How to Optimize Fertility in Males & Females

0:00ANDREW HUBERMAN: Welcome to the Huberman Lab podcast,

0:02where we discuss science and science-based tools

0:04for everyday life.

0:05[MUSIC PLAYING]

0:09I'm Andrew Huberman, and I'm a professor

0:10of neurobiology and ophthalmology

0:12at Stanford School of Medicine.

0:14Today we are discussing fertility.

0:16We will discuss male fertility and female fertility.

0:19And I should mention that today's discussion is not just

0:23for people who are seeking to conceive children

0:25or who want to know how their children were conceived,

0:27but it's really for everybody.

0:29And I say that because it is the story of all of us.

0:32All of us are here because a specialized set

0:35of cells, called germ cells--

0:38that is the sperm and the egg.

0:39And I'll make it very clear why they're called

0:41germ cells a little bit later.

0:43It has nothing to do with infection.

0:44But it's because a sperm cell and an egg cell arrived at one

0:50another, either in vivo-- inside of our mother-- or in vitro--

0:54so-called in vitro fertilization-- and then

0:55we're implanted into our mother and became us.

0:59And so understanding the process of how

1:02the egg cell and the sperm cell came to be

1:06is really the key to understanding

1:07how that fertilization process came to be.

1:10Now, I know everyone's thinking, I

1:11know how fertilization occurs.

1:13It occurs through sexual intercourse and so on.

1:15And we'll talk a little bit about that.

1:17But I promise you that if you understand

1:19the menstrual cycle--

1:21and the menstrual cycle in today's conversation

1:23can best be thought of as a biological cycle that

1:26occurs in females that allows the potential for fertilization

1:30by the sperm, because that's really what it is,

1:33and it's a beautifully orchestrated process

1:35that I'll describe to you.

1:36And I should say, all people, males and females, should

1:39really understand how the menstrual cycle works,

1:41how it impacts fertilization, but also

1:45how it impacts the brain and body, behavior, psychology,

1:48et cetera.

1:49And we'll also talk about spermatogenesis,

1:52how sperm cells come to be and how they arrive--

1:56that is, how they swim to the egg--

1:58and the incredible interplay between the biology

2:01of the sperm and the biology of the egg

2:05leads to this incredible thing that we call embryogenesis

2:08and the birth of the child and, of course,

2:11the development of that child into an infant, a toddler,

2:16an adolescent, a teen, and an adult.

2:19Today's discussion, again, is not just

2:21for those of you that are seeking to have children.

2:24And I say that because when you look at the data,

2:28you look at the literature on longevity and vitality,

2:31two themes in biology that oftentimes people lump together

2:35but aren't always the same-- for instance,

2:37there are a lot of things that we

2:38can do to increase our vitality that actually

2:41can harm our longevity.

2:43But there are a subset of biological rules and mechanisms

2:47that, when aligned, allow us to maximize both

2:51our vitality and our longevity.

2:54And I think it's fair to say that all of those mechanisms

2:57and tools are housed in the discussion

2:59around maximizing fertility.

3:01And that's true whether or not you're male or female.

3:04In other words, if you want children

3:06or if you don't, if you already have children

3:08or if you don't, understanding how fertility and fertilization

3:12occurs in the brain and body will

3:15allow you to maximize your vitality and longevity.

3:18And of course, today's discussion

3:20will provide an understanding of the biology

3:22and many actionable tools that will also help you conceive

3:25children, if that's your wish.

3:26So of course, as is characteristic of this podcast,

3:30we will discuss science-based tools,

3:32including behavioral tools, both the dos and the don'ts, and we

3:35will discuss nutrition-based tools and supplementation-based

3:39tools and some other practices, including things like

3:42acupuncture, which have quite good data to support them

3:46in terms of improving fertility.

3:47And we will discuss why those certain practices can work.

3:51And we will discuss prescription drugs

3:53that your doctor can prescribe to you if, for instance, you

3:57have a deficit at the level of hormone production

4:00or neurotransmitter production at the level of the brain

4:02or the pituitary gland--

4:03I'll explain what all of those things are soon--

4:05or the gonads, the ovary and the testes in females and males

4:10respectively.

4:12Again, by the end of today's episode,

4:13you will have a lot of knowledge and actionable tools related

4:16to maximizing fertility, and you will

4:18have a lot of knowledge and actionable tools related

4:21to maximizing vitality and longevity.

4:24Before we begin, I'd like to emphasize

4:26that this podcast is separate from my teaching and research

4:28roles at Stanford.

4:30It is, however, part of my desire and effort

4:32to bring zero cost to consumer information

4:34about science and science-related tools

4:36to the general public.

4:37In keeping with that theme, I'd like

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8:20Let's talk about fertility.

8:21And in doing so, let's take a step back from this word

8:24"fertility" and ask, what is fertility and fertilization

8:27really all about?

8:28Well, the obvious answer is that it's about producing offspring.

8:31But more importantly, it's about producing offspring

8:34that contain the genetic components of both parents

8:38and indeed contain half of the genes from one parent

8:41and half of the genes from another parent.

8:43Now, there are two general types of cells in the body.

8:46The most common types of cells in the body

8:48are called somatic cells.

8:49So these would be all the cells in your body

8:51except the egg in females and the sperm in males.

8:54The egg in females and the sperm males

8:57are part of what's called the germline.

8:59And again, it has nothing to do with infection.

9:00It's just that the cells of the germline have genes that cannot

9:05be modified by the behavior of the individual that houses

9:09those genes.

9:10What do I mean by that?

9:11Well, if I were to tell you that by exercising you can improve

9:14mitochondrial function, you can change hormones

9:18by reducing stress, you can reduce cortisol

9:20by hitting puberty, for instance, you

9:24will have the secretion of hormones that then change

9:26gene expression in other cells, leading

9:28to the development of body hair, facial hair,

9:31deepening the voice, breast growth, et cetera,

9:33you'd say, OK, great.

9:34Yeah, that all makes perfect sense.

9:36But that's all occurring in the so-called somatic cells.

9:39The germ cells or the germline cells--

9:41that is, the egg and the sperm--

9:43are a very unique and protected set

9:46of cells that are generated in a particular way

9:49and whose genetic components are not modifiable by experience.

9:55And when you take a step back and you think about it,

9:57you say, oh, that's right.

9:58There's no reason to think that exercising

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

10:05And you say, of course not.

10:06Well, why is that?

10:07Well, that's because there is a barrier

10:09between the genes of the germline cells and behaviors.

10:14They cannot be modified by behaviors and the various

10:16things that you do in your lifetime.

10:18Now, I suppose there's an exception

10:19in the negative direction.

10:21And what I'm referring to here is if you were to, say,

10:24be exposed to a chemical that could mutate the DNA

10:27of your egg or sperm or if you were to fertilize an embryo

10:32in a certain way or at a certain stage of life that it got

10:35an extra chromosome, for instance--

10:36we'll talk about this a little bit later--

10:38well, then, of course, you could end up

10:39with offspring that have modified

10:42DNA that don't faithfully represent half of the genes

10:45from mom and half of the genes from dad.

10:48But that's not the same as specific behaviors

10:51modifying the genes of those cells--

10:53the sperm and the egg cells--

10:55in a way that improves the offspring.

10:58So the key first thing to understand today

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

11:03is the vast majority of cells in your body,

11:04and the so-called germline cells, which

11:05are the egg and the sperm.

11:06The egg and the sperm are these highly protected populations

11:09of cells that, in females, actually come

11:13to be during embryogenesis.

11:16So for all females out there, you

11:18generate what today I'm going to refer to as a vault of cells.

11:22You have a vault of eggs that are your germline.

11:26Those eggs all contain all the chromosomes of your DNA.

11:32So it's going to be-- as most of you

11:33know, there are 23 chromosomes, and chromosomes exist in pairs.

11:37So the way to think about this is each pair is one strand,

11:40and you have 22 so-called autosomes,

11:42and then you have one sex chromosome.

11:44The sex chromosome will be either X or Y. So in a female,

11:47they have two X chromosomes.

11:48So in each one of the eggs that a woman has

11:51and that she's had since she was an embryo

11:53and that's contained in this vault,

11:55those eggs are, of course, going to be very immature at birth.

11:59She hasn't undergone puberty yet.

12:00And certainly, as an embryo, she hasn't undergone puberty.

12:03And those cells are going to contain

12:0523 pairs of chromosomes.

12:08This is very important--

12:0923 pairs of chromosomes.

12:12The chromosomes are essentially the wrapped-up DNA

12:16that contains all the genetic information

12:18to create any cell type in the body

12:20and actually to create an entirely new individual.

12:23Now, there are 23 pairs of chromosomes, 22 of which

12:26are called autosomes.

12:28If that doesn't make sense to you,

12:29just remember, autosome, OK, there's 22 of them.

12:32And then there's one so-called sex chromosome.

12:34The sex chromosomes are either X or Y. But this is a female,

12:37so she's going to have 23 pairs of chromosomes,

12:40and she's going to have two X chromosomes for the sex

12:44chromosomes.

12:45If this is already confusing to you, don't worry,

12:47I'll make it very clear how this all relates to fertility

12:50and how it relates to chromosomal segregation

12:53and a bunch of things that I think maybe you've heard of

12:55and that perhaps were opaque to you.

12:57But I promise to make them clear.

12:59But just understand that, within each of those eggs,

13:01they have 23 pairs of chromosomes.

13:03And for those of you that like nomenclature,

13:06I'll tell you that those cells are considered diploid.

13:09They're called the diploid, and that

13:11means that they have 23 pairs of chromosomes,

13:14as distinguished from cells that are

13:16haploid where there's only one set of those 23 chromosomes.

13:22So instead of 23 pairs, there's only 23 chromosomes.

13:25We'll come back to haploid cells a little bit later.

13:28So when a female is born, she has all these eggs

13:32in the reserve, in this vault, that she'll

13:34have for her entire life.

13:35She's not going to make any more.

13:37But they are very, very immature.

13:39So when a woman is in embryogenesis,

13:41she develops these very immature eggs.

13:44Today we're also going to talk about follicles,

13:46and we will be careful to distinguish follicles

13:50from eggs.

13:50They're often talked about interchangeably, online

13:53and elsewhere and even by fertility docs and OB/GYNs.

13:56But right now we're just talking about the egg cells, the eggs

14:00themselves, which are cells.

14:02Now, the goal of fertilization is

14:05to bring that egg cell into close enough proximity

14:08that it can be fertilized by a single sperm cell.

14:12And that sperm cell will bring 23 chromosomes, as well,

14:16that include--

14:17just as in the female egg, it'll have 22 autosomes and one sex

14:22chromosome.

14:23And in the male, that sex chromosome

14:24can either be an X chromosome, which then would give rise

14:28to female offspring, or a Y chromosome, which would

14:32give rise to male offspring.

14:33And today we're not talking about sexual differentiation.

14:36That's a topic of a previous and yet another future episode.

14:39But just to give you a sense of how X chromosomes and Y

14:43chromosomes can actually accomplish

14:45that sexual differentiation, both of body and brain.

14:49I'll just mention in two sentences that, for instance,

14:52if there's a Y chromosome as opposed to an X chromosome,

14:55that Y chromosome contains genes that suppress, for instance,

14:59the development of female genitalia

15:01and thereby give rise to male genitalia.

15:05So rather than the formation of a clitoris,

15:07it's the formation of a penis.

15:08And rather than the formation of ovaries,

15:10the formation of a testes.

15:12So that's more directed towards sexual differentiation.

15:14We're not going to get into that right now.

15:16We'll get into that in a future episode.

15:18But even if you're only tracking about 10%

15:21of what I'm saying right now, I promise you're doing great.

15:24If you're tracking more than 10%, well,

15:25then you're doing terrifically well,

15:27because the essence of fertility and fertilization is to bring

15:30together that haploid cell that is the sperm that only has 23

15:37chromosomes-- but not pairs of chromosomes

15:40because that's the DNA from dad--

15:42together with the egg, which, as I told you already,

15:45has 23 pairs of chromosomes.

15:47So part of the fertilization process

15:50has to be to get rid of one half of those 23 pairs

15:54in the female.

15:55You got to get rid of it, and you

15:58have to get the egg and the sperm in proximity

16:00so that the egg can potentially be fertilized

16:03by the sperm bringing the DNA, the 23

16:07single strands of chromosomes from dad,

16:11into a cell that has 23 single strands from mom.

16:16So I realize I'm probably being a little bit repetitive here,

16:18but I want everyone to understand this

16:21because it really frames up fertility and reproduction

16:24in the proper way.

16:26We've got a cell from mom, the egg, which

16:29has 23 pairs of chromosomes.

16:32We need to get rid of one set of those pairs

16:35so that there's only 23 chromosomes.

16:37We need to get rid of half of those chromosomes.

16:40And then we need to bring that cell together physically

16:43with the sperm cell that contains the 23

16:48chromosomal strands from dad.

16:50And we need to bring those together so that you

16:52get 23 chromosomal pairs from dad

16:54and 23 chromosomal pairs from mom.

16:58And in doing so, you create a cell, which

17:02then becomes multiple cells.

17:03That's going to be the developing embryo that

17:05has half the genes from mom and half the genes from dad.

17:08So I hope that's clear.

17:09That is the biological logic, which I realize

17:12is a bit of a tongue twister.

17:13But forgive me.

17:14It is the most accurate way to describe this process.

17:17We're trying to bring together the 23 single strands

17:21of chromosomes from dad and the 23

17:23single strands of chromosomes from mom into the same cell.

17:27Now, that requires a literal physical contact

17:31and pairing of the two cells.

17:33But as I mentioned before, all these eggs in mom

17:37are sitting in a vault, and they're very, very immature.

17:40So the ovulatory cycle and the menstrual cycle

17:44are really about first eliminating

17:47half of the chromosomal pairs in that 23 sets of chromosomes

17:51and not getting rid of, for instance, half--

17:54just going 1 to 11 or 12 to 23.

17:59That's not the goal.

18:00The goal is to have chromosomes 1, 2, 3, 4, 5,

18:026, all the way up to 23, but only to have

18:05half of the chromosomes there and to bring that cell together

18:09with the sperm cell, physically, then allow

18:11them to fuse and allow the chromosomes from dad

18:14and the chromosomes from mom to fuse within a single cell

18:18and duplicate into cells that contain half of the chromosomes

18:22from dad and half of the chromosomes from mom.

18:24That's what the ovulatory and menstrual cycle

18:26are really all about.

18:27So when thinking about it that way,

18:29I'd like to just initiate the discussion by focusing first

18:32on the female component, or the egg component,

18:35of fertility and fertilization.

18:39As I mentioned before, a female has all the eggs,

18:43albeit very immature eggs, that she's going to have at the time

18:46that she's born.

18:48Now, puberty will happen at some point

18:52and will allow the ovulatory and the menstrual cycle

18:55to commence.

18:57Now, one question that you perhaps are asking

18:58is, what controls the onset of puberty?

19:01And there are a number of different results,

19:04each of which could be an entire episode

19:05of a podcast on its own.

19:07But I'll just highlight a few things

19:08that we know about the onset of menses or menstruation,

19:12or it's sometimes also called a menarche.

19:14One thing that you'll notice about today's discussion

19:17is that if you were to take any number of your notes

19:19online and put them into a search function

19:22that you would see a lot of different language used

19:24for the same thing.

19:25So for instance, some people will

19:26talk about the egg and the follicle as the same thing,

19:28even though they are not.

19:29I'll explain the difference soon.

19:31Some people will talk about menses or menstruation

19:33or menarche as the exact same thing.

19:35And in fact, they are not the exact same thing,

19:37but oftentimes these words are used interchangeably.

19:40I'll do my best today to not overload you with nomenclature

19:43but rather to use the most commonly used terms

19:46for the different aspects of fertility and fertilization.

19:49But when it comes to the onset of puberty,

19:52first of all, most of you have probably

19:55heard that the onset of puberty is

19:58happening much earlier in females now

20:00than it was some years ago.

20:02And in fact, that is the case.

20:04And I'll talk about some statistics related

20:06to this which are pretty striking

20:08but don't necessarily point to anything detrimental.

20:11It doesn't necessarily mean that something bad is happening.

20:14What do we know for sure?

20:15Well, we know that there are a number

20:17of signals that come both through the brain

20:20and through the body--

20:22and more likely both-- in order to control the onset of puberty

20:25in females.

20:26A couple of examples-- the first is a mechanistic one.

20:29We know, for instance, that the entire process

20:33of the ovulatory menstrual cycle is initiated from the brain.

20:36We're going to get into this in a lot

20:37more detail in a few minutes.

20:39But there's a certain number of hormones and neurotransmitters

20:42that are communicated from the brain,

20:45a structure called the hypothalamus,

20:47which roughly sits above the roof of your mouth,

20:49and that communicates with a gland, an endocrine

20:53or hormone-releasing gland called the pituitary gland.

20:56The pituitary gland looks like a stalk that essentially

21:01extends out of the brain.

21:03It's also located not far from the roof of your mouth.

21:06And that has two sort of small marble

21:08or grape-sized protrusions, the anterior pituitary

21:13and the posterior pituitary.

21:15And they release different hormones into the bloodstream.

21:18Puberty is in part controlled by the fact

21:21that, up until puberty, there are

21:24neurons in the hypothalamus that release

21:26a neurotransmitter called GABA, which is inhibitory,

21:28and that prevents the neurons in the hypothalamus

21:32from releasing a very important hormone called

21:36gonadotropin-releasing hormone, or GnRH.

21:39So the first thing I'd really like everyone

21:41to know and commit to memory today is very easy--

21:43GnRH stands for gonadotropin-releasing hormone.

21:46This comes from the brain and will

21:48communicate to the pituitary to release certain hormones.

21:52Prior to puberty, in both males and females,

21:56there are neurons in the brain that are actively suppressing

21:59the neurons that release GnRH.

22:01It's like no puberty, no puberty, no puberty.

22:03You can't have puberty.

22:04You can't have puberty.

22:05And in fact, those cells are releasing this neurotransmitter

22:09called GABA because it's inhibitory.

22:11It prevents the firing of those neurons.

22:13So puberty is actively suppressed up

22:15until a certain point.

22:17It's also actively suppressed, at least in some species and we

22:20think at least partially in humans, by the tonic release--

22:24that means the ongoing release, around the clock--

22:27of a hormone called melatonin.

22:29Later in life-- in fact, after puberty--

22:32melatonin will be secreted only in the dark phase of each night

22:37and around the time that one goes to sleep.

22:39But in children and in particular

22:41in children prior to puberty, melatonin

22:44is released more or less constantly.

22:46Now, melatonin isn't the only source

22:48of suppression of puberty.

22:49It's also these neural mechanisms involving GABA.

22:53But it is certainly a great candidate for one

22:56of the reasons why puberty doesn't generally

22:58tend to happen at, say, age four age five.

23:00That would be very unusual.

23:03Another component of suppression of puberty

23:07is that typically in children they have relatively low body

23:11fat stores.

23:11Why is this important?

23:12Well, we know that one of the things that can trigger

23:15the onset of puberty-- in particular in females--

23:18is that when enough body fat accumulates,

23:22that body fat releases a hormone called leptin,

23:25and that hormone leptin travels in the bloodstream,

23:28across the blood-brain barrier, and goes to the hypothalamus

23:31and can trigger the onset of puberty

23:32by activating the neurons that release

23:35gonadotropin-releasing hormone.

23:37So many people believe that one of the reasons that puberty

23:41is happening earlier and earlier in females

23:43is because of the accumulation of more body fat at younger

23:48ages than was observed 30 or 40 and certainly 100 years ago.

23:52Now, I can already imagine a number of people are thinking,

23:55oh, this must relate to the obesity crisis.

23:58And indeed, there is a crisis of obesity.

23:59Obesity is something that is causing all sorts of problems

24:04with people's health at various levels, brain and body,

24:07and that is far more frequent today

24:09than it was even 20 years ago.

24:11So it is indeed a crisis because it

24:13has enormous detrimental effects for so many aspects

24:16of brain and body health and longevity.

24:20But this whole process of thinking about body fat

24:22signaling leptin to the hypothalamus and the onset

24:24of puberty doesn't necessarily have

24:27to do with the obesity crisis.

24:28It might relate, but it could also relate to, for instance,

24:31improved nutrition, which is allowing body

24:33fat stores to accumulate maybe not to the level of obesity

24:36but to accumulate earlier and at younger ages

24:40in females, which is then causing

24:42earlier puberty in females.

24:44To just highlight how that might be possible,

24:46I want to review some data that talk about the onset of menses,

24:50menstruation-- that is, puberty--

24:52in females according to country and according

24:55to age over the last 100 or more years.

24:59So what are the general trends in terms

25:00of the onset of puberty in females?

25:02Well, that's an easy one to answer.

25:04Over the last 100 years or so, the onset of puberty

25:09has been occurring much earlier with each passing decade.

25:13It's really an incredible set of statistics.

25:17I will provide a link to these data

25:18since I know a number of you are listening and not

25:20just watching on YouTube.

25:22This is from a study in which the onset of puberty

25:25has been analyzed from as early as the 1850s--

25:29in certain countries, there are data on that--

25:31out to the 1970s and in other countries

25:33starting at about 1900, extending out to about 1990.

25:37These are ongoing collections of data.

25:39But just to give you a sense of how the data are falling out

25:42in a couple of different countries,

25:44just to give you a flavor--

25:46but for those of you listening and for those of you watching,

25:50the essence of all of these findings

25:52is that puberty is happening much, much earlier

25:54with each passing decade.

25:56So for instance, in the United States, around 1900 or 1903,

26:02the average age of menarche, the onset of puberty, in females

26:06was about 14 years old, whereas in 1990, the average age is 11.

26:11So that's a pretty significant, we can say,

26:15acceleration of the onset of puberty.

26:17Now, of course, these are averages.

26:19So there will be exceptions.

26:20There's a distribution of data.

26:22Today, still, there will be young females who

26:25will undergo puberty at age 11 or 10 or maybe even 9

26:28and others who will undergo puberty at age 13, 14, maybe

26:31even 16 or 17.

26:33However, if we look at, for instance,

26:36the data from Norway, which dates back quite far-- they

26:38have excellent record-keeping-- to 1850, what we see

26:42is that the average age of the onset of female puberty in 1850

26:46in Norway was 17 years old, whereas in 1970, it's

26:5213 years old.

26:53So this is a dramatic acceleration

26:56of the onset of puberty.

26:57And you see a similar trend in other countries, as well.

26:59So if we were to look, for instance, in the UK,

27:03they have a smaller data set, meaning it only

27:05extends back to about 1940.

27:07But the average age of the onset of puberty in the UK in 1940

27:11was 13 and 1/2 years old.

27:13Again, this is just for females.

27:15And in 1970, it was closer to 13,

27:18with a trend towards declining even further.

27:20Unfortunately, they didn't continue

27:22to collect data out to 2022.

27:24And as a final point, if we were to look at, for instance,

27:27in Germany and Finland, the average onset

27:31of puberty in 1870 was 16 and 1/2 years old.

27:34By 1940, it was down to 13 and 1/2 years old.

27:38So all of these data have borne out over and over again,

27:42regardless of location in the world, which is important,

27:44because when you start to think about the obesity crisis,

27:46you can say, well, that's mainly in developed countries,

27:48believe it or not-- or perhaps not surprisingly.

27:51And maybe it has to do with the obesity crisis.

27:53And yet I don't think we can conclude that at all.

27:56Something is happening, however.

27:58It could be increased body fat stores

28:01due to overeating and obesity.

28:02However, it could also be-- unrelated to obesity,

28:05it could be, for instance, improved

28:07nutrition and the availability of quality nutrition, which

28:11can signal the maturation of the brain

28:13and body mechanisms that trigger the onset of puberty,

28:16ovulatory cycle, and menstruation.

28:18So we want to be very careful about leaping to conclusions

28:21about what these trends mean, but the trends themselves

28:24are very, very apparent.

28:25And as a final point, I should also

28:27mention that there are a number of different behavioral

28:29and psychosocial, as they're called, interactions that

28:32can influence puberty as well.

28:34This has been most strikingly observed in animals.

28:37And so I don't want anyone to be alarmed

28:39or to leap to any great conclusions about the onset

28:42of timing of puberty in humans, but I'd be remiss

28:44if I didn't tell you about a certain result which

28:46shows that if a young female is exposed to the odor--

28:52not necessarily the pheromones.

28:54There's a distinction between odors that we perceive

28:56and pheromones, which are subconscious.

28:59We don't actively perceive, but that can impact our biology,

29:03and pheromones effects in humans are very controversial.

29:05But we know, for instance, that if you take a female animal--

29:08and there's some evidence from humans

29:10that if you take a young prepubertal female

29:13and you expose her to the scent of a reproductively-competent

29:19male for a series of days, but maybe even as short

29:25as a few hours, and she is also not

29:29regularly being exposed to the scent of her father,

29:32that she can undergo puberty earlier.

29:34That's right.

29:35There is something about the odor

29:37and/or pheromones, or perhaps something else, that

29:42occurs when a young prepubertal female has a father that she's

29:47in regular contact with.

29:48He wouldn't necessarily have to live at home but that

29:50is around a lot that his smell is registered

29:54by her biological systems.

29:56That-- I don't want to say protects

29:58because it kind of skews the valence of the conversation,

30:02but that offsets or buffers the otherwise observed effect,

30:08which is that the scent of a reproductively-competent male,

30:11if it's present often enough or perhaps intensely enough,

30:14that it can trigger the onset of puberty in that female.

30:17In other words, the scent of a male that is not the father

30:22and we think also that is not biologically related to her

30:25can trigger earlier onset of puberty.

30:27And that effect can at least be partially buffered

30:32by her being in the presence of the scent

30:36from her biological father.

30:37Now, some of you are probably already leaping

30:40to conclusions about what this means.

30:41Should you not allow your daughter

30:43to be exposed to any males who are

30:45of reproductive age, et cetera?

30:47That's certainly not what I'm saying.

30:48There's a huge number of considerations

30:50that go into that calculation for everybody

30:52and circumstances, et cetera.

30:54But the point is that the odors of individuals, both related--

31:00in particular, closely related-- and non-related individuals,

31:05can shape the neural systems and the hormone systems that

31:10can trigger the onset of puberty or suppress

31:12the onset of puberty.

31:13So whether or not we're talking about onset

31:15of puberty at this age or that age

31:17and whether or not biologically-related male

31:20or non-biologically-related male scents around,

31:22et cetera, the thing I want everyone to know

31:25is that at some point during development,

31:27typically nowadays between the ages of 11 and 15

31:32or so-- again, there's variability there.

31:36The suppression of gonadotropin-releasing hormone

31:39released from the hypothalamus is removed,

31:41and then gonadotropin-releasing hormone

31:44can activate cells within the pituitary.

31:47And if you really want to know, it's

31:48the anterior pituitary in particular.

31:50And then the anterior pituitary gland,

31:53which sits at and kind of bridges the brain and the body

31:57because it allows the release of hormones into the bloodstream,

32:01that anterior pituitary is going to release

32:03two key hormones that everyone should know the name of

32:06and what they do.

32:07And when I say everyone, I mean males and females

32:09need to know about these hormones

32:11because they have an active role in both males and females.

32:14And of course, you should want to know

32:16and should know about the biology of everyone

32:19on the planet, in my opinion, because it tells you

32:21a lot more about humans than if you just

32:23focus on your own biology.

32:24But those two hormones are called

32:26luteinizing hormone, which is abbreviated LH,

32:31and follicle-stimulating hormone, which

32:34is abbreviated FSH.

32:35So the simple picture that you need to have in your mind

32:38is gonadotropin-releasing hormone from the brain,

32:41from the hypothalamus in particular,

32:43is causing the release of luteinizing

32:46hormone and follicle-stimulating hormone, GnRH stimulates

32:50LH, luteinizing hormone, and follicle-stimulating hormone,

32:53FSH.

32:55LH and FSH travel in the blood and can access all the cells

32:59and tissues of the body.

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

33:04many hormones-- and LH and FSH are included in this group--

33:08can travel into cells, and they can actually

33:12change the genetic expression of those cells.

33:15They can change which genes are turned on

33:16and which genes are turned off.

33:18And they can also attach to the surface of those cells

33:21and make those cells take on different properties.

33:23So they can mature those cells.

33:24So for instance, a good example of this outside

33:27of the context we've been talking about

33:28is the hormone testosterone can travel to the hair follicle

33:32and can stimulate changes in the genes of the cells of the hair

33:34follicle that can make hair grow.

33:37A different hormone, estrogen, can

33:39travel to the cells of the breast tissue

33:41and activate genes that control enlargement of the cells

33:44of the breast tissue.

33:45Prolactin, a different hormone, can travel to the mammary ducts

33:48and control the production and the secretion of milk.

33:52And in males, that can actually happen, in certain cases,

33:55although it's rare.

33:56But prolactin can also travel to areas of the brain

33:59that control libido, for instance.

34:01And just so you'll never forget it,

34:03males' elevated levels of prolactin

34:05are actually what set the refractory period

34:07after ejaculation and prevent erection

34:09for some period of time.

34:10So you'll never forget prolactin.

34:13The point being that different hormones

34:16have different effects on different cells,

34:17depending on what cells those are.

34:19Estrogen or estradiol is going to have different effects

34:21on the breast tissue than it would on skin,

34:24although as effects on both.

34:25Similarly, when LH and FSH, luteinizing hormone

34:29and follicle-stimulating hormone, travel in the blood

34:32to the gonad and the gonad is an ovary,

34:36it will have a certain set of consequences.

34:39And when luteinizing hormone and follicle-stimulating hormone

34:42travel in the blood to a gonad and that gonad

34:44happens to be a teste, then it will have a different set

34:47of biological implications.

34:49So let's focus now on what happens when

34:52LH and FSH arrive at the ovary.

34:54And let's assume now that we're talking about a female who

34:59has already undergone puberty, or perhaps we

35:02could even frame this in the context of a female who

35:05is about to undergo puberty.

35:07FSH and LH are now able to be released because she's

35:10undergoing puberty.

35:12But the same set of processes, essentially,

35:14would occur for any point from puberty onward until menopause,

35:19which is the depletion of that vault, that ovarian reserve

35:24of all those immature eggs.

35:25I'd like to take a brief break and acknowledge

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36:34OK, so we're now going to talk about ovulation

36:36and menstruation, and let's just remember

36:38what this is all about.

36:39This is all about creating the potential for an egg

36:42to be fertilized, and that egg needs

36:44to have half of the chromosomal pairs, so no pairs,

36:48but it's got to have 23 chromosomes just from mom.

36:51And we need to position that egg so

36:53that the egg can be met by the sperm

36:56and that sperm can penetrate that egg

36:59and donate its 23 individual strands of chromosomes

37:04to that egg so that you can bring together the DNA of dad

37:07and the DNA of mom.

37:09So the obligatory menstrual cycle

37:11occurs when luteinizing hormone and follicle-stimulating

37:16hormone have been released.

37:18And the ovulatory/menstrual cycle--

37:21and here I have to kind of pick what I want to call it.

37:24I guess to be really accurate, we would just call it

37:26the female reproductive cycle, but that includes underneath it

37:30both the menstrual cycle, as it's sometimes called,

37:32and the ovulatory cycle.

37:34So you decide.

37:34I'm going to interchangeably discuss the ovulatory cycle

37:38and the menstrual cycle.

37:39The problem is, when you say menstruation,

37:41people often think about just the period, the shedding

37:43of the uterine lining when fertilization has not occurred.

37:46So if I start saying ovulatory cycle,

37:49just keep in mind I'm referring to the entire thing.

37:52Now, this is probably also a good opportunity

37:54to say that if you heard that the ovulatory/menstrual cycle

37:59is 28 days long, that's true in some cases,

38:02but that's not always true.

38:04It's, on average, 28 days long.

38:07There are some females for which the ovulatory cycle will be

38:11shorter-- it can be as short as 21 days--

38:13and other females for which it will be 35 days long.

38:18Shorter than 21 days and longer than 35

38:20days is rare, although it does occur.

38:23One of the key things when thinking about fertility

38:25is if you talk to OB/GYNs who are focused on fertility, which

38:28I have in anticipation of this episode,

38:30they'll tell you that whether or not

38:33your cycle is 21 days long or 35 days long

38:36is not as much of an issue necessarily unless it's

38:40happening to become much shorter or much longer

38:44in a kind of erratic way.

38:45So if you're somebody who's consistently

38:47had 23 day long cycles and all of a sudden

38:50you're having 30 day long cycles, that's not necessarily

38:53an indication of anything bad.

38:54But if it's 21 days one month and it's 30 days the next month

38:58and it's 17 days the next month or even if it's always

39:01falling within that 21 to 35 day long cycle

39:05but it's very variable from each month or every other month

39:08or so, you probably want to talk to your OB/GYN

39:11because that could indicate a number of different things.

39:13Which things could it indicate?

39:15Well, that will become clear as I spell out

39:17the biology in a bit more detail.

39:19But this idea that the menstrual cycle/ovulatory cycle

39:22is always 28 days, that's just false.

39:24That's just not true.

39:25I should also mention that there is a common misconception that

39:29because the average menstrual cycle is 28 days-- indeed,

39:32the average is 28 days--

39:34and the lunar cycle is 28 days--

39:36and of course, there is a real biology

39:38to support the fact that the lunar

39:39cycle can't, in fact, impact certain aspects

39:42of human behavior.

39:43It does, and we'll talk about lunar cycles

39:45in a future episode.

39:46But there is zero data to support the idea

39:50that the menstrual cycle and the lunar cycle

39:53are linked in any kind of causal way.

39:56Sorry to break it to you.

39:57The lunar cycle and the tidal cycles at the ocean

40:01are definitely linked in ways that are super interesting

40:03related to the tilt of the Earth and the pull of gravity

40:05of different planets, and it's an incredible story

40:07into itself.

40:09But the lunar cycle and the menstrual cycle,

40:11despite having some weak correlation in terms

40:13of their duration or their so-called periodicity--

40:18no pun intended--

40:20well, there's no causal relationship whatsoever

40:22between the lunar cycle and the menstrual cycle.

40:25If any of you are aware of any real data

40:28that conflicts with what I just said,

40:30please put that in the comment section on YouTube.

40:33But this is pretty well established as far as I know.

40:36OK, so we need to bring together the so-called haploid contents,

40:42the 23 individual strands of chromosomes from the egg,

40:45to a place and a position where it could potentially

40:48be fertilized by the male.

40:49So what happens?

40:50Luteinizing hormone and follicle-stimulating hormone

40:52travel to the ovary.

40:54These hormones are able to access the ovary.

40:56There's a lot of blood supply to the ovary.

40:58And FSH and LH arrive at the ovary.

41:03The ovary has this vault, this ovarian reserve

41:06of immature cells.

41:07They reside within what are called follicles.

41:09The follicles are little spherical packages

41:12that can potentially provide a nice environment for those eggs

41:16to mature.

41:17And when FSH, in particular, arrives at the ovary,

41:23a small number of those follicles

41:25will split off from the reserve, they will exit the vault,

41:30and they will undergo maturation.

41:32And the key player here is follicle-stimulating hormone.

41:37And the first 14 days of the menstrual/ovulatory cycle

41:41is referred to as the follicular phase because

41:44of this relationship between FSH triggering the maturation

41:47of a subset of follicles.

41:49Now, typically in the context of a 28 day or so

41:53ovulatory/menstrual cycle, day one

41:55is designated as the first day of the period,

41:58of the shedding of the uterine lining

42:00from the previous ovulatory menstrual cycle in which

42:04fertilization did not occur.

42:07So day one is when the period initiates.

42:10It is days 1 through 14, approximately--

42:13because here we're just considering

42:14the average of a 28-day cycle, but it could be longer.

42:17It could be shorter.

42:17But the first half of that cycle is the so-called follicular

42:21phase, FSH, has triggered the departure

42:24of a subset of these follicles that contain immature eggs.

42:27And it is triggering the maturation of those eggs.

42:30Luteinizing hormone is also present, but also

42:33at relatively low levels.

42:35And it's during the first half of this ovulatory menstrual

42:37cycle that the main goal is to get those follicles to mature.

42:41So inside of those follicles, the egg is developing.

42:44It's growing.

42:45It's maturing.

42:47And in doing so, it's also making its own hormones.

42:51This, I think, is one of the most elegant aspects

42:54of the ovulatory menstrual cycle that, in a few minutes,

42:57you'll learn about something which still to this day,

42:59even though I've known about this stuff for decades now

43:01because of my training, still just blows my mind that you

43:05have one hormone, follicle-stimulating hormone,

43:07triggering the maturation of some eggs

43:10inside of some follicles and then those follicles themselves

43:12making another hormone that furthers the process

43:17and then soon, as you'll learn, create a hormone to trigger

43:21the second half of the process.

43:22Just a beautiful symphony of expression of different genes

43:26and different hormones to make everything

43:28work as optimally as possible.

43:30So as these different follicles mature, somehow--

43:33and we still don't know exactly how--

43:35one of those follicles containing an egg

43:38gets selected.

43:40It's either because it matures the fastest

43:42or there's something about it that

43:45is still not completely understood

43:48that allows it to be selected.

43:50And all the other follicles that are maturing

43:53degenerate and die.

43:54And they're gone.

43:55They don't go back into the ovarian reserve.

43:57They are now depleted from that bank account

44:01that is the ovarian reserve.

44:03They die off.

44:04But that single egg that, keep in mind,

44:08contains 23 pairs of chromosomes--

44:11we haven't gotten rid of one half of those 23

44:15sets of chromosomes yet.

44:16But that one will continue to mature.

44:18And then, at some point, that egg

44:23will start to undergo a process in which those chromosomes are

44:28pulled apart by little components

44:31within the egg called spindles.

44:33They literally have a physical pulling

44:35of the chromosomes apart.

44:36So now those 23 pairs are no longer attached to one another

44:40at the middle like they were before,

44:41like two beads of strings--

44:44or I should say, 23 short strands

44:47of beads that were at once connected to one another

44:51now are pulled apart so that you have

44:5323 chromosomes on each side, but they're

44:56pulled apart from one another.

44:58So that diploid cell is now starting

45:02to become a cell in which half of the chromosomes,

45:05half of those 23 pairs, are physically

45:08pulled away from the others.

45:10And then the egg actually starts to form its own

45:13what we call an involution of membrane

45:15around those 23 pairs, one set of them, and encapsulates them.

45:20So you sort of got an egg with two parts

45:22where the two sets of chromosomes,

45:24two sets of 23 chromosomes, are now separate

45:26from one another inside of the egg.

45:28And then one of those actually gets ejected from the egg,

45:32and the name of that thing that gets ejected--

45:34it's sort of like a little Hubble pod is how I imagine it,

45:37you know, from Star Wars or from any kind of Space Odyssey movie

45:41where some thing is ready to happen.

45:43A little Hubble pod shoots out of the ship.

45:45Well, that 23 pairs is now ejected from the egg.

45:49It's called the polar body.

45:50And that's going to degenerate.

45:52It's going to go away.

45:53And in doing so, take the egg cell, which was once

45:56diploid-- it had 23 pairs of chromosomes-- and making

45:59it haploid.

46:01And now what you've got, in ideal circumstances,

46:04is a beautifully pristine egg that was selected for

46:07and has 23 single strands of chromosomes, 22 autosomes

46:11and one sex chromosome.

46:12And that sex chromosome is going to be an X chromosome

46:15almost with certainty, because female--

46:19mother-- is creating that egg.

46:22So then the egg that contains just the appropriate 23

46:26single-stranded chromosomes is going

46:29to fuse with the wall of the ovary, and that egg

46:31will be released and will travel into the Fallopian tube.

46:36Now, we'll get back to that egg in a few moments.

46:38But that process, which represents the first half

46:40of the ovulatory menstrual cycle, again,

46:42was triggered by FSH and to some extent luteinizing hormone.

46:45But it is the ongoing maturation of that egg which also causes

46:51the production of estrogen, which allows that whole process

46:55to occur.

46:56And you could say, why?

46:57Well, the answer to the why is a very important

46:59biological principle that we are going

47:01to return to in a number of different contexts today,

47:03both as reference to female and male fertility.

47:08And the principle is a so-called negative feedback.

47:12So when estrogen is present at relatively low levels

47:15in females in the ovary, as it is

47:19during the development of these eggs, some of that estrogen,

47:22of course, is going to exit the ovary.

47:24It's going to go into the bloodstream.

47:26And it's going to travel back to the pituitary.

47:29Now, the pituitary can release things

47:32like follicle-stimulating hormone and luteinizing

47:34hormone.

47:34But the way I'd like you to think

47:36about the pituitary for sake of feedback loops

47:38is that it's sort of like a thermometer

47:41that you would put into a pool, like a backyard pool, that

47:44is attached to the heater.

47:46And for instance, if you were to put a thermometer into a pool

47:50that you would like to keep at 70 degrees

47:52and the temperature of that pool is 60 degrees,

47:55well, then that thermometer ought

47:57to trigger some sort of mechanism

47:59where the pool would heat up until the temperature

48:01of the pool hit 70 degrees, and then it

48:04should trigger that thermometer to turn off the heating system.

48:06That's kind of a negative feedback

48:08system that would keep the temperature more

48:10or less correct.

48:11That's a lot of the way that the system's related to estrogen

48:14and also testosterone and these different things

48:16like luteinizing hormone and follicle-stimulating hormone

48:19work as well.

48:20Typically, when the level of a hormone is too high,

48:24then it shuts down the production

48:26of the hormones that would trigger further production

48:28of that hormone.

48:28I know that's a mouthful.

48:29It's a lot to think about.

48:30And some of you are probably thinking, whoa,

48:31I'm getting dizzy now with biology.

48:33But I promise you, you can understand this.

48:35In females, when estrogen is relatively low--

48:38but not zero but is relatively low

48:40during that first follicular half of the ovulatory cycle--

48:43it actually triggers negative feedback on LH and FSH

48:47so that not too much is produced.

48:49But then just prior to ovulation,

48:51the levels of estrogen and the levels of some other hormones

48:54from those eggs--

48:56you have the eggs producing estrogen themselves--

48:59gets high enough that it actually

49:01triggers a positive feedback loop on the pituitary.

49:04So the pituitary is essentially observing

49:07the amount of estrogen in the bloodstream produced

49:09by the ovary, and the amount of estrogen

49:11towards the end of the second half of the menstrual cycle

49:14has increased and triggers a positive feedback loop.

49:18It triggers the pituitary to release more FSH and LH,

49:22and that helps trigger ovulation, that deployment

49:26or the release of that one mature proper selected

49:29egg that's haploid with the 23 individual pairs of chromosomes

49:33into the Fallopian tube.

49:35So let's just back up really quickly and just

49:37kind of summarize what's happened.

49:38Gonadotropin-releasing hormone from the hypothalamus

49:41triggers the release of follicle-stimulating hormone

49:43and luteinizing hormone.

49:44That travels to the ovary-- triggers

49:46the release of a subset of immature follicles

49:50with immature eggs.

49:51Those immature follicles and immature eggs

49:55start to mature, start to grow because

49:58of the presence of follicle-stimulating hormone.

50:00The growth of those eggs themselves increases estrogen.

50:04As the estrogen starts to accumulate in the environment,

50:06some of that travels back to the pituitary.

50:09And when levels of estrogen arriving at the pituitary

50:12are relatively low, the pituitary

50:15says, oh, we don't need to release

50:16any more follicle-stimulating and luteinizing hormone.

50:19However, at some point just prior to ovulation,

50:21enough estrogen has been produced by that one

50:24single selected mature egg and some

50:26of the other follicles around it that were maturing but then

50:29since died off that the estrogen triggers a positive feedback

50:33loop.

50:34The pituitary says, OK, and releases

50:37more follicle-stimulating hormone

50:38and luteinizing hormone.

50:39And bam, the egg, which has the proper genetic components,

50:44sets off out of the ovary and into the Fallopian tube.

50:48So-called ovulation has begun.

50:51That itself, what I just described,

50:53constitutes the first half of the ovulatory/menstrual cycle,

50:56which we call the follicular phase.

50:58And it's marked by the presence of FSH and some other things,

51:01but we can really think about it as marked by FSH

51:04from the pituitary and by estrogen, or estradiol, made

51:08within the ovary.

51:10Then comes the second half of the ovulatory/menstrual cycle,

51:13which I personally think is one of the coolest mechanisms

51:16in all of biology, which is that--

51:19remember the follicle that housed

51:21that one egg that was the selected

51:23egg that became the mature egg?

51:24And that follicle, which no longer contains the egg

51:27because the egg took off and ovulated,

51:29is called the corpus luteum.

51:30And the corpus luteum starts making three hormones, which

51:34include estradiol, I think called inhibin,

51:36but the most important hormone, the one that you really

51:38need to know about, is that it starts

51:40producing very high levels of progesterone.

51:44Progesterone levels start to increase

51:47about the time of ovulation, although just

51:50prior to ovulation.

51:51And over the next second half of the ovulatory cycle--

51:56so about 14 days if it's a 28-day cycle,

51:57a little bit longer or a little bit shorter,

51:59depending on the length of cycle.

52:01Levels of progesterone in the second half

52:03of the ovulatory cycle are going to increase by 1,400 fold

52:08compared to what they were in the first half

52:10of the ovulatory cycle.

52:12So again, if we were to characterize

52:14the menstrual/ovulatory cycle in broad strokes, what we would

52:18say is that FSH and estrogen mark

52:22the initial part the first half, the so-called follicular phase,

52:26and that the estrogen and FSH set in motion ovulation,

52:30and they prime the system for the production

52:33of a corpus luteum, which produces progesterone.

52:36And the second half of all of this

52:38is called the luteal phase.

52:41The second half of the ovulatory/menstrual cycle

52:43is the luteal phase because of corpus luteum,

52:46this otherwise discarded tissue that produces progesterone.

52:50What does progesterone do?

52:52Well, progesterone impacts the uterine lining,

52:56so-called endometrium or the lining,

52:58the mucous lining of the uterus where that egg that's ovulated

53:03is potentially going to implant if it's fertilized.

53:06And so in a kind of perfect way-- or I

53:09should say, in a seemingly perfect way--

53:12the egg is off on its way.

53:13It might get fertilized.

53:15The remnants of the compartment that let go of that egg

53:19produce a hormone that then prepares the endometrial lining

53:23of the uterus for the potential implantation of that egg.

53:27It's basically making the bed for the fertilized egg

53:30to potentially embed in, to implant in, and then

53:33achieve all the nourishment that it needs to grow, eventually,

53:37into a healthy embryo and child.

53:39Just an amazing set of biological mechanisms,

53:42if you ask me, because what you're observing here

53:45is an incredible economy of function

53:48whereby the same cellular components that

53:50are producing the egg, well, some of them

53:52are being discarded, but they're not being

53:54discarded without purpose.

53:56They're being discarded in a way that

53:57triggers the onset of hormonal expression

54:01that then prepares the fertilized

54:02egg to be in an enriched environment in which it

54:05can thrive.

54:06Now, I realize that was a lot of detail.

54:07But we have a couple of key themes.

54:09We've got the hypothalamus, GnRH.

54:11We've got the pituitary with LH and FSH,

54:14and those hormones travel to the ovary.

54:16The ovary has eggs in a vault, basically immature eggs

54:20in a vault. Some of those are activated by the presence

54:24of FSH and LH each month.

54:26And one of those eggs will be selected and will ovulate.

54:30The remnants of the follicle and egg

54:32that are not selected, the chromosomes that you don't need

54:35disappear in the polar body.

54:36And the corpus luteum gives rise to progesterone and sets

54:40in motion the second half of the ovulatory menstrual cycle,

54:44which is the luteal phase, which is essentially

54:46the potential for that fertilized egg

54:48to embed in a nice, nourishing environment.

54:50And of course, we should all be thinking,

54:52if the egg is fertilized and then it lays down

54:54in the nice, comfy uterine lining

54:56that's been prepared by progesterone

54:59in the corpus luteum, well, then everything's fine and good.

55:02But what if fertilization doesn't occur?

55:04Well, we all know what happens if fertilization doesn't occur.

55:07If fertilization does not occur for whatever reason,

55:09that uterine lining is going to shed.

55:12And that's actually what's referred to as the period.

55:14It's the actual removal--

55:17or the departure, rather--

55:19of the thickened endometrium lining

55:23of the uterus when fertilization has not occurred.

55:28And of course, if that happens, we

55:30need another ovulatory menstrual cycle.

55:32So how does that happen?

55:33Well, the hormone inhibin is also made by the corpus luteum

55:36and doesn't go quite as high as the hormone progesterone.

55:41But it kind of tracks that increase in progesterone

55:44that occurs in the second half of the ovulatory cycle.

55:47But then, if fertilization does not occur,

55:50inhibin levels start to drop.

55:53And what I haven't told you is what inhibin does.

55:55Inhibin, in concert with other hormones like estrogen,

55:59feed back to the hypothalamus and prevent the further release

56:03of follicle-stimulating hormone and luteinizing hormone.

56:05If you have an egg that gets fertilized and can implant,

56:09well, then you don't want more eggs to mature.

56:13You want to hold on to the ones in the vault.

56:15You don't want them to mature.

56:17And hormones like inhibin and, again,

56:19working with other hormones are going

56:21to prevent the secretion of things like FSH and LH.

56:24Now, typically, people are not getting pregnant every month.

56:27In fact, that's not possible.

56:29And part of the reason it's not possible

56:31is that if the fertilized egg implants,

56:33there are a number of different hormone cascades

56:35that shut down the production of things like GnRH, FSH, and LH

56:39in ways that prevent further maturation of follicles

56:42and a follicular phase.

56:43But in the instance where fertilization doesn't occur

56:47and menstruation occurs--

56:49and I should mention that the duration of menstruation,

56:52the actual bleeding, typically is anywhere from one

56:54to five days.

56:55The, quote, unquote, "heaviness,"

56:57the lightness or heaviness of that bleeding will depend on--

57:01you guessed it-- the amount of progesterone that is secreted

57:04from the corpus luteum.

57:05That's one of the key players there.

57:08And if menstruation occurs, well, then inhibin levels

57:14also drop.

57:14Progesterone levels also drop.

57:16And when that occurs, there's a positive feedback

57:20signal up at the level of the pituitary.

57:23The pituitary literally can register

57:25how much inhibin and progesterone and estrogen

57:28is present in the bloodstream.

57:29And if those levels are sufficiently low, well,

57:32then GnRH gets secreted again, FSH gets secreted again,

57:36and LH gets secreted again.

57:39And the first half the follicular phase

57:41of the menstrual cycle initiates all over again.

57:44It's hard to overstate how beautifully orchestrated

57:46this entire system is--

57:48The number of feedback loops and feed-forward loops.

57:51I think if you can just generally understand

57:53that the first half of the menstrual/ovulatory cycle

57:56is marked by the maturation of the follicles and FSH

57:58and that the second half is marked

58:00by the accumulation of progesterone

58:03and the thickening of the uterine lining

58:04should fertilization and implantation occur,

58:07I think that you will certainly understand

58:09the female reproductive cycle better than most people

58:12out there.

58:13It will also help you understand a number of things

58:15that are sometimes associated with the female reproductive

58:17cycle.

58:18For instance, there are data showing

58:19that, in many, not all, but in many women, in the four

58:24to five days prior to ovulation, there is

58:27a dramatic increase in libido.

58:28That dramatic increase in libido is

58:30triggered by a number of things, but some of those things

58:33include the spike in FSH that occurs,

58:36the spike in LH that occurs, and some associated increases

58:40in androgens, things like DHEA and testosterone,

58:44which, just as in males can be related to libido,

58:47in females trigger libido.

58:49You can imagine why this would be an effective mechanism

58:51to have in place in females if the goal, as it were, certainly

58:57of the egg, perhaps not of the woman as a whole,

59:00but if the goal is to fertilize the egg--

59:04so increases in libido just prior

59:05to the onset of ovulation.

59:08There's also been a lot of discussion and interest

59:11and, frankly, data exploring the malaise

59:14that it can occur at certain portions

59:16of the menstrual cycle.

59:18And there's a lot of misconception about this.

59:21A lot of people have focused on the malaise that can occur

59:25around the time of bleeding.

59:27But there are actually stronger data

59:30to support the fact that some, again, some, not all women

59:34experience a kind of malaise sometimes associated

59:36with anxiety, sometimes not, that's associated with the mid

59:40to second half of the luteal phase

59:44of the ovulatory/menstrual cycle.

59:47And that, despite what people commonly think,

59:51is not associated with elevated levels of estrogen.

59:53It's actually associated with the depletion in estrogen

59:56levels that can occur during certain portions

59:59of that second half of the luteal phase

1:00:01of the menstrual cycle.

1:00:03So again, this is highly variable.

1:00:06For some people, they might not experience

1:00:08any malaise at any point during their menstrual cycle.

1:00:11Other individuals also, for instance,

1:00:13might not experience any variation in their libido

1:00:15at any point during their menstrual cycle.

1:00:17Again, highly variable, and yet there

1:00:18are some statistically significant trends

1:00:21that have been observed that tracked

1:00:22very specific hormonal components

1:00:24within the menstrual cycle.

1:00:25Again, this will all be very contextual.

1:00:28And of course, this can play out in a number of different ways.

1:00:31So for instance, some women experience very heightened

1:00:33levels of sensitivity to caffeine

1:00:35at certain portions of their menstrual cycle.

1:00:37Other women experience more cramping than others

1:00:40at different portions of their menstrual cycle.

1:00:42Tremendous variation from individual to individual.

1:00:46One of the--

1:00:47I view it as an advantage.

1:00:48But one of the things that many females can really do

1:00:53and experience because they have cycles that occur every month

1:00:56that are fairly dramatic in terms of their levels

1:00:58of hormones-- so for instance, a more than 1,000-fold increase

1:01:02in progesterone during the luteal phase of the menstrual

1:01:05cycle and, I should also mention,

1:01:07a 200-fold increase in estrogen during the period just prior

1:01:10to ovulation.

1:01:11That's why they always say estrogen primes progesterone.

1:01:14That's what you learn in kind of basic endocrinology

1:01:16when you're learning the menstrual cycle.

1:01:17Estrogen in the first half of the menstrual cycle

1:01:19primes progesterone in the second half

1:01:21of the ovulatory/menstrual cycle.

1:01:24Well, those estrogen increases just prior to ovulation

1:01:27are in part responsible for the increases in libido.

1:01:32But it's also the presence of increased androgen just prior

1:01:35to ovulation.

1:01:36So there's a lot of complex interplay.

1:01:38I think what we will do is we will reserve

1:01:40the discussion about libido, per se,

1:01:43and some of the other aspects related

1:01:44to sexual differentiation that we

1:01:46were talking about earlier for a future episode.

1:01:48But hopefully now you have in mind

1:01:49what the ovulatory/menstrual cycle is.

1:01:51It is a signal from the brain, from the hypothalamus,

1:01:55which then triggers a signal from the pituitary,

1:01:57an endocrine gland, which then signals the release of hormones

1:02:02that travel to the ovary and that control

1:02:04two things, maturation of eggs and the identification of one

1:02:08egg in particular and then preparation of the milieu,

1:02:13the environment in which that fertilized egg could

1:02:15potentially land and mature into a healthy embryo and child.

1:02:21So if you have that framed up in your mind

1:02:23and even if you just extracted maybe 10% to 15%

1:02:26of the hormones and different aspects

1:02:27that I described up until now, I would consider you far more

1:02:32knowledgeable about this entire process than 99% of people

1:02:36out there, certainly not the OB/GYNs and urologists,

1:02:39but the 99% of individuals out there.

1:02:42It also frames up for us the second half

1:02:45of this whole story about fertility and fertilization,

1:02:47which is the generation of sperm and how the sperm eventually

1:02:52arrive at the egg and how certain sperm are selected

1:02:56to potentially fertilize that egg,

1:02:58whereas others never really stand a chance.

1:03:01So next we're going to talk about sperm.

1:03:03We're going to talk about what sperm are,

1:03:04where they are generated, and how they are generated,

1:03:06and how they need to travel both within the male

1:03:09and within the female in order to allow fertilization

1:03:12to potentially occur.

1:03:13I'd like to take a brief break and thank

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1:04:18So we've covered the ovulatory cycle in females.

1:04:21And I confess, it was a lot of information

1:04:24with a lot of biological nomenclature.

1:04:26But I promise you that many of those same themes

1:04:29and indeed the same names and nomenclature

1:04:31will show up in the discussion that we're

1:04:33going to have now, which is about the generation of sperm.

1:04:36Now, sperm are similar to eggs in the sense

1:04:40that they are part of the germline.

1:04:41They are these protected cells, protected in the sense

1:04:44that the activities of an individual

1:04:47are not going to change the genetic makeup of those cells.

1:04:52Now, again, there are instances in which

1:04:54mutagens, such as chemicals, could disrupt

1:04:57the genomes of the germ cells in males, just

1:05:00as it could in females.

1:05:01But in general, the activities, the things

1:05:04that we do, the experiences we have,

1:05:06doesn't tend to change the genome of those cells.

1:05:09However, there are a lot of lifestyle factors--

1:05:11dos and don'ts, nutrition and supplements and prescription

1:05:13drugs, et cetera-- that can indeed modify the quality

1:05:17of the sperm.

1:05:18And we'll talk about what sperm quality means.

1:05:20But the point is that the sperm cell, much like the egg cell,

1:05:27are both germline cells.

1:05:28They are not like somatic cells.

1:05:30They are unique populations.

1:05:31And let's just remember what the job of the sperm cell is.

1:05:34The job of the sperm cell is to deliver the genetic material

1:05:38from the father and to do that in the form of a haploid cell.

1:05:42So that means 23 chromosomes, 22 autosomes,

1:05:47one so-called sex chromosome--

1:05:50again, not sex the verb, at least not in this case.

1:05:52Sex, the verb, is a discussion we're

1:05:54going to have in a few minutes, but sex the noun.

1:05:57The sex chromosome can either be an X chromosome or a Y

1:06:00chromosome.

1:06:01So 22 autosomes and then one sex chromosome

1:06:04is going to be contained within the sperm

1:06:06because it's a haploid cell, not a diploid cell.

1:06:09Remember, the egg was diploid, then it became haploid.

1:06:11The sperm cells are cells that are

1:06:14created through the division of other cells.

1:06:16But after that division occurs through a process called

1:06:18meiosis, the sperm cell is going to contain 23 chromosomes,

1:06:24consisting of 22 autosomes and one sex chromosome.

1:06:27And the sperm that manages to deposit its DNA contents

1:06:32into the egg, to fertilize the egg,

1:06:34will either have an X sex chromosome or a Y sex

1:06:38chromosome.

1:06:39And the Y sex chromosome has a number

1:06:41of different genes on that chromosome that

1:06:44will suppress, for instance, the development

1:06:46of the female reproductive axis.

1:06:49One good example would be the Müllerian-inhibiting hormone,

1:06:52or MIH.

1:06:53The gene for Müllerian-inhibiting hormone,

1:06:55which is a hormone that prevents the formation of the Müllerian

1:06:58ducts, which is part of the female reproductive structure,

1:07:02well, that gene controls the prevention of the development

1:07:07of the female genitalia and in doing so promotes

1:07:12the development of the male genitalia.

1:07:13And there are other examples of genes

1:07:15that are on the Y chromosome that give you

1:07:16a what we call male phenotype.

1:07:19You have genotype and phenotype.

1:07:20By the way, in case you haven't heard this in a while

1:07:22from your high school biology--

1:07:24or if you never heard it, no big deal--

1:07:25karyotype is the complement of chromosome--

1:07:29XX or XY.

1:07:30And there are individuals out there

1:07:31that are XXY or XYY, a discussion for our episode

1:07:35on sex differentiation.

1:07:36That's karyotype with a K.

1:07:38Then there's genotype, which are the genes that you have.

1:07:41And then there's phenotype, spelled P-H-E-N-O-T-Y-P-E,

1:07:46phenotype.

1:07:47And the phenotype is how the genes,

1:07:51which then code for RNA, which code for protein,

1:07:54how those are expressed in terms of things like eye color.

1:07:57So eye color is a phenotype.

1:07:58Height is a phenotype.

1:07:59Hair color is a phenotype.

1:08:00So you have karyotype, genotype, and phenotype.

1:08:02Well, what we need to do is we need to bring together

1:08:05that sperm, which is haploidd it contains those 23

1:08:08chromosomal strandes--

1:08:10with either an X or a Y. Sex chromosome

1:08:13is the 23rd chromosome.

1:08:14We need to get that cell to the egg.

1:08:17And so when we talk about spermatogenesis, of course,

1:08:21we are talking about the generation of sperm cells.

1:08:24But what we're really talking about is the generation

1:08:26of cells whose job is to deliver the genetic material from dad

1:08:30to the egg within the female in a way that increases

1:08:35the probability that not only will that egg be fertilized

1:08:38but that it will progress in a healthy way with each set

1:08:42of chromosomes from mom and from dad--

1:08:44each set of 23 chromosomes, that is--

1:08:47will progress in a healthy way, will implant in a healthy way,

1:08:51and will maintain and grow in a healthy way to a healthy embryo

1:08:56and child and eventually adult. That's the job of the sperm.

1:09:01So as we talk about spermatogenesis,

1:09:03let's just remember that and why they're there

1:09:06in the first place.

1:09:06Now, a few things about sperm that are interesting,

1:09:09besides the fact that they're haploid

1:09:11and besides the fact that, as you all know, they swim.

1:09:14They have a head and a tail.

1:09:15They actually have a head, a mid region, and a tail,

1:09:17and that mid region turns out to be very important.

1:09:19It's something we'll come back to again and again.

1:09:21That mid region is really key for the ability for sperm

1:09:24to engage in forward progression to swim forward.

1:09:27It involves the activity of mitochondria,

1:09:30which are involved in generation of ATP, which

1:09:33is involved in all aspects of energy and all cells.

1:09:36But let's just remember that the sperm are swimming cells.

1:09:40And in order to create a really good swimmer

1:09:43or set of swimmers, you need a couple of things.

1:09:45First of all, within the testes is where the sperm develop.

1:09:49And unlike in females and unlike in the ovary,

1:09:53there's no vault of sperm.

1:09:55The sperm are continually being generated.

1:09:57It takes about 60 days for sperm to be

1:10:00born from their parent cells--

1:10:02because cells actually give rise to other cells,

1:10:04that's the it works-- to be born from their parent cells

1:10:06and then matured to the point where they

1:10:08can be a really good swimmer.

1:10:09Now, that doesn't mean that a bunch of sperm

1:10:13are made on day one, and then 60 days later, all those sperm

1:10:17are deployed in the form of ejaculate,

1:10:19and then the cycle starts over again.

1:10:21So it's a little different than the ovulatory menstrual cycle.

1:10:23Rather, at any given point in time-- like right now,

1:10:26if you have testes, you have some sperm in your testes that

1:10:29are immature and cannot swim, cannot deliver those contents

1:10:35to--

1:10:35those genetic contents, rather-- to the female egg.

1:10:38And you have some sperm that are mature,

1:10:40and you very likely have some sperm that are so mature

1:10:43that they are dying off or that they're dead.

1:10:46Almost certainly, also, regardless of your age,

1:10:48you have some sperm that are healthier than others, that are

1:10:51better swimmers than others.

1:10:53This is just the way the system works.

1:10:56Now, the process of spermatogenesis

1:10:59involves a couple of things, but a lot of the players

1:11:01are the same as the process of developing

1:11:03the so-called oocyte, the immature egg.

1:11:08We've got GnRH from the hypothalamus.

1:11:10That's going to be a player.

1:11:11We have FSH, follicle-stimulating hormone,

1:11:13although the name's a little bit of a misnomer in the context

1:11:16of spermatogenesis, because in the context of spermatogenesis,

1:11:19there is no follicle.

1:11:20What we're really talking about is

1:11:21FSH for stimulating the maturation of the sperm cell,

1:11:26so not egg follicle but sperm cell.

1:11:28But we still have GnRH, FSH, LH, and rather

1:11:32than the ovary being the target of those hormones,

1:11:34it's going to be the testes.

1:11:36So most everybody should know that the testes and the ovaries

1:11:40are the so-called gonads.

1:11:42The testes, of course, reside outside of the body.

1:11:46There are instances where the testes fail

1:11:49to descend during development.

1:11:50Certainly, if the testes don't descend

1:11:52on time, that's something that doctors need to be made aware

1:11:55of, the pediatrician should be made aware of,

1:11:56because that can prevent fertility.

1:12:00Why would that be?

1:12:01Well, it turns out that the testes

1:12:03reside outside the body in the scrotum

1:12:05because the temperature conditions

1:12:08under which spermatogenesis can occur

1:12:11and under which healthy sperm can be maintained

1:12:14are very restricted and is approximately 2 degrees cooler

1:12:20than the rest of the body.

1:12:21This is very important.

1:12:23I think this is something that used to be discussed a lot more

1:12:26but isn't discussed so much these days.

1:12:28But keeping the testes cool enough--

1:12:31doesn't necessarily mean keeping them cold, although there

1:12:33is a place for using cold exposure,

1:12:35deliberate cold exposure, to improve

1:12:37sperm quality and number and perhaps even

1:12:39testosterone levels.

1:12:40We'll talk about that a little bit later.

1:12:42But keeping the testes about 2 degrees

1:12:46cooler than the rest of the body is absolutely key.

1:12:49If sperm get too hot, they die.

1:12:51And if spermatocytes, the cells that give rise to sperm,

1:12:54get too warm, well, then oftentimes the sperm

1:12:57that develop are not healthy, not healthy

1:13:00in a number of ways.

1:13:01Either they can't engage in fast forward progression--

1:13:04that is, swimming-- or they will lack the ability

1:13:08to deposit their DNA contents within the egg.

1:13:11So again, whatever is contained in the ejaculate

1:13:14is going to be a mixture of different sperm qualities.

1:13:16And sperm of different ages will impact the quality, but also

1:13:20the temperature under which those sperm developed is

1:13:25going to impact their quality.

1:13:26And so we're going to get into tools a little bit

1:13:29later, as I mentioned, but just to give you a simple takeaway.

1:13:32If you are hoping to conceive in the next 90 days--

1:13:36the spermatogenesis cycle take 60 days,

1:13:38but then the sperm actually have to migrate from the testicle

1:13:41into the so-called epididymis, which is a related structure,

1:13:45and then into the vas deferens and then

1:13:47into the urethra, where it can be part of the ejaculate.

1:13:49In order for sperm to do all that properly,

1:13:53undergo that maturation and then exit in ejaculate in a way

1:13:56that's healthy or that the sperm is healthy,

1:13:59if you plan to conceive children or to try and conceive children

1:14:03in the next 90 days, you definitely want to avoid

1:14:06exposing your testicles-- that is, your scrotum--

1:14:10to elevated temperatures.

1:14:13So that means definitely avoiding hot tubs,

1:14:16definitely avoiding hot baths.

1:14:17Now, a brief hot bath or hot tub or hot shower

1:14:19isn't going to be a problem, although if you're

1:14:22really interested in conceiving, I would avoid hot tubs

1:14:24and hot baths as much as possible.

1:14:27Hot showers are probably fine.

1:14:29But if you're going to go into a sauna, for instance,

1:14:32you might want to rethink that decision.

1:14:33And if you do decide to, you almost certainly

1:14:35would want to bring a cold pack in that you could-- well,

1:14:39hopefully put some material between the cold pack

1:14:41and the scrotum so you don't get a cold burn.

1:14:43But put something there, but keep the scrotal tissue cool.

1:14:48Keep it cold to cool because heat exposure can really

1:14:52mutate and disrupt the developing sperm,

1:14:55and it can kill sperm.

1:14:57And so, again, that would be for an entire 90 days

1:15:00leading up to your attempts to conceive.

1:15:03Again, we'll get into more tools later, but a number of people

1:15:05also have probably heard of the boxers versus briefs

1:15:09controversy, I guess it is, or whether or not people call

1:15:13it going commando with no underwear of any kind-- boxers,

1:15:18briefs, briefs, or otherwise rather.

1:15:20It turns out that the data on that point to the fact

1:15:23that there isn't really a big difference in terms of sperm

1:15:25quality if people wear boxers or briefs

1:15:28or don't wear anything under their jeans or shorts at all.

1:15:33The scrotum has the ability to move the testicles far enough

1:15:37away from the body in order to achieve lower

1:15:39temperatures if it needs to.

1:15:40It achieves that through a muscle

1:15:42called the cremaster muscle, which

1:15:43is a really interesting muscle, believe it or not.

1:15:46I was reading up on the biology of the cremaster

1:15:48muscle, something I never thought

1:15:49I'd spend too much time on but that I ended up spending far

1:15:51too much time reading up about.

1:15:53And it's really fascinating.

1:15:54What you have is a muscle that is a smooth muscle

1:15:57tissue, unlike skeletal muscle, which is striated muscle,

1:16:01that is temperature dependent.

1:16:03So it has certain nerve endings, and it has certain receptors

1:16:06on it that allow it to respond to local temperature

1:16:09and then to relax in order to essentially let

1:16:13the testicles to descend further from the body or to contract

1:16:16and bring the testicles closer to the body

1:16:17in order to try and maintain the optimal temperature range.

1:16:20And it turns out the cremaster muscle can achieve that

1:16:23whether or not people are wearing boxers or briefs.

1:16:25Although it stands to reason that any kind of--

1:16:29there's no other name for it-- undergarments-- you know,

1:16:31I don't know why that word just seems kind of antiquated--

1:16:33but undergarment that allows some movement of the scrotum

1:16:37and the testicles should be sufficient to allow

1:16:39these temperature variations to occur and keep things in range.

1:16:44That said, a little bit later, we'll go into some detail,

1:16:47really--

1:16:47because it's important-- as to why,

1:16:50for instance, if you are somebody who has big thighs,

1:16:52believe it or not, that it actually

1:16:53can lower sperm count substantially, whether or not

1:16:56the big thighs occur because you're very muscular

1:16:58or the big thighs occur because you are overweight.

1:17:00It can increase the temperature.

1:17:02If you're sitting a lot, increases

1:17:04scrotal temperature, for sure.

1:17:05And there are some other things that can increase scrotal

1:17:08temperature, seat heaters in cars, for instance--

1:17:11terrible idea, just terrible idea if you're hoping

1:17:14to conceive in the near future--

1:17:16and again, hot tub, things of that sort.

1:17:20So temperature modulation of spermatogenesis and sperm

1:17:24quality and function is key.

1:17:26That relates a little bit more to tools.

1:17:27But what happens?

1:17:28How does the actual sperm develop?

1:17:31Well, contained within the testicle,

1:17:33you have the cells, the so-called spermatogonia,

1:17:36which differentiate into so-called spermatocytes.

1:17:38You don't have to remember all this.

1:17:40And the spermatocytes undergo this process of meiosis.

1:17:43Meiosis is a form of cell division, which

1:17:45reduces the chromosome number to those 23 individual strands as

1:17:49opposed to pairs.

1:17:51So it makes them haploid as opposed to diploid.

1:17:53Very, very important for reasons that we talked about earlier.

1:17:56And the meiosis process in these primordial sperm cells,

1:18:00these immature sperm cells, is similar to the meiosis process

1:18:04that occurs in eggs when the chromosomes segregate in

1:18:07that it involves these spindle-like structures

1:18:10within the cell.

1:18:11Now, why do I keep bringing up the spindles?

1:18:12Well, it turns out that the function

1:18:14of the spindle in the egg and the sperm

1:18:16is heavily dependent on mitochondrial function.

1:18:19And later when we get into tools for improving egg and sperm

1:18:22quality, you're going to hear about a lot of tools

1:18:24for improving mitochondria.

1:18:25And it's not just because the mitochondria

1:18:27are involved in energy-demanding aspects of cell biology.

1:18:31But it's also because the mitochondria in this context

1:18:34are very, very important for the removal of or the separation

1:18:39of one set of chromosomes to give you

1:18:41these two sets of haploid cells, the egg and the sperm.

1:18:44And this is so important because many failures at fertilization,

1:18:49many failures at implantation, many, many miscarriages,

1:18:53and many birth defects that do survive after birth that

1:18:57are very detrimental, such as trisomies and things like that,

1:19:01occur because the spindles don't effectively pull apart

1:19:05the chromosomes in typically the egg,

1:19:08but it can also occur in the sperm.

1:19:10So the spindles and the fact that mitochondria

1:19:12are rich on the spindle are very important for generating

1:19:15these haploid sperm-- again, 23 individual strands

1:19:17of chromosomes.

1:19:19That's occurring inside of the testes.

1:19:23So there's not as much long-distance migration

1:19:25of the spermatocytes and the sperm cells

1:19:29as there is the egg just when you

1:19:31think about the overall architecture of the uterus

1:19:33and the Fallopian tubes compared to the testicles,

1:19:35but there's still a lot of movement.

1:19:36So within the testicle, if you were

1:19:38to look at the testicle in cross-section--

1:19:40and I prefer to call it that rather than cut

1:19:42the testicle in half.

1:19:43Any time you talk about anatomy, you actually

1:19:44talk about slicing things.

1:19:45That's what you would do with a cadaver is what I teach

1:19:48and we do in my laboratory and, frankly,

1:19:52in biological laboratories all over the place.

1:19:54But when you talk about it, you talk about if you were to take

1:19:56a visual cross-section through the testicle,

1:19:58what you would find is that there are a lot of different

1:20:01little tubes, a lot of ducts, D-U-C-T-S, ducts.

1:20:05Those are pathways.

1:20:06And the main ducts that are important for this discussion

1:20:10are called the seminiferous tubules.

1:20:13So it's a mesh-like or network structure

1:20:16of tubes in the testicle.

1:20:18And the immature sperm sit on a little compartment

1:20:23along the edge of those tubes.

1:20:24And as they mature, they move towards the center

1:20:27of those tubes.

1:20:27And then when they are mature enough,

1:20:29those sperm cells actually drop into the hollow of the tube,

1:20:33and then can travel through those tubes

1:20:35to a structure that's along the side of the testicle called

1:20:40the epididymis.

1:20:42The epididymis, again, is a series of ducts.

1:20:45And then the epididymis converges with something

1:20:47called the vas deferens.

1:20:49I think in high school, we all remember this

1:20:51by thinking about it's the vast difference.

1:20:53I don't know who came up with that.

1:20:55I think it was a young girl sitting

1:20:57to the left of me that was like, oh, it's

1:20:58like the vast difference.

1:20:59I never forgot that.

1:21:00I don't know.

1:21:00Maybe it was the topic matter.

1:21:01Maybe it was her.

1:21:02Maybe it was some combination of the two.

1:21:03But in any case, the sperm go from the seminiferous

1:21:05tubules to the epididymis and then

1:21:09to the vas deferens and then are contained in the ejaculate,

1:21:12along with seminal fluid.

1:21:14Now, the seminal fluid is the carrier fluid

1:21:18for the sperm themselves.

1:21:21This is important because it turns out

1:21:23that a lot of things that can both negatively or positively

1:21:26impact the quality of the sperm relates not just

1:21:29to the sperm cells themselves and the temperature

1:21:31of the environment that they were matured in,

1:21:35but also to the semen quality.

1:21:38For instance, if you are a heavy drinker, if you are a smoker,

1:21:43or if you are a regular user of cannabis,

1:21:47especially if you smoke cannabis or vape cannabis,

1:21:51you create a lot of reactive oxygen species

1:21:54that disrupt the chemistry of the seminal fluid, which

1:21:57disrupts the sperm cells.

1:21:59So it's not a direct action always on the sperm cell

1:22:01itself, although it can be.

1:22:02So for instance, in the form of smoked tobacco or cannabis,

1:22:07there are a lot of carcinogens and mutagens

1:22:09that actually mutate the DNA, can cause DNA fragmentation,

1:22:12and debilitate sperm.

1:22:13But there are also a lot of things created by smoking

1:22:17in particular, regardless of what's being smoked,

1:22:20that can create elevated reactive oxygen species

1:22:24and disrupt the seminal fluid that the sperm are contained

1:22:28in in the so-called ejaculate, the semen.

1:22:31Now, this will also become a relevant conversation later

1:22:35when we briefly talk about vasectomies.

1:22:37Vasectomies are literally a cutting

1:22:41of the vas deferens, which leads to a situation,

1:22:45provided the surgery was done correctly,

1:22:46where men can still achieve all the other aspects

1:22:50of intercourse.

1:22:51They can still achieve erection.

1:22:53They can still achieve orgasm.

1:22:54They can still ejaculate.

1:22:57But when they ejaculate, the seminal fluid is released,

1:23:00but there are no sperm contained within the seminal fluid.

1:23:02And it turns out that vasectomies

1:23:04are a very effective form of birth control.

1:23:07And they always check to see if zero sperm

1:23:09and confirm that zero sperm are being

1:23:11released in the ejaculate.

1:23:12They are reversible.

1:23:13And that is, vasectomies are reversible, but not always.

1:23:17There are a subset of cases where it's not reversible,

1:23:19in which case if people still want to have children,

1:23:22you have to go in and actually surgically extract sperm

1:23:25from the testicles.

1:23:26But it's a process in which the vas deferens is altered

1:23:32or severed in a way that the sperm can't actually

1:23:34exit the testicle.

1:23:35They can get into the epididymis, usually,

1:23:37but not into the vas deferens and so on and so forth.

1:23:41So if you've ever wondered what a vasectomy is,

1:23:43that's what a vasectomy is.

1:23:44And I mentioned vasectomy now because it illustrates

1:23:48the difference between the seminal fluid, the semen,

1:23:51and the sperm that the semen contain.

1:23:54So 60 days to generate the sperm, another two weeks

1:23:59or so for the sperm to travel through the various ducts

1:24:02to the point where they can be contained in the ejaculate.

1:24:05Let's talk about the sperm cells themselves.

1:24:07The sperm cells, again, have these 23 pairs

1:24:12of single-strand chromosomes.

1:24:13They're haploid.

1:24:14They have either an X or a Y sex chromosome

1:24:16as the 23rd so-called sex chromosome.

1:24:19And as we all know, they have a head.

1:24:21The head tends to be oval in most cases.

1:24:24The head contains very important enzymes and proteins

1:24:27that are designed to fuse with the much larger egg

1:24:30and to actually take the membrane of the sperm cell

1:24:33and combine to actually mesh with the egg cell's membrane

1:24:40and then deliver the genetic contents to the egg cell,

1:24:44in other words, to fertilize the egg cell.

1:24:46Now, just behind the head is a region called the mid region.

1:24:50That mid region is a slightly thickened region.

1:24:54And here, of course, I'm talking about healthy sperm cell

1:24:57morphology.

1:24:57Morphology simply means shape.

1:24:59A mid region-- that mid region has a bunch

1:25:02of things related to cell motility

1:25:04and to the forward progression of the cells.

1:25:07First of all, it is chock a block full of mitochondria.

1:25:10In fact, if you were to look just

1:25:11behind the head of the sperm, what you'd see

1:25:14is that it is completely surrounded by mitochondria.

1:25:18There are mitochondria elsewhere in the cell, but most of them

1:25:21are contained in this mid region compartment

1:25:23just behind the head of the sperm.

1:25:25And that thick region is where the tail movement of the sperm,

1:25:30the flagellation back and forth, is actually generated from.

1:25:37Much like if you were to hold a rope, like a battle

1:25:40rope in the gym, and you were to whip the battle rope,

1:25:45the whip at the one end of the rope

1:25:47is what allows for the sort of-- let's just call it

1:25:52what it is-- the curves in the rope,

1:25:53the oscillations, the rising and falling

1:25:55of the rope all the way out to the end.

1:25:57It is the force of the whip right at that end that with

1:26:02the battle rope you're doing with your hand--

1:26:04and with the sperm, that is occurring just behind the head

1:26:07of the sperm--

1:26:08that is actually going to dictate how fast

1:26:11and how well that sperm can swim.

1:26:14And indeed, the sperm has to swim very far.

1:26:16How far?

1:26:17Well, on a relative scale--

1:26:19and again, these are estimations because they're going to be--

1:26:22how should we say?

1:26:23There will be differences in the distance

1:26:26from the head of the penis and where the ejaculation occurs

1:26:33to the cervix, depending on the relative size

1:26:35of the vaginal canal and the penis that

1:26:38delivers the ejaculate to the vaginal canal.

1:26:40But once the sperm arrive at the cervix, which

1:26:44is at the back of the vaginal canal

1:26:47just at the opening to the uterus,

1:26:49once the sperm arrive there, the distance

1:26:52from the cervix to the egg, of course,

1:26:55will vary depending on where that egg is

1:26:58in its ovulatory trajectory, its pathway.

1:27:00But it is akin, if you scale for size,

1:27:04to the distance between Los Angeles and San Francisco,

1:27:08which is many, many hundreds of miles.

1:27:10So those sperm have to swim very far.

1:27:12Now, of course, if the sperm are delivered in the vaginal canal

1:27:16somewhat further away, they will have further to go.

1:27:19If they're delivered right at the cervical opening,

1:27:21they will have less far to go.

1:27:22The very effective swimming sperm swim very fast.

1:27:27So they are able to accomplish that distance

1:27:29in just a few days.

1:27:30And this relates to a discussion that we

1:27:34will get into in a lot more detail

1:27:35later as to how often couples should have intercourse

1:27:39if they're trying to conceive.

1:27:41Many people might think, well, it's every day.

1:27:43However, the more frequent the ejaculation, the lower

1:27:46the concentration of sperm in each ejaculate.

1:27:49So this is not a discussion about how often

1:27:51to have intercourse depending to your preferences,

1:27:53for pleasure or bonding or whatever reason.

1:27:55This is a discussion about how often to have intercourse

1:27:58in order to optimize the probability of fertilization

1:28:02of the egg.

1:28:02There's some general rules that, of course, come to mind,

1:28:05which is ejaculations close to ovulation-- both before,

1:28:10during, or sometimes after--

1:28:12are obviously advantageous.

1:28:15But you will also hear OB/GYNs and urologist

1:28:18suggesting intercourse every other day

1:28:21leading up to the day of ovulation,

1:28:24starting about three to four days out

1:28:26from the day of ovulation.

1:28:28So we got a little bit sidetracked,

1:28:30albeit I think appropriately so, in focusing on fertilization.

1:28:34But what we were talking about right up until the point

1:28:36of that is the anatomy of the sperm itself,

1:28:39which is the head, the mid region that

1:28:41contains all those mitochondria, and then the tail.

1:28:44Now, what we haven't discussed is the actual generation

1:28:47of the sperm.

1:28:48So if you're a male or if you're a female,

1:28:51I think it's really important to understand

1:28:53how spermatogenesis works.

1:28:56Spermatogenesis works in much in the same way

1:29:00that the generation and maturation of eggs work,

1:29:03although, as I mentioned before, it's

1:29:05going to occur ongoing throughout the cycle

1:29:08of the male's life after puberty.

1:29:11We already talked about puberty, and I'll just

1:29:14cover this in two or three sentences

1:29:16as it relates to males.

1:29:17And it's essentially the same thing.

1:29:21The hypothalamus, up until the point of puberty,

1:29:24is providing suppression of the release

1:29:27of gonadotropin-releasing hormone.

1:29:29Then some biological clock, which is still not clearly

1:29:33understood-- it's probably not leptin coming from body fat.

1:29:38Again, unlike in the female, it's probably not leptin

1:29:40coming from body fat.

1:29:41But some other signal arrives to the hypothalamus,

1:29:44removes that inhibition, and GnRH,

1:29:46gonadotropin-releasing hormone, is now

1:29:48released onto the pituitary.

1:29:50A bunch of hormones are deployed from the pituitary

1:29:52as a consequence.

1:29:53The two most important ones for the context of this discussion

1:29:56are follicle-stimulating hormone and luteinizing hormone.

1:30:00Follicle-stimulating hormone and luteinizing hormone

1:30:02travel to the testes, and they're

1:30:05going to do two main things.

1:30:06One, they're going to trigger the production of testosterone.

1:30:10And they're going to trigger the production

1:30:12of the sperm themselves.

1:30:13They're going to set in motion, for essentially

1:30:15the rest of the life of the male, the production of sperm.

1:30:20They're going to initiate the spermatogenesis cycle,

1:30:22and that cycle is going to be ongoing

1:30:24at various stages for different sperm

1:30:26for the rest of the man's life.

1:30:28This is very different than the triggering of development

1:30:33of oocytes and eggs in females, where there's an existing

1:30:37vault. That vault can be depleted to the point of zero

1:30:40where it can't occur again.

1:30:41Men can generate sperm their entire lifetime.

1:30:43Of course, there's a diminishment

1:30:45of sperm production in very, very late age,

1:30:48say, 80s and 90s or 100s.

1:30:50But believe it or not, there are still sperm being produced.

1:30:52The quality of those sperm is another question.

1:30:55So everything we're going to talk about now

1:30:57is essentially puberty onward.

1:30:59Prior to that, testicles are present,

1:31:02but they're not generating sperm.

1:31:04Ejaculation isn't possible, or if it is possible,

1:31:07it's very unlikely and unusual, and it's not

1:31:10going to contain sperm.

1:31:12Everything we're going to talk about now

1:31:14is puberty forward, so puberty onward to the rest of life.

1:31:20And luteinizing hormone secreted from the pituitary acts

1:31:24on the testes and on a very specific cell type

1:31:27in the testes called the Leydig egg cells, or Leydig cells,

1:31:30L-E-Y-D-I-G, the Leydig cells.

1:31:33The Leydig cells of the testes are what produce testosterone.

1:31:37Testosterone is going to have two major effects.

1:31:41And here I mean really major because it

1:31:43has many, many hundreds of effects on different tissues

1:31:45of the body.

1:31:46In fact, that's the definition of a hormone, really.

1:31:48It's a substance that acts in an endocrine fashion.

1:31:51It can act on the very tissue that generated it.

1:31:53So for instance, testosterone made by the Leydig cells

1:31:55within the testes will act on the testes,

1:31:57as we'll talk about in a moment.

1:31:58But it can also act on other tissues.

1:32:01It can act on the pharynx and larynx

1:32:02and deepen the voice, as it does during puberty.

1:32:04It can act on the hair follicles and generate facial hair.

1:32:06It can act on the musculature and generate protein synthesis

1:32:10and development of muscle, bone, et

1:32:12cetera, all the things we associate

1:32:13with puberty and with testosterone typically.

1:32:17Restricting the conversation to the effects of testosterone

1:32:20on the testicle itself and on spermatogenesis,

1:32:23the Leydig cells make testosterone.

1:32:25And keep in mind that some of that testosterone

1:32:27will travel elsewhere in the body

1:32:29and do its thing for gene expression

1:32:31and the more acute effects of testosterone on the brain

1:32:34included.

1:32:35But the testosterone within the testes

1:32:37is at extremely high concentration.

1:32:40In fact, the concentration of intratesticular testosterone

1:32:44is at least 100 times higher than the concentration

1:32:47of testosterone anywhere else in the body,

1:32:49even though it's being secreted into the rest of the body.

1:32:52And that's because there are a number

1:32:54of different so-called binding proteins and enzymes

1:32:57that sequester the testosterone within the testes.

1:33:00So the Leydig cells are making testosterone,

1:33:02and a lot of that testosterone is acting on

1:33:04and is restricted to the testes.

1:33:06And that turns out to be very important because testosterone

1:33:11within the testes acts in concert

1:33:14with a different biological program that starts with FSH,

1:33:18follicle-stimulating hormone, that also travels to the testes

1:33:21and acts on a very specific set of cells that are called

1:33:25supporting cells or, more specifically,

1:33:27the Sertoli cells.

1:33:29The Sertoli cells are the cells that

1:33:32generate something called ABP, or androgen-binding protein.

1:33:36And it is the combination of testosterone from the Leydig

1:33:39cells and ABP from the Sertoli cells

1:33:43that is necessary for spermatogenesis.

1:33:46It's necessary for those spermatocytes

1:33:49to become what will eventually be healthy, mature sperm that

1:33:52have really nice shaped oval heads, have a mid region,

1:33:56chock a block through mitochondria,

1:33:57and can generate a fast whipping motion of the tail

1:34:00to swim from the cervix, or up the vagina into the cervix,

1:34:04and from the cervix to the egg to fertilize the egg.

1:34:07So it's really a basic set of chemical players that are

1:34:10involved here and so basic, in fact,

1:34:13that if you were to disrupt any one of these chemical players--

1:34:16either the luteinizing hormone, the FSH,

1:34:19the testosterone from the Leydig cells,

1:34:20or androgen-binding protein--

1:34:23you would observe pretty marked disruption

1:34:27in spermatogenesis or the elimination of sperm entirely.

1:34:31We'll get into a few deficits in sperm development

1:34:33and sperm number and sperm function a little bit later.

1:34:36But just keep in mind--

1:34:37or I should say, maybe sit back and just

1:34:39appreciate that the exact same players generate

1:34:42from the hypothalamus, which causes luteinizing

1:34:45hormone and follicle-stimulating hormone released

1:34:48from the pituitary, which travels to the gonad, which

1:34:51in this case is the testicle, which triggers

1:34:53the release of testosterone from Leydig

1:34:55cells, which triggers the action of the supporting cells,

1:35:00the Sertoli cells, which make androgen-binding protein.

1:35:03Testosterone and androgen-binding protein

1:35:05combine and create a chemical and actually

1:35:08a structural milieu in which those little spermatocytes

1:35:12can go from the walls, from literally

1:35:14the walls of the tubes of the seminiferous tubules,

1:35:17can mature into healthy, well-developed sperm,

1:35:19and can hop into those ducts, those little tubes,

1:35:23and then head off to the epididymis, where they will

1:35:25reside-- the epididymis is the tissue nearby the testicles

1:35:29or surrounding one portion of the testicle--

1:35:31and then eventually fuse with the vas deferens,

1:35:33can combine with or be contained with, rather,

1:35:36the seminal fluid, and then can be ejaculated via the urethra

1:35:41into the female, where then they can

1:35:43swim very quickly, effectively the distance, for them anyway,

1:35:46from Los Angeles to San Francisco,

1:35:48over the course of a very short period of time,

1:35:51and fertilize the egg.

1:35:53So that's the process of spermatogenesis, the maturation

1:35:56of sperm, which is ongoing throughout the lifespan

1:36:00from puberty onward.

1:36:01And in doing so, we talked about some of the hormonal elements--

1:36:04coming from the hypothalamus and coming from the pituitary,

1:36:07and within the testes themselves the Leydig cells, which

1:36:10produce testosterone, the Sertoli cells,

1:36:12which are the support cells that allow spermatogenesis to occur.

1:36:17With that in mind, next I'd like to think

1:36:20about what's actually contained in the ejaculate in terms

1:36:23of numbers of sperm and what's really being selected

1:36:26for in terms of the sperm that actually successfully

1:36:28fertilizes the egg and what sorts of elements

1:36:30come into play in dictating whether or not fertilization

1:36:34will or won't occur.

1:36:35And the major themes that we're going to discuss

1:36:37are frequency of ejaculation, but really

1:36:41that's just kind of a proxy for talking about maximizing

1:36:44sperm concentration and quality of sperm arriving at the egg--

1:36:48because, remember, ovulation and the menstrual cycle

1:36:51are really about creating the opportunity for fertilization.

1:36:55And we are also going to talk about how

1:36:58the vaginal duct, the vagina, and

1:37:01the milieu around the cervix and some other elements

1:37:04within the female herself contribute to

1:37:08and support the sperm in their journey to the egg

1:37:11and in the likelihood that they will fertilize the egg.

1:37:13So really what we need to talk about first is sperm quality.

1:37:17And we should also probably talk about ejaculate quality,

1:37:20because, as odd as that theme might seem,

1:37:24really the ejaculate quality, which

1:37:27has a number of different parameters,

1:37:29including the number of mature sperm

1:37:32that are not so mature that they're swimming slower

1:37:34or are dead, but also quality of sperm.

1:37:36They have, for instance, one tail.

1:37:37It's not entirely uncommon to see sperm

1:37:40with two tails because they just didn't form properly

1:37:43or sperm that are not moving very much.

1:37:45In fact, sperm motility is scored along a scale of 0,

1:37:481, 2, or 3, 3 being the best, fast forward progressing.

1:37:520 is not moving at all.

1:37:541, they're actually called twitchers.

1:37:57Twitchers are sperm that sort of just twitch in place

1:37:59but don't undergo forward progression.

1:38:012 is somewhere in between 1 and 3, not surprisingly.

1:38:06Different clinics, different OB/GYNs, different urologists

1:38:10will throw out different numbers.

1:38:12But in general, it is hoped that more than 50% of the sperm

1:38:17should be motile in some way or another, so not scoring a 0,

1:38:20but a 1, or 2, or ideally a 3.

1:38:23The concentration of sperm--

1:38:25of course, if it's higher within the ejaculate, the total number

1:38:30of sperm per milliliter of ejaculate, if that's higher,

1:38:33then there's a higher probability

1:38:35that one of those sperm will fertilize the egg.

1:38:38One thing I didn't mention before when

1:38:40discussing the production of eggs and ovulation--

1:38:42and I probably should have, so I will

1:38:43now-- is that most often only one

1:38:46ovary gives rise to an ovulating egg.

1:38:51It happens, but it's somewhat rare for two mature eggs, one

1:38:57from each ovary, to be deployed during a single ovulation.

1:39:00There's a name for that when it occurs and both are fertilized.

1:39:03It's called fraternal twins.

1:39:06If a single egg--

1:39:08that, of course, comes from a single ovary--

1:39:10is fertilized and the egg splits--

1:39:14and that's something that happens further along

1:39:16in the process of fertilization and differentiation

1:39:19of the embryo--

1:39:20well, then what you get are identical twins.

1:39:23There are other instances that are quite uncommon in which

1:39:26you can get fraternal twins through other circumstances.

1:39:28But in general, that's the way it works.

1:39:30But essentially what happens is one egg

1:39:32from one ovary-- that's the most common occurrence.

1:39:34The sperm, once ejaculated into the vaginal duct,

1:39:38are going to pass through the cervix

1:39:42and then are going to swim toward the egg.

1:39:44The egg could be at varying locations

1:39:47along the female reproductive axis.

1:39:50Now, this is actually a very important thing

1:39:52and actually gets right down to the safety of both the

1:39:56potentially developing embryo and the mother.

1:39:58There is something referred to as ectopic pregnancy,

1:40:01and that's when the pregnancy actually occurs

1:40:04within the Fallopian tubes.

1:40:05So the precise location in which fertilization

1:40:08between the sperm and the egg occurs can vary somewhat.

1:40:11But ideally, the fertilized egg implants into the endometrium

1:40:15or the endometrial lining of the uterus

1:40:17and develops there as opposed to within the Fallopian tubes,

1:40:20which is so-called ectopic pregnancy.

1:40:22Now, where the sperm and the egg meet exactly

1:40:25can vary, as I mentioned before.

1:40:27But in general, the faster swimming sperm

1:40:30and the more far along the ovulatory trajectory the egg

1:40:34are, the higher the probability of a successful fertilization

1:40:38because of the proximity to the implantation zone

1:40:40of the uterus.

1:40:41So basically it's all a probabilities game.

1:40:43It's a probabilities game related

1:40:45to the number of sperm cells that encounter the egg

1:40:47and where the egg is in terms of its ovulatory cycle

1:40:50and also its position where it is in the ovulatory cycle.

1:40:55The sperm parameters-- or I should

1:40:58say the semen parameters-- and ejaculate parameters

1:41:01that most clinicians want to see,

1:41:03if you were to give a sperm sample,

1:41:05would be somewhere in excess of 15 million sperm per milliliter

1:41:11of ejaculate.

1:41:12Now, there's a lot of discussion nowadays.

1:41:15It seems to be a very popular news theme

1:41:17to talk about diminishing sperm counts, the idea that 100

1:41:21years ago or maybe even 35 years ago, the typical male ejaculate

1:41:25contained 100 million sperm per milliliter,

1:41:28and nowadays it's down to 15 to 20 or 50.

1:41:31And indeed, sperm counts do seem to be declining.

1:41:34And the exact reasons for that are not clear.

1:41:36I confess I'm a little bit reluctant to talk about this

1:41:39because there have been a lot of back and forth discussions

1:41:42about the safety of EMFs, of electromagnetic fields,

1:41:44and it's not exactly what we're talking about here.

1:41:46But there are some excellent data

1:41:49contained in meta-analyses and reviews

1:41:50that I will provide links to and that we'll talk about

1:41:52in more detail in a minute that correlate

1:41:57the advent of smartphones and in particular caring

1:41:59of smartphones in the pocket with diminishing sperm counts.

1:42:03Although there are certain to be other factors that

1:42:06can explain diminishing sperm counts as well.

1:42:08Dr. Shanna Swan, for instance, has done beautiful work

1:42:12describing how the phthalates and the BPAs

1:42:16and so-called endocrine disruptors

1:42:18might be disrupting some of the milieu

1:42:19of the seminiferous tubules.

1:42:22So this would be reductions in testosterone and/or disruptions

1:42:24to the Sertoli cells and androgen-binding protein

1:42:27brought about by endocrine disruptors such as phthalates

1:42:29contained in pesticides and contained on printed receipts

1:42:32and things of that sort.

1:42:33There are some data that that is negatively

1:42:35impacting sperm counts.

1:42:38How much so is still debatable.

1:42:42There are also quite good data pointing

1:42:44to the fact that both the heat-related

1:42:47and the non-heat-related impact of smartphones and laptops

1:42:52contained on the lap are impacting sperm count

1:42:55and in a negative way.

1:42:57Again, there's going to be tremendous variation

1:42:59in the concentration of sperm from one

1:43:00individual to the next.

1:43:01It will vary according to age and a number of other factors

1:43:04that we'll talk about a little bit later.

1:43:07But in general, if somebody is wishing to conceive,

1:43:10then clinicians like to see a ejaculate volume

1:43:13of more than 2 milliliters.

1:43:16So ejaculate volume can be anywhere

1:43:18from 1.5 to 5 milliliters.

1:43:22And that will strongly be determined

1:43:24by how frequent ejaculation is occurring.

1:43:27There's a lot that goes into evaluating the quality

1:43:29of ejaculate and sperm.

1:43:30But basically these huge variations that are observed

1:43:35of anywhere from 15 million sperm per milliliter

1:43:38or, in some males who are not producing sperm for whatever

1:43:40reason-- we'll talk about those reasons in a little bit--

1:43:44as low as 5 million sperm per milliliter,

1:43:47all the way up to 100 or maybe even

1:43:48200 million sperm per milliliter.

1:43:51Huge variation-- the cause of which is not always clear

1:43:56but is certainly determined in part

1:43:58by the frequency of ejaculation.

1:44:00So because there are so many variables

1:44:03impacting why one male versus another male or even

1:44:06the same male across the lifespan

1:44:07might have variations in his concentration of sperm

1:44:10within the ejaculate, let's talk for a second about frequency

1:44:14of ejaculation as it relates to the goal of fertility,

1:44:17per se, because that's really what today's episode is all

1:44:19about.

1:44:20So what I'd like to talk about next

1:44:21is how people can increase the probability

1:44:24of a successful fertilization, focusing

1:44:26both on the components from the male side

1:44:29and from the female side.

1:44:30And I'm mainly going to couch this discussion in the context

1:44:33of the so-called natural method of sexual intercourse

1:44:36and ejaculation in vivo, within the female.

1:44:41But I will also touch on some parallel themes

1:44:43as it relates to in-vitro fertilization

1:44:45and intrauterine insemination.

1:44:48So the idea here is that we want the maximum number

1:44:52of high-quality sperm-- that is, rapidly forward,

1:44:55motile sperm that are of the correct morphology--

1:44:58that is, shape.

1:44:59That's going to require a lot of mitochondria

1:45:02in the mid region, a well-shaped head--

1:45:04so it's going to be an oval-shaped head.

1:45:06The tail is going to be a single tail, not multiple tails.

1:45:08These aren't going to be the twitcher type of--

1:45:11or immotile type of sperm that are either twitching in place

1:45:14or aren't moving forward.

1:45:15All of those components are going

1:45:17to be essential for increasing the probability

1:45:20of fertilization.

1:45:21But of course, there's the female side of it,

1:45:23too, which is that ovulation occurs

1:45:25on just one day during the menstrual ovulatory cycle.

1:45:28And that egg will be available for fertilization

1:45:31for approximately 24 hours.

1:45:33Now, keep in mind that the sperm can survive

1:45:35within the vaginal duct and within the area

1:45:38around the cervix and within the uterus

1:45:40and along the female reproductive tract for anywhere

1:45:44from three to five or it's even been

1:45:46described as up to seven days.

1:45:47But generally, it's going to be about three to five days.

1:45:50Now, most women can figure out the day of their ovulation

1:45:54by counting the total number of days of their typical cycle.

1:45:57And this is where it's really useful

1:45:58to have a cycle that's of more or less regular duration

1:46:02or, rather, of more or less regular length.

1:46:05So as we talked about earlier, if somebody's cycle

1:46:08is 21 days or 25 days and it's 21 or 25 days consistently

1:46:12or even 30 days consistently, that's

1:46:14going to be a far better scenario to favor fertilization

1:46:17than if it's 20 days one month and then 21

1:46:20days the next month, but then suddenly 30 days and then

1:46:23suddenly 35 days.

1:46:25Those varying durations of the ovulatory cycle

1:46:28make it very hard, obviously, to time

1:46:30and understand when ovulation is going to occur.

1:46:32So regular duration ovulatory cycles

1:46:36are the ideal circumstance, and they're the ideal circumstance,

1:46:39because even though the egg is only

1:46:41available for fertilization for a few days,

1:46:43those sperm can survive for some period of time, which

1:46:46leads to the issue of how often should couples

1:46:49be having intercourse.

1:46:51And here, I'm referring specifically

1:46:53to intercourse with ejaculation.

1:46:54How often should couples be having intercourse

1:46:56around the time of ovulation if the specific goal is

1:47:00successful fertilization of the egg and the creation of a baby?

1:47:05This is leaving aside all issues, which, of course, are

1:47:08interesting issues, related to how often people are having

1:47:11intercourse, whether or not there's ejaculation

1:47:13every time they have intercourse or not, for sake of pleasure

1:47:16or for sake of pair bonding and pleasure

1:47:19or for sake of any number of other potential goals

1:47:22of intercourse.

1:47:22Here I'm only referring to intercourse

1:47:24as it relates to the goal of fertilization of the egg.

1:47:29So knowing what we know about spermatogenesis and the fact

1:47:35that ejaculate is going to contain a certain concentration

1:47:39of sperm but that within that ejaculate some of the sperm

1:47:42will be older and less healthy and some will be optimally

1:47:46mature and some might even be a little bit

1:47:48immature-- although there's a tendency for the immature sperm

1:47:50to not have yet exited the seminiferous tubules, gone

1:47:55into the epididymis and vas deferens.

1:47:56But given that the ejaculate contains

1:47:58sperm of varying ages and therefore varying quality

1:48:02and given that with each successive ejaculation

1:48:05in a short period of time there's

1:48:07going to be a decrease in the concentration of sperm

1:48:10per milliliter of semen, of ejaculate,

1:48:13we can make some good arguments as

1:48:16to how often couples should have intercourse

1:48:19with ejaculation around the time of ovulation

1:48:21if the goal is to fertilize.

1:48:23If ovulation occurs on, for instance,

1:48:25day 14 of a cycle-- and here we're

1:48:26using the kind of standard average

1:48:28of 28 days of the cycle.

1:48:30But for some people with a 30-day cycle,

1:48:32it could be day 15, or with a shorter cycle,

1:48:36it could be day 12, for instance.

1:48:37But given a 28-day average cycle,

1:48:40let's say ovulation occurs on day 13 or on day 14.

1:48:44And typically, it would occur on day 14 of a 28-day cycle.

1:48:48Well, then, given how long sperm can survive inside

1:48:52of the woman, you might think that the optimal strategy would

1:48:55be to have as much intercourse with ejaculation in the three

1:48:58or four days leading up to ovulation, hope

1:49:01that those sperm have swam as far as they possibly

1:49:04can and will encounter the egg just as soon as possible

1:49:06after it ovulates.

1:49:08It turns out that's not the optimal strategy.

1:49:10The optimal strategy is really to maximize the concentration

1:49:13of healthy sperm within each ejaculate

1:49:16and to really center that around the day of ovulation.

1:49:19So what this involves generally and what

1:49:22the typical recommendation is is to abstain from intercourse

1:49:27with ejaculation about two or three

1:49:29days out from ovulation and then, on the day

1:49:33prior to ovulation and on the day of ovulation,

1:49:37to essentially introduce as much semen

1:49:40and ejaculate into the reproductive pathway

1:49:43of the female as possible.

1:49:45Now, that's the general recommendation

1:49:47that the OB/GYNs and the urologists that I spoke to

1:49:50gave.

1:49:51But you will also hear a different strategy.

1:49:54It's only slightly different.

1:49:55But the different strategy involves

1:49:57trying to maximize the concentration of healthy sperm

1:50:00within each ejaculate with the understanding that,

1:50:02with each subsequent ejaculation over about a 24-hour period,

1:50:06that there's going to be a dramatic reduction

1:50:09in the concentration of sperm.

1:50:10What that means is that if a couple, for instance,

1:50:12were to have intercourse with ejaculation many times

1:50:15on the day prior to ovulation, yes,

1:50:17that will introduce a lot of sperm

1:50:19into the reproductive pathway of the female, but what it means

1:50:23is that, on the day of ovulation if they were

1:50:25to have intercourse, the number of high quality sperm

1:50:29that will be available to the egg will be greatly diminished.

1:50:32And if none of the sperm that were introduced

1:50:35in the day prior managed to fertilize that egg,

1:50:38well, then essentially chances are off

1:50:40that there will be fertilization or they're greatly diminished.

1:50:43Rather, if they're having intercourse with ejaculation

1:50:47once or twice on the day prior to ovulation

1:50:50and then a maximal number of times with ejaculation

1:50:53on the day of ovulation, that itself

1:50:56can maximize the probability of fertilization.

1:50:58So which strategy is optimal?

1:51:00Should couples have as much intercourse

1:51:01with ejaculation on the day prior to ovulation

1:51:04and on the day of ovulation?

1:51:06Or should they have intercourse on the day prior to ovulation

1:51:10but not so frequently that it diminishes the concentration

1:51:13of sperm and then allows for intercourse

1:51:17with the maximum number of ejaculations

1:51:20on the day of ovulation?

1:51:21You really hear it both ways.

1:51:23And what this really boils down to is,

1:51:24frankly, that nobody knows.

1:51:26And the reason nobody knows is that there's

1:51:28tremendous variation among males in terms

1:51:30of the absolute concentration of sperm per milliliter

1:51:33of ejaculate and the amount of sperm per milliliter

1:51:39of ejaculate within a given time frame.

1:51:41But what everyone agrees on is that a period of abstinence

1:51:45ranging from 48 to 72 hours prior to an ejaculation

1:51:49increases the concentration of high-quality sperm

1:51:52within that first ejaculation to occur after the abstinence

1:51:56period.

1:51:57So again, to reiterate, if one's goal is to fertilize the egg,

1:52:00you want to take into consideration

1:52:02that most often there is going to be

1:52:05a dramatic decline in the concentration of sperm

1:52:08per ejaculate any time those ejaculations are occurring

1:52:12within a short period of time, say,

1:52:13within 12 to 24 hours of one another.

1:52:16Now, all of this, of course, also

1:52:18relates to the female biology and the extent

1:52:21to which the woman can precisely identify the day

1:52:25and timing of her ovulation.

1:52:26Some women feel as if and indeed are very accurate

1:52:30at estimating their time of ovulation

1:52:33to within a couple of hours or some women even

1:52:36report being able to feel their actual ovulation,

1:52:39whether or not they are feeling the ovulation

1:52:41itself, the deployment of the egg or not, isn't clear.

1:52:43I certainly wouldn't know.

1:52:45I've never produced eggs, nor have I ovulated,

1:52:47and I'm certainly not going to contest the idea

1:52:49that women can do that.

1:52:52I mean, it makes sense that some people

1:52:54have a very keen so-called interoceptive

1:52:57awareness, an awareness of the sensory events

1:52:59within their body.

1:53:01And while, of course, the ovaries are not

1:53:03thought of as an organ that we want

1:53:05to be able to sense what's going on in there in terms of feel,

1:53:08there are sensory endings within the ovary.

1:53:10And so the notion that one could literally sense changes

1:53:14within their ovary, including the deployment of the egg,

1:53:16is not outside the bounds of reason and, in fact,

1:53:20could likely be the case.

1:53:21Now, that said, there are a number of different ways

1:53:25that women will track their ovulation.

1:53:26One is the temperature method.

1:53:28So they'll actually measure intravaginal temperature.

1:53:30They're looking for changes in temperature

1:53:32that are consistent around the time of ovulation.

1:53:35We're going to have an expert guest on, an OB/GYN, who

1:53:38can tell us a lot more about the details and nuances

1:53:40of the temperature method.

1:53:42You'll see a lot of information about this online,

1:53:43but there's a lot of misunderstanding about it,

1:53:45as well.

1:53:46Other women will use apps that take into account

1:53:49either the temperature information

1:53:50if they're acquiring temperature information--

1:53:53that'll be entered into the app--

1:53:54as well as marking the onset of menstruation,

1:53:58the onset of bleeding, therefore,

1:54:00the start of the ovulatory cycle,

1:54:01because, of course, as we mentioned earlier,

1:54:03that marks day one of their cycle.

1:54:04And then, again and again, you can

1:54:06see how regularity of cycle duration

1:54:08or relative regularity of cycle duration

1:54:11really favors this whole process of being able to predict

1:54:14when one ovulates.

1:54:16And fortunately, if the goal is fertilization,

1:54:20there are some margins for error that are introduced by the fact

1:54:24that the sperm can survive within the female reproductive

1:54:27tract for some period of days, thereby reducing

1:54:31the need for absolute certainty about the time of ovulation

1:54:35and so on.

1:54:36In fact, it's pretty well known that around the time

1:54:38of ovulation a couple of things happen.

1:54:40Earlier, we talked about one thing,

1:54:42which is there's an increase in libido just prior to ovulation.

1:54:44This relates to, in part, an increase

1:54:47in some of the androgens, things like DHEA,

1:54:51but also testosterone and some related androgens

1:54:54that can increase libido both in males and females and changes

1:55:00to the reproductive pathway, the female in particular,

1:55:04a change in the pH-- that is, the relative acidity

1:55:07versus basic nature of the mucosal lining near the cervix

1:55:12and also vaginal secretions, such that,

1:55:14around the time of ovulation, the entire milieu of the vagina

1:55:19and the cervix and the locations in which fertilization can

1:55:23occur and certainly in which the sperm are swimming

1:55:25towards the opportunity for fertilization

1:55:27is shifted to support sperm motility and health.

1:55:31In other words, one of the best environments for sperm

1:55:33to survive is going to be within the female reproductive pathway

1:55:37itself.

1:55:38And as long as we're talking about vaginal secretions

1:55:40and mucus, it's important to point out

1:55:43that a number of commercially available lubricants

1:55:45can actually be detrimental for sperm health,

1:55:48even if they don't contain spermicide.

1:55:50So this is something that you'll want

1:55:52to discuss with your OB/GYN or, certainly if you're male,

1:55:56you could also discuss this with your urologist

1:55:58and your partner's OB/GYN.

1:56:01A lot of the commercially available lubricants

1:56:04contain chemicals that, while they may favorably

1:56:07change the consistency or the viscosity

1:56:10of the vaginal pathway for purposes of intercourse,

1:56:13certainly may not be the most favorable for maintaining

1:56:17the health of the sperm and the motility of the sperm.

1:56:20So again, here we're talking about intercourse only

1:56:23in the context of trying to maximize fertilization.

1:56:26And I should mention that there are

1:56:28certain lubricants that are more conducive to the sperm

1:56:30environment.

1:56:31But it's something that you'll really

1:56:33want to talk to your OB/GYN about

1:56:34or at least read up about if your interest is

1:56:37in trying to fertilize and develop an embryo.

1:56:40So we covered the optimal strategies

1:56:41for how often couples should have intercourse

1:56:44with ejaculation around the time of ovulation

1:56:48in order to maximize the probability

1:56:50that successful fertilization and ultimately pregnancy will

1:56:53occur.

1:56:54What we haven't covered yet, however,

1:56:56is how long couples should apply that method over time in order

1:57:01to achieve successful fertilization in pregnancy.

1:57:04Now, of course, if a couple decides

1:57:06that they want to conceive and they

1:57:07apply that method or any other method, for instance,