.540 | consisting of 22 autosomes and one sex chromosome.

01:06:27.620 | And the sperm that manages to deposit its DNA contents

01:06:32.180 | into the egg to fertilize the egg

01:06:34.320 | will either have an X sex chromosome or a Y sex chromosome.

01:06:39.280 | And the Y sex chromosome

01:06:41.000 | has a number of different genes on that chromosome

01:06:43.800 | that will suppress, for instance,

01:06:45.640 | the development of the female reproductive axis.

01:06:49.320 | One good example would be

01:06:50.360 | the Mullerian-Inhibiting Hormone or MIH,

01:06:53.480 | the gene for Mullerian-Inhibiting Hormone,

01:06:55.780 | which is a hormone that prevents

01:06:57.240 | the formation of the Mullerian ducts,

01:06:59.200 | which is part of the female reproductive structure.

01:07:02.480 | Well, that gene controls the prevention

01:07:07.060 | of the development of the female genitalia

01:07:09.660 | and in doing so promotes

01:07:12.060 | the development of the male genitalia.

01:07:13.660 | And there are other examples of genes

01:07:14.980 | that are on the Y chromosome

01:07:16.240 | that give you what we call male phenotype, right?

01:07:19.140 | You have genotype and phenotype.

01:07:20.620 | By the way, in case you haven't heard this in a while

01:07:22.940 | from your high school biology,

01:07:24.020 | or if you never heard it, no big deal,

01:07:25.740 | karyotype is the complement of chromosome XX or XY.

01:07:30.500 | And there are individuals out there that are XXY or XYY,

01:07:33.680 | a discussion for our episode on sex differentiation.

01:07:36.760 | That's karyotype with a K.

01:07:38.840 | Then there's genotype, which are the genes that you have.

01:07:41.120 | And then there's phenotype spelled P-H,

01:07:43.240 | P-H-E-N-O-T-Y-P-E, phenotype.

01:07:47.560 | And the phenotype is how the genes,

01:07:51.400 | which then code for RNA, which code for protein,

01:07:54.960 | how those are expressed in terms of things like eye color.

01:07:57.680 | So eye color is a phenotype, height is a phenotype,

01:07:59.720 | hair color is a phenotype.

01:08:00.720 | Okay, so you have karyotype, genotype, and phenotype.

01:08:02.960 | Well, what we need to do is we need to bring together

01:08:05.680 | that sperm, which is haploid,

01:08:07.640 | it contains those 23 chromosomal strands

01:08:10.760 | with either an X or a Y.

01:08:12.280 | Sex chromosome is the 23rd chromosome.

01:08:14.400 | We need to get that cell to the egg.

01:08:17.920 | And so when we talk about spermatogenesis,

01:08:20.720 | of course we're talking about the generation of sperm cells,

01:08:24.200 | but what we're really talking about

01:08:25.620 | is the generation of cells whose job

01:08:27.980 | is to deliver the genetic material from dad to the egg

01:08:31.040 | within the female in a way that increases the probability

01:08:36.040 | that not only will that egg be fertilized,

01:08:38.780 | but that it will progress in a healthy way

01:08:41.700 | with each set of chromosomes from mom and from dad,

01:08:44.860 | each set of 23 chromosomes that is,

01:08:46.600 | will progress in a healthy way,

01:08:49.320 | will implant in a healthy way,

01:08:51.800 | and will maintain and grow in a healthy way

01:08:55.040 | to a healthy embryo and child and eventually adult.

01:08:58.840 | That's the job of the sperm, okay?

01:09:01.240 | So as we talk about spermatogenesis,

01:09:03.280 | let's just remember that

01:09:05.120 | and why they're there in the first place.

01:09:06.720 | Now, a few things about sperm that are interesting,

01:09:09.540 | besides the fact that they're haploid

01:09:11.640 | and besides the fact that, as you all know, they swim,

01:09:14.320 | they have a head and a tail.

01:09:15.220 | They actually have a head, a mid-region, and a tail,

01:09:17.440 | and that mid-region turns out to be very important.

01:09:19.600 | It's something we'll come back to again and again.

01:09:21.060 | That mid-region is really key for the ability for sperm

01:09:24.460 | to engage in forward progression, to swim forward.

01:09:27.440 | It involves the activity of mitochondria,

01:09:30.020 | which are involved in generation of ATP,

01:09:33.200 | which is involved in all aspects of energy in all cells.

01:09:36.480 | But let's just remember that the sperm are swimming cells.

01:09:40.280 | And in order to create a really good swimmer

01:09:43.240 | or set of swimmers, you need a couple of things.

01:09:45.560 | First of all, within the testes is where the sperm develop.

01:09:50.160 | And unlike in females and unlike in the ovary,

01:09:53.560 | there's no vault of sperm.

01:09:55.080 | The sperm are continually being generated.

01:09:57.640 | It takes about 60 days for sperm to be born

01:10:01.080 | from their parent cells,

01:10:02.680 | because cells actually give rise to other cells,

01:10:04.600 | that's the way it works,

01:10:05.520 | to be born from their parent cells and then mature

01:10:07.440 | to the point where they can be a really good swimmer.

01:10:09.740 | Now, that doesn't mean that a bunch of sperm

01:10:13.560 | are made on day one, and then 60 days later,

01:10:16.840 | all those sperm are deployed in the form of ejaculate,

01:10:19.360 | and then the cycle starts over again.

01:10:21.020 | So it's a little different

01:10:21.860 | than the ovulatory menstrual cycle.

01:10:23.760 | Rather at any given point in time,

01:10:25.760 | like right now, if you have testes,

01:10:27.240 | you have some sperm in your testes that are immature

01:10:31.680 | and cannot swim, cannot deliver those contents

01:10:35.400 | to those genetic contents rather to the female egg,

01:10:38.920 | and you have some sperm that are mature,

01:10:40.460 | and you very likely have some sperm that are so mature

01:10:43.840 | that they are dying off or that they're dead.

01:10:46.160 | Almost certainly also, regardless of your age,

01:10:48.720 | you have some sperm that are healthier than others,

01:10:51.440 | are better swimmers than others.

01:10:53.080 | This is just the way the system works.

01:10:56.160 | Now, the process of spermatogenesis

01:10:59.440 | involves a couple of things,

01:11:00.460 | but a lot of the players are the same as the process

01:11:02.700 | of developing the so-called oocyte, the immature egg.

01:11:05.980 | We've got GnRH from the hypothalamus.

01:11:10.800 | That's going to be a player.

01:11:11.640 | We have FSH, follicle stimulating hormone,

01:11:13.880 | although the name's a little bit of a misnomer

01:11:15.780 | in the context of spermatogenesis,

01:11:17.360 | because in the context of spermatogenesis,

01:11:19.380 | there is no follicle.

01:11:20.700 | What we're really talking about as FSH for stimulating

01:11:23.540 | the maturation of the sperm cell,

01:11:26.180 | so not egg follicle, but sperm cell,

01:11:28.480 | but we still have GnRH, FSH, LH,

01:11:31.480 | and rather than the ovary being the target

01:11:33.580 | of those hormones, it's going to be the testes.

01:11:36.500 | So most everybody should know that the testes

01:11:39.780 | and the ovaries are the so-called gonads.

01:11:41.780 | The testes, of course, reside outside of the body.

01:11:46.180 | There are instances where the testes fail to descend

01:11:49.740 | during development.

01:11:50.700 | Certainly if the testes don't descend on time,

01:11:53.020 | that's something that doctors need to be made aware of,

01:11:55.180 | the pediatricians be made aware of,

01:11:56.980 | because that can prevent fertility.

01:11:59.960 | Why would that be?

01:12:00.860 | Well, it turns out that the testes reside outside the body

01:12:04.700 | in the scrotum because the temperature conditions

01:12:08.540 | under which spermatogenesis can occur

01:12:11.180 | and under which healthy sperm can be maintained

01:12:14.500 | are very restricted and is approximately two degrees cooler

01:12:20.340 | than the rest of the body.

01:12:21.820 | This is very important.

01:12:23.380 | I think this is something that used to be discussed

01:12:25.340 | a lot more, but isn't discussed so much these days,

01:12:29.000 | but keeping the testes cool enough

01:12:31.580 | doesn't necessarily mean keeping them cold,

01:12:32.980 | although there is a place for using cold exposure,

01:12:35.260 | deliberate cold exposure, to improve sperm quality

01:12:38.540 | and number and perhaps even testosterone levels.

01:12:40.820 | We'll talk about that a little bit later,

01:12:42.300 | but keeping the testes about two degrees cooler

01:12:46.540 | than the rest of the body is absolutely key.

01:12:49.200 | If sperm get too hot, they die.

01:12:51.940 | And if spermatocytes, the cells that give rise to sperm,

01:12:54.540 | get too warm, well then oftentimes the sperm that develop

01:12:58.500 | are not healthy, not healthy in a number of ways.

01:13:01.100 | Either they can't engage in fast forward progression

01:13:03.820 | and that is swimming, or they will lack the ability

01:13:08.540 | to deposit their DNA contents within the egg.

01:13:11.460 | So again, whatever is contained in the ejaculate

01:13:14.060 | is going to be a mixture of different sperm qualities

01:13:16.300 | and sperm of different ages will impact the quality,

01:13:19.600 | but also the temperature under which those sperm developed

01:13:24.600 | is going to impact their quality.

01:13:26.800 | And so we're going to get into tools a little bit later,

01:13:29.440 | as I mentioned, but just to give you a simple takeaway,

01:13:32.540 | if you are hoping to conceive in the next 90 days,

01:13:36.040 | the spermatogenesis cycle takes 60 days,

01:13:38.200 | but then the sperm actually have to migrate

01:13:40.040 | from the testicle into the so-called epididymis,

01:13:43.380 | which is a related structure,

01:13:45.360 | and then into the vas deferens and then into the urethra

01:13:48.160 | where it can be part of the ejaculate.

01:13:49.980 | In order for sperm to do all that properly,

01:13:53.180 | undergo that maturation and then exit in ejaculate

01:13:55.960 | in a way that's healthy or that the sperm is healthy,

01:13:58.660 | if you plan to conceive children

01:14:02.360 | or to try and conceive children in the next 90 days,

01:14:05.320 | you definitely want to avoid exposing your testicles,

01:14:08.980 | that is your scrotum, to elevated temperatures.

01:14:13.040 | So that means definitely avoiding hot tubs,

01:14:16.220 | definitely avoiding hot baths.

01:14:17.640 | Now, a brief hot bath or hot tub or hot shower

01:14:19.840 | isn't going to be a problem,

01:14:21.040 | although if you're really interested in conceiving,

01:14:23.640 | I would avoid hot tubs and hot baths as much as possible,

01:14:27.420 | hot showers are probably fine.

01:14:28.880 | But if you're going to go into a sauna, for instance,

01:14:32.080 | you might want to rethink that decision,

01:14:33.600 | and if you do decide to,

01:14:34.640 | you almost certainly would want to bring a cold pack in

01:14:37.980 | that you could hopefully put some material

01:14:40.120 | between the cold pack and the scrotum

01:14:42.220 | so you don't get a cold burn, but put something there,

01:14:44.860 | but keep the scrotal tissue cool, keep it cold to cool,

01:14:49.860 | because heat exposure can really mutate

01:14:53.240 | and disrupt the developing sperm and it can kill sperm.

01:14:57.220 | And so again, that would be for an entire 90 days

01:15:00.860 | leading up to your attempts to conceive.

01:15:03.540 | Again, we'll get into more tools later,

01:15:04.940 | but a number of people also have probably heard

01:15:07.600 | of the boxers versus briefs controversy, I guess it is,

01:15:12.140 | or whether or not people call it going commando

01:15:14.840 | with no underwear of any kind, boxers, briefs,

01:15:19.360 | or otherwise, rather.

01:15:21.040 | Turns out that the data on that point to the fact

01:15:23.000 | that there isn't really a big difference

01:15:24.840 | in terms of sperm quality if people wear boxers or briefs

01:15:29.000 | or don't wear anything under their jeans or shorts at all.

01:15:32.260 | The scrotum has the ability to move the testicles

01:15:37.280 | far enough away from the body

01:15:38.740 | in order to achieve lower temperatures.

01:15:40.360 | If it needs to, it achieves that through a muscle

01:15:42.160 | called the cremaster muscle,

01:15:43.660 | which is a really interesting muscle, believe it or not.

01:15:46.480 | I was reading up on the biology of the cremaster muscle,

01:15:48.400 | something I never thought I'd spend too much time on,

01:15:50.600 | but that I ended up spending far too much time

01:15:52.920 | reading up about, and it's really fascinating.

01:15:54.520 | What you have is a muscle that has a smooth muscle tissue,

01:15:58.860 | unlike skeletal muscle, which is striated muscle,

01:16:01.560 | that is temperature dependent.

01:16:03.000 | So it has certain nerve endings

01:16:05.040 | and it has certain receptors on it

01:16:07.080 | that allow it to respond to local temperature

01:16:09.320 | and then to relax in order to essentially let the testicles

01:16:13.860 | to descend further from the body

01:16:15.440 | or to contract and bring the testicles closer to the body

01:16:17.900 | in order to try and maintain the optimal temperature range.

01:16:20.680 | And it turns out the cremaster muscle can achieve that

01:16:23.360 | whether or not people are wearing boxers or briefs,

01:16:25.320 | although it stands to reason that any kind of,

01:16:28.400 | there's no other name for it, undergarments,

01:16:31.320 | I don't know why that word just seems kind of antiquated,

01:16:33.600 | but undergarment that allows some movement

01:16:36.320 | of the scrotum and the testicles

01:16:38.340 | should be sufficient to allow these temperature variations

01:16:41.540 | to occur and keep things in range.

01:16:44.080 | That said, a little bit later,

01:16:45.420 | we'll go into some detail really,

01:16:47.720 | because it's important as to why, for instance,

01:16:50.460 | if you are somebody who has big thighs, believe it or not,

01:16:53.220 | that it actually can lower sperm count substantially,

01:16:55.660 | whether or not the big thighs occur

01:16:56.620 | because you're very muscular,

01:16:57.580 | the big thighs occur because you are overweight,

01:17:00.820 | it can increase the temperature.

01:17:02.440 | If you're sitting a lot,

01:17:03.440 | increases scrotal temperature for sure.

01:17:06.080 | And there are some other things

01:17:07.200 | that can increase scrotal temperature,

01:17:08.840 | seat heaters in cars, for instance, terrible idea,

01:17:12.440 | just terrible idea if you're hoping to conceive

01:17:14.440 | in the near future.

01:17:15.340 | And again, hot tub, things of that sort.

01:17:19.960 | Okay, so temperature modulation of spermatogenesis

01:17:24.240 | and sperm quality and function is key,

01:17:26.540 | that relates a little bit more to tools, but what happens?

01:17:28.720 | How does the actual sperm develop?

01:17:31.160 | Well, contained within the testicle, you have the cells,

01:17:35.000 | the so-called spermatogonia,

01:17:36.760 | which differentiate into so-called spermatocytes.

01:17:38.940 | You don't have to remember all this.

01:17:40.320 | And the spermatocytes undergo this process of meiosis.

01:17:43.120 | Meiosis is a form of cell division,

01:17:45.040 | which reduces the chromosome number

01:17:47.120 | to those 23 individual strands as opposed to pairs, right?

01:17:51.040 | So it makes them haploid as opposed to diploid.

01:17:53.460 | Very, very important for reasons

01:17:55.000 | that we talked about earlier.

01:17:56.120 | And the meiosis process in these primordial sperm cells,

01:18:00.640 | these immature sperm cells is similar

01:18:03.560 | to the meiosis process that occurs in eggs

01:18:06.080 | when the chromosomes segregate

01:18:07.560 | in that involves these spindle-like structures

01:18:10.860 | within the cell.

01:18:11.700 | Now, why do I keep bringing up the spindles?

01:18:12.960 | Well, it turns out that the function of the spindle

01:18:14.900 | in the egg and the sperm is heavily dependent

01:18:17.400 | on mitochondrial function.

01:18:19.200 | And later, when we get into tools

01:18:20.760 | for improving egg and sperm quality,

01:18:22.400 | you're going to hear about a lot of tools

01:18:23.720 | for improving mitochondria.

01:18:25.160 | And it's not just because the mitochondria are involved

01:18:27.440 | in energy demanding aspects of cell biology,

01:18:31.280 | but it's also because the mitochondria in this context

01:18:34.200 | are very, very important for the removal of,

01:18:38.640 | or the separation of one set of chromosomes

01:18:40.920 | to give you these two sets of haploid cells,

01:18:42.720 | the egg and the sperm.

01:18:44.400 | And this is so important

01:18:46.280 | because many failures at fertilization,

01:18:49.660 | many failures at implantation,

01:18:52.040 | many, many miscarriages and many birth defects

01:18:55.560 | that do survive after birth that are very detrimental,

01:18:58.460 | such as trisomies and things like that occur

01:19:01.880 | because the spindles don't effectively

01:19:04.640 | pull apart the chromosomes in typically the egg,

01:19:08.080 | but it can also occur in the sperm.

01:19:10.360 | Okay, so the spindles and the fact that mitochondria

01:19:12.880 | are rich on the spindle are very important

01:19:14.920 | for generating these haploid sperm,

01:19:16.440 | again, 23 individual strands of chromosomes,

01:19:18.600 | that's occurring inside of the testes, okay?

01:19:22.880 | So there's not as much long distance migration

01:19:25.960 | of the spermatocytes and the sperm cells

01:19:29.980 | as there is the egg, just when you think about

01:19:32.220 | the overall architecture of the uterus

01:19:33.900 | and the fallopian tubes compared to the testicles,

01:19:35.500 | but there's still a lot of movement.

01:19:36.560 | So within the testicle,

01:19:37.920 | if you were to look at the testicle in cross-section,

01:19:40.440 | and I prefer to call it that

01:19:41.640 | rather than cut the testicle in half,

01:19:43.060 | anytime you talk about anatomy,

01:19:44.140 | you actually talk about slicing things,

01:19:45.380 | that's what you would do with a cadaver is what I teach,

01:19:48.480 | and we do in my laboratory

01:19:50.600 | and frankly in biological laboratories all over the place.

01:19:54.180 | But when you talk about it,

01:19:55.020 | you talk about if you were to take a visual cross-section

01:19:58.140 | through the testicle,

01:19:59.060 | what you would find is that

01:20:00.260 | there are a lot of different little tubes,

01:20:01.900 | a lot of ducts, D-U-C-T-S, ducts, those are pathways.

01:20:06.900 | And the main ducts that are important for this discussion

01:20:10.620 | are called the seminiferous tubules, okay?

01:20:13.140 | So it's a mesh-like or network structure of tubes

01:20:17.460 | in the testicle, and the immature sperm

01:20:20.540 | sit on a little compartment along the edge of those tubes,

01:20:24.680 | and as they mature,

01:20:25.900 | they move towards the center of those tubes,

01:20:27.740 | and then when they are mature enough,

01:20:29.500 | those sperm cells actually drop into the hollow of the tube

01:20:33.340 | and then can travel through those tubes

01:20:35.880 | to a structure that's along the side of the testicle

01:20:40.120 | called the epididymis.

01:20:42.220 | The epididymis, again, is a series of ducts,

01:20:45.180 | and then the epididymis

01:20:46.820 | converges with something called the vas deferens, okay?

01:20:50.300 | I think in high school, we all remember this

01:20:51.740 | by thinking about it's the vas deferens.

01:20:53.540 | I don't know who came up with that.

01:20:55.060 | Maybe, I think it was a young girl sitting to the left of me

01:20:58.100 | that was like, "Oh, it's like the vas deferens."

01:20:59.600 | I never forgot that.

01:21:00.440 | I don't know, maybe it was the topic matter,

01:21:01.440 | maybe it was her, maybe it was some combination of the two,

01:21:03.140 | but in any case, the sperm go from the seminiferous tubules

01:21:06.780 | to the epididymis and then to the vas deferens

01:21:10.140 | and then are contained in the ejaculate

01:21:12.780 | along with seminal fluid.

01:21:14.660 | Now, the seminal fluid is the carrier fluid

01:21:18.740 | for the sperm themselves.

01:21:21.680 | This is important because it turns out

01:21:22.980 | that a lot of the things that can both negatively

01:21:25.300 | or positively impact the quality of the sperm

01:21:28.400 | relates not just to the sperm cells themselves

01:21:31.260 | and the temperature of the environment

01:21:32.440 | that they were matured in,

01:21:35.420 | but also to the semen quality.

01:21:38.420 | For instance, if you are a heavy drinker,

01:21:42.700 | if you are a smoker,

01:21:43.840 | or if you are a regular user of cannabis,

01:21:47.660 | especially if you smoke cannabis or vape cannabis,

01:21:51.420 | you create a lot of reactive oxygen species

01:21:54.680 | that disrupt the chemistry of the seminal fluid,

01:21:57.460 | which disrupts the sperm cells.

01:21:59.020 | So it's not a direct action always on the sperm cell itself,

01:22:01.900 | although it can be.

01:22:02.740 | So for instance, in the form of smoked tobacco or cannabis,

01:22:07.480 | there are a lot of carcinogens and mutagens

01:22:09.180 | that actually mutate the DNA,

01:22:10.480 | can cause DNA fragmentation and debilitate sperm.

01:22:13.520 | But there are also a lot of things

01:22:15.620 | created by smoking in particular,

01:22:19.420 | regardless of what's being smoked,

01:22:20.940 | that can create elevated reactive oxygen species

01:22:24.100 | and disrupt the seminal fluid

01:22:26.700 | that the sperm are contained in

01:22:28.940 | in the so-called ejaculate, the semen.

01:22:31.280 | Now, this will also become a relevant conversation later

01:22:35.020 | when we briefly talk about vasectomies.

01:22:37.500 | Vasectomies are literally a cutting of the vas deferens,

01:22:42.500 | which leads to a situation,

01:22:45.000 | provided the surgery was done correctly,

01:22:47.040 | where men can still achieve

01:22:49.480 | all the other aspects of intercourse.

01:22:51.000 | They can still achieve erection.

01:22:53.020 | They can still achieve orgasm.

01:22:54.900 | They can still ejaculate.

01:22:57.220 | But when they ejaculate, the seminal fluid is released,

01:23:00.300 | but there are no sperm contained within the seminal fluid.

01:23:02.760 | And it turns out that vasectomies

01:23:04.720 | are a very effective form of birth control.

01:23:07.540 | And they always check to see if zero sperm

01:23:09.860 | and confirm that zero sperm

01:23:10.880 | are being released in the ejaculate.

01:23:12.660 | They are reversible.

01:23:14.200 | That is, vasectomies are reversible, but not always.

01:23:17.800 | There are a subset of cases where it's not reversible,

01:23:19.940 | in which case, if people still want to have children,

01:23:21.500 | you have to go in and actually surgically extract sperm

01:23:25.420 | from the testicles.

01:23:26.580 | But it's a process in which the vas deferens is altered

01:23:31.580 | or severed in a way that the sperm

01:23:33.460 | can't actually exit the testicle.

01:23:36.120 | They can get into the epididymis usually,

01:23:37.660 | but not into the vas deferens and so on and so forth.

01:23:41.260 | So if you've ever wondered what a vasectomy is,

01:23:43.060 | that's what a vasectomy is.

01:23:44.420 | And I mentioned vasectomy now

01:23:47.460 | because it illustrates the difference

01:23:49.240 | between the seminal fluid, the semen,

01:23:50.940 | and the sperm that the semen contain, okay?

01:23:54.200 | So 60 days to generate the sperm,

01:23:56.940 | another two weeks or so for the sperm to travel

01:24:01.220 | through the various ducts to the point

01:24:02.480 | where they can be contained in the ejaculate.

01:24:05.300 | Let's talk about the sperm cells themselves.

01:24:07.900 | The sperm cells, again, have these 23 pairs

01:24:12.380 | of single-strand chromosomes.

01:24:13.860 | They're haploid, they have either an X or a Y.

01:24:16.080 | Sex chromosome is the 23rd so-called sex chromosome.

01:24:19.280 | And as we all know, they have a head.

01:24:21.060 | The head tends to be oval in most cases.

01:24:24.140 | The head contains very important enzymes and proteins

01:24:27.660 | that are designed to fuse with the much larger egg

01:24:30.900 | and to actually take the membrane of the sperm cell

01:24:33.700 | and combine to actually mesh with the egg cell's membrane

01:24:38.700 | and then deliver the genetic contents to the egg cell,

01:24:44.580 | in other words, to fertilize the egg cell.

01:24:46.880 | Now just behind the head is a region called the mid-region.

01:24:50.540 | That mid-region is a slightly thickened region.

01:24:54.340 | And here, of course,

01:24:55.180 | I'm talking about healthy sperm cell morphology.

01:24:57.640 | Morphology simply means shape.

01:24:59.360 | A mid-region, that mid-region has a bunch of things

01:25:02.760 | related to cell motility

01:25:04.560 | and to the forward progression of the cells.

01:25:07.520 | First of all, it is chock-a-block full of mitochondria.

01:25:10.820 | In fact, if you were to look just behind the head

01:25:12.500 | of the sperm, what you'd see is that

01:25:14.900 | it is completely surrounded by mitochondria.

01:25:18.980 | There are mitochondria elsewhere in the cell,

01:25:20.380 | but most of them are contained

01:25:21.660 | in this mid-region compartment

01:25:22.900 | just behind the head of the sperm.

01:25:26.060 | And that thick region is where the tail movement

01:25:29.700 | of the sperm, the flagellation back and forth

01:25:34.700 | is actually generated from.

01:25:37.960 | Much like if you were to hold a rope,

01:25:40.140 | like a battle rope in the gym

01:25:41.860 | and you were to whip the battle rope,

01:25:45.040 | the whip at the one end of the rope

01:25:47.020 | is what allows for the,

01:25:49.440 | let's just call it what it is,

01:25:52.620 | the curves in the rope, the oscillations,

01:25:54.700 | the rising and falling of the rope

01:25:56.460 | all the way out to the end, right?

01:25:57.700 | It is the force of the whip right at that end

01:26:02.500 | that you're, with the battle rope,

01:26:03.740 | you're doing with your hand and then with the sperm

01:26:05.300 | that is occurring just behind the head of the sperm

01:26:08.420 | that is actually going to dictate how fast

01:26:11.620 | and how well that sperm can swim.

01:26:14.160 | And indeed the sperm has to swim very far.

01:26:16.780 | How far?

01:26:17.620 | Well, on a relative scale,

01:26:19.420 | and again, these are estimations

01:26:21.080 | because they're going to be, how should we say?

01:26:23.780 | There will be differences in the distance

01:26:26.880 | from the head of the penis

01:26:29.880 | and where the ejaculation occurs to the cervix

01:26:33.960 | depending on the relative size of the vaginal canal

01:26:37.220 | and the penis that delivers the ejaculate

01:26:39.220 | to the vaginal canal.

01:26:40.340 | But once the sperm arrive at the cervix, okay,

01:26:44.260 | which is at the back of the vaginal canal,

01:26:46.580 | just at the opening to the uterus,

01:26:49.440 | once the sperm arrive there,

01:26:52.340 | the distance from the cervix to the egg,

01:26:55.540 | of course will vary depending on where that egg is

01:26:57.980 | in its ovulatory trajectory, its pathway,

01:27:01.020 | but it is a kin based, if you scale for size,

01:27:04.500 | to the distance between Los Angeles and San Francisco,

01:27:08.780 | which is many, many hundreds of miles.

01:27:10.580 | So those sperm have to swim very far.

01:27:12.660 | Now, of course, if the sperm are delivered

01:27:14.860 | in the vaginal canal somewhat further away,

01:27:17.620 | they will have further to go.

01:27:19.100 | If they're delivered right at the cervical opening,

01:27:21.100 | they will have less far to go.

01:27:22.900 | The very effective swimming sperm swim very fast.

01:27:27.600 | So they are able to accomplish that distance

01:27:29.660 | in just a few days.

01:27:30.860 | And this relates to a discussion

01:27:33.460 | that we will get into in a lot more detail later

01:27:36.140 | as to how often couples should have intercourse

01:27:39.820 | if they're trying to conceive.

01:27:41.440 | Many people might think, well, it's every day.

01:27:43.200 | However, the more frequent the ejaculation,

01:27:45.220 | the lower the concentration of sperm in each ejaculate.

01:27:49.160 | So this is not a discussion about how often

01:27:51.060 | to have intercourse, depending to your preferences

01:27:53.540 | for pleasure or bonding or whatever reason,

01:27:55.720 | this is a discussion about how often to have intercourse

01:27:58.560 | in order to optimize the probability

01:28:00.340 | of fertilization of the egg.

01:28:02.860 | There's some general rules that of course come to mind,

01:28:05.380 | which is ejaculations close to ovulation,

01:28:09.020 | both before, during, or sometimes after

01:28:12.860 | are obviously advantageous.

01:28:15.740 | But you will also hear OBGYNs and urologists

01:28:18.540 | suggesting intercourse every other day

01:28:21.420 | leading up to the day of ovulation,

01:28:23.940 | starting about three to four days out

01:28:26.600 | from the day of ovulation.

01:28:28.400 | So we got a little bit sidetracked,

01:28:30.120 | albeit I think appropriately so,

01:28:32.140 | and focusing on fertilization.

01:28:34.720 | But what we were talking about

01:28:35.920 | right up until the point of that

01:28:37.660 | is the anatomy of the sperm itself,

01:28:39.700 | which is the head, the mid region

01:28:41.320 | that contains all those mitochondria, and then the tail.

01:28:44.240 | Now, what we haven't discussed

01:28:46.340 | is the actual generation of the sperm.

01:28:48.380 | So if you're a male or if you're a female,

01:28:51.420 | I think it's really important to understand

01:28:53.740 | how spermatogenesis works.

01:28:55.520 | Spermatogenesis works in much in the same way

01:29:00.120 | that the generation and maturation of eggs work.

01:29:03.620 | Although, as I mentioned before,

01:29:04.840 | it's going to occur ongoing

01:29:06.860 | throughout the cycle of the male's life after puberty.

01:29:11.680 | We already talked about puberty,

01:29:12.840 | and I'll just cover this in two or three sentences

01:29:16.100 | as it relates to males.

01:29:17.680 | And it's essentially the same thing.

01:29:19.920 | The hypothalamus up until the point of puberty

01:29:24.300 | is providing suppression of the release of gonadotropin

01:29:28.200 | releasing hormone.

01:29:29.260 | Then some biological clock,

01:29:31.340 | which is still not clearly understood,

01:29:34.440 | it's probably not leptin coming from body fat.

01:29:38.060 | Again, unlike in the female,

01:29:39.580 | it's probably not leptin coming from body fat,

01:29:41.640 | but some other signal arrives to the hypothalamus,

01:29:44.900 | removes that inhibition,

01:29:45.960 | and GnRH, gonadotropin-releasing hormone,

01:29:48.380 | is now released onto the pituitary.

01:29:50.500 | A bunch of hormones are deployed from the pituitary.

01:29:52.820 | As a consequence, the two most important ones

01:29:54.980 | for the context of this discussion

01:29:56.660 | are follicle-stimulating hormone and luteinizing hormone.

01:30:00.260 | Follicle-stimulating hormone and luteinizing hormone

01:30:02.540 | travel to the testes,

01:30:05.000 | and they're going to do two main things.

01:30:06.600 | One, they're going to trigger the production of testosterone,

01:30:10.200 | and they're going to trigger the production

01:30:12.340 | of the sperm themselves.

01:30:13.760 | They're going to set in motion

01:30:15.340 | for essentially the rest of the life of the male,

01:30:18.420 | the production of sperm.

01:30:20.500 | They're going to initiate the spermatogenesis cycle,

01:30:22.660 | and that cycle is going to be ongoing at various stages

01:30:24.880 | for different sperm for the rest of the man's life.

01:30:29.020 | This is very different than the triggering

01:30:32.740 | of development of oocytes in eggs in females,

01:30:36.260 | where there's an existing vault,

01:30:38.220 | that vault can be depleted to the point of zero,

01:30:40.460 | where it can't occur again.

01:30:41.460 | Men can generate sperm their entire lifetime.

01:30:43.860 | Of course, there's a diminishment of sperm production

01:30:46.860 | in very, very late age, say '80s and '90s or '00s,

01:30:50.260 | but believe it or not, there's still sperm being produced.

01:30:52.260 | The quality of those sperm is another question.

01:30:55.140 | So everything we're going to talk about now

01:30:57.300 | is essentially puberty onward, okay?

01:30:59.880 | Prior to that, testicles are present,

01:31:02.320 | but they're not generating sperm.

01:31:04.620 | Ejaculation is impossible, or if it is possible,

01:31:07.320 | it's very unlikely and unusual,

01:31:09.720 | and it's not going to contain sperm.

01:31:11.520 | Everything we're going to talk about now is puberty forward.

01:31:17.340 | Okay, so puberty onward to the rest of life.

01:31:20.420 | And luteinizing hormones secreted from the pituitary

01:31:24.180 | acts on the testes and on a very specific cell type

01:31:27.860 | in the testes called the Leydig cells, or Leydig cells,

01:31:30.580 | L-E-Y-D-I-G, the Leydig cells.

01:31:33.060 | The Leydig cells of the testes

01:31:35.140 | are what produce testosterone.

01:31:36.820 | Testosterone is going to have two major effects,

01:31:41.440 | and here I mean really major,

01:31:42.940 | because it has many, many hundreds of effects

01:31:44.920 | on different tissues of the body.

01:31:46.020 | In fact, that's the definition of a hormone, really.

01:31:48.540 | It's a substance that acts in an endocrine fashion.

01:31:51.040 | It can act on the very tissue that generated it.

01:31:53.420 | So for instance, testosterone made by the Leydig cells

01:31:55.700 | within the testes will act on the testes,

01:31:57.260 | as we'll talk about in a moment,

01:31:58.220 | but it can also act on other tissues.

01:32:00.840 | It can act on the pharynx and larynx

01:32:02.820 | and deepen the voice as it does during puberty.

01:32:04.420 | It can act on the hair follicles and generate facial hair.

01:32:06.900 | It can act on the musculature and generate protein synthesis

01:32:10.900 | and development of muscle, bone, et cetera.

01:32:12.460 | Okay, all the things we associate with puberty

01:32:14.100 | and with testosterone typically.

01:32:15.700 | Restricting the conversation to the effects of testosterone

01:32:20.260 | on the testicle itself and on spermatogenesis,

01:32:23.320 | the Leydig cells make testosterone

01:32:25.780 | and keep in mind that some of that testosterone

01:32:27.980 | will travel elsewhere in the body and do its thing

01:32:30.540 | for gene expression and the more acute effects

01:32:32.300 | of testosterone on the brain included.

01:32:34.720 | But the testosterone within the testes

01:32:37.900 | is at extremely high concentration.

01:32:40.660 | In fact, the concentration of intratesticular testosterone

01:32:44.980 | is at least a hundred times higher

01:32:47.140 | than the concentration of testosterone

01:32:48.660 | anywhere else in the body,

01:32:49.660 | even though it's being secreted into the rest of the body.

01:32:52.980 | And that's because there are a number of different

01:32:54.740 | so-called binding proteins and enzymes

01:32:57.680 | that sequester the testosterone within the testes.

01:33:00.460 | So the Leydig cells are making testosterone.

01:33:02.260 | A lot of that testosterone is acting on

01:33:04.780 | and is restricted to the testes.

01:33:06.740 | And that turns out to be very important

01:33:09.100 | because testosterone within the testes

01:33:12.740 | acts in concert with a different biological program

01:33:16.540 | that starts with FSH, follicle stimulating hormone,

01:33:19.360 | that also travels to the testes

01:33:21.520 | and acts on a very specific set of cells

01:33:24.780 | that are called supporting cells

01:33:26.580 | or more specifically the Sertoli cells.

01:33:29.960 | The Sertoli cells are the cells that generate

01:33:33.400 | something called ABP or androgen binding protein.

01:33:36.420 | And it is the combination of testosterone

01:33:39.060 | from the Leydig cells and ABP from the Sertoli cells

01:33:43.140 | that is necessary for spermatogenesis.

01:33:46.760 | It's necessary for those spermatocytes

01:33:49.320 | to become what will eventually be healthy,

01:33:51.680 | mature sperm that have really nice shaped oval heads,

01:33:55.340 | have a mid-region chock-a-block through mitochondria

01:33:57.860 | and can generate a fast whipping motion of the tail

01:34:00.280 | to swim from the cervix or up the vagina to the cervix

01:34:04.140 | and from the cervix to the egg to fertilize the egg.

01:34:07.860 | So it's really a basic set of chemical players

01:34:10.420 | that are involved here.

01:34:11.780 | And so basic in fact, that if you were to disrupt

01:34:14.860 | any one of these chemical players,

01:34:16.420 | either the luteinizing hormone, the FSH,

01:34:19.240 | the testosterone for the Leydig cells

01:34:20.660 | or androgen binding protein,

01:34:23.060 | you would observe pretty marked disruption

01:34:27.580 | in spermatogenesis or the elimination of sperm entirely.

01:34:31.080 | We'll get into a few deficits in sperm development

01:34:33.740 | and sperm number and sperm function a little bit later,

01:34:36.140 | but just keep in mind where I should say,

01:34:38.580 | maybe sit back and just appreciate

01:34:40.220 | that the exact same players generate from the hypothalamus,

01:34:43.780 | which causes luteinizing hormone and follicle stimulated

01:34:47.340 | hormone release from the pituitary,

01:34:49.820 | which travels to the gonad,

01:34:51.120 | which in this case is the testicle,

01:34:52.960 | which triggers the release of testosterone from Leydig cells,

01:34:56.600 | which triggers the action of the supporting cells,

01:34:59.900 | the sertoli cells, which make androgen binding protein,

01:35:03.520 | testosterone and androgen binding protein combine

01:35:06.000 | and create a chemical and actually a structural milieu

01:35:09.760 | in which those little spermatocytes can go from the walls,

01:35:14.300 | from literally the walls of the tubes

01:35:15.960 | of the seminiferous tubules,

01:35:17.640 | can mature into healthy, well-developed sperm

01:35:19.780 | and can hop into those ducts, those little tubes,

01:35:23.020 | and then head off to the epididymis where they will reside.

01:35:26.260 | The epididymis is the tissue nearby the testicle

01:35:29.020 | or surrounding one portion of the testicle,

01:35:30.980 | and then eventually fuse with the vas deferens,

01:35:34.040 | can combine with or be contained with rather

01:35:36.780 | the seminal fluid, and then can be ejaculated

01:35:40.180 | via the urethra into the female

01:35:42.380 | where then they can swim very quickly,

01:35:44.920 | effectively the distance for them anyway,

01:35:46.900 | from Los Angeles to San Francisco

01:35:48.880 | over the course of a very short period of time

01:35:51.580 | and fertilize the egg.

01:35:53.820 | So that's the process of spermatogenesis,

01:35:55.700 | the maturation of sperm, which is ongoing

01:35:58.840 | throughout the lifespan from puberty onward.

01:36:01.840 | And in doing so,

01:36:02.680 | we talked about some of the hormonal elements

01:36:04.540 | coming from the hypothalamus and coming from the pituitary

01:36:07.580 | and within the testes themselves,

01:36:09.420 | the Leydig cells, which produce testosterone,

01:36:11.420 | the sertoli cells, which are the support cells

01:36:13.820 | that allow spermatogenesis to occur.

01:36:16.420 | With that in mind, next I'd like to think about

01:36:20.520 | what's actually contained in the ejaculate

01:36:22.680 | in terms of numbers of sperm,

01:36:24.760 | and what's really being selected for

01:36:26.340 | in terms of the sperm that actually successfully

01:36:28.280 | fertilizes the egg,

01:36:29.480 | and what sorts of elements come into play

01:36:32.360 | in dictating whether or not fertilization

01:36:34.560 | will or won't occur.

01:36:35.720 | And the major themes that we're going to discuss

01:36:37.900 | are frequency of ejaculation,

01:36:40.500 | but really that's just kind of a proxy

01:36:42.600 | for talking about maximizing sperm concentration

01:36:46.040 | and quality of sperm arriving at the egg, right?

01:36:48.920 | Because remember, ovulation and the menstrual cycle

01:36:51.200 | are really about creating the opportunity for fertilization.

01:36:54.700 | And we are also going to talk about how the vaginal duct,

01:37:00.480 | the vagina, and the milieu around the cervix,

01:37:04.000 | and some other elements within the female herself

01:37:07.520 | contribute to and support the sperm

01:37:10.140 | in their journey to the egg

01:37:11.540 | and in the likelihood that they will fertilize the egg.

01:37:13.820 | So really what we need to talk about first is sperm quality.

01:37:17.400 | And we should also probably talk about ejaculate quality,

01:37:20.780 | because as odd as that theme might seem,

01:37:24.900 | really the ejaculate quality,

01:37:27.760 | which has a number of different parameters,

01:37:29.400 | including the number of mature sperm

01:37:32.580 | that are not so mature that they're swimming slower or dead,

01:37:35.480 | but also quality sperm that have, for instance, one tail,

01:37:37.760 | it's not entirely uncommon to see sperm with two tails,

01:37:41.140 | right, because they just didn't form properly,

01:37:43.140 | or sperm that are not moving very much.

01:37:45.740 | In fact, sperm motility is scored along a scale

01:37:48.600 | of zero, one, two, or three,

01:37:50.160 | three being the best for fast-forward progressing,

01:37:52.840 | zero is not moving at all.

01:37:54.600 | One, they're actually called twitchers, right?

01:37:57.620 | Twitchers are sperm that sort of just twitch in place,

01:37:59.560 | but don't undergo forward progression.

01:38:02.000 | Two is somewhere in between one and three,

01:38:04.240 | not surprisingly.

01:38:05.220 | Different clinics, different OB/GYNs,

01:38:09.720 | different urologists will throw out different numbers,

01:38:12.080 | but in general, it is hoped that more than 50%

01:38:16.960 | of the sperm should be motile in some way or another,

01:38:19.280 | so not scoring a zero, but a one, a two, or ideally a three.

01:38:23.740 | The concentration of sperm, of course,

01:38:26.940 | if it's higher within the ejaculate,

01:38:29.440 | the total number of sperm per milliliter of ejaculate,

01:38:32.980 | if that's higher, then there's a higher probability

01:38:35.380 | that one of those sperm will fertilize the egg.

01:38:38.440 | One thing I didn't mention before when discussing

01:38:40.640 | the production of eggs in ovulation,

01:38:42.200 | and I probably should have, so I will now,

01:38:44.120 | is that most often only one ovary

01:38:47.820 | gives rise to an ovulating egg, right?

01:38:51.680 | It happens, but it's somewhat rare for two mature eggs,

01:38:56.680 | one from each ovary to be deployed

01:38:59.440 | during a single ovulation.

01:39:01.080 | There's a name for that when it occurs

01:39:02.520 | and both are fertilized, it's called fraternal twins.

01:39:06.300 | If a single egg, that of course comes from a single ovary,

01:39:10.380 | is fertilized and the egg splits,

01:39:12.660 | and that's something that happens further along the process

01:39:16.780 | of fertilization and differentiation of the embryo,

01:39:19.920 | well, then what you get are identical twins, okay?

01:39:23.220 | There are other instances that are quite uncommon

01:39:26.500 | in which you can get fraternal twins

01:39:27.740 | through other circumstances,

01:39:28.740 | but in general, that's the way it works.

01:39:30.340 | But essentially what happens is one egg from one ovary,

01:39:33.180 | that's the most common occurrence.

01:39:34.800 | The sperm, once ejaculated into the vaginal duct,

01:39:38.860 | are going to pass through the cervix

01:39:42.540 | and then are going to swim toward the egg.

01:39:44.680 | The egg could be at varying locations

01:39:47.900 | along the female reproductive axis.

01:39:50.820 | Now, this is actually a very important thing

01:39:52.820 | and actually gets right down to the safety

01:39:55.340 | of both the potentially developing embryo and the mother.

01:39:58.480 | There is something referred to as ectopic pregnancy,

01:40:01.160 | and that's when the pregnancy actually occurs

01:40:04.280 | within the fallopian tubes.

01:40:05.980 | So the precise location in which fertilization

01:40:08.300 | between the sperm and the egg occurs can vary somewhat,

01:40:11.420 | but ideally the fertilized egg implants into the endometrium

01:40:15.260 | or the endometrial lining of the uterus

01:40:17.500 | and develops there as opposed to within the fallopian tubes,

01:40:20.500 | which is so-called ectopic pregnancy.

01:40:22.340 | Now, where the sperm and the egg meat exactly can vary,

01:40:26.740 | as I mentioned before,

01:40:28.100 | but in general, the faster swimming sperm

01:40:30.820 | and the more far along the ovulatory trajectory the egg are,

01:40:35.480 | the higher the probability of a successful fertilization

01:40:38.080 | because of the proximity

01:40:39.260 | to the implantation zone of the uterus.

01:40:41.420 | So basically it's all a probabilities game.

01:40:43.780 | It's a probabilities game related

01:40:45.360 | to the number of sperm cells that encounter the egg

01:40:47.640 | and where the egg is in terms of its ovulatory cycle

01:40:50.580 | and also its position where it is in the ovulatory cycle.

01:40:55.320 | The sperm parameters, I should say the semen parameters

01:40:59.360 | and ejaculate parameters that most clinicians want to see

01:41:03.240 | if you were to give a sperm sample would be somewhere

01:41:06.660 | in excess of 15 million sperm per milliliter of ejaculate.

01:41:11.660 | Now there's a lot of discussion nowadays,

01:41:15.080 | it seems to be a very popular news theme

01:41:17.140 | to talk about diminishing sperm counts.

01:41:20.240 | You know, the idea that a hundred years ago

01:41:22.000 | or maybe even 35 years ago,

01:41:23.820 | the typical male ejaculate contained

01:41:25.560 | a hundred million sperm per milliliter.

01:41:28.120 | And nowadays it's down to 15 to 20 or 50.

01:41:31.000 | And indeed sperm counts do seem to be declining

01:41:34.400 | and the exact reasons for that are not clear.

01:41:36.680 | I confess I'm a little bit reluctant to talk about this

01:41:38.520 | because there have been a lot of back and forth discussions

01:41:42.060 | about the safety of EMFs of electromagnetic fields.

01:41:45.200 | That's not exactly what we're talking about here

01:41:46.800 | but there are some excellent data contained

01:41:49.460 | in meta-analysis and reviews that I will provide links to

01:41:51.860 | and that we'll talk about in more detail in a minute

01:41:54.760 | that correlate the advent of smartphones

01:41:58.720 | and in particular carrying of smartphones in the pocket

01:42:01.920 | with diminishing sperm counts.

01:42:03.260 | Although there are certain to be other factors

01:42:05.840 | that can explain diminishing sperm counts as well.

01:42:08.500 | Dr. Shaina Swan, for instance, has done beautiful work

01:42:12.600 | describing how the phthalates and the BPAs

01:42:16.200 | and so-called endocrine disruptors might be disrupting

01:42:18.920 | some of the milieu of the seminiferous tubules.

01:42:22.040 | So this would be reductions in testosterone

01:42:23.640 | and or disruptions to the sertoli cells

01:42:25.900 | and androgen binding protein brought about

01:42:27.640 | by endocrine disruptors such as phthalates

01:42:29.880 | contained in pesticides and contained on printed receipts

01:42:32.760 | and things of that sort.

01:42:33.720 | There are some data that that is negatively impacting

01:42:37.060 | sperm counts.

01:42:38.060 | How much so is still debatable.

01:42:42.640 | There are also quite good data pointing to the fact

01:42:45.320 | that both the heat related and the nonheat related impact

01:42:49.820 | of smartphones and laptops contained on the lap

01:42:54.180 | are impacting sperm counts and in a negative way.

01:42:57.180 | Again, there's going to be tremendous variation

01:42:59.100 | in the concentration of sperm from one individual to the next

01:43:01.740 | it will vary according to age and a number of other factors

01:43:04.700 | that we'll talk about a little bit later.

01:43:07.260 | But in general, if somebody is wishing to conceive,

01:43:10.400 | then clinicians like to see a ejaculate volume

01:43:13.860 | of more than two milliliters.

01:43:16.660 | So ejaculate volume can be anywhere from 1.5 to five

01:43:21.660 | milliliters, and that will strongly be determined

01:43:24.140 | by how frequent ejaculation is occurring.

01:43:27.020 | There's a lot that goes into evaluating the quality

01:43:29.380 | of ejaculate and sperm, but basically these huge variations

01:43:34.380 | that are observed of anywhere from 15 million sperm

01:43:37.980 | per milliliter or in some males who are not producing sperm

01:43:40.460 | for whatever reason, we'll talk about those reasons

01:43:42.340 | in a little bit.

01:43:43.480 | The as low as 5 million sperm per milliliter,

01:43:47.540 | all the way up to a hundred or maybe a 200 million

01:43:49.480 | sperm per milliliter, huge variation.

01:43:52.520 | The cause of which is not always clear,

01:43:56.080 | but is certainly determined in part by the frequency

01:43:59.560 | of ejaculation.

01:44:00.400 | So because there are so many variables impacting

01:44:04.040 | why one male versus another male or even the same male

01:44:06.840 | across the lifespan might have variations

01:44:08.680 | in his concentration of sperm within the ejaculate.

01:44:12.360 | Let's talk for a second about frequency of ejaculation

01:44:15.640 | as it relates to the goal of fertility per se,

01:44:18.080 | 'cause that's really what today's episode is all about.

01:44:20.260 | So what I'd like to talk about next is how people can

01:44:22.940 | increase the probability of a successful fertilization

01:44:26.080 | focusing both on the components from the male side

01:44:29.320 | and from the female side.

01:44:30.560 | And I'm mainly going to couch this discussion in the context

01:44:33.440 | of the so-called natural method of sexual intercourse

01:44:36.760 | and ejaculation in vivo, right, within the female.

01:44:41.520 | But I will also touch on some parallel themes

01:44:43.640 | as it relates to in vitro fertilization

01:44:45.600 | and intrauterine insemination, okay?

01:44:48.120 | So the idea here is that we want the maximum number

01:44:52.800 | of high quality sperm that is rapidly forward motile sperm

01:44:56.760 | that are of the correct morphology that is shape,

01:44:59.600 | that's going to require a lot of mitochondria

01:45:02.240 | in the mid region, a well-shaped head.

01:45:04.440 | So it's going to be an oval shaped head.

01:45:06.200 | The tail is going to be a single tail, not multiple tails.

01:45:08.840 | These aren't going to be the twitcher type of,

01:45:11.360 | or immotile type of sperm that are either twitching in place

01:45:14.560 | or aren't moving forward.

01:45:15.800 | All of those components are going to be essential

01:45:18.400 | for increasing the probability of fertilization.

01:45:21.320 | But of course there's the female side of it too,

01:45:23.000 | which is that ovulation occurs on just one day

01:45:26.400 | during the menstrual ovulatory cycle.

01:45:28.720 | And that egg will be available for fertilization

01:45:31.500 | for approximately 24 hours.

01:45:33.560 | Now keep in mind that the sperm can survive

01:45:35.880 | within the vaginal duct and within the area

01:45:38.760 | around the cervix and within the uterus

01:45:40.720 | and along the female reproductive tract

01:45:43.380 | for anywhere from three to five,

01:45:45.240 | or it's even been described as up to seven days,

01:45:47.720 | but generally it's going to be about three to five days.

01:45:50.480 | Now, most women can figure out the day of their ovulation

01:45:54.320 | by counting the total number of days of their typical cycle.

01:45:57.480 | And this is where it's really useful to have a cycle

01:45:59.600 | that's of more or less regular duration

01:46:02.320 | or rather of more or less regular length.

01:46:05.560 | So as we talked about earlier,

01:46:07.520 | if somebody's cycle is 21 days or 25 days

01:46:10.400 | and it's 21 or 25 days consistently

01:46:12.440 | or even 30 days consistently,

01:46:14.440 | that's going to be a far better scenario

01:46:16.200 | to favor fertilization than if it's 20 days one month

01:46:20.200 | and then 21 days the next month,

01:46:21.480 | but then suddenly 30 days and then suddenly 35 days.

01:46:24.960 | Those varying durations of the ovulatory cycle

01:46:28.100 | make it very hard obviously to time

01:46:30.400 | and understand when ovulation is going to occur.

01:46:32.820 | So regular duration ovulatory cycles

01:46:36.740 | are the ideal circumstance.

01:46:38.380 | And they're the ideal circumstance

01:46:39.720 | because even though the egg is only available

01:46:41.640 | for fertilization for a few days,

01:46:42.860 | those sperm can survive for some period of time,

01:46:45.840 | which leads to the issue of

01:46:47.840 | how often should couples be having intercourse?

01:46:51.080 | And here I'm referring specifically

01:46:53.040 | to intercourse with ejaculation.

01:46:54.500 | How often should couples be having intercourse

01:46:56.620 | around the time of ovulation

01:46:58.400 | if the specific goal is successful fertilization

01:47:02.640 | of the egg and the creation of a baby, okay?

01:47:05.120 | This is leaving aside all issues,

01:47:08.120 | which of course are interesting issues

01:47:09.440 | related to how often people are having intercourse,

01:47:12.280 | whether or not there's ejaculation

01:47:13.900 | every time they have intercourse or not

01:47:15.640 | for sake of pleasure or for sake of pair bonding and pleasure

01:47:19.420 | or for sake of any number of other

01:47:21.260 | potential goals of intercourse.

01:47:22.960 | Here I'm only referring to intercourse

01:47:24.960 | as it relates to the goal of fertilization of the egg, okay?

01:47:29.480 | So knowing what we know about spermatogenesis

01:47:34.480 | and the fact that ejaculate is going to contain

01:47:37.900 | a certain concentration of sperm,

01:47:39.920 | but that within that ejaculate,

01:47:41.920 | some of the sperm will be older and less healthy

01:47:45.280 | and some will be optimally mature

01:47:47.000 | and some might even be a little bit immature,

01:47:48.760 | although there's a tendency for the immature sperm

01:47:50.800 | to not have yet exited the seminiferous tubules,

01:47:53.840 | gone into the epididymis and vas deferens.

01:47:56.920 | But given that the ejaculate contains sperm

01:47:58.880 | of varying ages and therefore varying quality,

01:48:02.360 | and given that with each successive ejaculation

01:48:05.120 | in a short period of time,

01:48:07.180 | there's going to be a decrease in the concentration of sperm

01:48:10.400 | per milliliter of semen of ejaculate,

01:48:14.080 | we can make some good arguments

01:48:16.120 | as to how often couples should have intercourse

01:48:19.340 | with ejaculation around the time of ovulation

01:48:21.880 | if the goal is to fertilize.

01:48:23.320 | If ovulation occurs on, for instance, day 14 of a cycle,

01:48:26.360 | here we're using the kind of standard average of 28 days

01:48:29.400 | of the cycle, but for some people with a 30-day cycle,

01:48:32.680 | that could be day 15 or with a shorter cycle,

01:48:36.140 | it could be day 12, for instance,

01:48:37.880 | but given a 28-day average cycle,

01:48:40.360 | let's say ovulation occurs on day 13 or on day 14,

01:48:44.260 | and typically would occur on day 14 of a 28-day cycle.

01:48:48.300 | Well, then given how long sperm can survive

01:48:51.720 | inside of the woman,

01:48:53.160 | you might think that the optimal strategy would be

01:48:55.600 | to have as much intercourse with ejaculation

01:48:58.360 | in the three or four days leading up to ovulation,

01:49:01.620 | hope that those sperm swim as far as they possibly can

01:49:04.540 | and will encounter the egg just as soon as possible

01:49:06.920 | after it ovulates.

01:49:08.360 | It turns out that's not the optimal strategy.

01:49:10.240 | The optimal strategy is really to maximize

01:49:12.440 | the concentration of healthy sperm within each ejaculate

01:49:16.600 | and to really center that around the day of ovulation.

01:49:20.000 | So what this involves generally

01:49:22.280 | and what the typical recommendation is,

01:49:24.260 | is to abstain from intercourse with ejaculation

01:49:28.640 | about two or three days out from ovulation,

01:49:32.340 | and then on the day prior to ovulation

01:49:34.700 | and on the day of ovulation,

01:49:37.440 | to essentially introduce as much semen and ejaculate

01:49:41.540 | into the reproductive pathway of the female as possible.

01:49:45.460 | Okay, now that's the general recommendation

01:49:47.700 | that the OB/GYNs and the urologists that I spoke to gave,

01:49:51.740 | but you will also hear a different strategy.

01:49:54.080 | It's only slightly different,

01:49:55.560 | but the different strategy involves

01:49:57.640 | trying to maximize the concentration of healthy sperm

01:50:00.840 | within each ejaculate with the understanding

01:50:02.720 | that with each subsequent ejaculation

01:50:04.740 | over about a 24-hour period,

01:50:06.960 | that there's going to be a dramatic reduction

01:50:09.280 | in the concentration of sperm.

01:50:10.460 | What that means is that if a couple, for instance,

01:50:12.600 | were to have intercourse with ejaculation

01:50:15.120 | many times on the day prior to ovulation,

01:50:17.200 | yes, that will introduce a lot of sperm

01:50:19.760 | into the reproductive pathway of the female,

01:50:22.320 | but what it means is that on the day of ovulation,

01:50:25.460 | if they were to have intercourse,

01:50:26.920 | the number of high-quality sperm

01:50:29.120 | that will be available to the egg

01:50:31.520 | will be greatly diminished,

01:50:32.720 | and if none of the sperm that were introduced

01:50:35.240 | in the day prior managed to fertilize that egg,

01:50:38.500 | well, then essentially chances are off

01:50:40.760 | that there will be fertilization

01:50:42.320 | or they're greatly diminished.

01:50:43.680 | Rather, if they're having intercourse with ejaculation

01:50:47.660 | once or twice on the day prior to ovulation

01:50:50.120 | and then a maximum number of times with ejaculation

01:50:53.840 | on the day of ovulation,

01:50:55.320 | that itself can maximize the probability of fertilization.

01:50:58.680 | So which strategy is optimal?

01:51:00.000 | Should couples have as much intercourse with ejaculation

01:51:02.580 | on the day prior to ovulation and on the day of ovulation,

01:51:06.440 | or should they have intercourse

01:51:08.880 | on the day prior to ovulation,

01:51:10.520 | but not so frequently

01:51:12.160 | that it diminishes the concentration of sperm

01:51:14.600 | and then allows for intercourse

01:51:17.280 | with the maximum number of ejaculations

01:51:20.040 | on the day of ovulation, you really hear it both ways.

01:51:23.020 | And what this really boils down to

01:51:24.360 | is frankly that nobody knows.

01:51:26.360 | And the reason nobody knows

01:51:27.520 | is that there's tremendous variation among males

01:51:29.760 | in terms of the absolute concentration

01:51:32.200 | of sperm per milliliter of ejaculate

01:51:35.500 | and the amount of sperm per milliliter of ejaculate

01:51:40.280 | within a given timeframe.

01:51:41.800 | But what everyone agrees on is that a period of abstinence

01:51:45.800 | ranging from 48 to 72 hours prior to an ejaculation

01:51:49.840 | increases the concentration of high quality sperm

01:51:52.800 | within that first ejaculation to occur

01:51:55.120 | after the abstinence period, okay?

01:51:57.880 | So again, to reiterate,

01:51:58.960 | if one's goal is to fertilize the egg,

01:52:00.820 | you want to take into consideration that most often

01:52:04.760 | there's going to be a dramatic decline

01:52:07.380 | in the concentration of sperm per ejaculate

01:52:10.080 | anytime those ejaculations are occurring

01:52:12.280 | within a short period of time,

01:52:13.400 | say within 12 to 24 hours of one another.

01:52:16.280 | Now, all of this, of course,

01:52:18.000 | also relates to the female biology

01:52:21.200 | and the extent to which the woman can precisely identify

01:52:24.760 | the day and timing of her ovulation.

01:52:26.800 | Some women feel as if, and indeed are very accurate

01:52:30.840 | at estimating their time of ovulation

01:52:33.600 | to within a couple of hours,

01:52:35.000 | or some women even report being able to feel

01:52:37.800 | their actual ovulation,

01:52:39.440 | whether or not they are feeling the ovulation itself,

01:52:41.400 | the deployment of the egg or not isn't clear.

01:52:43.960 | I certainly would know.

01:52:45.000 | I've never produced eggs, nor have I ovulated,

01:52:47.940 | and I'm certainly not going to contest the idea

01:52:49.680 | that women can do that.

01:52:52.460 | I mean, it makes sense that some people have a very keen

01:52:56.200 | so-called interoceptive awareness,

01:52:57.960 | an awareness of the sensory events within their body.

01:53:01.300 | And while, of course, the ovaries are not thought of

01:53:04.360 | as an organ that we want to be able to sense

01:53:06.360 | what's going on in there in terms of feel,

01:53:08.640 | there are sensory endings within the ovary.

01:53:10.540 | And so the notion that one could literally sense

01:53:14.160 | changes within their ovary,

01:53:15.360 | including the deployment of the egg,

01:53:16.780 | is not outside the bounds of reason.

01:53:19.860 | And in fact, could likely be the case.

01:53:21.940 | Now, that said, there are a number of different ways

01:53:25.080 | that women will track their ovulation.

01:53:26.560 | One is the temperature method.

01:53:28.000 | So they'll actually measure intravaginal temperature.

01:53:30.880 | They're looking for changes in temperature

01:53:32.360 | that are consistent around the time of ovulation.

01:53:35.120 | We're going to have an expert guest on an OB-GYN

01:53:37.800 | who can tell us a lot more about the details

01:53:40.400 | and nuances of the temperature method.

01:53:41.960 | You'll see a lot of information about this online,

01:53:43.740 | but there's a lot of misunderstanding about it as well.

01:53:46.620 | Other women will use apps that take into account

01:53:49.260 | either the temperature information,

01:53:50.840 | if they're acquiring temperature information,

01:53:53.680 | that'll be entered into the app,

01:53:54.920 | as well as marking the onset of menstruation,

01:53:58.840 | the onset of bleeding,

01:53:59.800 | therefore the start of the ovulatory cycle.

01:54:01.800 | Because of course, as we mentioned earlier,

01:54:03.060 | that marks day one of their cycle.

01:54:04.840 | And then again and again,

01:54:06.280 | you can see how regularity of cycle duration

01:54:08.960 | or relative regularity of cycle duration

01:54:11.720 | really favors this whole process

01:54:13.200 | of being able to predict when one ovulates.

01:54:16.240 | And fortunately, if the goal is fertilization,

01:54:20.440 | there are some margins for error

01:54:22.800 | that are introduced by the fact that

01:54:25.000 | the sperm can survive within the female reproductive tract

01:54:27.680 | for some period of days,

01:54:29.820 | thereby reducing the need for absolute certainty

01:54:33.680 | about the time of ovulation and so on.

01:54:36.000 | In fact, it's pretty well known

01:54:37.720 | that around the time of ovulation,

01:54:39.820 | a couple of things happen.

01:54:40.700 | Earlier, we talked about one thing,

01:54:42.000 | which is there's an increase in libido

01:54:43.420 | just prior to ovulation.

01:54:44.920 | This relates to impart an increase in some of the androgens,

01:54:49.480 | things like DHEA, but also testosterone

01:54:52.840 | and some related androgens that can increase libido

01:54:57.080 | both in males and females.

01:54:59.160 | And changes to the reproductive pathway, the female,

01:55:03.080 | in particular, a change in the pH,

01:55:05.460 | that is the relative acidity versus basic nature

01:55:08.900 | of the mucosal lining near the cervix

01:55:12.200 | and also vaginal secretions,

01:55:14.100 | such that around the time of ovulation,

01:55:16.620 | the entire milieu of the vagina and the cervix

01:55:20.860 | and the locations in which fertilization can occur

01:55:23.700 | and certainly in which the sperm are swimming

01:55:25.700 | towards the opportunity for fertilization

01:55:27.800 | is shifted to support sperm motility and health.

01:55:31.080 | In other words, one of the best environments

01:55:32.940 | for sperm to survive is going to be within

01:55:35.880 | the female reproductive pathway itself.

01:55:38.280 | And as long as we're talking about vaginal secretions

01:55:40.760 | and mucus, it's important to point out

01:55:43.160 | that a number of commercially available lubricants

01:55:46.060 | can actually be detrimental for sperm health,

01:55:48.400 | even if they don't contain spermaticide.

01:55:51.340 | So this is something that you'll want to discuss

01:55:52.840 | with your OB/GYN or certainly if you're male,

01:55:56.840 | you could also discuss this with your urologist

01:55:58.920 | and your partner's OB/GYN.

01:56:01.700 | A lot of the commercially available lubricants

01:56:04.140 | contain chemicals that while they may favorably

01:56:07.380 | change the consistency or the viscosity

01:56:10.180 | of the vaginal pathway for purposes of intercourse,

01:56:13.860 | certainly may not be the most favorable

01:56:16.700 | for maintaining the health of the sperm

01:56:18.900 | and the motility of the sperm.

01:56:20.020 | So again, here we're talking about intercourse

01:56:23.220 | only in the context of trying to maximize fertilization.

01:56:26.380 | And I should mention that there are certain lubricants

01:56:29.220 | that are more conducive to the sperm environment,

01:56:31.660 | but it's something that you'll really want to talk

01:56:33.460 | to your OB/GYN about, or at least read up about

01:56:36.560 | if your interest is in trying to fertilize

01:56:38.880 | and develop an embryo.

01:56:40.060 | So we covered the optimal strategies

01:56:41.760 | for how often couples should have intercourse

01:56:44.880 | with ejaculation around the time of ovulation

01:56:48.100 | in order to maximize the probability

01:56:50.340 | that successful fertilization

01:56:52.060 | and ultimately pregnancy will occur.

01:56:54.540 | What we haven't covered yet, however,

01:56:56.540 | is how long couples should apply that method over time

01:57:01.320 | in order to achieve successful fertilization and pregnancy.

01:57:04.420 | Now, of course, if a couple decides

01:57:06.040 | that they want to conceive and they apply that method

01:57:08.660 | or any other method, for instance,

01:57:11.100 | and they achieve fertilization and a successful pregnancy

01:57:14.700 | the very first month that they try,

01:57:16.760 | well, then there's no other work to do

01:57:18.460 | at least until that child is born

01:57:20.000 | and if and only if they decide

01:57:21.940 | they want to have more children.

01:57:23.060 | However, many couples find that they do not conceive

01:57:27.320 | in the first month of trying,

01:57:28.980 | even when they apply the optimal methods

01:57:30.920 | and even if their age and every other factor

01:57:33.600 | related to egg quality and sperm quality is optimized.

01:57:36.800 | Now, I think it's the rare instance

01:57:38.620 | in which egg quality and sperm quality are optimized.

01:57:41.940 | In fact, the word optimal and optimization

01:57:44.260 | and optimized is a little bit misleading in general

01:57:46.340 | because no one really knows what that is.

01:57:48.360 | But of course, there is an ideal,

01:57:49.860 | there's a perfect standard

01:57:51.660 | to which everyone would like to achieve.

01:57:53.600 | But of course, we all enter the picture

01:57:55.580 | with genetic variables, environmental variables,

01:57:58.500 | and so forth, many of which we'll talk about

01:58:00.780 | because you can in fact adjust them

01:58:02.580 | in the direction that you would like

01:58:03.660 | to improve sperm and egg quality,

01:58:05.820 | but most people simply will not succeed

01:58:09.780 | in achieving a successful fertilization

01:58:12.660 | the first month that they try.

01:58:14.500 | Now, there is a truth that governs

01:58:17.020 | how many tries it ought to take

01:58:19.620 | in order to achieve successful fertilization

01:58:22.540 | and ultimately pregnancy.

01:58:23.680 | And it's very age dependent and in particular,

01:58:26.100 | it's dependent on the age of the mother

01:58:28.340 | because the age and quality of the egg,

01:58:30.540 | while it's not the only factor,

01:58:32.900 | is certainly one of the most determining factors

01:58:35.940 | in whether or not successful fertilization occurs.

01:58:38.320 | And as women age,

01:58:39.580 | the quality of the eggs tends to diminish over time,

01:58:42.220 | largely due to changes in the mitochondrial function

01:58:44.940 | and the spindle that pulls the chromosomes apart,

01:58:47.540 | although there could be other factors involved as well.

01:58:50.320 | Now, before continuing any further,

01:58:51.740 | I just want to acknowledge that this whole language

01:58:53.780 | around egg quality and sperm quality

01:58:56.580 | is not the greatest language

01:58:58.020 | because it's entirely subjective.

01:59:00.300 | And yet the word quality in these instances

01:59:03.620 | is really there to explain a broad variety of factors

01:59:06.740 | that can in fact be measured.

01:59:08.020 | Things like the number of follicles

01:59:09.860 | that are deployed each month in a woman's ovulation

01:59:12.620 | or the number of motile sperm

01:59:14.740 | or the number of morphologically

01:59:16.820 | that is correctly shaped sperm in the male and so forth.

01:59:19.500 | So when we talk about egg quality or sperm quality,

01:59:21.420 | we're really referring to an amalgam of different features

01:59:25.580 | related to the different aspects of ovulation

01:59:28.980 | leading to successful fertilization

01:59:30.740 | or the different aspects of sperm

01:59:32.620 | related to whether or not they can arrive

01:59:34.660 | and deliver their DNA contents and so forth.

01:59:36.660 | So I will use the words egg quality and sperm quality

01:59:39.220 | just as general themes

01:59:40.140 | because that's what a lot of the clinicians use.

01:59:42.800 | But I do understand that it's a little bit of a loaded term

01:59:45.120 | in both instances,

01:59:46.380 | and it doesn't relate to any one specific parameter per se.

01:59:50.560 | So getting back to this issue of how long couples should try

01:59:53.140 | according to the age of the female

01:59:55.500 | and perhaps also the age of the male.

01:59:57.300 | Well, most of the data that have been collected

01:59:59.820 | relate to the age of the females I mentioned before.

02:00:02.440 | And what we're about to discuss

02:00:04.300 | is within the scientific literature

02:00:05.960 | described as what's called fecundability,

02:00:08.620 | which is the amount of time over which a given couple

02:00:12.340 | needs to attempt to conceive,

02:00:14.220 | of course, by having intercourse with ejaculation

02:00:16.820 | around the time of ovulation.

02:00:18.820 | It assumes that all the other things

02:00:20.260 | are being done correctly.

02:00:22.140 | And what we know is that there's a strong

02:00:24.220 | age dependent effect

02:00:25.740 | that largely rests on the age of the egg

02:00:28.380 | that is of the female.

02:00:29.980 | And what we know is that for females 30 years old or younger,

02:00:34.980 | if they have intercourse with ejaculation

02:00:38.600 | around the time of ovulation,

02:00:39.840 | say on the day before and on the day of ovulation,

02:00:43.200 | and there could be other intercourse with ejaculation

02:00:45.660 | around that time as well.

02:00:47.820 | On average, that will result

02:00:50.380 | in a successful fertilization in pregnancy

02:00:52.360 | about 20% of the time

02:00:54.920 | on the first month of attempting,

02:00:56.680 | the first ovulation cycle.

02:00:58.820 | Now, if fertilization in pregnancy occurs, great, right?

02:01:01.780 | There'll be at least a nine month lag

02:01:03.280 | until they decide whether or not

02:01:04.780 | they want to try and conceive again.

02:01:06.600 | However, most couples,

02:01:08.680 | even if the woman is 30 years old or younger

02:01:11.300 | will not successfully conceive on that first attempt.

02:01:15.020 | And that's because the probability is not 100%, it's 20%.

02:01:18.340 | So 80% of the time they simply will not conceive,

02:01:21.400 | which means that they hopefully will try again

02:01:24.780 | the very next month.

02:01:26.040 | And if they successfully conceive, great.

02:01:28.380 | And if they don't, then they ought to try again

02:01:30.140 | the next month, the next month and so forth.

02:01:32.020 | Now, the typical advice that an OB-GYN would give you

02:01:35.580 | is that for a woman 30 years or younger

02:01:39.260 | and leaving aside the age of the father,

02:01:42.940 | but still assuming that egg quality and sperm quality

02:01:46.920 | are sufficiently high to achieve fertilization,

02:01:49.740 | that the couple should,

02:01:52.780 | or if the woman's trying to have kids alone,

02:01:54.340 | the woman should attempt to conceive

02:01:56.300 | over the period of six months, why?

02:01:59.240 | Well, if you think about it,

02:02:00.080 | if there's a 20% chance in the first month

02:02:03.180 | and it's unsuccessful, well, then on the second month,

02:02:05.540 | there'll also be a 20% chance,

02:02:07.020 | on the third month also a 20% chance.

02:02:09.020 | What I'm describing here is what obviously

02:02:11.900 | is independent probabilities.

02:02:14.540 | That is, if you were to flip a coin

02:02:16.260 | and the probability of getting heads is 50%,

02:02:18.300 | the probability of getting tails is 50%, of course,

02:02:21.580 | you don't expect that the previous flip

02:02:23.960 | had anything to do with the result

02:02:25.340 | that you'll get on the subsequent flip.

02:02:26.660 | That's what independent probabilities are.

02:02:28.320 | However, when it comes to fecundability,

02:02:32.000 | we're really talking about something

02:02:33.280 | which is called cumulative pregnancy rate,

02:02:35.780 | which is not really independent probabilities.

02:02:38.200 | Now, why would that be?

02:02:39.260 | Why would it be that if you did not successfully conceive

02:02:41.740 | in the first month of trying,

02:02:43.320 | that by simply trying again and again and again,

02:02:45.760 | the probability of conceiving would increase?

02:02:48.020 | Well, the reason for that

02:02:49.320 | is that this whole business of fertilization

02:02:51.160 | is not just about what's happening with the egg,

02:02:53.100 | it's also about what's happening with the sperm.

02:02:55.300 | So there are a number of different events

02:02:57.280 | related to the biology of the egg

02:02:58.980 | and the biology of the sperm,

02:03:00.440 | which you are now very familiar with

02:03:01.820 | from everything I've talked about up until now.

02:03:03.980 | And there are a bunch of chance events,

02:03:06.240 | for instance, that the sperm won't actually arrive

02:03:08.380 | at the egg in time,

02:03:09.340 | or that the egg won't arrive at the sperm in time,

02:03:12.220 | because of course it's a bi-directional migration

02:03:14.020 | of those two cell types,

02:03:14.900 | or that for whatever reason, fertilization won't occur.

02:03:18.200 | So what we're really talking about

02:03:19.440 | when we talk about the cumulative pregnancy rate over time

02:03:22.860 | is the fact that there are multiple probabilities at work.

02:03:25.980 | And yes, those are somewhat independent

02:03:28.120 | in the sense that the biology of the sperm

02:03:30.100 | doesn't really strictly depend on the biology of the egg,

02:03:32.500 | at least not until they meet and fertilize,

02:03:34.540 | but the likelihood of pregnancy

02:03:37.740 | depends on those independent probabilities,

02:03:39.940 | which makes this a cumulative pregnancy rate.

02:03:42.780 | Now, if any of that is confusing,

02:03:44.100 | what it basically means is that

02:03:45.700 | for the egg and the sperm to meet and to fertilize,

02:03:47.780 | a number of different events

02:03:49.080 | that carry some intentionality, right?

02:03:52.080 | The sperm swims towards the egg and so forth,

02:03:53.760 | the egg doesn't have a personality in there,

02:03:56.800 | at least not yet,

02:03:57.780 | but it quote unquote wants to be fertilized, right?

02:04:00.220 | It is in principle receptive to fertilization.

02:04:03.560 | Well, in order for that to happen,

02:04:06.220 | there are going to be some events related to chance

02:04:08.060 | that could limit the ability for that to happen,

02:04:10.380 | and there'll be other events dictated

02:04:11.700 | by the biology of those two cell types

02:04:13.340 | that are driving that event to happen,

02:04:15.760 | that are biasing the event to yes, happen.

02:04:17.820 | And so what we're talking about

02:04:19.080 | when we talk about cumulative pregnancy rate

02:04:21.120 | is how much of the biology of the woman

02:04:24.260 | is skewed towards fertilization to be likely to occur, okay?

02:04:27.900 | So to make this very simple,

02:04:30.060 | all we need to know is that

02:04:31.080 | for women 30 years old or younger,

02:04:33.300 | because the probability of getting pregnant

02:04:36.180 | on any one attempt to conceive is 20%,

02:04:41.180 | well, then if that doesn't occur the first time,

02:04:44.580 | then she should simply repeat that

02:04:46.020 | at least five and probably six times

02:04:48.440 | before deciding to go to an OB-GYN

02:04:50.540 | and conclude that there's something going on

02:04:52.520 | either with the egg,

02:04:53.360 | or of course it could be with the sperm, okay?

02:04:55.240 | Because 20 times five is 100,

02:04:57.120 | so we're talking about cumulative percent.

02:04:58.720 | So 20, 40, 60, 80, 100,

02:05:01.400 | and the six month there would take you to 120%,

02:05:05.540 | which is a different thing altogether.

02:05:07.600 | But in general, that's why OB-GYNs

02:05:09.720 | will tell their female patients,

02:05:10.860 | "Look, if you're setting out to conceive,

02:05:12.720 | try for about five or six months,

02:05:14.420 | and if you're not successful, come back and see me."

02:05:17.180 | Now, for women who are age 31 to 33,

02:05:21.400 | the probability of conceiving in that first month

02:05:23.440 | drops to about 18%.

02:05:25.320 | So women in that age range and their partners

02:05:27.460 | should certainly try and conceive naturally

02:05:29.720 | over a period of six or seven months

02:05:32.040 | in order to get to that 100% cumulative probability.

02:05:34.680 | And then for women who are age 34 to 37,

02:05:38.040 | the probability of conceiving in that first month of trying,

02:05:41.440 | and certainly every month thereafter, is about 11%.

02:05:45.240 | So when the age of the woman starts extending out

02:05:47.240 | to about 34 or 35 years old,

02:05:49.600 | then the typical advice of the OB-GYN

02:05:51.620 | is going to be to attempt to conceive

02:05:53.760 | over a period of about nine months to a year

02:05:56.600 | before deciding to take some sort of medical intervention.

02:06:00.860 | And then of course, as the age of the woman increases,

02:06:03.680 | so too does the quality of the eggs go down.

02:06:06.480 | Now, that's not true for every woman.

02:06:08.040 | There are many women who in their late 30s and 40s

02:06:10.200 | and even early 50s

02:06:11.740 | have successfully conceived healthy children,

02:06:14.340 | although the probability of that,

02:06:16.320 | the likelihood of it drops substantially.

02:06:18.620 | So for instance, for women who are age 38 to 39,

02:06:21.980 | the probability of a successful conception

02:06:24.380 | by natural conception intercourse with ejaculation

02:06:27.700 | is going to be about 5%, right?

02:06:30.040 | So it's really dropped to a quarter of what it was

02:06:32.820 | when that woman was 30.

02:06:35.280 | Again, these are averages only.

02:06:37.000 | What does that mean?

02:06:37.840 | Well, it means that if you are age 38 or older,

02:06:41.080 | chances are that you should probably go to your OB-GYN

02:06:44.620 | right at the outset of your desire to conceive

02:06:46.780 | and ask what you can do to improve egg quality.

02:06:49.160 | Otherwise, if you were to extend the math out, right?

02:06:51.540 | We know that if you're age 30 or younger,

02:06:53.780 | 20% chance in any one given month,

02:06:55.840 | that means about four to six months of trying,

02:06:57.980 | well, you can simply multiply that times four or five

02:07:02.120 | for someone in their late 30s or early 40s.

02:07:05.080 | And so what you're really talking about

02:07:06.280 | is several years of trying

02:07:07.520 | and of course what's happening

02:07:08.400 | during those several years,

02:07:09.760 | the woman is getting older and as a consequence,

02:07:11.920 | the quality of the eggs is declining even further.

02:07:14.740 | So if you are 35, 36 years old,

02:07:18.760 | it might not be entirely unreasonable

02:07:20.520 | to talk to your OB-GYN right at the outset

02:07:22.640 | of desiring to conceive,

02:07:24.240 | but you could also just take the approach

02:07:25.780 | of trying to conceive naturally

02:07:27.220 | for about a year or a year and a half

02:07:29.000 | before deciding to do that.

02:07:30.320 | Keeping in mind that all the while you can't stop time,

02:07:33.320 | so biological time and aging

02:07:34.840 | is going to occur in the backdrop.

02:07:36.840 | But hopefully this description of cumulative pregnancy rate

02:07:40.400 | makes sense.

02:07:41.240 | Again, the idea is that while it's true

02:07:43.820 | that every single month there's an independent chance

02:07:47.080 | of the woman getting pregnant,

02:07:49.720 | and that chance is dropping from about 20% at age 30

02:07:53.320 | over time to about really one to 3% for women 40 or older.

02:07:57.680 | There's also this notion of cumulative probability,

02:08:00.420 | which involves multiple biological events

02:08:02.680 | in both the egg and the sperm

02:08:04.120 | that have to converge in time and space

02:08:06.440 | in order for successful fertilization to occur.

02:08:08.960 | As long as we're on this topic,

02:08:10.120 | I think it's only fair to address the issue of miscarriage.

02:08:13.600 | And miscarriages can arise from a variety of sources.

02:08:16.300 | They can arise from genetic defects,

02:08:18.400 | they can arise from issues in the milieu of the uterus,

02:08:21.580 | they can arise from issues with the sperm for that matter.

02:08:24.640 | We really don't want to put all the weight

02:08:26.820 | and all the responsibility on the egg.

02:08:29.240 | This is always an egg sperm dynamic.

02:08:31.280 | And when I say egg sperm dynamic,

02:08:32.940 | now hopefully that calls to mind

02:08:34.440 | the huge library of information

02:08:35.840 | that we've been covering up until now

02:08:37.000 | about chromosomal segregation and the coming together

02:08:39.920 | of these different cell types and their genetic information.

02:08:42.800 | Any number of different steps

02:08:44.360 | within the process of fertilization leading up to pregnancy

02:08:47.420 | can lead to miscarriage.

02:08:49.440 | However, the probability of miscarriage

02:08:52.740 | greatly increases as a function of the age of the egg.

02:08:57.520 | And the basic numbers on this

02:09:00.020 | are that for women who are 35 years or older,

02:09:04.000 | about 25% of successful fertilizations lead to miscarriages.

02:09:09.000 | Now, when those miscarriages occur during pregnancy

02:09:12.080 | can be highly variable.

02:09:13.280 | Sometimes it's within the first trimester,

02:09:15.240 | sometimes it could be later,

02:09:17.320 | but the probability is about 25%.

02:09:20.380 | That probability increases greatly over time

02:09:24.120 | such that by the time women are in their early 40s,

02:09:27.160 | so 40 or older, the probability of miscarriage

02:09:29.720 | after a successful fertilization is going to be about 50%.

02:09:33.640 | And this could be due to a number of factors

02:09:35.760 | as I mentioned before,

02:09:36.840 | but one common reason

02:09:38.400 | is that there can be chromosomal abnormalities,

02:09:41.380 | and that could be related typically

02:09:43.540 | to the segregation of the egg

02:09:46.360 | when half of the chromosomes in that egg are removed,

02:09:48.960 | taking it from diploid to haploid.

02:09:50.600 | If you recall, there's that little polar body,

02:09:53.040 | which is the removal of the chromosomes

02:09:56.040 | that's ejected from the egg that will eventually ovulate.

02:09:58.560 | And sometimes not all the chromosomes

02:10:00.420 | that were supposed to be ejected in that polar body

02:10:03.880 | are ejected and as a consequence,

02:10:05.360 | there are multiple chromosomes

02:10:06.760 | or duplications of chromosomes, things like trisomies.

02:10:09.500 | Sometimes too many chromosomes move away

02:10:11.500 | and they're actually removal of entire chromosomes,

02:10:13.660 | meaning both strands so that you have chromosomal deletions.

02:10:16.540 | And in that case, typically fertilization won't occur,

02:10:19.380 | but there are instances in which fertilization will occur.

02:10:21.740 | So a woman will get a positive pregnancy test,

02:10:23.860 | her periods will stop.

02:10:25.540 | And the couple will think that they're advancing

02:10:27.880 | along the steps to a successful pregnancy,

02:10:31.040 | and then there will be sadly a miscarriage.

02:10:33.820 | Many, many times those miscarriages are the consequence

02:10:37.280 | of the fact that when there are extra chromosomes there

02:10:40.080 | or there are too few chromosomes present,

02:10:43.640 | that embryogenesis can simply not progress in a healthy way.

02:10:48.480 | There are some instances in which all of the chromosomes

02:10:51.800 | and all the chromosomal arrangements are perfectly normal

02:10:54.160 | and miscarriages can still occur.

02:10:57.040 | I'm going to do a future episode about pregnancy

02:11:00.060 | and embryonic development,

02:11:01.340 | where we will get into this more deeply,

02:11:03.120 | but just understand that the frequency of miscarriages

02:11:06.380 | increases dramatically after about age 34,

02:11:10.200 | and then continues to increase dramatically,

02:11:12.820 | extending well out until the 40s.

02:11:15.140 | Now, a very important consideration

02:11:16.960 | in terms of understanding and predicting fertility

02:11:19.480 | and fecundability, this word that describes the probability

02:11:23.000 | of getting pregnant on a given try and over time

02:11:26.360 | is trying to address how quote unquote fertile a woman is,

02:11:31.360 | and importantly, how quote unquote fertile a male is.

02:11:36.000 | And we'll talk about the male side in a moment,

02:11:38.520 | but when trying to address how fertile a woman is,

02:11:41.560 | of course, age is going to be one of the major factors,

02:11:44.840 | but just one factor, right?

02:11:46.800 | We already talked about how age determines the likelihood

02:11:49.660 | of a successful pregnancy.

02:11:51.240 | If the intercourse and ejaculation is being carried out

02:11:55.560 | at the correct times and with viable sperm

02:11:58.600 | capable of fertilizing eggs,

02:12:00.840 | and then of course there's the issue of egg quality,

02:12:03.080 | but in general, most women would like to know

02:12:05.960 | how fertile they are as a function of their age, right?

02:12:10.120 | And I actually think this is one of the most important

02:12:12.320 | topics in this whole space around fertility

02:12:14.740 | that isn't often discussed or at least isn't often discussed

02:12:17.520 | until women are in their late 30s or 40s,

02:12:20.880 | when oftentimes they will look back

02:12:23.080 | and wish that either they had frozen their eggs

02:12:24.960 | or they had frozen fertilized embryos,

02:12:27.060 | which is a whole thing unto itself.

02:12:29.520 | Let me talk about that when we have an episode

02:12:31.540 | on in vitro fertilization in more depth,

02:12:34.120 | but there is a fairly straightforward way or set of ways

02:12:38.440 | that women can determine their basic level of fertility.

02:12:42.680 | Leaving aside a lot of the detailed issues

02:12:44.760 | about the quality of eggs and so forth,

02:12:47.040 | one thing that you already learned is that

02:12:48.920 | there's this vault, there's this reserve

02:12:50.660 | that we call the ovarian reserve,

02:12:52.320 | and that each month a certain number of follicles

02:12:55.520 | leave that reserve and there's the opportunity

02:12:59.240 | based on the ovulation of a single egg

02:13:02.000 | to fertilize that egg and for the woman to get pregnant.

02:13:05.360 | And one thing that we know for sure is that

02:13:07.680 | the size of the population that's released from that vault

02:13:11.680 | each month has a very strong positive correlation

02:13:16.360 | with the size of the reserve in the vault itself, okay?

02:13:19.720 | So the way to think about this perhaps is that

02:13:23.080 | the vault is like a bank account,

02:13:24.520 | has a certain amount of money or in this case eggs in it.

02:13:28.480 | And you could imagine if someone's reasonably logical

02:13:31.980 | that if they have more money in their bank account,

02:13:34.280 | then they're going to withdraw a larger amount each month

02:13:37.520 | than if they have a small amount each month

02:13:38.960 | if the idea is to make that vault, that bank of eggs

02:13:43.200 | available to them over the longest period of time.

02:13:46.860 | And indeed biology is pretty smart.

02:13:48.740 | It doesn't deploy or release half the follicles in one month

02:13:53.360 | and then just slowly trickle out the remainder of follicles.

02:13:56.120 | No, that's not how it works.

02:13:57.040 | What you find is that of course in younger women,

02:13:59.820 | so say in their late teens, 20s and 30s,

02:14:04.020 | the ovarian reserve in the vault

02:14:05.740 | is going to have more eggs in it.

02:14:07.620 | And the number of follicles and eggs

02:14:09.940 | that leave that vault each month is going to be quite high.

02:14:12.620 | So one way to evaluate how quote unquote fertile you are,

02:14:17.760 | again, just one way is to go to your OBGYN

02:14:20.840 | and say that you would like to know

02:14:22.200 | how many follicles you have in a given month.

02:14:24.840 | And of course, they'll look at them on both sides

02:14:26.560 | in both ovaries.

02:14:28.120 | And for instance, if a woman has, you know,

02:14:31.200 | just two or three follicles that are out each month,

02:14:34.600 | well then the assumption, again, it's just an assumption,

02:14:37.180 | but the assumption that's pretty good

02:14:39.200 | because there's this positive correlation

02:14:41.360 | that generally occurs is that that ovarian reserve

02:14:44.920 | that the number of eggs in the vault is fairly low

02:14:48.280 | compared to someone who say has 20 follicles

02:14:50.880 | or 30 follicles each month, okay?

02:14:53.160 | And that's the typical trend.

02:14:54.440 | Again, these are averages.

02:14:55.520 | And it's very important to not get attached

02:14:57.480 | to any one number here.

02:14:58.720 | Again, these are averages.

02:15:00.160 | So for instance, there are women

02:15:01.600 | who only deploy five follicles and eggs each month

02:15:06.320 | out of their ovarian vault,

02:15:07.880 | but who find themselves to be very fertile, right?

02:15:10.480 | And there could be a number of different factors

02:15:11.760 | to explain that.

02:15:12.600 | Other women will have 20 or 30 eggs and follicles

02:15:15.760 | that leave that vault, the ovarian reserve each month,

02:15:18.400 | and they will have a harder time getting pregnant

02:15:20.200 | for any number of different reasons.

02:15:21.460 | But in general, the more eggs and follicles

02:15:23.940 | that leave the vault each month,

02:15:26.320 | the higher number of eggs that are still in reserve,

02:15:28.760 | meaning the greater amount of time

02:15:30.480 | over which a given woman could still attempt

02:15:33.540 | to have successful fertilizations.

02:15:35.900 | Now this small collection of follicles and eggs

02:15:39.200 | that are released each month actually has a name.

02:15:41.040 | They're called antral follicles.

02:15:42.340 | These are small follicles.

02:15:43.340 | They tend to be about two to nine millimeters across.

02:15:45.840 | The way these are analyzed or measured

02:15:47.680 | is women will go into the OBGYN office and by ultrasound,

02:15:52.000 | typically there's some local anesthesia,

02:15:53.680 | but it's not often a general anesthesia,

02:15:55.880 | but by local anesthesia, sometimes no anesthesia,

02:15:59.120 | they will essentially count the number of follicles

02:16:01.920 | that are present in each side,

02:16:03.520 | on the ovary on the left and the ovary on the right,

02:16:06.720 | and give a woman some sense of how many follicles she has.

02:16:09.900 | And typically this is done over a series of months

02:16:12.320 | to determine how many eggs are leaving

02:16:14.920 | the ovarian reserve each month,

02:16:16.200 | and therefore how many eggs she is likely to still have

02:16:19.920 | in the ovarian reserve.

02:16:21.520 | Now there's a non-invasive way to do this as well,

02:16:24.120 | although typically an OBGYN will do both

02:16:26.900 | what I just described with ultrasound

02:16:28.480 | and measure something called AMH,

02:16:30.600 | which is anti-Mullerian hormone,

02:16:32.640 | which is a hormone that is released

02:16:34.660 | by that antral follicle population,

02:16:37.060 | the population of follicles and eggs

02:16:38.840 | that leave the ovarian reserve each month.

02:16:41.440 | So one is a blood draw measure of a hormone AMH,

02:16:44.440 | the other is a structural imaging measure

02:16:46.760 | of the antral follicles directly.

02:16:48.500 | Again, the typical trend is for the number

02:16:52.000 | of antral follicles to decline over time.

02:16:54.560 | So one might expect, for instance,

02:16:56.440 | that a woman in her 20s or 30s might have 20, 30,

02:17:00.020 | maybe even 40 antral follicles

02:17:02.180 | that are exiting the reserve each month.

02:17:03.760 | And again, that's the total across both ovaries.

02:17:07.120 | Again, these are just averages,

02:17:08.400 | these are going to be distributions,

02:17:09.560 | there will be people with far fewer,

02:17:10.800 | there will be people with far more,

02:17:12.400 | but that over time, regardless of where a woman starts out

02:17:16.960 | from one decade to the next half decade and decade and so on

02:17:21.960 | that the number of antral follicles will decline

02:17:24.440 | and the amount of, or the levels of AMH will also decline.

02:17:28.800 | So what does this all mean?

02:17:30.580 | What this means is that if you are a woman

02:17:32.720 | who is in her 20s or 30s or 40s, whatever your age,

02:17:37.680 | if you are interested in conceiving in the future,

02:17:40.200 | it's very likely a good idea to go to your OB/GYN

02:17:44.560 | and get either your AMH levels measured

02:17:47.240 | or your follicle count measured.

02:17:49.260 | And to do that several times in a given period,

02:17:52.360 | and I don't mean a menstrual period,

02:17:53.480 | I mean a given period of time across several months

02:17:56.100 | to determine what is the average number of follicles,

02:17:58.060 | what's your average AMH level,

02:17:59.820 | thereby giving you some window into how many eggs

02:18:05.040 | you are likely to still have in your ovarian reserve.

02:18:07.380 | I cannot tell you how many women that I've spoken to

02:18:09.760 | and how many OB/GYNs more importantly,

02:18:11.760 | 'cause they speak to many more women about this

02:18:13.360 | than I ever have or ever will,

02:18:16.100 | wish that they had done this earlier, right?

02:18:18.620 | They think, oh, well, I'm in my 20s,

02:18:20.280 | so I'm likely to have a ton of follicles,

02:18:21.760 | or they got pregnant once before

02:18:23.480 | and so they're not so concerned about the number of follicles

02:18:25.760 | or their AMH levels.

02:18:27.160 | But over and over again,

02:18:28.920 | I was told in researching for this episode

02:18:30.840 | that the earlier and more frequent

02:18:32.940 | that women do this procedure of measuring AMH

02:18:36.400 | and measuring their follicle count,

02:18:38.520 | the higher the probability that they will eventually

02:18:40.660 | have a successful fertilization in pregnancy

02:18:42.880 | when they seek to do so.

02:18:44.400 | Now, the mirror image of all this, of course, is the sperm.

02:18:47.960 | And there's a kind of common misconception out there

02:18:51.000 | that the sperm, you only need one,

02:18:53.560 | and indeed you only need one,

02:18:54.960 | but actually you need many,

02:18:57.020 | and it's only one that's able

02:18:59.240 | to successfully fertilize the egg.

02:19:01.240 | So this whole concept of you only need one

02:19:03.760 | is both dismissive of the sperm,

02:19:05.640 | but more importantly dismissive of the biology

02:19:07.560 | of the sperm and the egg, okay?

02:19:09.840 | It only takes one successful sperm and one successful egg,

02:19:13.840 | but that's sort of like telling a woman,

02:19:15.280 | hey, you only need one egg, right?

02:19:17.280 | You need one egg of sufficient quality

02:19:19.840 | in the right time and place,

02:19:21.980 | and you need one sperm of sufficient quality

02:19:24.720 | in the right time and place

02:19:26.340 | in order to get successful fertilization

02:19:28.120 | and hopefully pregnancy.

02:19:29.940 | But you need a lot of sperm

02:19:33.560 | in order to get a high probability

02:19:36.580 | that that one sperm will be able

02:19:38.500 | to successfully fertilize the egg.

02:19:40.280 | So we have this image of sperm

02:19:41.480 | as kind of these dumb operators

02:19:43.220 | that just sort of swim mindlessly towards anything.

02:19:46.640 | I mean, if they bump into an egg,

02:19:47.980 | then they fertilize the egg,

02:19:48.900 | and that's really not the way it works.

02:19:50.760 | As I talked about earlier, the sperm with its head,

02:19:53.160 | its mid-region, its tail,

02:19:54.500 | chock-a-block with mitochondria in the mid-region

02:19:57.280 | is really an active motile cell

02:19:59.640 | that indeed will just swim forward

02:20:01.940 | if it's a healthy forward progressing sperm.

02:20:04.500 | But, you know, many males out there

02:20:06.660 | just simply do not have any knowledge

02:20:09.000 | of how many quality sperm that they happen to have.

02:20:11.740 | Now, given the fact that sperm analysis

02:20:13.420 | is relatively inexpensive,

02:20:15.440 | and also the fact that freezing sperm

02:20:17.600 | is relatively inexpensive,

02:20:19.440 | I think it stands to reason that most men

02:20:21.120 | should at least get some window

02:20:23.160 | into the numbering quality of their sperm.

02:20:25.840 | Now, it's a fair assumption to say

02:20:27.240 | that if someone is in their late teens or early 20s

02:20:30.480 | or 30s that they probably have high quality sperm.

02:20:33.580 | But again, as with the egg

02:20:35.400 | and the importance of measuring AMH

02:20:37.320 | and follicle count across time,

02:20:39.880 | men should really evaluate the quality

02:20:41.800 | and number of their sperm.

02:20:42.800 | And we talked a little bit earlier

02:20:43.960 | about some of the parameters

02:20:45.400 | that urologists and OBGYNs like to see

02:20:49.200 | when evaluating sperm, right?

02:20:50.800 | You know, there's a minimum number

02:20:52.520 | or concentration of sperm that they'd like to see

02:20:54.900 | if a couple is going to use IVF in vitro fertilization.

02:20:58.000 | And typically that's going to be

02:20:59.040 | about 15 to 20 million per mil of sperm or semen.

02:21:03.840 | And typically they want to see

02:21:05.260 | somewhere between two and five milliliters of semen overall

02:21:09.400 | in a given ejaculate

02:21:10.340 | after a 72 to 48 hour abstinence period.

02:21:13.820 | Because of course, the more ejaculations,

02:21:15.860 | the smaller the volume of the ejaculate

02:21:18.580 | in a short period of time,

02:21:21.060 | but after 48 to 72 hours,

02:21:23.180 | you more or less maximize the volume of ejaculate.

02:21:26.300 | And then of course, they want to see 50,

02:21:28.520 | but typically 60% or more of motile sperm

02:21:31.620 | in order to get IVF, but more is better.

02:21:33.940 | And of course, there is an enormous range,

02:21:35.500 | as I mentioned before.

02:21:36.360 | Some males will have anywhere from 10 to 20 million

02:21:40.740 | sperm per milliliter of ejaculate,

02:21:43.340 | and some men will have 100 to 200 million, okay?

02:21:47.580 | But just because they have 100 to 200 million

02:21:49.340 | doesn't mean that all of those sperm are of high quality

02:21:51.980 | and can fertilize eggs sometimes.

02:21:53.820 | More than half will be twitchers

02:21:55.660 | and some will be in motile and so on and so forth.

02:21:57.660 | So it's very straightforward

02:21:59.640 | what I believe most people should do

02:22:01.060 | and what the urologist I spoke to

02:22:02.640 | in advance of this episode, I had said to do,

02:22:05.460 | which is to simply do a sperm analysis.

02:22:07.880 | Refrain from ejaculation for 48 to 72 hours,

02:22:11.200 | give a sperm sample, have that sperm sample analyzed.

02:22:14.600 | The cost of the sperm analysis is not typically that much,

02:22:18.680 | okay, and considering that conception

02:22:21.680 | and healthy conception and fertilization

02:22:23.480 | is an expensive process

02:22:24.760 | if you have to go the in vitro fertilization route,

02:22:27.560 | it stands to reason that the cost is pretty well justified.

02:22:30.040 | You also have the option to freeze sperm over time.

02:22:32.800 | There is evidence that the age of the father

02:22:35.280 | and therefore the age of the sperm

02:22:37.560 | can dictate whether or not there's a higher instance

02:22:39.920 | of problematic pregnancy or developmental outcomes,

02:22:44.400 | including autism, that is true.

02:22:46.600 | You probably heard that if the father is 40 years or older,

02:22:49.780 | the incidence of autism is increased significantly.

02:22:52.920 | That is true, although the overall probability

02:22:56.880 | of having an autistic offspring if somebody,

02:22:59.880 | if the father that is, is 40 years or older

02:23:01.680 | is still quite a bit lower than you would imagine.

02:23:04.840 | It's not as if the probability suddenly skyrockets, okay?

02:23:08.320 | So we will have an episode on autism

02:23:10.340 | and genetic and non-genetic influences on autism

02:23:14.840 | and other aspects of the autism spectrum.

02:23:16.980 | But the point is this, I believe,

02:23:20.560 | and the urologists I spoke to

02:23:22.360 | who are interested in fertility and male health

02:23:24.760 | and sexual health suggests that men get their sperm analyzed

02:23:29.300 | at least once every five years.

02:23:31.640 | And certainly if they're going to want to conceive children

02:23:34.960 | in the distant future,

02:23:36.040 | that they consider freezing their sperm

02:23:37.660 | because that too is fairly nominal cost

02:23:40.160 | in order to freeze sperm at a younger age.

02:23:42.280 | And of course, if you can freeze and use sperm

02:23:44.640 | from the time in which you were younger,

02:23:46.360 | why wouldn't you, right?

02:23:47.760 | I mean, you can still opt to go for natural pregnancy later

02:23:50.720 | if that's what you want to do,

02:23:51.940 | but having that in reserve is generally a good idea.

02:23:55.400 | And I discussed some of the parameters that are looked for.

02:23:57.960 | And perhaps most importantly,

02:24:00.260 | there is the possibility of an underlying issue

02:24:02.780 | whereby for instance,

02:24:04.080 | there is very little sperm in an ejaculate.

02:24:09.080 | As I mentioned earlier,

02:24:10.140 | the seminal fluid in the ejaculate

02:24:11.780 | could have zero sperm in it,

02:24:13.060 | but the volume of ejaculate could appear completely normal.

02:24:15.940 | So just because your ejaculate volume is normal to you

02:24:19.300 | or is in that range of two to five milliliters,

02:24:22.900 | well then it doesn't necessarily mean

02:24:24.360 | that there are any sperm there

02:24:25.480 | or that there are very few sperm there.

02:24:28.040 | And the few sperm that are there

02:24:30.320 | or the many sperm that are there are functionally motile.

02:24:32.960 | So get this analyzed, it's really worth doing.

02:24:35.500 | And again, it's not something you have to do every year,

02:24:37.440 | it's something that you want to do

02:24:39.140 | probably every five years,

02:24:40.320 | at least until the point where you've conceived

02:24:41.800 | as many children as you ever want to conceive.

02:24:43.840 | So the basic takeaway here is that if you're a woman,

02:24:46.480 | to get your egg count, your antral follicle count that is,

02:24:50.920 | and therefore your reserve of eggs indirectly measured,

02:24:54.960 | and of course also get your AMH levels measured.

02:24:57.560 | And if you're a male to have a sperm analysis

02:24:59.680 | and to do that relatively early,

02:25:01.180 | in fact, another incentive for doing that early

02:25:02.980 | is that you have a comparison point.

02:25:04.900 | So that for instance, if you are in your early twenties

02:25:07.260 | and you're not thinking about having kids at all,

02:25:08.720 | or you're thinking that you might someday have kids,

02:25:10.340 | but it's a really someday someday far off in the future,

02:25:13.440 | well, it's wonderful to have a reference point

02:25:15.800 | from which to compare your biology in your early twenties

02:25:19.560 | to your biology in your mid or late thirties or forties,

02:25:22.280 | when you might happen to be interested in conceiving.

02:25:25.400 | And if that doesn't provide incentive enough,

02:25:28.480 | I should mention, and this is important to point out,

02:25:30.880 | and then I think both males and females are not aware of,

02:25:34.540 | is that one in five couples that have issues with fertility,

02:25:38.900 | the issue ends up falling on the biology,

02:25:42.900 | that is the quality of the sperm or a lack of number

02:25:46.040 | of sperm.

02:25:46.880 | So, you know, I think there's a misconception

02:25:48.680 | that when fertility is an issue,

02:25:50.460 | it's always an issue with the eggs

02:25:52.400 | and this age dependent decline in egg quality,

02:25:55.980 | again, that's the best language we have available to us

02:25:58.320 | at the moment, this age dependent decline in egg quality

02:26:01.380 | is often to blame, but not always.

02:26:03.500 | One in five couples that have challenges conceiving,

02:26:06.420 | turns out that it's going to be an issue with the sperm.

02:26:08.380 | And of course there are a number of different sperm analyses

02:26:10.480 | that should all the other parameters of sperm appear normal.

02:26:13.840 | Now, for instance, you can get a DNA fragmentation analysis.

02:26:17.680 | You can see whether or not the DNA of the sperm

02:26:19.380 | are somehow disrupted.

02:26:20.980 | Urologists these days are excellent at figuring out,

02:26:24.600 | for instance, if a male has lots and lots of sperm,

02:26:27.180 | everything looks great,

02:26:28.020 | but the shape of the head of the sperm isn't quite right.

02:26:30.980 | If it's not oval enough and it's too rounded,

02:26:33.060 | that could be a genetic defect under which conditions

02:26:36.140 | there is zero probability of the male ever

02:26:41.140 | naturally conceiving, right?

02:26:42.920 | Regardless of who the female partner is, believe it or not,

02:26:45.400 | males can have a ton of sperm,

02:26:47.080 | but if they carry a certain genetic defect,

02:26:49.500 | those sperm will be incapable of depositing

02:26:51.960 | those 23 chromosomes into the egg.

02:26:55.040 | However, there are ways in which that sperm can be coaxed

02:26:59.540 | or forced to fertilize the egg and deposit

02:27:01.640 | its genetic contents by in vitro fertilization

02:27:03.660 | and then implantation into the female.

02:27:05.220 | So again, lots of reasons to have a egg reserve analysis

02:27:09.700 | by ultrasound and AMH for females,

02:27:11.360 | and lots of reasons for males to have a sperm analysis.

02:27:15.020 | And of course, typically with a sperm analysis

02:27:17.060 | and a ovarian reserve analysis will be a hormone analysis.

02:27:22.060 | And I'm a very strong believer in people getting an insight

02:27:26.500 | that is a window into their hormonal composition,

02:27:29.480 | not just when they encounter problems,

02:27:31.780 | but starting at a pretty early age,

02:27:33.800 | even if it's only done once every five years or so,

02:27:36.140 | having a reference point to your 20s and to your 30s

02:27:39.520 | and mid 30s for when you felt a certain way,

02:27:41.580 | maybe as in the case for many people I know,

02:27:44.200 | they actually feel better in their 40s

02:27:45.840 | than they did in their 20s,

02:27:46.760 | because they're doing a lot of things

02:27:47.840 | to support their health, that is possible.

02:27:49.640 | But in many cases, people start feeling not as well,

02:27:52.880 | or their fertility seems to be dropping off,

02:27:55.060 | or any number of different parameters

02:27:56.720 | that we've discussed today

02:27:58.120 | were related to vitality and longevity

02:27:59.840 | seem to be dropping off over time,

02:28:01.680 | and they want to get a insight into what could be the issue.

02:28:04.720 | And hormones are sometimes not always,

02:28:06.320 | but sometimes involved in those underlying issues.

02:28:09.200 | And there's nothing as valuable as having a reference point

02:28:13.160 | from a time in which things were going well

02:28:15.540 | to evaluate the, for instance, the levels of hormones,

02:28:18.820 | not just testosterone,

02:28:19.940 | but also estrogen and progesterone and so forth.

02:28:22.880 | So you need a comparison point

02:28:24.120 | in order to determine what really needs to be changed.

02:28:26.560 | So all of this is a strong push for people

02:28:29.420 | to use your insurance if you're able to put it on insurance,

02:28:32.300 | oftentimes people are.

02:28:34.460 | And if not, to try and find a reasonable

02:28:37.120 | or reasonably priced way to do a sperm and egg analysis,

02:28:42.120 | and to ideally do a hormone analysis as well.

02:28:45.240 | It's really going to set you up

02:28:46.440 | for the maximum probability of being able

02:28:48.300 | to conceive children when you want to,

02:28:49.760 | and also to avoid a bunch of other health-related issues

02:28:53.040 | that involve hormones and reproductive health,

02:28:56.420 | and in general, to support your mental health

02:28:58.720 | and physical health.

02:28:59.840 | So I've been talking about a bunch of things to do.

02:29:01.960 | There are a couple of things to be mindful of

02:29:03.980 | to actively avoid if your goal is to be and remain fertile.

02:29:08.420 | And that's regardless of whether or not

02:29:10.260 | you want to conceive children in the future or not.

02:29:13.340 | Now, in the context of this discussion,

02:29:15.060 | the same things that we've heard to be true

02:29:17.040 | for other aspects of our health turn out to also be true.

02:29:19.880 | So let's just start with the basics.

02:29:22.720 | Everybody should be getting approximately six to eight hours

02:29:26.680 | of sleep every night.

02:29:27.600 | That should be quality sleep.

02:29:29.160 | Optimizing your sleep is fundamental

02:29:31.080 | to balancing your hormones.

02:29:32.520 | Now, balancing your hormones is kind of a catchphrase

02:29:34.720 | for all things related to proper hormone regulation.

02:29:38.080 | Sleep is the fundamental layer of mental health,

02:29:40.080 | physical health, and performance of all kinds,

02:29:42.560 | and believe it or not, fertility.

02:29:44.760 | When people are not sleeping well or enough,

02:29:47.500 | stress hormones, in particular cortisol,

02:29:49.580 | shift to peaking later in the day,

02:29:51.760 | and those elevated cortisol levels later in the day

02:29:54.160 | cause a bunch of different problems

02:29:56.360 | in both males and females, many of which impact fertility.

02:29:59.200 | So controlling cortisol starts with controlling your sleep.

02:30:02.920 | It also impacts testosterone and estrogen levels.

02:30:06.800 | So of course the proper ratios of testosterone

02:30:08.880 | and estrogen will vary from males to females,

02:30:11.300 | but in order to get those right,

02:30:12.880 | or as right as they can be without other interventions,

02:30:15.880 | you want to make sure you're getting enough quality sleep.

02:30:17.820 | How much sleep?

02:30:18.660 | Most people need about six to eight hours of sleep per night.

02:30:21.700 | Waking up once, maybe twice per night

02:30:23.720 | in the middle of the night and going back to sleep

02:30:25.320 | is not such a big deal,

02:30:26.140 | but six to eight hours of solid sleep would be ideal.

02:30:28.960 | Some people need a little bit less

02:30:30.240 | in order to function, five hours.

02:30:32.440 | Some people need a little bit more.

02:30:33.560 | Developing teenagers and babies and kids need a lot more.

02:30:36.200 | People who are sick or recovering from injury

02:30:37.960 | need a lot more.

02:30:38.800 | We've done multiple episodes on sleep.

02:30:40.940 | We have a toolkit for sleep available free

02:30:43.000 | at HubermanLab.com.

02:30:44.400 | You go there, you don't even have to sign up

02:30:46.160 | for the newsletter, although you can if you want.

02:30:47.720 | Just go to Toolkit for Sleep under the menu,

02:30:50.280 | and you'll be able to download that,

02:30:51.960 | or you can even just view it on the screen

02:30:53.080 | if you don't want to download it.

02:30:54.040 | It has lots of tools.

02:30:54.880 | We've done an episode called Perfect Your Sleep

02:30:58.140 | that has a lot of tools.

02:31:00.060 | They're all timestamped for you.

02:31:01.300 | We've done a Master Your Sleep episodes.

02:31:02.820 | Lots of tools to get your sleep right.

02:31:04.180 | Get your sleep right if you are wishing to conceive

02:31:07.060 | and/or to simply have healthy biology

02:31:09.760 | to be fertile or otherwise.

02:31:11.160 | That's just fundamental.

02:31:12.040 | Now, there are other things to not do,

02:31:15.660 | and those, again, fall into the somewhat obvious categories,

02:31:18.480 | but I think a lot of people aren't aware

02:31:19.740 | of just how striking an effect these certain behaviors

02:31:24.100 | that you want to avoid can have

02:31:25.500 | in diminishing your fertility for both males and females.

02:31:28.240 | So let's talk about those.

02:31:29.080 | So the first one is smoking.

02:31:30.660 | And when we talk about smoking here,

02:31:32.060 | we're talking about smoking nicotine,

02:31:34.780 | and we're talking about smoking cannabis.

02:31:36.680 | And indeed, there are strong data,

02:31:38.340 | and I will put a reference

02:31:39.680 | to one of the better, larger analyses of these data.

02:31:42.360 | There are strong data showing

02:31:43.540 | that cannabis reduces fertility.

02:31:45.920 | Now, I can already hear the screams from the back,

02:31:48.460 | although they're probably fairly drawled out screams

02:31:52.380 | from the back of people saying they smoke cannabis

02:31:54.820 | and they had no trouble conceiving.

02:31:57.020 | Certainly there will be exceptions,

02:31:58.420 | but whether or not you're male or female,

02:32:00.400 | smoking cannabis is a bad idea

02:32:02.140 | if you want to conceive a healthy child.

02:32:03.900 | Can you still conceive a healthy child

02:32:05.320 | while smoking cannabis?

02:32:07.660 | Probably certain people can.

02:32:09.300 | Many people will greatly decrease the probability

02:32:12.900 | of a healthy fertilization in pregnancy by smoking cannabis.

02:32:16.260 | There are excellent data to support that.

02:32:18.980 | As well, nicotine, both smoked or vaped,

02:32:22.260 | is going to disrupt the process of fertilization

02:32:27.160 | and can disrupt pregnancy dramatically, okay?

02:32:29.660 | So just avoid it altogether.

02:32:31.080 | How does this happen?

02:32:31.920 | Well, it turns out that smoking increases

02:32:33.860 | what are called reactive oxygen species.

02:32:35.580 | This greatly disrupts the quality of the egg

02:32:38.740 | at the level of the spindle and mitochondria

02:32:40.340 | and a number of other features.

02:32:41.980 | And in the sperm, turns out that smoking

02:32:44.540 | doesn't necessarily disrupt the sperm directly,

02:32:46.940 | although it can cause DNA fragmentation,

02:32:49.780 | which can cause all sorts of abnormalities,

02:32:51.860 | can prevent fertilization,

02:32:53.220 | can lead to birth defects in the offspring.

02:32:55.100 | But more importantly,

02:32:56.980 | it increases what are called reactive oxygen species

02:32:59.380 | in the seminal fluid, in the semen that contain the sperm.

02:33:02.060 | This very, under normal circumstances,

02:33:04.940 | under healthy circumstances,

02:33:06.220 | beautifully orchestrated chemistry of fluid

02:33:09.240 | that allows the sperm to thrive in their trajectory

02:33:13.160 | and attempt to fertilize the egg

02:33:14.900 | and lead to a healthy pregnancy.

02:33:16.280 | So if you are a smoker and you want to conceive,

02:33:19.820 | the best advice I can give you is to quit smoking

02:33:21.820 | and yes, that includes cannabis as well.

02:33:23.580 | Now, I am not somebody who believes that cannabis

02:33:25.780 | across the board is not useful.

02:33:27.060 | There are medical applications and other applications.

02:33:29.200 | I talk about that in an episode

02:33:30.820 | all about cannabis for health and disease

02:33:33.300 | and notice health was in there too.

02:33:34.840 | So you cannabis smokers don't come after me with,

02:33:37.680 | I guess, whatever it is with bongs and pipes

02:33:40.000 | or whatever it is that you want or with vapes.

02:33:42.140 | The point is that while it can be beneficial

02:33:45.200 | for certain populations, it's certainly bad for others.

02:33:48.580 | And if you're trying to conceive,

02:33:50.500 | it is bad for fertility and for a healthy pregnancy, okay?

02:33:54.000 | Now that's smoking and vaping, by the way, okay?

02:33:57.740 | Vaping is included there.

02:33:59.440 | Now the next category of don'ts relates to alcohol.

02:34:03.480 | Now everyone has heard that drinking during pregnancy

02:34:05.780 | is a bad idea.

02:34:07.140 | You may have heard and some people have talked about

02:34:09.000 | the fact that there are cultures in which they allow,

02:34:13.420 | if you will, or even condone sadly,

02:34:16.360 | one or two drinks while pregnant provided it's just champagne

02:34:19.840 | or something of that sort.

02:34:20.800 | That is a terrible idea.

02:34:22.340 | I did an episode all about alcohol,

02:34:24.560 | both its potential health effects

02:34:26.680 | of which there turned out to be zero.

02:34:28.600 | And yes, that includes red wine.

02:34:30.520 | It is far better to not drink at all.

02:34:32.560 | And if you're going to drink the limit,

02:34:34.140 | if you're a healthy adult,

02:34:35.100 | who's not trying to conceive not pregnant

02:34:36.800 | and you don't have issues with alcoholism

02:34:38.860 | is probably two drinks per week total.

02:34:41.900 | That's right, two drinks per week total.

02:34:44.080 | And that's the level that you really should consider

02:34:46.320 | if you're a drinker,

02:34:47.160 | if you're somebody who's trying to conceive.

02:34:48.840 | However, for a woman who becomes pregnant,

02:34:51.480 | the total number of drinks

02:34:52.600 | that you should allow yourself per week while pregnant

02:34:54.880 | and breastfeeding is indeed zero.

02:34:57.860 | There is absolutely no evidence

02:34:59.760 | that one can quote unquote get away

02:35:01.440 | with drinking during pregnancy.

02:35:03.180 | And people say, well, I had a perfectly healthy child,

02:35:04.840 | but of course you don't know

02:35:05.920 | what the health of that child would have been

02:35:07.640 | had you not drank at all.

02:35:09.600 | Now I'm not here with any generally strong stance

02:35:11.920 | against alcohol.

02:35:12.800 | I myself am somebody who has a drink every once in a while,

02:35:17.200 | although I don't consider myself somebody

02:35:18.880 | who has a strong proclivity for alcohol.

02:35:21.720 | And of course at this moment,

02:35:23.680 | I'm not trying to conceive children

02:35:25.360 | and I'm certainly not pregnant.

02:35:26.880 | So that's safe for me,

02:35:28.880 | but frankly I haven't had a drink in a very long time.

02:35:31.680 | And so I don't miss it and that's me,

02:35:33.520 | but I do realize that a lot of people enjoy alcohol.

02:35:36.800 | And so it's that two drinks per week limit

02:35:38.900 | that really sets the upper limit and threshold

02:35:41.480 | beyond which you start running into issues

02:35:43.200 | with cellular mutation.

02:35:45.260 | You start running into issues of oxidative stress,

02:35:48.740 | greatly increase cancer risk in particular,

02:35:51.080 | breast cancer risk,

02:35:51.920 | all that's covered in the alcohol episode that we did.

02:35:54.920 | You can find it at hubermanlab.com and timestamped

02:35:57.440 | if you want to navigate to specific topics and so forth,

02:35:59.720 | find out all about the data,

02:36:01.120 | supporting the statements that I'm making,

02:36:02.840 | so on and so forth.

02:36:04.080 | Now, if you're somebody who's seeking to conceive

02:36:06.300 | or you fall into this category

02:36:07.780 | that some couples describe themselves as,

02:36:09.940 | we're not trying, but we're not not trying,

02:36:12.100 | meaning they're not using birth control.

02:36:13.500 | They're kind of letting chance run its course.

02:36:16.920 | Well, then you should definitely be aware

02:36:18.840 | of the data showing that even just one bout,

02:36:22.400 | one bout of so-called binge drinking,

02:36:24.920 | which is five to six drinks in a given night

02:36:28.440 | or half day in a 12 hour period,

02:36:30.440 | one bout of five to six drinks,

02:36:32.160 | if you're a woman or you're a man,

02:36:35.400 | greatly increases both the likelihood of mutations

02:36:40.420 | in the embryo that would result from a fertilization.

02:36:43.960 | And at the same time, for reasons that should be obvious

02:36:46.160 | to you based on all the biology we've talked about,

02:36:48.320 | a greatly reduced probability of fertilization.

02:36:51.020 | Now, that absolutely does not mean that you should use

02:36:53.800 | the ingestion of five or six drinks

02:36:55.340 | as a method of birth control.

02:36:57.520 | That is not what I'm saying here.

02:36:58.880 | What I'm saying is that if you go out on a given night

02:37:02.520 | and you have five or six drinks

02:37:04.160 | and you happen to become pregnant,

02:37:05.600 | the probability that that pregnancy will be disrupted

02:37:09.280 | in some way is greatly increased.

02:37:11.720 | What the exact consequences are, no one can tell you.

02:37:15.120 | But also if you're somebody who is interested

02:37:17.920 | in conceiving a child, well, then you absolutely

02:37:21.300 | should abstain from ingesting drinks more than one or two

02:37:26.000 | during the time in which you're trying to conceive.

02:37:27.960 | And ideally it would be zero.

02:37:29.800 | And you certainly would want to avoid

02:37:31.680 | drinking multiple drinks per night.

02:37:33.620 | And so this idea of going out and having, you know,

02:37:36.000 | three or four drinks or four or five drinks

02:37:38.240 | in a given night at a time in which you're also trying

02:37:41.280 | to conceive children, the biology tells us,

02:37:44.680 | the epidemiology tells us that this is just a terrible idea.

02:37:47.600 | It's going to reduce the likelihood of fertility

02:37:50.200 | and successful pregnancy.

02:37:51.700 | And if there is a successful pregnancy,

02:37:53.740 | the word success needs to be in quotes, right?

02:37:56.340 | I mean, I think every parent, every species for that matter,

02:38:00.180 | wants to increase the probability

02:38:02.440 | of having healthy offspring.

02:38:04.400 | And so to my mind anyway, and to the OBGYNs

02:38:07.580 | and the urologists that are focused on fertility

02:38:10.000 | that I spoke to, everyone will say,

02:38:12.040 | try as hard as you can to avoid

02:38:14.760 | these so-called binge drinking episodes.

02:38:16.640 | And again, these episodes are one night

02:38:18.120 | of consuming five to six drinks.

02:38:19.720 | Now, another important thing to remember in this context

02:38:22.020 | is that the negative effects of consuming five or six drinks

02:38:26.000 | in a given night extend over many weeks

02:38:29.200 | following the ingestion of that alcohol.

02:38:31.840 | If you're a male, what that means is that's going to impact

02:38:35.600 | the quality of your sperm and greatly decrease

02:38:38.940 | the likelihood of successful fertilization

02:38:41.880 | and/or healthy pregnancy over the period

02:38:45.500 | of that entire spermatogenesis window,

02:38:48.140 | which is, as we talked about before, 60 to 90 days, right?

02:38:52.040 | 60 to generate the sperm and then in some additional time

02:38:54.220 | for the sperm to be transported to the point

02:38:55.660 | where they could be ejaculated.

02:38:57.220 | If you're a woman and you have five or six drinks

02:39:00.180 | on a given night, well, then you are going to disrupt

02:39:02.660 | the quality, not of just the egg that eventually ovulates,

02:39:06.940 | but indeed the entire pool of follicles

02:39:09.120 | that leaves the ovarian vault and reserve

02:39:11.260 | and from which the one egg will be selected.

02:39:13.700 | In other words, you are reducing the quality

02:39:17.260 | of all of the eggs that you happened to deploy that month.

02:39:20.400 | Now, some of you who were really following

02:39:22.280 | the biology earlier might say,

02:39:23.740 | well, what if I have those five or six drinks

02:39:25.220 | during the time in which I'm menstruating,

02:39:27.340 | just in which there's bleeding present

02:39:29.820 | and therefore I haven't yet ovulated?

02:39:32.560 | Ah, but if you remember the biology

02:39:34.300 | we talked about earlier specifically,

02:39:37.440 | there is a subset of follicles and eggs

02:39:39.240 | that leave that ovarian reserve quite a bit before

02:39:43.360 | that one egg is selected for and ovulates.

02:39:46.300 | And of course there are all the different hormonal cascades

02:39:48.660 | in the general milieu of the ovary,

02:39:50.540 | which are important and are being regulated

02:39:52.540 | by different hormones.

02:39:53.420 | And yes, indeed, the regulation of those hormones

02:39:55.940 | is strongly impacted by alcohol

02:39:58.080 | through a number of different pathways,

02:39:59.340 | through the regulation of the neurotransmitter GABA

02:40:01.680 | up in the brain, right?

02:40:02.820 | It's actually a lot of GABA and GABA receptors

02:40:04.780 | in the hypothalamus,

02:40:05.620 | the very region from which gonadotropin-releasing hormone,

02:40:08.400 | our old friend from a couple hours ago in this discussion,

02:40:11.860 | going to disrupt GnRH secretion.

02:40:14.140 | You can disrupt pituitary function with alcohol.

02:40:17.100 | Again and again, what we're seeing is that consuming

02:40:20.280 | more than one or two drinks per week of alcohol

02:40:23.580 | is really detrimental to the entire process of fertility

02:40:26.700 | and the entire process of healthy pregnancy.

02:40:29.420 | And that's true from both the male side and the sperm,

02:40:32.120 | and it's true from the female side and the egg.

02:40:34.700 | So my simple advice on this is if you are wishing

02:40:37.640 | to have a healthy fertilization and pregnancy,

02:40:41.000 | the best thing to do would be avoid alcohol together.

02:40:43.200 | And if you're going to drink to really limit that drinking

02:40:45.600 | to one or two drinks per week, maximum.

02:40:48.720 | So those are the major don'ts.

02:40:49.860 | Really avoid excessive stress.

02:40:51.620 | And I should mention excessive stress is not

02:40:53.640 | just best avoided by getting enough quality sleep at night,

02:40:55.860 | although that is the primary way.

02:40:57.580 | There are other ways to avoid stress.

02:40:58.840 | We've done entire episodes about this,

02:41:00.300 | and we have a toolkit related to reducing stress

02:41:02.520 | with very simple zero cost tools.

02:41:04.180 | Again, you can find all that at HubermanLab.com.

02:41:06.340 | And I should mention if you want to find any episode

02:41:08.340 | or topic or timestamp, that website is keyword search

02:41:13.300 | available, so you can just go to HubermanLab.com,

02:41:15.700 | put into the search function, stress tools,

02:41:18.000 | and a bunch of different links will pop up

02:41:19.860 | related to those topics.

02:41:22.040 | Likewise with sleep, likewise with any number

02:41:23.940 | of different topics you might be interested in.

02:41:25.580 | So get enough quality sleep and thereby reduce stress

02:41:29.000 | and also directly buffer stress with real-time tools

02:41:31.680 | to buffer stress that I've talked about in the episodes

02:41:34.880 | that you can access.

02:41:35.760 | And there are ways to greatly reduce your overall level

02:41:39.240 | of stress to limit any cortisol that's released

02:41:41.880 | to early in the day, which is when you want cortisol released

02:41:44.680 | and not have it late in the day and so on and so forth.

02:41:46.920 | So reduce your stress.

02:41:48.260 | And as I just told you, by all means,

02:41:53.020 | do not drink more than two drinks per week

02:41:55.320 | and zero is better than two.

02:41:56.800 | If anyone tells you, oh, there's all this resveratrol

02:41:59.960 | in red wine and that's good for us,

02:42:01.980 | the data simply tell us that there's not enough

02:42:03.680 | resveratrol in red wine to really have

02:42:05.400 | any positive health benefit.

02:42:06.520 | The data around resveratrol and health benefits itself

02:42:09.920 | is under question nowadays.

02:42:11.360 | Zero alcohol is better than any alcohol.

02:42:14.200 | Two drinks per week is the limit.

02:42:15.880 | Also limit or eliminate or avoid nicotine

02:42:20.880 | and ideally cannabis smoking and vaping at the time

02:42:24.200 | in which you are trying to get pregnant.

02:42:26.520 | And certainly if you are pregnant,

02:42:28.000 | avoid all of the things as best you can

02:42:30.240 | that I just described a moment ago.

02:42:32.280 | Now there are a couple other don'ts

02:42:33.520 | that are really important.

02:42:34.840 | One of the most important don'ts relates to STIs

02:42:37.720 | or sexually transmitted infections.

02:42:39.860 | Everyone who's sexually active should get an STI check.

02:42:42.420 | In fact, if you go to a fertility clinic

02:42:44.640 | or you go for sperm analysis or you go for egg analysis,

02:42:47.180 | almost always they will do an STI check

02:42:49.960 | even if you happen to be in a monogamous relationship,

02:42:52.380 | even if you happen to be not sexually active

02:42:54.220 | and you're somebody who's seeking to use IVF

02:42:56.040 | with a sperm donor or something of that sort,

02:42:58.140 | why would they do that?

02:42:59.040 | Why is there so much concern about that?

02:43:00.860 | Is it about avoiding giving birth to a child

02:43:03.900 | that has something like a herpes infection or HIV?

02:43:08.440 | Well, certainly that's one reason,

02:43:09.780 | but that's a down the line reason

02:43:11.160 | because at the time when someone goes into the clinic

02:43:12.980 | for one of these sperm or egg analyses,

02:43:15.340 | I mean, that's well in advance of any pregnancy, right?

02:43:18.240 | The reason is there are a number of STIs

02:43:20.840 | in particular chlamydia for which it greatly increases

02:43:24.280 | the probability of miscarriage.

02:43:25.840 | So chlamydia is one of those very insidious

02:43:28.920 | and cryptic STIs because a lot of people,

02:43:31.360 | both males and females don't even realize

02:43:33.140 | that they have chlamydia and then they can carry chlamydia

02:43:37.040 | at the time in which they conceive

02:43:38.340 | and then that can lead to ectopic pregnancies

02:43:40.120 | and or miscarriages.

02:43:41.560 | So by all means, get an STI check

02:43:44.040 | if you are somebody who's seeking to conceive children

02:43:46.560 | or evaluating your fertility generally.

02:43:49.440 | Chlamydia can also have damaging effects on the epididymis

02:43:51.940 | and on the various other aspects of male reproductive health.

02:43:55.200 | In the future, we will do an episode

02:43:56.500 | all about sexual health.

02:43:57.560 | This is not the time for that, but get an STI check

02:44:00.280 | if your goal is to conceive a healthy child.

02:44:02.700 | Now, the other thing that can have a very negative impact

02:44:05.200 | on fertility and healthy pregnancy is a viral infection.

02:44:10.240 | For instance, if a male has had a severe viral illness,

02:44:13.880 | and this could be any number of different viral illnesses

02:44:15.720 | from flu to cold or any number of different viruses,

02:44:18.140 | pick your favorite virus, in the previous 70 to 90 days,

02:44:23.060 | that can greatly diminish the number

02:44:25.100 | and or quality of sperm, okay?

02:44:28.040 | So that's really important.

02:44:29.400 | This is also important if you're going to go in

02:44:30.720 | and do a sperm analysis and you had a viral infection

02:44:33.380 | in the previous 70 to 90 days,

02:44:35.480 | well, then you need to be aware of that

02:44:37.100 | because it could greatly impact the parameters

02:44:39.060 | of that sperm analysis.

02:44:40.460 | Likewise, for women, if you've had a serious viral infection

02:44:42.960 | in the previous 30 days,

02:44:43.960 | does that mean you should not try and conceive?

02:44:45.420 | Not necessarily, but you should talk to your OBGYN about that.

02:44:49.380 | There are data showing that viral infection,

02:44:52.520 | in particular of influenza in the mother,

02:44:54.680 | in the first trimester of pregnancy, has some correlation.

02:44:58.440 | It's not 100%, but some correlation

02:45:00.860 | with negative mental health outcomes

02:45:02.520 | of the offspring sometime later, including schizophrenia.

02:45:05.400 | This is some of the work that was done at Caltech

02:45:07.320 | a number of years ago and other laboratories as well.

02:45:11.280 | Those data are still being built up over time.

02:45:13.740 | Again, it's not one for one, it's not causal.

02:45:16.640 | So if you did get an influenza or a cold

02:45:19.320 | or other kind of viral infection during the first trimester

02:45:21.560 | or any trimester of pregnancy, I don't want to cause alarm,

02:45:24.460 | but you should talk to your OBGYN about this.

02:45:26.980 | The goal of course is to avoid viral illness

02:45:28.920 | at any time when you're trying to conceive

02:45:30.280 | or have a healthy pregnancy.

02:45:32.680 | But of course, sometimes people will get ill

02:45:34.720 | and the children can turn out to be perfectly normal

02:45:37.500 | and fine, but it is something that you want to avoid

02:45:39.720 | and it will impact your egg analysis

02:45:42.300 | and it will impact sperm analysis.

02:45:44.480 | And one thing I found really surprising

02:45:45.960 | in researching this episode was that one in 25 men

02:45:50.960 | carry a copy of a mutation for cystic fibrosis.

02:45:55.600 | Now, some of you are probably familiar with cystic fibrosis

02:45:58.520 | as a condition that can cause issues with the lungs,

02:46:01.460 | the accumulation of fluid in the lungs or other tissues.

02:46:04.680 | Cystic fibrosis, in order to express that way

02:46:07.440 | of accumulation of fluid in the lungs,

02:46:09.220 | you really need two copies, right?

02:46:10.640 | You need two mutant copies

02:46:12.640 | or you need two copies of the cystic fibrosis gene.

02:46:15.460 | One in 25 men will carry just one copy

02:46:19.220 | and therefore will not have any symptoms of cystic fibrosis,

02:46:22.960 | but those one in 25 men will have defects

02:46:27.160 | in the architecture of the vas deferens,

02:46:30.080 | the duct through which the ejaculate needs to pass

02:46:33.740 | in order to eventually be ejaculated out of the urethra.

02:46:37.420 | And so what that means is that these men can have

02:46:40.400 | what appears to be normal semen volume,

02:46:42.240 | but that they won't have normal numbers of sperm.

02:46:45.580 | And that's not because of a deficit in making the sperm,

02:46:48.540 | the testes can function just fine,

02:46:49.920 | the brain and the pituitary communicating

02:46:52.320 | with the testes just fine,

02:46:53.640 | but that literally the passageway by which those sperm arrive

02:46:56.780 | within the seminal fluid and are eventually ejaculated

02:46:59.480 | is disrupted by the cystic fibrosis gene.

02:47:01.680 | Luckily, if somebody has just one copy

02:47:04.060 | of the cystic fibrosis gene and they're male,

02:47:05.960 | and this is the issue,

02:47:08.060 | the vas deferens either can be repaired

02:47:11.100 | by a urologist who's expert

02:47:14.100 | in the surgical repair of vas deferens,

02:47:15.740 | or sperm can be extracted from the testicle directly,

02:47:18.580 | which might sound like a painful procedure,

02:47:20.420 | but I believe nowadays,

02:47:22.180 | in talking with various experts on this,

02:47:24.060 | turns out that it can be done with a minimum of discomfort.

02:47:26.860 | And certainly if the goal is to have a healthy child,

02:47:29.240 | you're going to need those sperm,

02:47:30.420 | so you're going to want to get them one way or the other,

02:47:32.540 | regardless of the discomfort.

02:47:34.200 | Now, before getting into some of the things

02:47:35.800 | that you can do in the positive sense

02:47:37.500 | to increase your fertility,

02:47:38.800 | we do need to touch on just a few other things

02:47:40.740 | that you want to avoid in order

02:47:42.240 | to avoid diminishing your fertility.

02:47:44.500 | And this mainly relates to males,

02:47:46.020 | but it will also be relevant to females.

02:47:48.580 | And of course, when I say also relevant to females,

02:47:50.700 | I'm referring to the fact that if it's a woman and a man

02:47:53.660 | who are trying to conceive,

02:47:55.540 | then she of course is going to be interested

02:47:57.680 | in her egg quality, but also the sperm quality.

02:47:59.840 | And of course, there are women who are conceiving

02:48:01.460 | by way of sperm donor through IVF or IUI or otherwise,

02:48:05.700 | but in any case, the need to understand and maximize

02:48:10.700 | the quality of both the egg and the sperm is paramount.

02:48:13.360 | So in order for men to maximize the quality of their sperm,

02:48:16.660 | as I mentioned earlier,

02:48:17.800 | does not seem to be a big difference

02:48:19.400 | whether or not they use boxers or briefs

02:48:21.200 | or whether or not they quote unquote go commando.

02:48:23.620 | They don't wear any boxers or briefs of any kind.

02:48:26.060 | However, it is important to keep the testicles cool enough.

02:48:30.580 | They need to be about two degrees cooler

02:48:32.540 | than the rest of the body.

02:48:33.780 | And there are a number of different ways to do that.

02:48:36.300 | As I mentioned before, avoid going in hot tubs

02:48:38.960 | during the period in which you're trying

02:48:40.420 | to conceive children.

02:48:42.660 | You should also avoid going in saunas during the period

02:48:45.340 | in which you were trying to conceive children.

02:48:46.700 | And if you do go in the sauna,

02:48:48.160 | you can bring an ice pack there

02:48:49.640 | and you can put it on the testicles

02:48:52.040 | in order to offset the heat of the sauna

02:48:55.060 | and keep the testicles cool while in the sauna.

02:48:57.620 | The other thing that you'll definitely want to do

02:49:00.580 | is avoid putting a laptop or any other hot device

02:49:03.620 | directly onto your lap.

02:49:04.860 | There are a number of different devices

02:49:08.380 | that you can put on your lap.

02:49:09.380 | You could put books or a box or there are these devices

02:49:11.680 | that are designed to dispel the heat from the laptop.

02:49:14.780 | I would say if you're trying to conceive,

02:49:16.180 | just keep the laptop off of your lap,

02:49:18.100 | just put it on a table or standing desk or whatever,

02:49:20.020 | just keep it off of your lap.

02:49:22.260 | Also, there are some really interesting data showing

02:49:24.540 | that the amount of time that men spent sitting,

02:49:27.420 | regardless of whether or not they sit with their ankle

02:49:30.700 | on their opposite knee or with knees spread,

02:49:33.700 | the classic man spread stance

02:49:35.660 | or any other kind of seated stance

02:49:38.600 | is going to increase the temperature of the scrotum

02:49:42.020 | for reasons that are somewhat obvious.

02:49:43.820 | If you think about the architecture of all this,

02:49:45.380 | I think both men and women, if you put enough thought to it,

02:49:47.180 | you go, oh yeah, that would increase the temperature.

02:49:49.340 | Obviously avoid seat heaters in cars or otherwise,

02:49:53.320 | but reducing the total amount of time that you spend seated

02:49:57.260 | is really important if you want to keep

02:49:59.560 | the temperature milieu of the scrotum optimal

02:50:02.020 | for sperm quality and fertilization.

02:50:04.500 | And as I mentioned earlier,

02:50:05.540 | it's going to be important to make sure

02:50:07.420 | that your legs are not really big to the point

02:50:09.920 | where they are creating a hotter than is healthy environment

02:50:14.500 | for the scrotum and testicles.

02:50:16.220 | So a hotter than normal environment for the testicles

02:50:19.460 | can be caused by legs that are very large,

02:50:21.900 | upper thighs that are very large due to obesity

02:50:24.920 | or due to those upper thighs being too muscular.

02:50:27.800 | So by all means, don't skip leg day,

02:50:29.420 | but be aware that if you're somebody

02:50:30.540 | who's trying to conceive, you want to do whatever you can

02:50:33.280 | to reduce the temperature of the scrotum,

02:50:36.100 | or at least not let it get too hot for too long, okay?

02:50:40.000 | So I can think of all sorts of reasons now

02:50:43.720 | that men are going to come up with

02:50:44.960 | to do the man spread stance of their knees really far apart,

02:50:48.640 | even further if they have large legs.

02:50:50.500 | That's not a discussion we want to have here,

02:50:52.060 | and that's not really what today's discussion is about.

02:50:53.940 | Really the principle is what's most important,

02:50:55.580 | which is to keep the temperature of the scrotum and testicles

02:50:59.420 | lower than the rest of your body.

02:51:01.320 | There's a direct blood flow from the body to the testicle

02:51:04.200 | that provides blood flow.

02:51:05.220 | It's designed in a way that that blood pathway

02:51:09.700 | should be outside the body

02:51:11.260 | and as far away from the body as possible

02:51:13.860 | in order to get the temperature milieu

02:51:15.600 | of the scrotum and testicle correct

02:51:17.060 | for healthy sperm quality.

02:51:19.020 | Now, a topic that is sure to be a bit controversial,

02:51:21.500 | but it really shouldn't be

02:51:22.340 | because the data, at least to me, are very clear

02:51:25.820 | is this issue of phone use and sperm quality.

02:51:29.900 | Now, this can open up a whole array of issues

02:51:33.720 | related to things like EMFs,

02:51:35.480 | and you've got people out there that have, you know,

02:51:37.460 | ideas about 5G and all of this stuff.

02:51:40.260 | That is not what this discussion is about.

02:51:42.100 | The discussion I'm about to have with you

02:51:44.180 | relates to the fact that the electromagnetic fields

02:51:47.100 | and the heat-related effects of smartphones

02:51:51.060 | can indeed have a detrimental effect on sperm quality

02:51:54.540 | and yes, indeed, on testosterone levels as well.

02:51:57.600 | I'm going to refer you to a paper.

02:51:59.280 | We will link it in the show note captions.

02:52:00.780 | The title of this paper

02:52:01.620 | is "Effects of Mobile Phone Usage on Sperm Quality."

02:52:05.100 | No time-dependent relationship on usage,

02:52:07.680 | a systematic review and updated meta-analysis.

02:52:10.100 | This is a paper that came out in 2021

02:52:13.260 | and talks about the fact

02:52:14.940 | that phones emit a radiofrequency electromagnetic waves,

02:52:17.980 | which are called RF, radiofrequency, EMW,

02:52:21.060 | so electromagnetic waves,

02:52:22.580 | at a low level between 80 and 2,200 megahertz

02:52:26.660 | that can be absorbed by the human body.

02:52:28.260 | We know this, okay, this is not controversial,

02:52:30.500 | and have potential adverse effects on brain, heart,

02:52:32.620 | endocrine system, and reproductive function.

02:52:34.180 | That has been established.

02:52:36.140 | Keep in mind, there is basically no controversy

02:52:39.220 | that radiofrequency waves and EMFs

02:52:41.500 | can have a negative impact on biological tissues.

02:52:43.660 | The question is how intense are those radiofrequency waves

02:52:47.860 | and EMFs, and how detrimental are those

02:52:51.180 | on those biological tissues, okay?

02:52:53.140 | It's a matter of degrees,

02:52:54.760 | but there is very little controversy

02:52:56.360 | as to whether or not they have an effect

02:52:57.720 | on biological tissues,

02:52:58.740 | and I'm aware of absolutely zero data

02:53:01.020 | showing that they can have a positive effect

02:53:02.420 | on biological tissues.

02:53:03.860 | Since what we're mainly talking about now are smartphones,

02:53:06.480 | we want to separate out the heat effects of smartphones

02:53:08.900 | from the EMFs related to the fact

02:53:10.700 | that they are Wi-Fi smartphones,

02:53:12.740 | or they're using cellular towers and Wi-Fi,

02:53:16.500 | one or the other combination, okay?

02:53:18.140 | So there are a number of different things in the phone

02:53:20.140 | that could be detrimental.

02:53:21.160 | We need to separate those out.

02:53:22.120 | Why?

02:53:22.960 | Well, because you might have heard

02:53:24.280 | that carrying your phone in your pocket

02:53:25.700 | can reduce your testosterone levels and sperm count,

02:53:28.540 | and guess what?

02:53:29.560 | That is true.

02:53:31.060 | The data contained within this meta-analyses

02:53:33.220 | and other meta-analyses clearly point out

02:53:35.640 | that it can reduce sperm count

02:53:37.940 | and maybe testosterone levels significantly,

02:53:40.100 | but certainly sperm count and motility significantly.

02:53:43.120 | It reduces sperm quality.

02:53:44.880 | So should you avoid putting your phone in your pocket?

02:53:48.580 | Certainly your front pocket, I would suggest yes, right?

02:53:51.140 | If you are somebody who is seeking to conceive, right?

02:53:53.800 | I'm not somebody who is going to stop using my smartphone.

02:53:56.500 | I don't expect anyone's

02:53:57.340 | going to stop using their smartphone.

02:53:58.440 | The question is,

02:53:59.520 | should you carry it in your front pocket if you're a male?

02:54:02.560 | I think to be on the safe side,

02:54:04.100 | the answer is probably avoid doing that.

02:54:06.120 | Too much of the time, ideally, don't do it at all.

02:54:08.920 | Then people will say, well, what if I turn off the Wi-Fi

02:54:13.080 | or I turn off the cellular access,

02:54:15.640 | then is it still a problem?

02:54:16.940 | Well, it's a problem due to the heat-related effects.

02:54:19.940 | And then people say,

02:54:20.940 | well, I don't actually feel the heat of the phone.

02:54:22.580 | It doesn't get that warm.

02:54:24.160 | But the temperature effects of the phone, it turns out,

02:54:28.780 | are enough even under conditions

02:54:30.940 | in which people don't report it to be uncomfortably warm

02:54:33.980 | that it can change the temperature milieu of the testicle

02:54:36.520 | in ways that can diminish sperm quality.

02:54:38.100 | How much and how that relates to fertility

02:54:40.780 | and healthy pregnancy, not clear,

02:54:42.280 | but since we're talking about things to avoid

02:54:44.760 | if your goal is to have a healthy fertilization

02:54:48.340 | in pregnancy, well, then by all means,

02:54:50.240 | just don't carry it in your front pocket.

02:54:51.800 | Then people say, well, what about back pocket

02:54:53.240 | or what about backpack?

02:54:54.280 | Look, it's very clear that avoiding being too close

02:54:57.720 | to the phone is probably better for your sperm quality

02:55:01.040 | than putting the phone very close to your testicles

02:55:04.220 | or anywhere else on your body.

02:55:06.040 | But it's also the reality that most people

02:55:07.940 | are going to carry a phone nowadays, all right?

02:55:10.280 | It's just the reality.

02:55:11.180 | I think the current estimates,

02:55:14.040 | and it's discussed in this paper,

02:55:15.020 | that 90% of the human population has a smartphone, 90%,

02:55:19.920 | which is incredible, the adult population, of course,

02:55:22.400 | although a lot of kids have them as well.

02:55:24.180 | So this paper goes on to detail a number

02:55:25.980 | of different studies and outcomes from studies,

02:55:27.980 | but basically what they find, and here I'm paraphrasing,

02:55:30.060 | is that the data indicate that sperm quality declines

02:55:33.820 | when people start using a mobile phone.

02:55:35.460 | So from the point they start using a mobile phone,

02:55:37.200 | regardless of the usage time, this is important.

02:55:39.340 | It used to be thought that it was four hours a day

02:55:41.120 | or more of holding your phone or having that phone close

02:55:45.120 | to your body was going to diminish sperm quality.

02:55:46.980 | It turns out that it's not related to usage time.

02:55:48.980 | That's even the title of the paper.

02:55:50.540 | It's just the fact that people are using mobile phones

02:55:52.700 | is reducing sperm count and quality.

02:55:55.740 | That's the reality.

02:55:56.580 | Is it entirely responsible for all the reductions

02:55:59.620 | in sperm quality and maybe even the reductions

02:56:01.420 | in testosterone levels that we're observing

02:56:03.180 | from decade to decade going forward?

02:56:05.460 | I doubt that's the case.

02:56:06.660 | Is it likely to be one of the major players?

02:56:09.200 | I've got my bet on the fact that it is

02:56:12.260 | based on the data that I've observed.

02:56:14.020 | And so if any of you would like to peruse the data

02:56:16.140 | in this meta analysis, they're quite good.

02:56:17.980 | This study looked at 18 studies that include 4,280 samples.

02:56:22.460 | They were able to separate out the radio frequency

02:56:25.020 | versus the heat effects, and they were able to eliminate

02:56:28.060 | this time of usage variable that previously we thought

02:56:31.540 | if you were exposed to a lot of cell phone contact,

02:56:35.500 | that it was far worse than if you were exposed

02:56:37.060 | to a little bit.

02:56:37.900 | If you're exposed to any at all,

02:56:39.220 | you're going to diminish sperm quality.

02:56:40.600 | What does that mean?

02:56:41.560 | Does that mean that no matter what you do,

02:56:42.960 | if you own a smartphone,

02:56:44.320 | that you're going to diminish sperm quality?

02:56:46.060 | I think the short answer is yes,

02:56:47.620 | but that you can mitigate it.

02:56:49.560 | What might you do?

02:56:50.400 | Well, keeping your phone away from your groin

02:56:52.740 | or as far from your groin as possible

02:56:54.180 | if you're a male who's wishing to conceive

02:56:55.800 | and maybe even a male who's wishing

02:56:57.100 | to maximize his testosterone levels,

02:56:59.180 | because it does appear that radio frequency waves

02:57:01.900 | and the heat from the phone,

02:57:03.280 | so both of those factors independently and together,

02:57:06.040 | of course, can disrupt the lytic cells of the testes

02:57:08.940 | and the production of testosterone

02:57:10.520 | and intertesticular testosterone

02:57:12.680 | is important for sperm production.

02:57:14.500 | The exact biological variables leading to all these changes

02:57:17.320 | isn't exactly clear, but if you're like me, you say, okay,

02:57:20.320 | probably not a problem for most males to carry their phone,

02:57:23.820 | but probably best to not carry it in the front pocket,

02:57:26.660 | maybe even avoid carrying the back pocket as well.

02:57:28.900 | Again, in the future,

02:57:29.720 | we will have an episode all about Bluetooth.

02:57:31.820 | We'll talk about various aspects of EMFs.

02:57:34.720 | It's a super interesting data set,

02:57:37.000 | and it's a data set for which there's a ton of controversy.

02:57:40.140 | It's really interesting, however,

02:57:42.320 | and there are more and more quality data

02:57:43.660 | coming out all the time.

02:57:44.740 | And I think going forward,

02:57:45.740 | we are going to see that indeed

02:57:47.380 | there are some negative effects of smartphones

02:57:49.100 | related to both the radio frequency transmission

02:57:52.400 | and the fact that they generate heat.

02:57:55.620 | And in general, heat is not good for biological tissues.

02:57:58.700 | So any discussion about heat and sperm

02:58:00.680 | and how heat is detrimental to sperm

02:58:03.600 | has to raise this issue of whether or not cold

02:58:06.040 | is good for the testicle.

02:58:07.360 | Okay, well, now there's a lot of data starting to come out

02:58:10.620 | about the positive effects,

02:58:12.360 | the positive biological effects of deliberate cold exposure

02:58:16.820 | on different aspects of brain biology,

02:58:19.840 | such as the release of dopamine and norepinephrine

02:58:22.060 | and on the biology of the body, to some extent metabolism,

02:58:25.380 | but more so the impact on brown fat stores,

02:58:27.740 | which are good for us, so-called brown fat thermogenesis.

02:58:30.680 | There's a lot related to deliberate cold exposure.

02:58:33.360 | And we've done entire episodes on deliberate cold exposure.

02:58:36.000 | Again, you can find that at hubermanlab.com.

02:58:37.860 | We did a guest episode with an expert

02:58:39.980 | on the use of cold for health and performance

02:58:42.620 | with my colleague, Craig Heller,

02:58:43.640 | from Stanford Department of Biology.

02:58:45.300 | We also have a toolkit on how to apply deliberate

02:58:48.860 | cold exposure for health for both females and for males,

02:58:52.340 | for sports performance, cognitive performance,

02:58:54.100 | mood, sleep, et cetera.

02:58:55.380 | You can find all that, again, hubermanlab.com,

02:58:57.260 | totally zero cost.

02:58:59.060 | Just go into the menu, go to newsletter and scroll down

02:59:01.380 | and you'll find those.

02:59:03.380 | When thinking about sperm quality,

02:59:06.240 | we want to remember that excessive heat is bad.

02:59:08.980 | Now, does that mean that deliberate cold is good?

02:59:11.740 | Well, it turns out that one of the major causes

02:59:14.700 | of lowered sperm count and overall reduced sperm quality,

02:59:19.700 | that's quite common, is the presence

02:59:21.700 | of what's called a varicell.

02:59:22.860 | A varicell is kind of like varicose veins

02:59:25.340 | of the veins that innervate the testicle.

02:59:28.700 | And what it essentially does is it means

02:59:32.100 | that blood will pool in the testicular region.

02:59:36.180 | It can't circulate back to the body quickly enough

02:59:38.480 | and therefore the temperature of that environment increases.

02:59:40.700 | There's some other things that varicells do,

02:59:42.640 | which can be obstructive at the physical level,

02:59:44.660 | so they're not just temperature related.

02:59:46.760 | It's pretty clear that using deliberate cold exposure

02:59:50.460 | can be healthy for the sperm because of the ways,

02:59:53.100 | not that cold directly supports testosterone

02:59:56.660 | or sperm quality, but rather because cold reduces heat.

03:00:00.860 | Okay, so you will find available online,

03:00:04.440 | I think they're actually called, forgive me,

03:00:07.260 | but that's what they're called.

03:00:08.220 | I didn't name them, called Snowballs.

03:00:09.580 | These are, they're sort of like gel pack cold briefs

03:00:14.520 | that you can buy and men will wear for some period of time.

03:00:17.580 | I don't think you wear them all day.

03:00:18.820 | You wear them for some period of time.

03:00:20.940 | A lot of people are now using cold showers and ice baths

03:00:23.980 | and circulating cold baths or going into a cold ocean

03:00:26.340 | or lake for any number of different reasons

03:00:28.660 | I talked about earlier.

03:00:29.480 | I myself start every day with either a one to three minute

03:00:33.160 | cold shower or one to three minute immersion up to my neck

03:00:36.480 | in a cold bath, cold water, circulating water

03:00:40.780 | or a cold shower.

03:00:41.920 | I do that mainly for the psychological effects

03:00:43.620 | related to the long lasting increases

03:00:45.380 | in dopamine and epinephrine.

03:00:47.140 | But there are other data starting to come out

03:00:48.640 | showing that that sort of approach or similar approaches

03:00:52.500 | can increase testosterone levels and maybe even sperm counts

03:00:55.400 | can reduce cortisol late in the evening

03:00:57.160 | if the cold exposure is done early in the day,

03:00:58.920 | so on and so forth.

03:00:59.760 | So a lot of interesting data coming out

03:01:01.520 | in really good journals that are peer reviewed

03:01:04.660 | and so on in humans.

03:01:06.760 | I should mention those studies are done in humans

03:01:08.980 | to support the use of deliberate cold exposure.

03:01:10.940 | But again, if you're going to use deliberate cold exposure

03:01:12.920 | to improve sperm quality, can it work?

03:01:15.260 | Yes, indeed it can work.

03:01:16.680 | Either indirectly by increasing testosterone

03:01:19.120 | or directly by improving sperm quality.

03:01:21.220 | But both of those effects are likely to be indirect

03:01:23.840 | by virtue of reducing the temperature of the testicle

03:01:26.700 | overall, not because there's any sort of magic effect

03:01:29.880 | of cold on the testicle.

03:01:31.460 | Now I have to imagine that a number of you,

03:01:32.900 | in particular, the females listening to this,

03:01:35.520 | are going to say, is deliberate cold exposure,

03:01:38.480 | and for that matter, is deliberate heat exposure

03:01:40.300 | like sauna or hot tub, good or bad for the ovary,

03:01:43.600 | for eggs and for fertility?

03:01:45.120 | Now there are fewer data to look to, unfortunately,

03:01:49.440 | but what we do know is that deliberate cold exposure

03:01:52.400 | done in the way that I just described

03:01:54.020 | one to three minutes a day, ideally early in the day

03:01:56.380 | through cold shower or immersion up to the neck,

03:01:58.480 | doesn't have to be an ice bath,

03:01:59.440 | could be cold circulating water

03:02:01.400 | or even non-circulating cold water.

03:02:03.520 | And people will say, well, how cold?

03:02:05.120 | I should have mentioned that before, how cold?

03:02:08.200 | There is no way I can tell you

03:02:09.880 | exactly how cold the water should be

03:02:11.400 | because for some people, 60 degrees Fahrenheit

03:02:13.760 | will be exceedingly cold.

03:02:15.140 | For other people, 40 degrees is going to be more appropriate.

03:02:17.520 | How cold should you make it?

03:02:18.920 | If you're going to embrace these practices,

03:02:20.920 | you want to, according to the literature,

03:02:23.120 | what you want to do is make it uncomfortably cold

03:02:25.720 | such that you really want to get out, but safe, right?

03:02:28.260 | You don't want to go into 30 degree water immediately.

03:02:31.240 | You can actually have a heart attack and die if you do that.

03:02:33.560 | So you want to progress gradually into the cold.

03:02:36.880 | So you don't want to shock your system too much,

03:02:38.940 | although it is the adrenaline evoked by that,

03:02:42.040 | that quickening or shortening or elimination of the breath

03:02:44.420 | for a short period of time

03:02:45.260 | when you get into uncomfortably cold water

03:02:47.400 | that correlates with, or is actually the reflection of,

03:02:50.600 | would be more accurate to say,

03:02:51.800 | the release of adrenaline and then dopamine and so forth,

03:02:54.620 | which has been very well-documented.

03:02:56.680 | So uncomfortably cold, but safe to stay in.

03:03:00.120 | And I cannot tell you an exact number

03:03:02.680 | that is uncomfortably cold, but safe for you.

03:03:04.940 | It's going to differ person by person.

03:03:06.360 | You want to figure that out.

03:03:07.280 | Just like I can't tell you how much weight

03:03:08.580 | that you should squat in order to achieve

03:03:10.640 | some effective resistance training for the legs.

03:03:13.160 | It's going to differ depending on your strength

03:03:15.980 | and your prior experience and so forth.

03:03:17.600 | So ease into it, be safe.

03:03:19.360 | But it does appear that both for men,

03:03:21.340 | for reasons I talked about a few minutes ago,

03:03:23.240 | and for women, that deliberate cold exposure

03:03:27.260 | can be beneficial for fertility and for hormone production,

03:03:31.660 | but in particular for females

03:03:33.300 | in terms of regulating cortisol and for hormone production.

03:03:36.140 | Now you might say, okay, getting into cold is stressful.

03:03:38.260 | How can that be helpful for regulating stress?

03:03:40.040 | Well, it turns out when you get into the cold,

03:03:41.860 | you get a big surge in adrenaline and then dopamine,

03:03:44.140 | which is very long lasting,

03:03:45.440 | provided that's done in the early part of the day.

03:03:47.520 | So I would say not too close to sleep.

03:03:50.100 | Then what you do is you restrict

03:03:51.700 | your maximum cortisol release to a period earlier in the day

03:03:55.000 | that buffers, reduces that is the likelihood

03:03:59.180 | that you would have excessive amounts of cortisol

03:04:01.580 | later in the day, which not only can disrupt sleep,

03:04:03.720 | but is correlated with a number of other hormonal effects

03:04:07.260 | that are not good for us

03:04:08.260 | and therefore not good for fertility.

03:04:10.140 | So here what I'm describing are positive

03:04:11.920 | yet indirect effects of a cold on hormone levels,

03:04:16.420 | both in males and in females.

03:04:19.040 | So for men, we talked about increased testosterone,

03:04:21.720 | improved sperm quality that was indirect, right?

03:04:23.700 | You're reducing the temperature of the testicle,

03:04:26.100 | but it's not that cold itself

03:04:27.420 | is positively impacting those things.

03:04:29.060 | Does that make sense?

03:04:29.900 | Heat is bad, therefore reducing temperature is good.

03:04:32.440 | Likewise with females, deliberate cold exposure

03:04:35.320 | can be good for the overall fertility process,

03:04:38.180 | not because cold is good for the ovary

03:04:40.680 | or being cold is good for the ovary

03:04:43.000 | or for luteinizing hormone or for follicle stimulating

03:04:45.980 | hormone or anything else like that,

03:04:47.680 | but rather that using deliberate cold exposure

03:04:50.980 | as a way to restrict stress in a deliberate way

03:04:53.500 | to a particular time of day

03:04:55.680 | increases the release of cortisol then

03:04:57.820 | and indirectly reduces the amount of cortisol

03:05:00.380 | that's released at other times along the 24 hour cycle.

03:05:03.720 | Okay, so these are positive yet indirect effects.

03:05:06.340 | So if you're a woman who really is interested

03:05:09.100 | in exploring deliberate cold exposure

03:05:10.660 | or who enjoys it or is already doing it

03:05:12.780 | and you're wishing to conceive, great.

03:05:15.120 | Explore it, do it safely of course,

03:05:16.900 | but explore it and continue to do it.

03:05:18.240 | However, if you're somebody who just hates the cold

03:05:20.300 | and doesn't want to go anywhere near it,

03:05:21.740 | there's no reason to think that you absolutely need it

03:05:23.540 | provided that your stress, your sleep and other factors

03:05:26.020 | are all being carried out properly.

03:05:27.860 | The next things that we'll talk about

03:05:29.100 | in terms of positive things or things that we can do

03:05:31.920 | in order to maximize fertility for both females and males

03:05:34.780 | are the things that you also generally hear about elsewhere.

03:05:37.980 | Right along with sleep and avoiding alcohol

03:05:40.600 | and avoiding nicotine and avoiding cannabis,

03:05:43.100 | avoiding excessive heat for the testicle,

03:05:44.940 | avoiding excessive stress is that you want to try

03:05:49.380 | to get enough exercise, right?

03:05:51.700 | Why would exercise have anything to do with any of this?

03:05:54.420 | Well, exercise and that is both a combination

03:05:57.500 | of resistance training and cardiovascular exercise

03:05:59.860 | is going to improve the health of the mitochondria

03:06:02.340 | in particular cardiovascular exercise.

03:06:04.340 | And I realized that for you fitness experts out there,

03:06:06.520 | anytime someone says cardio,

03:06:08.120 | people kind of roll their eyes like, what is that?

03:06:10.340 | There's endurance training, there's interval training,

03:06:12.660 | there's HIIT training, there's sprints,

03:06:14.840 | there's all sorts of different things.

03:06:15.900 | Some of those overlap, some of them are separate.

03:06:18.100 | Indeed, that's the case.

03:06:19.360 | But we can use a general rule of thumb here,

03:06:21.940 | which is that for most people getting anywhere from 30

03:06:25.160 | and ideally 45 to 60 minutes of exercise per day

03:06:29.380 | for six days per week, maybe even seven,

03:06:31.460 | but most people like to take a day off

03:06:33.260 | or need to take a complete day off each week,

03:06:35.300 | six to seven days per week is going to be good

03:06:38.060 | for mitochondrial health and function.

03:06:39.680 | It's also going to impact all the other things

03:06:41.240 | like quality sleep, mood, reducing stress,

03:06:43.460 | and so on and so forth.

03:06:44.540 | So exercise we can handle pretty quickly

03:06:47.240 | by just saying everyone should be doing it.

03:06:49.780 | Now, when people are pregnant,

03:06:51.360 | they might have to of course change the amount of exercise

03:06:54.000 | or the type of exercise that they're doing.

03:06:55.960 | There are varying opinions on that,

03:06:57.280 | but certainly the type of exercise

03:06:59.580 | and the amount can vary when people are pregnant.

03:07:01.900 | But if you're seeking to conceive,

03:07:03.860 | getting enough exercise is good

03:07:04.980 | because it's good for the mitochondria.

03:07:06.200 | The mitochondria are present in that mid-region of the sperm

03:07:10.480 | and mitochondria are critical for chromosomal segregation

03:07:14.420 | and the spindle and other aspects of the formation

03:07:17.260 | of a healthy egg ovulation and fertilization in the female.

03:07:20.480 | One thing that I know a lot of people

03:07:21.720 | are interested in nowadays is so-called intermittent fasting

03:07:24.720 | or time restricted feeding.

03:07:26.300 | I mean, let's be fair.

03:07:27.140 | Everybody is restricting their feeding time

03:07:29.060 | because hopefully everybody is sleeping

03:07:30.660 | at some point in the 24 hour cycle

03:07:32.660 | and nobody's eating while they are sleeping.

03:07:35.440 | That said, many people are employing

03:07:37.900 | a so-called eight hour feeding window or a 10 hour feeding

03:07:40.640 | window or a 12 hour feeding window.

03:07:41.980 | And indeed there are some data to support the idea

03:07:44.600 | that that can be a good thing for a number

03:07:46.960 | of different biological and health parameters.

03:07:48.740 | However, also a lot of data, especially recently,

03:07:52.740 | pointed to the fact that your overall number of calories

03:07:55.940 | and the quality of your food sources

03:07:57.900 | is going to be the most important variable.

03:07:59.900 | And some people simply find that time restricted feeding

03:08:02.660 | and intermittent fasting as it's also called

03:08:05.200 | is just a convenient way to ensure that your total intake

03:08:08.440 | of calories is not excessive for what you need.

03:08:11.320 | Now, with all that said, there is evidence

03:08:14.160 | that I've covered in a solo episode

03:08:15.840 | and will soon have an expert guest on,

03:08:17.560 | showing that time restricted feeding

03:08:20.680 | can have certain positive outcomes for various aspects

03:08:24.360 | of organ, cellar, and tissue health.

03:08:26.960 | Okay, this is somewhat controversial,

03:08:28.680 | but there is growing evidence that by restricting

03:08:31.080 | your feeding window to say eight hours or 10 hours

03:08:33.440 | or 12 hours, that it is better than if you were to eat

03:08:36.500 | over a longer period of each 24 hour cycle.

03:08:39.560 | Again, the data are still incoming.

03:08:42.000 | The reason we want to talk about time restricted feeding

03:08:43.940 | intermittent fasting is that a lot of people do use it

03:08:46.760 | because they find it easier to not eat at certain periods

03:08:49.700 | of their 24 hour cycle than to restrict calories.

03:08:52.780 | But again, keep in mind, you have to restrict calories

03:08:56.200 | if your goal is to maintain or lose weight, all right?

03:08:58.540 | A discussion that we've covered in that episode

03:09:00.660 | on intermittent fasting and in the episode

03:09:02.600 | with Dr. Lane Norton, and that we will cover

03:09:05.120 | in other episodes in the future.

03:09:06.980 | So refer to those episodes at hubermanlab.com

03:09:10.740 | if you would like to learn more

03:09:12.120 | about intermittent fasting per se.

03:09:14.160 | For sake of this conversation,

03:09:16.020 | a number of people are probably asking,

03:09:17.740 | if I restrict my feeding to a certain window each 24 hours,

03:09:22.480 | because that's what's convenient or because I'm excited

03:09:24.640 | about the potential positive effects

03:09:26.120 | of intermittent fasting, is that going to disrupt

03:09:29.520 | the likelihood of fertility and thereby a healthy pregnancy.

03:09:34.520 | And the short answer to that is if you are a female

03:09:37.680 | and you are having regular menstrual cycles,

03:09:39.740 | that is a fairly consistent duration.

03:09:42.400 | So maybe it's 21 days, maybe it's 35 or anywhere in between,

03:09:45.540 | but it's fairly consistent from month to month

03:09:47.440 | and you are following intermittent fasting

03:09:49.240 | time restricted feeding, well then chances are pretty good

03:09:52.400 | that it's not disrupting your fertility

03:09:56.040 | and likelihood of fertilization in a healthy pregnancy.

03:09:58.880 | Of course, during pregnancy, you need to talk to your doctor

03:10:01.920 | and make sure that you're eating in a way that's supportive

03:10:04.380 | both of you and of the developing fetus.

03:10:06.360 | That's extremely important.

03:10:07.840 | I am not aware of data exploring in a regimented way

03:10:12.120 | time restricted feeding during pregnancy, okay?

03:10:14.180 | So please, please, please, if you're pregnant,

03:10:16.620 | do not jump on a time restricted feeding

03:10:18.520 | so-called intermittent fasting diet.

03:10:19.840 | Talk to your OB/GYN, talk to your doctor,

03:10:23.640 | talk to multiple doctors for that matter

03:10:25.800 | before doing anything like that,

03:10:27.400 | because of course you're now eating for two,

03:10:29.360 | or if you have twins in there, you're eating for three,

03:10:31.960 | and very important.

03:10:33.240 | If however, you're not yet pregnant

03:10:34.520 | and you want to be fertile, get pregnant,

03:10:37.920 | or simply maintain a fertile potential and biology,

03:10:42.520 | you're following intermittent fasting,

03:10:44.520 | it's going to be the regularity of those periods

03:10:47.080 | and regularity of cycle length

03:10:48.600 | that will tell you whether or not that's a good idea or not.

03:10:51.460 | Keeping in mind, of course,

03:10:52.920 | that if your total number of calories is too low,

03:10:56.200 | your periods will cease.

03:10:57.760 | That's a well-known effect.

03:10:59.660 | But of course, stress can also induce

03:11:02.760 | cessation of menstruation.

03:11:05.560 | And there are other factors that can induce

03:11:07.240 | cessation of menstruation as well.

03:11:09.160 | Some of them start with changes in the brain,

03:11:12.080 | literally in the hypothalamus,

03:11:13.220 | some of them occur in the pituitary.

03:11:15.040 | Many of the lifestyle factors can do that,

03:11:17.520 | but most typically it's going to be

03:11:19.120 | excessive caloric restriction,

03:11:21.160 | or it's going to be a caloric deficit

03:11:23.800 | brought on by excess physical activity.

03:11:26.360 | So even if someone's eating a lot,

03:11:28.320 | if they're not eating enough

03:11:30.520 | to offset their physical activity,

03:11:32.040 | or they're not eating enough of in particular fats,

03:11:35.320 | the essential fatty acids and protein,

03:11:37.520 | but also carbohydrates,

03:11:38.800 | well, then menstruation can cease.

03:11:40.520 | And of course, if menstruation is ceasing,

03:11:41.920 | chances are almost with certainty

03:11:44.100 | that you're not getting regular ovulations.

03:11:46.280 | Now, in terms of males and whether or not

03:11:48.200 | intermittent fasting is going to disrupt

03:11:49.880 | spermatogenesis and testosterone production,

03:11:53.680 | there's essentially no data we can look to,

03:11:56.340 | but we can look to the general logic around the relationship

03:11:59.720 | between body fat, testosterone, and spermatogenesis.

03:12:03.480 | And this was something that was covered

03:12:05.160 | in a discussion I had on

03:12:07.160 | optimization of hormone health for males

03:12:09.880 | that I had with Dr. Kyle Gillette,

03:12:11.280 | who's a medical doctor and obesity specialist.

03:12:13.840 | Again, you can find that episode at hubermanlab.com

03:12:15.980 | if you want to learn all about hormone optimization in males.

03:12:19.120 | And essentially the story is as follows.

03:12:21.680 | If a male is excessively overweight,

03:12:24.640 | he's carrying too much body fat in particular,

03:12:26.920 | not too much muscle, although that can be an issue too,

03:12:29.140 | but too much body fat is typically the issue.

03:12:31.560 | So, you know, more than say 20% body fat,

03:12:35.600 | well then losing body fat is going to be the primary goal

03:12:39.240 | for maximizing testosterone, sperm health,

03:12:41.760 | and spermatogenesis.

03:12:43.840 | If, however, a male is already lean,

03:12:46.300 | well then actually increasing calories

03:12:49.820 | will increase testosterone.

03:12:51.200 | So it's a bit of a complicated story,

03:12:53.680 | although not so complicated

03:12:54.840 | that none of us can understand it.

03:12:56.220 | Basically, if you're overweight,

03:12:57.880 | you should focus on losing weight

03:12:59.120 | in order to maximize sperm quality and health.

03:13:01.540 | If you are very lean,

03:13:03.280 | well then restricting your calories to the point

03:13:05.880 | where you are starting to lose weight

03:13:08.020 | or you're dropping even more body fat

03:13:10.720 | is unlikely to increase your testosterone further, right?

03:13:13.760 | Doesn't necessarily mean it's bad

03:13:15.360 | or that you shouldn't try and go, for instance,

03:13:17.560 | from 15% to 10% body fat.

03:13:19.320 | I'm not saying that that's bad

03:13:20.380 | and that will reduce your testosterone,

03:13:22.100 | but in general, if you're already very lean,

03:13:23.900 | so, you know, 10% body fat, 5% body fat,

03:13:26.860 | and you start restricting calories further,

03:13:28.380 | your testosterone levels will drop.

03:13:30.720 | So in the context of intermittent fasting,

03:13:33.200 | it's really not an issue of whether or not

03:13:34.480 | your feeding window is eight hours or 12 hours.

03:13:36.600 | It's really an issue of whether or not

03:13:37.600 | you're getting enough calories

03:13:38.600 | to offset the physical demands and activities of your life,

03:13:42.640 | whether or not you're on a maintenance diet

03:13:44.120 | to maintain your weight.

03:13:45.440 | And of course, you have to put all that in the context

03:13:47.100 | of whether or not you're overweight or lean to begin with.

03:13:49.600 | The simple thing to take away from this

03:13:51.180 | is if you're a male who's using, because you like it,

03:13:54.220 | intermittent fasting, so-called time-restricted feeding,

03:13:56.680 | and you're following an eight hour

03:13:58.820 | or maybe even a one meal per day type approach,

03:14:00.880 | although I don't really recommend that

03:14:02.240 | for a number of reasons we could talk about separately.

03:14:04.500 | If you're eating over the course of eight

03:14:05.920 | or 10 or 12 hours per day,

03:14:07.920 | because that's what works for you,

03:14:09.340 | and you are ingesting enough calories

03:14:11.500 | to maintain your weight if you're already lean,

03:14:14.260 | or you are ingesting fewer calories

03:14:18.600 | than you are burning in order to lose weight

03:14:20.440 | because you are already overweight

03:14:22.900 | and you want to lose body fat,

03:14:24.360 | you're probably optimizing for all the things

03:14:26.160 | that you need to do in order to improve sperm quality

03:14:28.880 | and testosterone levels.

03:14:30.420 | Now, also in that episode that I did with Dr. Kyle Gillette

03:14:33.040 | on optimizing hormones for males,

03:14:35.160 | we talked about testosterone replacement therapy.

03:14:37.360 | It's not a topic I want to get into in any detail right now,

03:14:40.080 | but I will say this.

03:14:41.800 | Remember earlier when we were talking about spermatogenesis

03:14:44.340 | and the fact that in order for sperm to be generated

03:14:46.960 | consistently every month ongoing from the time of puberty

03:14:50.800 | until essentially the time that a man dies,

03:14:54.140 | you need two things.

03:14:55.100 | You need testosterone production

03:14:56.700 | from the Leydig cells of the testes,

03:14:58.920 | and you need spermatogenesis to be supported

03:15:02.600 | by that androgen binding protein

03:15:04.480 | coming from the support cells from the Sertoli cells.

03:15:07.520 | So you need testosterone

03:15:08.480 | and you need androgen binding protein

03:15:10.100 | and you need the Leydig cells and the Sertoli cells active.

03:15:13.420 | When men take exogenous, meaning from outside the body,

03:15:16.320 | testosterone either by cream or by patch or by pellets

03:15:19.120 | or more typically by injection,

03:15:20.640 | the most typical TRT approach nowadays

03:15:22.720 | is testosterone sipinate,

03:15:23.920 | which is biologically identical

03:15:26.320 | to the kind of testosterone you would make.

03:15:28.800 | Well, because of negative feedback loops,

03:15:30.600 | which you also learned about earlier,

03:15:33.000 | the testicles themselves shut down

03:15:36.320 | their own testosterone production.

03:15:37.760 | Why would that be?

03:15:38.580 | Okay, so you're taking testosterone in by syringe

03:15:41.120 | or by patch or any other method.

03:15:43.840 | So the circulating testosterone and the amount that arrives

03:15:46.540 | at the testicle is going to be

03:15:49.260 | hopefully clinically appropriate, not super physiological,

03:15:51.720 | but it'll be somewhere in the healthy reference range,

03:15:53.720 | maybe a little bit higher.

03:15:55.440 | Nowadays, some people are going a little bit higher,

03:15:57.320 | so we're not talking about full blown

03:15:58.720 | quote unquote anabolic steroid use,

03:16:00.640 | keeping in mind, of course, that estrogen is a steroid,

03:16:03.200 | testosterone is a steroid,

03:16:04.020 | but when we think about steroids,

03:16:04.920 | we mean like performance enhancing drugs,

03:16:06.400 | so super physiological doses.

03:16:08.600 | We're talking about within physiological

03:16:10.680 | or near physiological ranges.

03:16:12.480 | So if someone's taking their testosterone in

03:16:14.480 | from an outside exogenous source,

03:16:16.600 | the levels of circulating testosterone

03:16:19.820 | will be sufficiently high

03:16:20.960 | that the pituitary will register that

03:16:23.320 | and will stop making luteinizing hormone

03:16:26.280 | and generally follicle stimulating hormone as well.

03:16:29.040 | And as a consequence,

03:16:30.440 | spermatogenesis is vastly reduced or eliminated.

03:16:34.520 | In other words, for men who are on TRT

03:16:37.840 | or who are taking testosterone from an external source,

03:16:42.120 | the number of sperm that they're going to make

03:16:43.840 | is going to be dramatically reduced.

03:16:45.460 | There are things that they can do to offset that,

03:16:47.360 | like taking HCG, human chorionic gonadotropin,

03:16:50.140 | which is just kind of a mimic for luteinizing hormone

03:16:52.120 | to stimulate the testes to continue to make testosterone.

03:16:56.380 | And some men will also, or instead,

03:16:59.280 | take FSH to stimulate the sertoli cells

03:17:02.720 | to support spermatogenesis, excuse me,

03:17:06.820 | or both or some combination.

03:17:08.180 | Some people take clomiphene, clomid.

03:17:10.200 | There are any number of different ways to bypass

03:17:12.480 | or offset the sperm-reducing effects

03:17:15.540 | of taking exogenous testosterone.

03:17:17.540 | This is a conversation that was covered

03:17:19.320 | in a fair amount of detail in that episode with Dr. Gillette,

03:17:21.880 | but just keep in mind that if you are taking testosterone

03:17:25.680 | from an exogenous source,

03:17:27.360 | your sperm counts will dramatically be reduced

03:17:30.080 | unless you do something to offset it.

03:17:31.480 | So if you are wishing to conceive,

03:17:33.240 | you need to think about whether or not

03:17:34.680 | you're going to offset the testosterone replacement therapy

03:17:38.280 | or whether or not you're going to come off it entirely.

03:17:40.460 | So you'll need to talk to a urologist

03:17:42.160 | and a chronologist about that.

03:17:44.400 | And again, a number of these different themes

03:17:46.600 | and ways to go about tapering off TRT

03:17:48.600 | were covered in that episode with Dr. Kyle Gillette.

03:17:51.120 | So if you're on TRT or you're considering taking it

03:17:53.340 | and you're interested in having children,

03:17:54.720 | not just now, but at any point,

03:17:56.480 | you really want to take these things into consideration.

03:17:58.800 | Now, I do want to point out

03:18:00.000 | that for the number of you out there

03:18:02.320 | who are taking supplements,

03:18:03.880 | some of which we've talked about on this podcast,

03:18:05.880 | I've talked about on other podcasts such as Tonga Ali,

03:18:08.280 | turns out that there are a lot of men and women

03:18:09.720 | taking Tonga Ali to reduce sex hormone binding

03:18:12.640 | globulin levels to increase testosterone and estrogen,

03:18:15.340 | in some cases, libido and so forth.

03:18:17.160 | Those approaches, meaning supplement-based approaches

03:18:21.100 | to increase testosterone or free testosterone

03:18:25.580 | or some related hormones are not going to shut down

03:18:29.080 | your own endogenous testosterone production

03:18:31.480 | and reduce the number of sperm that you make.

03:18:34.040 | Or at least as far as we know,

03:18:35.800 | disrupt ovulation in any kind of way,

03:18:37.520 | provided that the dosages are within normal ranges.

03:18:39.720 | Again, supplementation to support your hormones

03:18:43.040 | should not disrupt ovulation or spermatogenesis

03:18:47.400 | or testosterone production, quite the opposite.

03:18:49.600 | It should enhance it.

03:18:50.840 | What I just described around TRT

03:18:52.360 | is taking exogenous testosterone

03:18:54.240 | and that itself is an entirely different beast.

03:18:57.160 | Now, with all of that said,

03:18:58.600 | there are some supplements out there

03:19:00.840 | that include testosterone as a ingredient

03:19:05.300 | that's been snuck in to various formulas

03:19:08.920 | that include blends and things of that sort.

03:19:10.560 | You want to be aware of that.

03:19:11.580 | And we did an episode about how to develop

03:19:13.720 | a rational guide to supplementation.

03:19:16.080 | I highly recommend listening to that episode.

03:19:18.120 | Again, it's timestamped,

03:19:19.120 | available free at hubermanlab.com in all formats,

03:19:22.100 | because it talks about which supplements

03:19:24.480 | are likely to be clean, quote unquote,

03:19:26.280 | to contain the things that you expect them to contain.

03:19:28.460 | There's more and more evidence coming out

03:19:29.940 | that a lot of supplements, including some, for instance,

03:19:33.400 | supplements that contain testicle

03:19:35.320 | or the extracts of testicles can contain testosterone.

03:19:38.360 | Whether or not that can shut down

03:19:39.600 | your own endogenous testosterone production isn't clear.

03:19:42.300 | No one's really explored that in detail,

03:19:44.020 | but based on everything we just talked about with TRT,

03:19:45.920 | it stands to reason that it might either reduce it

03:19:48.200 | or shut it down.

03:19:49.040 | It's just never been explored yet.

03:19:50.860 | So by all means, make sure that you know what you're taking

03:19:53.880 | if you're taking supplements.

03:19:54.900 | But again, the major point here

03:19:57.060 | is that for both females and males,

03:19:58.620 | taking supplements to support healthy hormone production,

03:20:02.560 | including things like Tonga Ali,

03:20:04.800 | is not the same as taking hormones or bioidentical hormones,

03:20:09.100 | which indeed can shut down

03:20:10.720 | your own endogenous production of hormones

03:20:12.940 | and thereby reduce both egg quality

03:20:15.720 | and the chance of fertilization and healthy pregnancy

03:20:18.120 | and sperm quality and the chance of fertilization

03:20:20.240 | and healthy pregnancy.

03:20:21.480 | Anytime there's a discussion about fertility and pregnancy,

03:20:25.680 | there seems to also be a parallel discussion

03:20:27.680 | about sex determination.

03:20:29.420 | That is, what factors can influence

03:20:31.880 | whether or not the child that's born is male or female?

03:20:35.360 | That is, whether or not it has double X chromosomes,

03:20:38.040 | so one X chromosome from mom, one X chromosome from dad,

03:20:40.700 | because the egg was fertilized by a sperm

03:20:42.740 | that had an XX chromosome, that 23rd chromosome,

03:20:46.240 | or whether or not the offspring is male,

03:20:48.480 | whether or not it has the X chromosome from mom,

03:20:50.140 | because it's always going to be the X chromosome in that egg

03:20:53.960 | and a Y chromosome from the sperm

03:20:56.000 | that fertilized that particular egg.

03:20:57.920 | Now, of course, there are instances out there

03:20:59.600 | of people that have XXY chromosomes or XYY chromosomes,

03:21:04.600 | but the vast majority of people out there

03:21:07.880 | are going to have either an XX chromosome,

03:21:11.260 | so we call that a female karyotype, right?

03:21:14.680 | This is different than genotype and phenotype,

03:21:16.960 | but a female karyotype would be XX,

03:21:20.320 | or a male karyotype, which would be XY, okay?

03:21:24.880 | Now, despite the fact that it is the egg and the sperm

03:21:27.280 | and the chromosomes that they carry

03:21:28.380 | that are going to determine the chromosomes,

03:21:30.980 | there's a lot of lore and discussion about the factors

03:21:34.320 | that can bias which sperm will fertilize the egg

03:21:38.160 | and thereby whether or not you're going to get an XX female

03:21:41.100 | or an XY male chromosome and therefore offspring.

03:21:44.620 | Now, not only is the lore around this whole issue

03:21:47.360 | of sex determination rather prominent,

03:21:50.100 | but it is also somewhat unusual

03:21:52.360 | and perhaps even interesting.

03:21:53.820 | So for instance, Aristotle himself proposed

03:21:57.680 | that if a man is thinking about himself

03:22:00.900 | and his own pleasure more than his partner

03:22:05.320 | and her pleasure at the point of ejaculation,

03:22:08.580 | then the offspring will be male.

03:22:11.160 | Aristotle also asserted that if a man is thinking more

03:22:13.680 | about his partner and her pleasure

03:22:15.780 | at the point in which he ejaculates,

03:22:17.920 | well, then the offspring would be female.

03:22:20.840 | Of course, we have zero reason to believe

03:22:23.600 | that there's any truth to Aristotle's theory.

03:22:26.060 | There are no data to support that.

03:22:27.960 | In fact, I'm not even sure how you would run that experiment

03:22:30.080 | because you can't really look at people's thoughts.

03:22:33.280 | You'd have to rely on honest self-report.

03:22:36.240 | And even if people were to faithfully report

03:22:39.500 | what they were thinking about at the moment of ejaculation,

03:22:42.200 | this would involve, of course,

03:22:43.240 | bringing people into the laboratory

03:22:44.540 | and somehow measuring or analyzing their thoughts

03:22:47.780 | or gathering their thoughts during the sexual intercourse

03:22:50.940 | at the point of ejaculation,

03:22:52.100 | then figuring out which biological sex

03:22:54.740 | was the offspring, et cetera.

03:22:56.640 | Just a near impossible

03:22:57.900 | and probably not the most important experiment

03:23:00.480 | to invest our time doing.

03:23:02.080 | Nonetheless, there continues to be a lot of lore

03:23:06.240 | about what determines the sex of the offspring.

03:23:08.640 | Most notably, there's a lot of lore and discussion

03:23:11.120 | and rumor about the idea that particular sexual positions

03:23:15.260 | at the point of ejaculation during intercourse

03:23:18.020 | can somehow bias the likelihood that a pregnancy

03:23:21.780 | will be either resulting in male or female offspring.

03:23:26.340 | Now, again, there are zero data to support this.

03:23:28.780 | And yet this whole notion of sex determination

03:23:31.840 | is a really interesting one

03:23:33.100 | that people seem to be somewhat obsessed by.

03:23:35.400 | So much so that, again, if you go online

03:23:38.200 | or if you were to talk to people in the sort of,

03:23:41.160 | let's call it holistic or peripheral health spaces

03:23:44.720 | related to fertility, there is discussion about,

03:23:47.400 | okay, well, you take this sexual position

03:23:49.260 | at the point of ejaculation to get a boy

03:23:50.980 | and you take that sexual position

03:23:52.200 | at the point of ejaculation to get a girl,

03:23:54.000 | or you do this in the early part of the day

03:23:56.680 | or the later part of the day.

03:23:58.320 | Again, all for which there is zero data

03:24:01.520 | to support any kind of systematic relationship

03:24:04.300 | between what I just discussed

03:24:05.400 | and the biological sex of the offspring.

03:24:07.440 | That said, there are now emerging methods

03:24:11.280 | that people are using in order to separate out the sperm

03:24:16.280 | that will indeed give rise to a male offspring

03:24:20.280 | versus a female offspring.

03:24:21.720 | Now, this of course is done in the context

03:24:23.780 | of in vitro fertilization.

03:24:25.560 | We haven't talked too much about in vitro fertilization,

03:24:27.860 | but in vitro fertilization involves, as the name suggests,

03:24:31.040 | taking an egg and taking a sperm, pairing them in a dish.

03:24:35.300 | This can be done a number of different ways,

03:24:37.920 | but just to briefly describe the IVF procedure,

03:24:41.000 | IVF involves administering supra,

03:24:44.660 | meaning greater than normal,

03:24:45.940 | supra physiological levels of follicle stimulating hormone

03:24:50.100 | and luteinizing hormone

03:24:51.920 | during the follicular phase of a woman's cycle.

03:24:54.560 | What that causes is the maturation of not just one egg

03:24:58.960 | that would be ovulated, but multiple follicles and eggs.

03:25:03.720 | And then ovulation itself is suppressed

03:25:06.880 | also through the administration of exogenous hormones.

03:25:10.160 | And then under ultrasound guidance,

03:25:12.560 | an OB/GYN goes in and collects the mature eggs and follicles,

03:25:16.480 | puts them in a dish, and then sperm are delivered

03:25:19.120 | to that dish, and those could either be sperm

03:25:21.020 | that were frozen previously or more typically,

03:25:23.860 | or ideally it would be live sperm collected that day

03:25:27.180 | that are washed through a very straightforward procedure.

03:25:31.140 | And then those sperm either are allowed to compete

03:25:33.640 | for those eggs and fertilize those eggs

03:25:35.760 | and allow them to advance to a very early embryo stage

03:25:39.660 | before those embryos are frozen

03:25:41.160 | and eventually implanted into a woman

03:25:43.400 | in order to have them be carried to full term, ideally,

03:25:47.300 | or there's a procedure in which specific sperm are selected

03:25:51.240 | because they have the best morphology,

03:25:52.860 | motility, and so forth, and in a process called ICSI,

03:25:56.280 | in which the sperm themselves are literally forced

03:26:01.760 | to fertilize that particular egg.

03:26:03.960 | Now, under those conditions,

03:26:07.140 | typically a couple or a woman,

03:26:10.960 | if she's doing this on her own with a sperm donor,

03:26:13.200 | will get multiple fertilized embryos, okay,

03:26:16.600 | that are carried to a multicellular stage

03:26:20.180 | so that it's clear that they could grow into a child

03:26:23.380 | if they were implanted into a viable host,

03:26:26.700 | sometimes the surrogate,

03:26:27.600 | sometimes the woman who wants the child herself.

03:26:30.300 | And under those conditions,

03:26:31.540 | it is possible to look at the genetic makeup,

03:26:33.700 | including the karyotype of those early nascent embryos,

03:26:37.780 | in which case people really can select the sex

03:26:40.780 | of their offspring.

03:26:41.620 | That is, they will have some embryos that are XX,

03:26:45.880 | some embryos that are XY.

03:26:47.540 | It's very likely also that they will have some embryos

03:26:50.880 | that have karyotypes or genotypes, which are not ideal,

03:26:54.800 | in that they would potentially lead to a miscarriage

03:26:57.260 | or some other genetic defect.

03:26:58.540 | And so typically people do not select

03:27:01.420 | to implant those embryos

03:27:04.060 | if they have the option to implant embryos

03:27:06.940 | that are of either XX or XY karyotype

03:27:10.600 | and the normal chromosomal arrangements,

03:27:13.620 | for obvious reasons.

03:27:15.420 | So the whole point here is that sex selection is possible,

03:27:20.180 | but only using in vitro fertilization.

03:27:23.320 | The other thing that is becoming clear to us

03:27:25.660 | in more recent years is that sex selection

03:27:28.660 | is actually possible at the level of the sperm

03:27:31.060 | even prior to fertilization.

03:27:33.180 | This is an emerging data set,

03:27:35.340 | and this is largely happening in clinics

03:27:37.300 | outside of the United States,

03:27:38.640 | but there are some clinics that have figured out methods

03:27:41.200 | in which they can take a sperm sample

03:27:43.240 | and they can spin that sperm sample in a centrifuge

03:27:46.840 | at a rate that separates out the sperm

03:27:49.000 | into what are called different fractions.

03:27:50.720 | So for those of you who've done a little bit of biology

03:27:52.340 | with centrifuges, when you spin any kind of substance

03:27:55.280 | that includes multiple things in it of different weights,

03:27:58.520 | when you spin them, the things of different weights

03:28:00.200 | segregate out into different fractions

03:28:02.400 | along the depth of the tube.

03:28:03.560 | And then you can take out one fraction or the next

03:28:05.840 | simply with a little pipette.

03:28:06.820 | You take out the top fraction,

03:28:07.920 | the middle fraction, and so forth.

03:28:09.440 | And what these clinics have figured out

03:28:11.320 | is that if they spin the sperm sample

03:28:13.580 | at the correct spin rate,

03:28:16.200 | that the sperm that will give rise to male offspring

03:28:21.200 | and the sperm that will give rise to female offspring

03:28:23.640 | segregate out into different fractions,

03:28:25.640 | allowing them to take each of those fractions separately

03:28:29.840 | and to apply them to eggs, if it's in vitro fertilization,

03:28:33.880 | and give rise very reliably,

03:28:36.240 | certainly much more than chance,

03:28:37.800 | to either male or female embryos.

03:28:41.480 | They also, of course, can choose to do this

03:28:43.880 | outside the context of in vitro fertilization.

03:28:46.040 | So some people are now opting to have their sperm samples

03:28:49.200 | spun out in this way,

03:28:50.700 | separate out the sperm that give rise

03:28:52.800 | to male or female offspring,

03:28:54.240 | and then to only use the fraction

03:28:57.500 | that they are interested in, right?

03:28:58.980 | So if they want a boy, they'll use one fraction.

03:29:00.560 | If they want a girl, they'll use different fraction.

03:29:02.920 | And then to use those fractions in the context

03:29:06.280 | of what's called IUI or intrauterine insemination,

03:29:09.640 | which is, as the name suggests,

03:29:11.360 | rather than having the man deliver the ejaculate

03:29:14.740 | with his penis and the sperm with his penis,

03:29:16.400 | they have a device.

03:29:18.400 | The devices are now commercially sold,

03:29:20.480 | believe it or not, they're sold over the counter

03:29:21.840 | and on the internet, so people will even do this at home.

03:29:24.000 | And so what they're doing is they'll take the sperm

03:29:26.120 | and they'll do IUI in order to bias the probability

03:29:31.120 | that they're going to get a male or a female offspring.

03:29:33.680 | Again, this is something that's now emerging.

03:29:36.340 | It's not commonplace.

03:29:37.880 | Most of the time, people simply roll the dice, as it were,

03:29:42.280 | by having either intercourse and just hoping for

03:29:45.960 | or not caring if they get a male or a female offspring,

03:29:49.080 | or in the instance of IVF,

03:29:50.480 | selecting male or female offspring,

03:29:52.040 | sometimes largely on the basis of the chromosomal arrangements

03:29:55.200 | So of course, some people might prefer to have one

03:29:59.680 | or the other biological sex as their offspring,

03:30:02.040 | but of course, the healthy chromosomal arrangements

03:30:05.120 | are going to be paramount for getting a healthy child.

03:30:08.000 | And as I mentioned before,

03:30:10.120 | unhealthy chromosomal arrangements

03:30:11.600 | or abnormal chromosomal arrangements

03:30:13.280 | often lead to miscarriage and/or birth defects.

03:30:16.480 | So selecting for healthy chromosomal arrangements

03:30:19.480 | is always paramount,

03:30:20.760 | but some people are selecting for biological sex.

03:30:22.800 | And indeed, some couples who can conceive naturally

03:30:27.540 | are opting for IUI in order to be able

03:30:31.000 | to select biological sex because of this ability

03:30:33.680 | to spin out the sperm samples to different fractions

03:30:37.000 | and select the male or female sperm.

03:30:39.940 | That is the sperm that would give rise

03:30:41.580 | to a male or female offspring.

03:30:42.860 | So this is a rapidly emerging theme, believe it or not.

03:30:46.880 | Who knew?

03:30:48.200 | And of course, it has nothing to do

03:30:49.600 | with Aristotle's assertions

03:30:50.840 | about what people are thinking about

03:30:52.120 | at the point of ejaculation,

03:30:53.640 | nor does it have anything to do with body position

03:30:56.360 | at the point of ejaculation.

03:30:57.960 | But I do find it rather interesting that

03:31:00.280 | even in this day and age,

03:31:01.320 | people seem to be continually pursuing

03:31:04.780 | new and different ways to understand

03:31:06.600 | why one sperm or another sperm

03:31:08.520 | happens to fertilize the egg.

03:31:11.600 | And when that information is not available,

03:31:14.180 | because frankly, it's not available yet,

03:31:15.680 | we don't know why a sperm containing a Y chromosome

03:31:18.960 | or sperm containing an X chromosome

03:31:20.380 | is more likely to fertilize an egg.

03:31:22.160 | I mean, there's some ideas, for instance,

03:31:23.580 | that older fathers tend to have more daughters

03:31:25.720 | as opposed to sons.

03:31:26.940 | But when you really look at the data, it's pretty mixed.

03:31:29.000 | So if you've heard that before,

03:31:30.760 | has a particular nickname

03:31:32.760 | that I'm not going to describe on the podcast,

03:31:34.560 | you can look it up online.

03:31:35.820 | But if any of you are aware of any other kind of ideals

03:31:39.780 | or lore, no matter how ridiculous or crazy,

03:31:42.460 | please put them in the comment section on YouTube.

03:31:44.080 | I'd be very curious to learn about those,

03:31:46.440 | mostly out of interest and curiosity.

03:31:49.420 | But look, sometimes these outrageous stories,

03:31:52.400 | such as notions of body position

03:31:54.580 | and how they influence biological sex,

03:31:56.980 | even though they turn out not to be true,

03:31:58.240 | they turn out to be interesting for other reasons.

03:32:00.360 | And in fact, next, we're going to talk about

03:32:02.160 | how body position during sexual intercourse

03:32:04.500 | can in fact influence fertility and pregnancy.

03:32:08.660 | So another common theme around fertility and pregnancy

03:32:11.120 | that you'll hear about

03:32:12.440 | is that for couples that are trying to get pregnant,

03:32:15.260 | that during intercourse,

03:32:16.980 | they should do whatever it is that works for them.

03:32:19.720 | But then after the man ejaculates,

03:32:23.260 | that the woman should try and position her ankles

03:32:26.520 | above her head or somehow otherwise tilt her pelvis back

03:32:31.520 | in order to increase the rate and or probability

03:32:35.120 | that the sperm swim toward the egg,

03:32:37.500 | as opposed to the other direction.

03:32:39.480 | Now, I talked to a couple of different OBGYNs

03:32:42.440 | and urologists that are focused on fertility

03:32:45.460 | about this topic.

03:32:46.640 | And it turns out you get pretty mixed answers

03:32:48.800 | as to whether or not there's any validity to this idea

03:32:51.320 | that the woman's body position

03:32:53.320 | after the man ejaculates inside of her

03:32:55.900 | can somehow influence the probability of pregnancy.

03:32:58.980 | One group of experts told me

03:33:00.660 | that there is no reason for a woman

03:33:02.660 | to need to continue to lie down, elevate the ankles,

03:33:05.720 | or in any way tilt her pelvis back

03:33:08.360 | in order to increase the probability

03:33:10.380 | of successful fertilization.

03:33:12.880 | The other group suggested that indeed

03:33:15.120 | there is a strong reason to believe

03:33:17.920 | that tilting the pelvis back,

03:33:20.320 | maybe even keeping the ankles elevated

03:33:22.120 | and having a woman lie on her back for about 15 minutes

03:33:26.500 | with the pelvis positioned at about 20 degrees back

03:33:30.880 | is ideal for optimizing fertilization.

03:33:33.900 | I mean, they were really specific about the recommendation.

03:33:36.020 | So I find this interesting that within the cohort

03:33:39.200 | of extremely well-trained MDs, OBGYNs,

03:33:43.520 | and urology, fertility docs, and OBGYNs,

03:33:46.680 | you see a split that has nothing to do

03:33:48.300 | with whether or not the physician was male or female,

03:33:51.840 | or their training or their institution, none of that.

03:33:54.560 | There just seemed to be a sort of even split

03:33:56.160 | between the two.

03:33:57.000 | Now, granted, it wasn't the largest sample size

03:33:58.480 | that I could have obtained,

03:33:59.400 | and yet I do find it interesting

03:34:00.880 | that there's this split in the opinion about this.

03:34:05.160 | One group, the group that said,

03:34:07.440 | "No, pelvic position doesn't really matter.

03:34:10.360 | Don't worry about it.

03:34:11.480 | It's not going to influence the rates of fertilization,"

03:34:14.540 | argue that the sperm swim very quickly

03:34:17.540 | and that if they are released near the cervix,

03:34:19.440 | they're going to swim very quickly toward the egg

03:34:22.040 | in order to fertilize it, regardless of pelvic position.

03:34:25.880 | The other group said, "Well, yes, sperm swim quickly."

03:34:30.220 | And even if they're released right at the entry

03:34:33.040 | to the cervix, that the sperm still have

03:34:36.080 | a long distance to go.

03:34:37.020 | Again, if you were to scale this,

03:34:39.080 | according to the size of the sperm

03:34:40.320 | versus the size of a human body, an entire human body,

03:34:43.520 | what you'd scale it to is the distance

03:34:45.600 | between Los Angeles and San Francisco,

03:34:47.300 | and it needs to undergo that basically within 24 hours or so,

03:34:50.020 | although, as we mentioned earlier,

03:34:51.440 | sperm can survive quite a while inside of the woman's body,

03:34:54.980 | maybe three or five days at least.

03:34:57.820 | So in both cases, they acknowledge it's a long distance,

03:35:00.100 | but on the one hand, you have a group of experts

03:35:02.400 | that are saying the sperm more or less know what to do

03:35:04.780 | and are going to do it regardless of the position

03:35:06.480 | of the woman after ejaculation inside her,

03:35:09.020 | and the other group saying,

03:35:10.480 | "No, we want to do everything we can to bias the likelihood

03:35:13.120 | that the sperm will fertilize the egg."

03:35:15.460 | Okay, well, setting aside the basic argument

03:35:19.920 | that tilting back of the pelvis and lying stationary or so

03:35:24.920 | for about 15 minutes after sexual intercourse

03:35:28.320 | and ejaculation is not an expensive endeavor,

03:35:32.320 | although it requires a little bit of time,

03:35:36.280 | and it forces people to remain motionless

03:35:38.580 | or close to motionless,

03:35:40.320 | and they're not up and around and moving about.

03:35:42.680 | Aside from that, it's a relatively low investment,

03:35:45.280 | so one argument is,

03:35:46.640 | "Well, if it could bias the likelihood of fertilization

03:35:49.880 | at all and people want to get pregnant,

03:35:52.880 | why wouldn't they do that?"

03:35:54.580 | Okay, so that's a reasonable argument,

03:35:56.020 | but it doesn't really point to the mechanism.

03:35:58.460 | The arguments that point to a potential mechanism

03:36:00.620 | are that if you recall what we were talking about

03:36:03.500 | when we talked about sperm quality,

03:36:05.400 | sperm quality involves a bunch of different measures

03:36:07.620 | like concentration of sperm per milliliter semen,

03:36:10.300 | morphology of those sperm, how many are forward motile.

03:36:14.600 | It turns out that in any one ejaculate sample,

03:36:18.040 | the total number of forward motile

03:36:21.120 | and yet fast forward motile sperm

03:36:24.520 | that are also of the highest quality morphology

03:36:28.640 | is actually quite low.

03:36:30.280 | And so the idea here is that you want to get as many sperm

03:36:34.500 | of the highest quality swimming toward the egg

03:36:36.780 | because those sperm stand the highest probability

03:36:39.680 | of fertilizing that egg.

03:36:41.400 | And in fact, this relates to some of the discussion

03:36:42.920 | we were having earlier about behavioral do's and don'ts

03:36:46.360 | for sake of increasing the probability of fertilization.

03:36:50.560 | And the one that is most important here is cannabis.

03:36:53.920 | It turns out that the data on cannabis

03:36:55.700 | really do support the idea that some of you may have heard

03:36:59.040 | from parents and teachers.

03:37:00.880 | I don't know, I did hear this from parents and teachers

03:37:03.800 | that cannabis can disrupt the swimming styles of sperm

03:37:08.800 | in ways that are not supportive of fertilization,

03:37:11.800 | that it can turn more of the sperm into twitchers.

03:37:14.080 | Although when I learned about this,

03:37:15.180 | I was not informed of the word twitchers.

03:37:16.600 | What I was told is that if you use cannabis,

03:37:20.160 | that the sperm don't know which direction to go,

03:37:22.380 | that they're confused almost implying

03:37:25.160 | that the sperm themselves are high on cannabis.

03:37:27.840 | Well, that's certainly not the argument that I'm making here

03:37:31.420 | but it does seem to be the case that people who use cannabis

03:37:35.080 | even once the sperm that are generated

03:37:38.680 | during that particular month or two months

03:37:43.140 | during which or after which they use cannabis

03:37:45.700 | have less forward motility

03:37:49.280 | and possibly altered morphology as well.

03:37:51.300 | Okay, I want to be very clear.

03:37:52.440 | I did not say that if you use cannabis once

03:37:54.840 | you are forever disrupting the motility

03:37:58.160 | and morphology of your sperm.

03:37:59.320 | I did not say that.

03:38:00.160 | What I said is that if you use cannabis once,

03:38:02.800 | then the sperm that are generated in the 60 days

03:38:06.000 | after that cannabis use are going to have a higher incidence

03:38:10.360 | of disrupted motility and perhaps morphology as well.

03:38:14.400 | Okay, remember sperm are continually generated

03:38:17.400 | every 60 days or so.

03:38:20.000 | And so if you use cannabis once

03:38:22.360 | you are not forever disrupting your sperm

03:38:24.280 | but if you are using cannabis

03:38:26.140 | and then you are looking to conceive in the next 60 days,

03:38:28.920 | you're going to be reducing, we think significantly so,

03:38:32.880 | the number of quality, forwardly motile sperm.

03:38:36.640 | So the simple takeaway from this is avoid cannabis use.

03:38:39.460 | Although if you are going to use cannabis,

03:38:41.400 | and again, there are medical uses of cannabis

03:38:44.120 | and beneficial uses of cannabis for certain populations.

03:38:46.560 | It can be bad for other populations.

03:38:48.260 | We talked about that in the Huberman Lab podcast

03:38:50.500 | all about cannabis.

03:38:51.520 | But if you're going to use cannabis,

03:38:53.220 | you should try and abstain from cannabis

03:38:55.880 | in the two months prior to the attempt to fertilize

03:38:59.680 | and get pregnant.

03:39:01.080 | Now I'm not aware of any data on how cannabis use

03:39:04.640 | by the woman can influence the likelihood

03:39:06.960 | of fertilization in pregnancy.

03:39:08.560 | And I want to couch this whole discussion around cannabis

03:39:11.260 | under the umbrella of something that came up in the episode

03:39:13.480 | that I did on cannabis, which is that

03:39:15.600 | for about half of people out there, male and female, okay?

03:39:19.640 | So here we're not distinguishing by biological sex.

03:39:22.580 | About half of people that use cannabis

03:39:25.640 | report it as an aphrodisiac.

03:39:27.280 | It makes them want to have sexual intercourse

03:39:29.740 | more than if they don't use cannabis.

03:39:31.720 | And for the other half, it actually has the opposite effect

03:39:34.680 | by way of an influence on a hormone called prolactin,

03:39:37.480 | which suppresses the dopamine system,

03:39:39.480 | the testosterone, and the estrogenic system.

03:39:42.240 | And so this whole idea that cannabis is an aphrodisiac

03:39:45.160 | seems to be true for about half of the human population

03:39:47.680 | and not for the other half of the human population.

03:39:50.060 | So I mentioned that because I know a number of people

03:39:52.520 | use cannabis as an aphrodisiac,

03:39:55.600 | but they like to use cannabis before intercourse.

03:39:57.600 | It was actually very surprising to me to discover

03:40:00.620 | when I researched that cannabis episode

03:40:02.620 | that approximately 15, 1.5% of women who are pregnant

03:40:07.620 | continue to use cannabis during pregnancy.

03:40:10.440 | And that's a very alarming statistic.

03:40:12.620 | And everything we know is that the use of cannabis

03:40:16.320 | during pregnancy is detrimental to the health,

03:40:19.120 | in particular the brain development of the fetus.

03:40:21.340 | So that's a real concern.

03:40:23.120 | I highly recommend women abstain from cannabis use

03:40:25.900 | during pregnancy.

03:40:27.500 | Talk to your OB/GYN about it if you're using it all

03:40:30.200 | or considering using it all.

03:40:31.720 | So based on what I told you earlier about the fact

03:40:33.760 | that cannabis use is not good for egg quality,

03:40:37.600 | and the fact that cannabis use

03:40:39.400 | can disrupt the motility of sperm,

03:40:40.880 | and therefore is not good for sperm quality,

03:40:44.320 | and it can disrupt the patterns of swimming in sperm

03:40:47.280 | in ways that reduce the likelihood of fertility,

03:40:50.260 | I think the take-home message is clear,

03:40:51.620 | which is that whether or not

03:40:53.280 | you want to be a cannabis user or not,

03:40:55.480 | if you are going to try and conceive,

03:40:57.540 | and certainly while you're pregnant,

03:40:58.700 | you're going to want to avoid the use of cannabis,

03:41:00.900 | and that is smoked cannabis and vaped cannabis.

03:41:03.980 | And during pregnancy, the consumption of cannabis,

03:41:07.980 | even in edible form or in tincture form,

03:41:09.980 | is also going to be detrimental to the developing fetus.

03:41:13.020 | But of course, we started this conversation

03:41:15.220 | in the context of body position,

03:41:17.580 | in particular at the point of ejaculation,

03:41:19.520 | in determining the sex of the offspring

03:41:21.520 | and/or the likelihood

03:41:23.780 | of getting a successful fertilization in pregnancy.

03:41:26.780 | And I think that given that the tilting back of the pelvis,

03:41:31.000 | so again, this is elevating the pelvis by about 20 degrees,

03:41:34.280 | I don't think it has to be exact, exact,

03:41:36.300 | but about 20 degrees for about 15 minutes

03:41:38.940 | post-ejaculation inside of the woman,

03:41:41.800 | or I suppose if people are using IUI,

03:41:43.720 | intrauterine insemination,

03:41:45.740 | since that seems to be the consensus among those experts

03:41:48.760 | that believe that pelvic tilt backward

03:41:53.140 | can be beneficial

03:41:54.620 | for increasing the probability of fertilization.

03:41:56.740 | And given that it involves no cost,

03:41:58.620 | but a little bit of time,

03:41:59.660 | seems to me that if you want to get pregnant,

03:42:01.720 | that that would be the right thing to do.

03:42:03.740 | And as far as I know, there's no information,

03:42:05.380 | nor was I able to obtain any recommendations from experts

03:42:09.020 | about what the ideal body position of the male is

03:42:12.340 | after ejaculation,

03:42:13.420 | if the goal is to increase the probability

03:42:15.460 | of fertilization in pregnancy.

03:42:17.420 | So we've been talking about behavioral interventions,

03:42:19.640 | some dos and some don'ts,

03:42:20.700 | that people can do to increase their fertility

03:42:22.700 | and the likelihood that any fertilized egg

03:42:25.340 | will be carried to term successfully.

03:42:27.740 | And soon we'll also talk about things

03:42:29.660 | that people can take to improve their fertility.

03:42:32.260 | Now keep in mind that this entire discussion

03:42:34.400 | is about fertility,

03:42:35.940 | but also remember as we discussed

03:42:38.020 | at the beginning of the episode,

03:42:40.260 | trying to increase your fertility

03:42:42.940 | is one of the best ways to think about

03:42:44.960 | trying to create and maintain optimal physical health.

03:42:49.500 | So for people that are trying to conceive

03:42:51.060 | and for people who are not trying to conceive,

03:42:53.300 | optimizing your fertility status,

03:42:55.180 | whether or not you're male or female,

03:42:56.900 | it's one of the best ways to target those approaches.

03:42:59.860 | And there are now a lot of data supporting the idea

03:43:02.420 | that acupuncture of all things

03:43:04.740 | can be very beneficial for improving

03:43:06.920 | both female and male fertility

03:43:08.700 | and should a woman get pregnant

03:43:11.000 | for improving the quality of outcomes.

03:43:13.320 | That is the likelihood that there will be

03:43:15.820 | a successful pregnancy that is carried to term,

03:43:19.640 | not premature and so on and so forth.

03:43:22.480 | Now, for some of you out there,

03:43:23.640 | you might think, oh, of course acupuncture.

03:43:25.200 | Acupuncture has been known to work for thousands of years.

03:43:27.760 | And therefore it's not surprising

03:43:30.220 | that it would assist with fertility and pregnancy.

03:43:33.380 | For many of you out there, however,

03:43:35.240 | probably thinking acupuncture,

03:43:36.520 | that seems kind of like fringe science.

03:43:38.520 | But what I can assure you is that

03:43:40.420 | there are now quite a few clinical trials

03:43:42.920 | funded by government agencies

03:43:44.340 | like the National Institutes of Health

03:43:46.860 | showing that acupuncture is a very effective treatment

03:43:49.420 | for a number of different things,

03:43:50.780 | including fertility and pregnancy,

03:43:52.820 | but for hormone status, for stress relief,

03:43:56.100 | but even for chronic illnesses of different kinds,

03:43:59.020 | including autoimmune illnesses.

03:44:00.660 | So this is no longer considered fringe science.

03:44:02.860 | In fact, one of the best laboratories in the world

03:44:05.420 | working on this is a laboratory

03:44:07.160 | out of Harvard Medical School

03:44:08.700 | run by a guy named Chufu Ma.

03:44:10.860 | Chufu's lab has really been exploring in a mechanistic way

03:44:14.660 | how the different stimulation sites

03:44:16.860 | that are used in acupuncture,

03:44:18.180 | so where the needles are inserted,

03:44:19.940 | tap into neural pathways

03:44:21.640 | that link the different organs of the body.

03:44:23.860 | So for instance, they've found that stimulation

03:44:26.860 | of a particular site on the lower limb

03:44:29.820 | can reduce inflammation dramatically throughout the body

03:44:33.180 | by way of neural pathways that originate in the lower limb

03:44:36.780 | and extend to areas such as the kidney and the pancreas.

03:44:39.920 | So all these quote-unquote ancient maps of the human body

03:44:43.640 | as they relate to acupuncture

03:44:44.900 | are now being parsed at the level of mechanism,

03:44:47.340 | which I think is wonderful

03:44:48.380 | because it not only is showing us

03:44:50.660 | that so much of what has been purported and reported

03:44:54.280 | in the landscape of acupuncture

03:44:56.240 | actually has an underlying mechanistic basis.

03:44:58.840 | And with additional mechanistic understanding, of course,

03:45:01.420 | always arrive new and better practices.

03:45:03.620 | That's the idea to evolve these fields of acupuncture,

03:45:06.820 | to evolve the fields of mechanistic understanding

03:45:08.920 | of our biology and health.

03:45:10.500 | And so the issue of whether or not acupuncture

03:45:13.880 | can assist in getting pregnant

03:45:15.740 | and in carrying a child to term

03:45:18.460 | and for that child to be healthy

03:45:19.980 | are really starting to emerge in a major way.

03:45:23.340 | And rather than go into all those data in detail,

03:45:25.700 | what I can tell you is that there are clinical trials

03:45:28.360 | and data supporting the fact that female fertility itself

03:45:31.340 | can be supported by acupuncture through several mechanisms.

03:45:35.440 | One of which is the balancing,

03:45:38.100 | and I realize that's a somewhat tricky term

03:45:39.580 | and I'll define it better in a moment,

03:45:40.960 | the balancing of hormones

03:45:42.040 | across the ovulatory/menstrual cycle,

03:45:46.120 | including regulating levels of FSH

03:45:48.120 | so that they're not too high nor too low

03:45:50.440 | and restricting the FSH to the follicular phase

03:45:53.560 | of the menstrual cycle,

03:45:55.840 | as well as using acupuncture to improve things

03:45:59.680 | like blood flow and the health of the ovary itself

03:46:02.560 | and other aspects of the female reproductive axis.

03:46:05.840 | So acupuncture can operate at the chemical level

03:46:09.060 | impacting hormones.

03:46:10.120 | It can act at the mechanical level

03:46:12.500 | impacting the different tissues

03:46:14.320 | through which the egg has to pass and so on and so forth.

03:46:17.100 | Likewise, on the male side,

03:46:18.960 | acupuncture has been shown to improve semen volume,

03:46:22.960 | quality of sperm, sperm motility, et cetera,

03:46:26.600 | and in large part through changes in the neural pathways

03:46:30.440 | that innervate the very tissues and vascular input

03:46:34.840 | to the scrotum and testicles,

03:46:36.600 | because as we learned earlier,

03:46:38.820 | temperature regulation of the scrotum and testicles

03:46:40.820 | is so vital for getting healthy sperm

03:46:43.440 | and increasing sperm quality.

03:46:45.460 | In addition, there are good data to support the idea

03:46:48.320 | that acupuncture can increase levels

03:46:50.960 | of testosterone-free testosterone

03:46:52.680 | and the sorts of hormones that are going to support

03:46:55.240 | healthy hormone production and sperm production in males.

03:46:59.320 | And this is distinct from applying testosterone

03:47:03.260 | from an exogenous source, right?

03:47:04.720 | So when we're talking about acupuncture

03:47:06.140 | and increasing levels of testosterone,

03:47:07.680 | we're talking about increasing levels

03:47:09.160 | of endogenous testosterone.

03:47:11.180 | So those Leydig cells can support the Sertoli cells

03:47:13.660 | and the Sertoli cells can make that androgen binding protein

03:47:16.260 | and you get enhanced spermatogenesis.

03:47:18.700 | You can find evidence for all of these different features,

03:47:21.040 | both changes to the chemical milieu, that is the hormones,

03:47:23.420 | and changes to the mechanical milieu,

03:47:25.340 | including, for instance, improvement of the pathways

03:47:28.580 | leading from the seminiferous tubules to the epididymis

03:47:31.100 | to the vas deferens, basically clearing out the plumbing

03:47:33.680 | so that more quality ejaculate can be delivered,

03:47:36.340 | which of course is going to increase

03:47:37.740 | the probability of fertilization.

03:47:39.820 | So when you hear that acupuncture can improve

03:47:41.960 | the likelihood of pregnancy, that's an accurate statement

03:47:45.220 | for which there are now increasing amounts

03:47:47.300 | of mechanistic data.

03:47:48.580 | If you want to learn more about how acupuncture

03:47:50.900 | can be used to contribute

03:47:52.580 | to improve fertilization in pregnancy,

03:47:55.060 | there are a number of different excellent reviews on this,

03:47:57.700 | both as it relates to females and as it relates to males.

03:48:01.460 | One of the best papers that I happen to like

03:48:04.020 | is one that we'll provide a link to in the references

03:48:06.220 | entitled Acupuncture and Herbal Medicine

03:48:07.940 | for Female Fertility, an Overview of Systematic Reviews.

03:48:10.820 | So a review of reviews.

03:48:13.420 | This was published recently in 2021.

03:48:16.180 | We'll provide a link to that.

03:48:17.540 | And there's also going to be a link to a review

03:48:20.860 | that relates to acupuncture for male fertility

03:48:23.500 | and hormone augmentation.

03:48:25.180 | I should just mention briefly

03:48:26.820 | that if you're going to look at scientific papers,

03:48:29.580 | one thing that you'll want to consider

03:48:31.340 | is also looking at the references that they reference.

03:48:33.740 | Now, of course, papers tend to reference a ton of references

03:48:36.260 | in particular in reviews.

03:48:37.560 | So what you'll want to do is look for the references

03:48:39.900 | that are showing up most often in the introduction.

03:48:42.880 | Those references often are going to be

03:48:44.820 | the most prominent recent reviews

03:48:46.860 | or the most important findings in recent years.

03:48:49.480 | That's not always the case, but that's often the case.

03:48:51.800 | So if you read the first couple of paragraphs

03:48:53.540 | of these papers, and these are openly available

03:48:55.420 | as full text, by the way, online, if you go to these links,

03:48:58.680 | you'll be able to access the best papers,

03:49:01.280 | the most relevant papers in the context

03:49:03.300 | of acupuncture supporting female

03:49:05.580 | and acupuncture supporting male fertility

03:49:08.580 | and hormone status.

03:49:09.740 | Now I'd like to discuss things that both men and women

03:49:12.460 | can take in order to maximize their fertility.

03:49:15.460 | And again, and again, when we're talking about fertility,

03:49:19.520 | we're talking about people who want to conceive

03:49:21.900 | and have children, but also we're talking about

03:49:24.900 | a basic measure of overall health status.

03:49:27.940 | So if you're somebody who does not want to conceive children,

03:49:31.060 | I still encourage you to think about

03:49:32.960 | whether or not you would want to do certain things

03:49:34.980 | or not do certain things

03:49:36.500 | in order to maximize your fertility

03:49:38.480 | as a means to maximize your vitality and longevity,

03:49:41.880 | because that's really what maximizing fertility is about

03:49:44.880 | for a lot of people.

03:49:46.140 | That said, I know a lot of people

03:49:47.540 | would like to conceive children,

03:49:48.820 | perhaps not right away, but in the future.

03:49:50.780 | And what I'm about to describe

03:49:52.260 | are some tools and interventions,

03:49:54.400 | that is things that one can take

03:49:56.940 | in order to improve their hormone status,

03:50:00.100 | but also in particular, the quality of their eggs

03:50:03.120 | and the quality of their sperm in the short and long term.

03:50:06.440 | The first on the list of things that people can take

03:50:09.000 | in order to improve egg quality or sperm quality

03:50:11.600 | is L-carnitine.

03:50:13.320 | L-carnitine is present in various foods,

03:50:15.580 | in particular in red meats.

03:50:17.420 | But again, it's going to be very hard

03:50:18.900 | to get sufficient levels of L-carnitine

03:50:20.820 | to improve egg quality and sperm quality

03:50:23.020 | unless you're going to take it in supplement form.

03:50:25.100 | The typical recommendation based on peer reviewed studies,

03:50:28.300 | they've shown significant improvements in egg quality,

03:50:30.820 | that is chromosomal arrangements,

03:50:33.200 | that is the likelihood of fertility or pregnancy rather,

03:50:36.480 | the likelihood of sperm being forward fast swimmers

03:50:39.960 | as opposed to twitchers or remote tile

03:50:41.500 | and having proper morphology.

03:50:42.660 | All those measures has been demonstrated

03:50:45.500 | to be significantly improved

03:50:47.360 | by the ingestion of L-carnitine.

03:50:48.820 | How much L-carnitine?

03:50:50.000 | Well, that depends on how you're obtaining the L-carnitine.

03:50:52.540 | If you're obtaining it in capsule form,

03:50:56.180 | one to three grams per day of capsule form L-carnitine

03:51:00.320 | is what's been suggested to improve egg quality

03:51:02.860 | and sperm quality.

03:51:04.180 | Now, one to three grams per day can be taken all at once

03:51:07.220 | or spread out throughout the 24 hour cycle.

03:51:09.280 | It can be taken with or without food,

03:51:12.180 | does not seem to matter.

03:51:13.860 | And when taken for a period of 30 to 60 days,

03:51:17.540 | it does seem to significantly improve all the parameters

03:51:20.580 | that have been discussed for egg quality and sperm quality.

03:51:23.700 | Now, the mechanism for that effect is pretty clear.

03:51:26.180 | L-carnitine is involved in the processing of lipids fats

03:51:31.180 | in terms of mitochondrial function.

03:51:34.100 | And as we talked about before,

03:51:35.460 | mitochondria are vital for the organization

03:51:39.240 | and action of the spindle that pulls apart the chromosomes,

03:51:41.740 | taking that cell within the female

03:51:44.340 | from diploid to haploid, which is essential.

03:51:47.320 | You really want just the 23 individual chromosomal strands.

03:51:51.120 | You don't want chromosomal repeats.

03:51:53.680 | It's also involved in the actual fusion of the egg

03:51:56.760 | as it exits the ovary and enters the ovulation cycle.

03:52:01.080 | Mitochondria are also important, as we talked about before,

03:52:03.560 | for the forward motility of sperm

03:52:05.000 | because of the enrichment of mitochondria

03:52:06.400 | in that mid-region just behind the head

03:52:08.280 | that caused the whipping flagellation of the tail

03:52:11.460 | allowing for forward movement,

03:52:12.880 | as well as other aspects of cellular morphology.

03:52:15.260 | So it makes a lot of sense

03:52:16.480 | as to why L-carnitine supplementation would be beneficial.

03:52:19.640 | Again, it's one to three grams per day

03:52:21.760 | over a period of about 30 to 60 months.

03:52:23.400 | If you're hoping to conceive in the upcoming months,

03:52:25.620 | recommend taking it for at least 30 days prior to that.

03:52:28.420 | Of course, based on the data we talked about before,

03:52:32.200 | cumulative probability, fecundability, et cetera,

03:52:34.480 | there's no reason to not continue to try for pregnancy

03:52:37.040 | before taking L-carnitine,

03:52:38.640 | but L-carnitine is going to improve egg and sperm quality.

03:52:41.560 | And so you might actually take the stance

03:52:44.820 | that even if you don't have any problem getting pregnant,

03:52:48.420 | wouldn't you want to maximize the quality of the egg

03:52:51.720 | that gets fertilized

03:52:52.620 | and the quality of the sperm that fertilizes that egg.

03:52:55.180 | So that's additional rationale for taking L-carnitine.

03:52:58.340 | One important note,

03:52:59.760 | if you are going to take L-carnitine in oral form,

03:53:02.120 | in capsule form, it can increase something called TMAO.

03:53:05.980 | TMAO can cause stiffening of the arteries.

03:53:08.380 | You don't want TMAO levels to go too high.

03:53:10.720 | One way to offset the increases in TMAO

03:53:13.360 | caused by oral L-carnitine

03:53:15.060 | is to take 600 milligrams of garlic per day.

03:53:18.940 | I suppose you could eat cloves of garlic.

03:53:20.280 | That would work just as well

03:53:21.200 | because garlic contains something called allicin,

03:53:23.340 | which can offset the increase in TMAO.

03:53:26.140 | But 600 milligram capsules of garlic are going to be,

03:53:29.560 | or garlic extract rather,

03:53:31.620 | is going to be the most probably cost-effective

03:53:34.460 | and simplest way to do this.

03:53:36.960 | And also they are going to create that garlic smell.

03:53:39.680 | Some people like the smell of garlic, some people don't.

03:53:41.580 | So if you're going to take oral L-carnitine,

03:53:43.600 | I suggest also taking 600 milligrams a day

03:53:46.280 | of garlic extract.

03:53:48.300 | And you can do that at any time throughout the day.

03:53:49.980 | It doesn't have to be with the L-carnitine.

03:53:52.480 | The next item on the list of compounds

03:53:54.340 | that have been shown to improve egg quality

03:53:55.940 | and sperm quality, and quite robustly so, is coenzyme Q10.

03:54:00.620 | Coenzyme Q10 is something

03:54:02.420 | that you can actually measure levels of in your blood.

03:54:05.300 | Most physicians will say

03:54:06.300 | that they want to see your levels of coenzyme Q10

03:54:08.360 | to be somewhere between 0.5 and 2.5.

03:54:10.680 | It's going to depend on the units.

03:54:12.140 | Most people, I realize, are not going to run off

03:54:13.740 | and get their CoQ10 measured.

03:54:15.760 | It's not included in most standard blood tests,

03:54:17.800 | but if you were to measure your CoQ10,

03:54:19.460 | that's the range that you want to look for.

03:54:21.700 | That said, many people opt to supplement with CoQ10,

03:54:25.260 | and you'll find that many fertility docs,

03:54:27.760 | OBGYNs, and urologists that are trying

03:54:29.940 | to assist their male patients with fertility

03:54:31.620 | will suggest CoQ10 because, again,

03:54:33.600 | it supports the health of mitochondria.

03:54:36.200 | Mitochondria are so vital to so many aspects

03:54:39.220 | of the formation and fertilization of the egg and sperm

03:54:44.220 | that, of course, fertilizes the egg.

03:54:47.580 | The coenzyme Q10 dosages that are most often suggested

03:54:50.980 | and that you'll observe

03:54:52.340 | in the peer-reviewed research literature on humans,

03:54:55.340 | I should add, is 100 to 400 milligrams per day,

03:54:59.740 | and the coenzyme Q10 is taken generally with a meal

03:55:03.060 | and ideally a meal that contains fat.

03:55:05.780 | And there's even some idea that taking coenzyme Q10

03:55:08.740 | with your dinner, assuming that dinner includes some fat,

03:55:12.700 | you don't have to add additional fat,

03:55:14.160 | is going to be more advantageous

03:55:15.680 | than taking coenzyme Q10 early in the day,

03:55:18.460 | although that's probably a detail

03:55:19.840 | that's getting a little too far down in the wheat.

03:55:21.540 | So again, 100 to 400 milligrams of coenzyme Q10 per day,

03:55:24.820 | whether or not you're a man or a woman,

03:55:26.700 | for improving the likelihood of fertility

03:55:29.400 | by way of improving egg and sperm quality.

03:55:31.500 | And again, if you're somebody

03:55:32.420 | who just doesn't have any problem getting pregnant

03:55:34.500 | or if you're already producing many sperm

03:55:36.960 | of quality morphology, this is another case

03:55:39.220 | in which you could take a step back and just say,

03:55:41.040 | well, why wouldn't I want to further optimize

03:55:43.200 | the quality of the egg and the sperm?

03:55:44.500 | Because the quality of the egg and the sperm

03:55:45.900 | ultimately are going to determine

03:55:47.700 | not just whether or not you have a successful pregnancy,

03:55:49.940 | but are going to determine admittedly in ways

03:55:53.540 | that will forever remain cryptic to you,

03:55:55.940 | but nonetheless are going to be important

03:55:57.500 | in determining the qualities of the brain tissue

03:56:00.820 | and body tissue of your offspring.

03:56:02.780 | The third item on the list of compounds

03:56:04.480 | which are commonly suggested or prescribed

03:56:08.340 | by fertility docs nowadays for men and women

03:56:10.860 | wishing to conceive and or optimize their fertility

03:56:13.420 | as a basis for general vitality and health is inositol.

03:56:17.760 | Now inositol has many uses.

03:56:19.800 | So you'll hear about the use of inositol

03:56:21.480 | for reducing anxiety or improving mood

03:56:23.980 | or even for the treatment of depression.

03:56:25.300 | We talked about inositol

03:56:26.460 | in previous episodes of this podcast.

03:56:28.920 | For instance, I talked about inositol

03:56:31.580 | and in particular taking 900 milligrams of myoinositol

03:56:35.380 | prior to sleep, which is something that I do

03:56:37.400 | along with the other supplements

03:56:39.200 | that I take and recommend for sleep

03:56:40.720 | such as magnesium threonate, apigenin and theanine.

03:56:44.460 | If you're curious about those,

03:56:45.600 | you can see our newsletter on sleep

03:56:47.080 | or our perfect your sleep episode

03:56:48.580 | or the master sleep episode talks about behavioral

03:56:50.640 | and supplementation based tools for improving sleep.

03:56:53.260 | But myoinositol is not just suggested or prescribed

03:56:58.260 | for people that are wishing to get pregnant

03:57:01.260 | and for general health,

03:57:02.680 | but myoinositol is often recommended

03:57:05.280 | for people that want to improve egg and sperm quality

03:57:08.040 | because of the way that it can positively impact

03:57:11.400 | insulin sensitivity.

03:57:12.920 | Insulin sensitivity might sound like a bad thing

03:57:15.600 | to people out there,

03:57:16.540 | but it turns out that you want to be insulin sensitive.

03:57:19.840 | The last thing you want is to be insulin insensitive.

03:57:22.420 | Insulin insensitivity is associated with type 2 diabetes,

03:57:25.420 | with obesity and even for people

03:57:26.800 | who are not challenged with obesity,

03:57:29.640 | you want your cells to be insulin sensitive.

03:57:31.820 | You don't want a lot of insulin floating around

03:57:33.540 | in your system with your cells unable to use that insulin.

03:57:37.820 | That's really what insulin insensitivity is about.

03:57:40.220 | Myoinositol at dosages of one to five grams per day,

03:57:45.220 | it's pretty high, one to five grams per day,

03:57:46.980 | keeping in mind that 1,000 milligrams is one gram,

03:57:50.240 | has been suggested to improve egg quality and sperm quality.

03:57:53.800 | Now, one point of, I wouldn't say caution,

03:57:56.500 | but of note is that myoinositol can reduce anxiety

03:58:00.020 | and it can be a slight sedative,

03:58:01.260 | which is why some folks, including myself,

03:58:03.660 | take almost a gram, 900 milligrams prior to sleep.

03:58:06.920 | If you're going to take five grams of myoinositol,

03:58:10.900 | you would want to restrict that to the late evening

03:58:13.300 | or second half of your day.

03:58:14.380 | And I don't suggest starting that high.

03:58:15.900 | I would start with one or two grams

03:58:17.380 | and then working your way up,

03:58:18.620 | seeing what you can tolerate

03:58:20.380 | in terms of the level of anti-anxiety

03:58:23.460 | and drowsiness that it produces.

03:58:26.340 | One to five grams per day of myoinositol

03:58:28.700 | is what suggested for both men and women

03:58:30.460 | wishing to improve egg health and sperm health.

03:58:34.300 | But for women, it's also often suggested to include also,

03:58:38.740 | okay, so to take myoinositol,

03:58:40.660 | but to also take d-chiroinositol.

03:58:43.540 | D-chiroinositol has elements in it

03:58:46.740 | that can be both pro and anti-androgenic.

03:58:50.180 | Androgens are things like testosterone

03:58:51.900 | and related molecules.

03:58:53.500 | There are a number of different causes of infertility

03:58:56.280 | and disruption to egg quality,

03:58:58.160 | age being the most significant factor.

03:59:00.680 | But another significant and very common factor,

03:59:03.380 | even among young women who are of fertile age,

03:59:06.800 | is having too many androgens

03:59:09.140 | and as it relates to something called

03:59:10.480 | polycystic ovarian syndrome.

03:59:12.260 | And we'll do an entire episode about menopause and PCOS

03:59:15.020 | and a number of other things that relate to fertility

03:59:17.640 | because it's an entire and very interesting

03:59:20.380 | other discussion that we need to have.

03:59:22.220 | But the recommendation is that women take

03:59:24.160 | one to five grams of myoinositol,

03:59:26.220 | but also d-chiroinositol

03:59:29.000 | because of the ways that it can balance androgens

03:59:32.000 | and offset some of the negative effects

03:59:34.040 | of polycystic ovarian syndrome,

03:59:36.280 | or even for women who do not have

03:59:37.840 | polycystic ovarian syndrome,

03:59:39.540 | because of the ways that d-chiroinositol

03:59:41.540 | can balance androgens in ways that are beneficial.

03:59:44.700 | The dosages of d-chiroinositol that are recommended

03:59:48.620 | tend to be 1/25th to 1/40th of the myoinositol dose.

03:59:53.380 | So you have to get out your calculator.

03:59:54.700 | Remember 1,000 milligrams equals one gram.

03:59:57.020 | So figure out if you're taking one gram

03:59:58.820 | of myoinositol per day or two grams,

04:00:01.340 | you're going to want to convert that to milligrams.

04:00:03.740 | So let's say you're taking two grams

04:00:05.420 | of myoinositol per day, that's 2,000 milligrams,

04:00:08.340 | then you'd want to divide that by 25.

04:00:10.700 | And that's how many milligrams of d-chiroinositol

04:00:13.900 | you would want to take as well.

04:00:15.460 | Or you could go with the lower end dose

04:00:17.380 | and divide it by 40 and take that number of milligrams

04:00:21.140 | of d-chiroinositol along with the inositol.

04:00:24.340 | Again, probably taking it later in the day

04:00:26.200 | is going to be good.

04:00:27.100 | And it's not clear at all that taking it with food

04:00:29.860 | or without food makes any difference whatsoever.

04:00:31.660 | So I would suggest you do either.

04:00:33.740 | Keep in mind as I'm discussing these recommendations,

04:00:36.260 | I may call them prescriptions,

04:00:37.460 | but none of these are prescription drugs.

04:00:38.820 | And of course you should always discuss any supplements

04:00:41.700 | that you're planning to take or stop taking

04:00:44.020 | for that matter with your physician.

04:00:45.640 | I don't say that to protect me, I say that to protect you.

04:00:48.260 | Anytime you're going to add or change something

04:00:49.940 | in your overall health regimen,

04:00:51.060 | you want to discuss that

04:00:52.080 | with your trusted healthcare professional.

04:00:54.620 | Typically I would hope a board certified MD.

04:00:57.620 | The fourth item in the list of commonly suggested supplements

04:01:01.500 | for men and women wishing to optimize egg

04:01:04.400 | and sperm quality respectively is omega-3 fatty acids.

04:01:08.700 | And now here we're talking about something

04:01:10.240 | that could be obtained from food

04:01:11.760 | and can be obtained from food.

04:01:12.840 | So if you're consuming a fatty ocean fish,

04:01:15.600 | things like sardines, anchovies, salmon with the skin,

04:01:19.280 | chances are you're going to get some quality omega-3s.

04:01:22.620 | Omega-3s are also available in plant-based sources.

04:01:25.540 | It's also available in krill for that matter.

04:01:28.060 | But most people find it difficult

04:01:29.540 | to reach the threshold required

04:01:31.900 | for optimizing mental health and physical health.

04:01:34.620 | That is the threshold of the EPA essential fatty acids.

04:01:37.720 | And so for that matter,

04:01:39.440 | I've suggested before in this podcast

04:01:41.420 | and many fertility docs will suggest

04:01:43.440 | that their patients take omega-3 fatty acids

04:01:47.360 | in supplement form, it could be taken in liquid form

04:01:49.520 | or in capsule form, but enough of those

04:01:51.220 | so that you're getting at least one gram per day

04:01:53.960 | of the EPA form of omega-3s, okay?

04:01:56.380 | So at least one gram per day

04:01:57.780 | and as high as two or even three grams per day

04:02:00.380 | of the EPA form.

04:02:01.860 | So you'll need to look at the packaging

04:02:03.220 | because oftentimes you'll say high potency omega-3s,

04:02:06.400 | you'll say 1,500 milligrams of omega-3s,

04:02:10.000 | but that's not 1,500 milligrams of the EPA form.

04:02:13.220 | You look on the back of the label and you'll say,

04:02:15.140 | each serving contains 750 milligrams of EPA.

04:02:18.780 | You want to get above that one gram dosage per day

04:02:22.080 | and as high as three grams per day of the EPAs.

04:02:25.080 | The most cost-effective way to do that

04:02:26.640 | is going to be liquid form omegas,

04:02:28.900 | but that's a little bit inconvenient for many people

04:02:30.720 | and some people don't like the taste.

04:02:31.800 | That's why they rely on the capsule form omegas.

04:02:34.780 | And of course there are compounds

04:02:36.400 | that can impact fertility status,

04:02:38.400 | quality of eggs, quality of sperm,

04:02:40.640 | not by adjusting mitochondria or insulin sensitivity

04:02:44.180 | or creating a general milieu of support

04:02:47.080 | for the egg and the sperm production and function,

04:02:50.580 | such as the compounds that I just listed off do,

04:02:53.640 | but rather compounds that influence the hormones involved

04:02:58.120 | in the generation of sperm and the generation of the eggs

04:03:00.680 | involved in the ovulatory cycle

04:03:02.660 | and the spermatogenesis cycle that is.

04:03:04.840 | Now, these are going to come in different forms

04:03:07.440 | and I want to just emphasize that the supplements

04:03:10.640 | that do this, that adjust hormones in these ways

04:03:12.760 | that can be beneficial are distinct from hormone therapy

04:03:16.300 | or bioidentical hormones, okay?

04:03:18.200 | Distinct from hormone therapy or bioidentical hormones

04:03:20.860 | because as we discussed earlier,

04:03:22.840 | when you take a hormone like testosterone

04:03:25.120 | or even estrogen for that matter

04:03:26.460 | from an exogenous and outside source,

04:03:28.440 | you're going to disrupt the feedback pathways

04:03:31.220 | inside of your body

04:03:32.120 | and you're going to shut down your own endogenous production.

04:03:34.740 | The supplements I'm about to describe do not do that

04:03:38.480 | and yet can adjust levels of hormones in more subtle ways

04:03:41.680 | that could be beneficial for the process

04:03:44.440 | of maximizing fertility for males and for females.

04:03:47.920 | The first of which on this list that I'd like to discuss

04:03:50.280 | has been discussed in previous podcasts as well,

04:03:52.220 | which is a substance called tongkat ali.

04:03:54.600 | Tongkat ali also goes by other names,

04:03:57.400 | but when taken at 400 milligrams per day,

04:03:59.960 | sometimes separated into two dosages,

04:04:01.540 | but typically taken as once a day, early in the day,

04:04:04.880 | because it can be a little bit stimulating,

04:04:07.780 | although not anxiety provoking, I've never heard of that,

04:04:10.480 | can be a little bit stimulating,

04:04:11.780 | but 400 milligrams a day of tongkat ali

04:04:13.640 | has been shown to increase free testosterone

04:04:16.700 | by way of reducing something called sex hormone

04:04:18.580 | binding globulin.

04:04:19.420 | It's also been shown to increase luteinizing hormone,

04:04:21.960 | the net effect of which has been described as a subtle

04:04:25.920 | but significant increase in libido

04:04:28.800 | and some of the other parameters

04:04:30.360 | associated with increased androgens

04:04:32.360 | like free testosterone in males and females.

04:04:34.520 | So a number of people out there

04:04:35.560 | are taking tongkat ali in this way,

04:04:36.960 | 400 milligrams per day,

04:04:38.120 | restricted to the early part of the day with or without food.

04:04:42.520 | People always ask, do you need to cycle tongkat ali?

04:04:44.840 | I'm not aware of any need to cycle tongkat ali.

04:04:47.020 | In fact, it tends to work better,

04:04:48.680 | meaning the effects on libido

04:04:50.600 | and some other hormone profiles tend to increase over time.

04:04:53.880 | Again, tongkat ali is an option,

04:04:55.960 | as certainly none of these things are requirements.

04:04:58.440 | We're simply listing off options,

04:05:00.040 | but many people, both males and females

04:05:02.320 | seem to benefit from and like tongkat ali,

04:05:05.360 | even if they're not seeking to conceive.

04:05:07.640 | There's no reason to think that tongkat ali

04:05:09.280 | directly improves egg or sperm quality,

04:05:11.440 | except in males, the increase in androgen

04:05:13.680 | created by tongkat ali supplementation

04:05:15.880 | can indeed lead to improved spermatogenesis.

04:05:19.040 | So there's a growing amount of data

04:05:20.800 | in the research literature on tongkat ali.

04:05:22.680 | Many people find it beneficial.

04:05:24.360 | And so it's something that both men and women

04:05:26.260 | wishing to conceive and or optimize their fertility

04:05:28.720 | just as a general health parameter might want to explore.

04:05:31.920 | The other supplement that's been shown to improve

04:05:34.480 | both egg quality and sperm quality,

04:05:37.600 | and there I'm referring to a number of different parameters

04:05:41.040 | related to egg quality and sperm quality,

04:05:43.060 | as well as to increase libido fairly substantially

04:05:47.060 | is a substance called shilajit.

04:05:48.860 | Shilajit spelled S-H-I-L-A-G-I-T.

04:05:53.520 | Shilajit is actually a compound

04:05:56.880 | that's used in Ayurvedic medicine,

04:05:58.700 | but there's some really good research studies

04:06:00.700 | exploring the supplementation with shilajit

04:06:04.160 | at about 250 milligrams twice per day.

04:06:06.960 | And this has been looked at in males and in females.

04:06:09.640 | It does seem to significantly increase two hormones.

04:06:12.860 | One is testosterone

04:06:14.520 | and the other is follicle stimulating hormone.

04:06:17.480 | And for that reason, shilajit is often considered a tonic

04:06:21.080 | that people use both as an aphrodisiac to increase libido,

04:06:25.560 | as well as to increase fertility.

04:06:28.200 | Now, one note of caution,

04:06:30.000 | if you're a woman and you're considering taking shilajit

04:06:32.640 | in order to increase testosterone

04:06:34.080 | and follicle stimulating hormone,

04:06:35.360 | keep in mind that the ovulatory cycle

04:06:37.040 | is this very tightly regulated cycle

04:06:40.280 | in which you want low but elevated levels

04:06:43.880 | of follicle stimulating hormone early in the follicular phase

04:06:46.800 | then it peaks right before ovulation

04:06:48.760 | and then low levels of follicle stimulating hormone

04:06:51.420 | in the second half of your cycle.

04:06:52.720 | For that reason, using shilajit chronically

04:06:55.760 | around the entire course of your ovulatory cycle

04:06:58.960 | could be a little bit risky.

04:07:00.000 | And I'd recommend that you talk to your OB/GYN

04:07:03.260 | prior to doing that or if doing that at all.

04:07:06.800 | For males, it's a little bit less of an issue

04:07:08.620 | because as I mentioned earlier,

04:07:09.900 | sperm are constantly being generated

04:07:11.760 | and the presence of FSH

04:07:13.840 | is going to increase spermatogenesis.

04:07:16.320 | Now, Shilajit is not FSH itself.

04:07:19.320 | Shilajit stimulates the release of FSH

04:07:22.360 | and it stimulates the release of testosterone.

04:07:24.560 | So again, there's no reason to think

04:07:25.700 | that it would shut down your endogenous testosterone

04:07:27.880 | or FSH production.

04:07:29.920 | Although there are limited amount of data

04:07:31.940 | that really explore that in detail.

04:07:33.840 | Many people use Shilajit in order to increase

04:07:36.960 | their testosterone FSH, their libido

04:07:39.880 | and various aspects of sperm health.

04:07:43.800 | Again, the dosages of Shilajit

04:07:45.360 | are about 250 milligrams, two times per day.

04:07:47.580 | One issue with Shilajit is it often comes as a tar.

04:07:50.920 | It was a little hard to measure out the dosages.

04:07:52.960 | Yes, a tar, it's this kind of thick gummy substance

04:07:56.180 | that you're supposed to dissolve in water.

04:07:57.800 | And the recommendations are you take a little bead

04:07:59.640 | and dissolve it in water.

04:08:00.920 | It is available in capsule form where the ability

04:08:03.120 | to control the dosage is made a little bit easier.

04:08:06.880 | But of course, as with any supplement,

04:08:08.600 | I recommend starting with the lowest possible dosage.

04:08:11.040 | So you might want to start with a small,

04:08:12.920 | very small bead of Shilajit dissolved in water,

04:08:15.600 | taken once per day, and then increase the dosage as needed

04:08:18.820 | in order to obtain the effects that you want.

04:08:21.480 | Things like Shilajit start to bring us into the realm

04:08:24.040 | of what can only be described as a little bit unwieldy.

04:08:27.080 | Here we're saying you can't really control the dosage.

04:08:28.960 | Now you're talking about hormones

04:08:30.120 | that need to be tightly regulated,

04:08:31.520 | at least for females across the ovarian cycle.

04:08:33.840 | For males, yes, it has been shown

04:08:35.560 | to increase testosterone and FSH,

04:08:37.760 | improve sperm motility and sperm count pretty significantly.

04:08:40.840 | No reason to think that you couldn't do that chronically

04:08:43.940 | with Shilajit, and yet I do want to acknowledge

04:08:46.640 | that Shilajit as this black tar substance

04:08:49.480 | contains a lot of different things.

04:08:51.200 | In fact, it comes from a mineral pitch.

04:08:53.080 | What is that?

04:08:53.920 | It comes from literally the dirt and plants

04:08:56.160 | that have been compressed by rocks in the Himalayas.

04:08:58.480 | So it was pretty esoteric stuff

04:09:00.280 | when it really comes down to it.

04:09:01.400 | But the biological effects of Shilajit

04:09:03.760 | in both males and females seem to be related

04:09:06.000 | to the fact that it is highly enriched

04:09:07.760 | in something called fulvic acid.

04:09:09.440 | And fulvic acid is involved

04:09:10.740 | in a lot of different cellular processes,

04:09:12.800 | not the least of which, at least in this context,

04:09:15.140 | is the transport of molecules across cell membranes.

04:09:19.360 | And for hormones to have their effect,

04:09:20.880 | they need to cross cell membranes on the outside

04:09:22.720 | and the inside of the cell.

04:09:24.540 | So maybe that's how it's having its effect.

04:09:26.340 | Again, the mechanisms of exactly how Shilajit

04:09:29.380 | increases testosterone in FSH and thereby libido,

04:09:32.780 | egg quality, and sperm quality aren't entirely clear,

04:09:35.280 | but for the more adventurous of you out there

04:09:38.300 | who want to experiment with Shilajit,

04:09:39.540 | whether or not you're trying to conceive or not,

04:09:42.380 | it might be something to consider,

04:09:43.820 | but of course, do talk to your physician.

04:09:45.720 | The next compound that I want to discuss is zinc.

04:09:48.860 | And then this discussion mainly pertains to males,

04:09:51.260 | although I, of course, should point out

04:09:53.240 | that females should get the recommended daily allowance

04:09:56.700 | of zinc each day.

04:09:58.140 | Males, on the other hand, seem to benefit

04:10:00.560 | from having additionally high levels of zinc intake.

04:10:04.240 | Now, that can be obtained through foods.

04:10:05.840 | You know, you often hear,

04:10:06.680 | oh, you know, oysters are enriched in zinc,

04:10:08.520 | and oysters are an aphrodisiac, you know.

04:10:11.660 | I don't know who's doing the marketing for oysters,

04:10:13.300 | but it's really terrific.

04:10:14.940 | I think that seems to have persisted.

04:10:16.640 | And maybe it's true, oysters are enriched in zinc.

04:10:21.160 | What does zinc do for fertility?

04:10:23.700 | Well, in males, we know,

04:10:25.140 | based on a really nice set of studies,

04:10:27.600 | that zinc dosages that are pretty high

04:10:29.900 | of about 120 milligrams taken twice per day,

04:10:33.500 | and that's quite a lot, with meals,

04:10:35.920 | can significantly increase testosterone

04:10:38.580 | and dihydrotestosterone.

04:10:40.460 | And this probably shouldn't come as a surprise to us.

04:10:42.700 | It turns out that zinc is highly enriched in human testes

04:10:46.520 | and in the testes of other animals,

04:10:48.060 | including fish and other mammals.

04:10:49.820 | It was actually in 1921 that it was observed in fish

04:10:54.720 | that zinc levels skyrocket in the testes of fish

04:10:58.560 | during their breeding season.

04:10:59.880 | So zinc is correlated with increases in breeding,

04:11:03.080 | but you never know which direction

04:11:04.340 | that correlation is running.

04:11:05.860 | Turns out that zinc in both animals,

04:11:09.460 | including fish, other mammals, and in humans,

04:11:12.380 | strongly impacts the enzymatic functions in the testes,

04:11:15.500 | including the function of androgen binding protein.

04:11:18.820 | So it seems that high levels of zinc

04:11:20.340 | can increase spermatogenesis

04:11:21.920 | and testosterone levels very significantly.

04:11:25.140 | This was explored in a really nice study

04:11:26.820 | that I'll provide a reference to.

04:11:27.840 | It's an older study, but I really like it.

04:11:29.520 | It's called "Effect of Zinc Administration

04:11:31.160 | on Plasma Testosterone, Dihydrotestosterone, and Sperm Count."

04:11:34.740 | This is but just one study among many now.

04:11:38.140 | This dates back to 1981,

04:11:39.960 | but there've been studies subsequently

04:11:42.220 | that point to the fact that supplementation with zinc

04:11:44.140 | at those high levels can really be helpful

04:11:46.940 | in terms of increasing sperm count, testosterone,

04:11:50.640 | and even testicular size of all things.

04:11:53.060 | So one important point about taking zinc,

04:11:56.120 | this 120 milligrams of zinc two times daily

04:11:59.220 | definitely needs to be done with meals.

04:12:00.780 | If you've ever taken zinc on an empty stomach,

04:12:02.860 | even if you just take 15 or 30 milligrams of zinc,

04:12:05.540 | you can feel very nauseous, not well for a few hours.

04:12:09.120 | So make sure that you're taking zinc with full meals.

04:12:11.820 | So this would mean that you're taking

04:12:14.020 | in at least two full meals per day.

04:12:16.860 | I should also mention that zinc supplementation

04:12:19.700 | did not appear to impact gonadotropin-releasing hormone

04:12:23.160 | or prolactin, so it seems to be a fairly targeted effect

04:12:26.340 | on the testosterone and related pathways in males.

04:12:28.840 | As far as I know, there have not been systematic

04:12:31.280 | explorations of the effects of high levels

04:12:33.780 | of zinc administration on females.

04:12:35.580 | I would hope that those studies would soon be done.

04:12:37.580 | But meanwhile, if you're a male

04:12:39.040 | and you're interested in improving sperm quality

04:12:40.900 | and your testosterone levels overall for whatever reason,

04:12:44.020 | zinc likely is a good candidate.

04:12:46.060 | And that pretty much summarizes the compounds

04:12:48.260 | that men and women should take

04:12:49.900 | in order to maximize egg quality,

04:12:51.740 | sperm quality, and fertility.

04:12:53.500 | And then of course, we start to enter the landscape

04:12:55.380 | of other things that men and women can take

04:12:57.460 | in order to improve fertility.

04:12:58.740 | And those other things generally are prescription drugs.

04:13:02.400 | And so I just want to mention what a few of those are,

04:13:05.140 | but of course, these are things that you would absolutely

04:13:07.140 | have to obtain prescriptions for from your MD.

04:13:11.140 | And your MD would, without question,

04:13:14.080 | would want to take blood tests prior to prescribing

04:13:16.480 | these things.

04:13:17.320 | So for instance, if men have been taking

04:13:20.000 | exogenous testosterone through the use of anabolic steroids,

04:13:23.180 | like performance enhancing drugs,

04:13:24.540 | or even testosterone replacement therapy,

04:13:26.560 | their endogenous testosterone levels

04:13:28.160 | are going to be very low,

04:13:29.200 | and their sperm counts are going to be very low,

04:13:31.220 | unless for instance, they are prescribed

04:13:32.980 | in taking something like HCG, human chorionic gonadotropin,

04:13:37.020 | which mimics LH and would stimulate the testes

04:13:39.760 | to produce testosterone and through some indirect pathways,

04:13:42.760 | rescue spermatogenesis, although not to the same degree

04:13:45.900 | as if people are not taking exogenous sources

04:13:49.060 | of testosterone.

04:13:50.360 | Some men, even if they've never touched TRT

04:13:53.420 | or exogenous testosterone of any kind,

04:13:56.200 | will be prescribed to take HCG because of its ability

04:13:59.560 | to stimulate the testes to produce more testosterone

04:14:02.060 | and sperm, so they're just taking HCG alone.

04:14:04.660 | Other men will take, or will be prescribed rather, FSH

04:14:07.980 | in order to stimulate spermatogenesis, or HCG and FSH,

04:14:11.820 | or clomiphene, which can regulate all sorts of things

04:14:14.900 | in the both testosterone and estrogen-related pathways

04:14:17.680 | at the level of brain and pituitary and gonad testes.

04:14:22.680 | Likewise for women, if they're low in FSH,

04:14:25.780 | they might be prescribed FSH.

04:14:27.860 | If they are low in luteinizing hormone,

04:14:30.620 | they might be prescribed HCG.

04:14:32.100 | If they're low in testosterone,

04:14:33.200 | they might even be prescribed testosterone,

04:14:34.820 | and if their testosterone is too high

04:14:36.380 | and they're dealing with PCOS,

04:14:37.700 | they might be prescribed anti-androgens and androgen blockers

04:14:41.900 | and on and on and on.

04:14:43.280 | There are so many different hormones

04:14:45.100 | that can impact the different aspects of the ovulatory

04:14:47.580 | and the spermatogenesis cycle that the OB-GYNs

04:14:51.940 | and the urologists focus on male fertility nowadays

04:14:54.660 | really have an excellent handle on which levers

04:14:57.340 | and buttons and threads to pull and push and so forth

04:15:00.020 | in order to set in motion a proper ovulatory cycle

04:15:03.460 | and a proper spermatogenesis cycle.

04:15:06.060 | Everything we talked about up until now

04:15:08.160 | and in the early phase of this episode,

04:15:09.800 | especially about how the brain commands the pituitary

04:15:13.620 | and the pituitary commands the gonads,

04:15:15.580 | and then the gonads, the ovary or the testes,

04:15:17.760 | send feedback signals to the pituitary

04:15:19.940 | to then influence the pituitary.

04:15:21.600 | All of that incredible orchestra, that dance,

04:15:24.520 | is so tightly regulated in a way that really provides

04:15:27.940 | the OB-GYNs and the fertility docs

04:15:29.940 | concerned with male fertility exceptional tools

04:15:33.020 | to, for instance, figure out if a man

04:15:35.060 | is not producing any sperm, but his testosterone levels

04:15:38.380 | are well within normal range.

04:15:40.220 | Well, then there's some very clear sets of explorations

04:15:43.100 | and potential treatments, some of which are mechanical,

04:15:45.060 | making sure the epididymis and vas deferens are clear,

04:15:47.660 | allowing the sperm to enter the ejaculate

04:15:49.780 | and the ejaculate to enter the urethra

04:15:51.420 | and obviously to enter the female,

04:15:54.160 | as well as for a woman who's not ovulating

04:15:57.980 | to adjust her levels of FSH

04:16:00.020 | or maybe even to apply acupuncture in conjunction

04:16:03.300 | with supplementation and various prescription

04:16:05.900 | hormone therapies to adjust fertility and ovulation

04:16:09.300 | and the probability of successful pregnancy.

04:16:11.860 | So there's a vast landscape of prescription drugs

04:16:14.520 | and surgical interventions of varying degrees

04:16:17.380 | of invasiveness, and some are, for instance,

04:16:21.500 | outpatient procedures, some require general anesthesia,

04:16:24.780 | et cetera, in order to maximize male and female fertility.

04:16:28.480 | What I've tried to do today is to provide you

04:16:31.900 | with a deep dive understanding

04:16:34.980 | of the ovulatory and menstrual cycle.

04:16:36.740 | We talked about the brain, the pituitary,

04:16:38.180 | the ovary, the fallopian tubes,

04:16:39.540 | and in fact, the whole female reproductive axis

04:16:41.860 | as it relates to fertility and reproduction.

04:16:46.080 | I also describe the male reproductive axis

04:16:49.900 | as it relates to the brain, the pituitary,

04:16:51.780 | the gonad, the testes, and the various ducts,

04:16:54.540 | the pathways out of the testes that allow the sperm

04:16:58.240 | to be enriched within the semen and then the semen

04:17:01.600 | and the ejaculate to exit through the urethra.

04:17:04.200 | I did all that as a way to frame the various tools

04:17:06.800 | and interventions that can really assist

04:17:09.640 | in increasing fertility, egg quality, and sperm quality.

04:17:13.380 | So when we discuss mitochondria in the context

04:17:15.540 | of the development of an egg or the development of sperm

04:17:18.580 | and its ability to swim quickly forward,

04:17:21.860 | now it should make sense as to why a given intervention,

04:17:24.520 | whether or not it's L-carnitine or whether or not

04:17:26.780 | it's exercise or whether or not it's getting enough sleep

04:17:28.820 | and limiting stress, why all that should matter,

04:17:30.860 | and why, in fact, mechanistically,

04:17:32.940 | those interventions can work.

04:17:34.860 | Because indeed there are many interventions

04:17:36.600 | that we can all do and use to support our fertility.

04:17:40.300 | And again, as a more general theme today,

04:17:42.620 | I really wanted to A, teach you

04:17:44.460 | about the human reproductive axis.

04:17:46.620 | I do find the biology of the ovulatory and menstrual cycle

04:17:50.180 | and spermatogenesis to be absolutely fascinating to me.

04:17:53.380 | And again, if you're somebody who's interested in conceiving

04:17:55.820 | or if you've already conceived children,

04:17:57.680 | and even if you don't want more children,

04:17:59.780 | this is really the aspect of our biology

04:18:02.200 | that allowed us to be here.

04:18:04.420 | It's the aspect of our biology that determined

04:18:07.060 | whether or not we are male or female.

04:18:09.060 | It's the aspect of our biology that determines so, so much,

04:18:11.700 | and yet I think that most of us

04:18:13.620 | generally are not taught this in school,

04:18:15.720 | or at least not at the depth that we discussed it today.

04:18:18.380 | So hopefully that information was in and of itself

04:18:21.060 | interesting and perhaps useful as well.

04:18:23.260 | And I do think that even if people are not wishing

04:18:25.440 | to conceive more children,

04:18:27.060 | that the information related to fertility

04:18:28.980 | and optimizing egg and sperm health is of value

04:18:32.020 | in the sense that optimizing egg and sperm health

04:18:35.260 | can be used as a proxy for optimizing

04:18:37.940 | our body and brain health generally.

04:18:39.740 | In other words, and here I'm admittedly taking words

04:18:43.820 | out of the mouths of the various wonderful doctors,

04:18:46.820 | the OBGYNs and urologists that helped inform me

04:18:50.300 | in anticipation of this episode,

04:18:52.140 | what is good for the woman is good for the egg

04:18:55.000 | and for fertility and for her pregnancy.

04:18:57.020 | And what's good for the man is good for the quality

04:19:01.460 | and production of sperm and for fertility and pregnancy.

04:19:05.680 | Put differently, whether or not we are male or female,

04:19:08.900 | the things that we can do to optimize our fertility

04:19:11.700 | are the exact same things that we should all be doing

04:19:14.700 | to optimize our vitality and our longevity.

04:19:17.500 | And I realized today's episode was so much the deep dive

04:19:20.540 | and fairly broad as well,

04:19:22.300 | that it ended up being fairly long and extensive.

04:19:25.220 | And yet we still have not touched

04:19:27.580 | on any of the important themes

04:19:28.980 | that I know a number of people want to know about.

04:19:30.980 | So for instance, menopause, andropause, PCOS,

04:19:35.980 | and other themes related to hormones

04:19:37.700 | and reproductive function in biology.

04:19:39.340 | And I promise that we will have episodes,

04:19:41.380 | both solo episodes and episodes with expert guests

04:19:44.840 | in the future to cover all of those topics in detail.

04:19:47.380 | Meanwhile, the information discussed in today's episode

04:19:50.180 | should serve as a basic foundation

04:19:52.460 | for those discussions going forward.

04:19:54.020 | And hopefully we're of interest to you in their own right.

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04:21:52.060 | Thank you once again for joining me for today's discussion,

04:21:54.560 | all about the biology surrounding this incredible thing

04:21:57.380 | that we call fertility,

04:21:58.360 | including the ovulatory cycle, spermatogenesis,

04:22:01.280 | fertilization itself,

04:22:02.680 | and all the events leading up to pregnancy.

04:22:05.540 | And last, but certainly not least,

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How to Optimize Fertility in Males & Females | Huberman Lab Podcast

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