How to Optimize Fertility in Males & Females

ANDREW HUBERMAN: Welcome to the Huberman Lab podcast,

where we discuss science and science-based tools

for everyday life.

[MUSIC PLAYING]

I'm Andrew Huberman, and I'm a professor

of neurobiology and ophthalmology

at Stanford School of Medicine.

Today we are discussing fertility.

We will discuss male fertility and female fertility.

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

for people who are seeking to conceive children

or who want to know how their children were conceived,

but it's really for everybody.

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

All of us are here because a specialized set

of cells, called germ cells--

that is the sperm and the egg.

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

germ cells a little bit later.

It has nothing to do with infection.

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

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

so-called in vitro fertilization-- and then

we're implanted into our mother and became us.

And so understanding the process of how

the egg cell and the sperm cell came to be

is really the key to understanding

how that fertilization process came to be.

Now, I know everyone's thinking, I

know how fertilization occurs.

It occurs through sexual intercourse and so on.

And we'll talk a little bit about that.

But I promise you that if you understand

the menstrual cycle--

and the menstrual cycle in today's conversation

can best be thought of as a biological cycle that

occurs in females that allows the potential for fertilization

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

and it's a beautifully orchestrated process

that I'll describe to you.

And I should say, all people, males and females, should

really understand how the menstrual cycle works,

how it impacts fertilization, but also

how it impacts the brain and body, behavior, psychology,

et cetera.

And we'll also talk about spermatogenesis,

how sperm cells come to be and how they arrive--

that is, how they swim to the egg--

and the incredible interplay between the biology

of the sperm and the biology of the egg

leads to this incredible thing that we call embryogenesis

and the birth of the child and, of course,

the development of that child into an infant, a toddler,

an adolescent, a teen, and an adult.

Today's discussion, again, is not just

for those of you that are seeking to have children.

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

you look at the literature on longevity and vitality,

two themes in biology that oftentimes people lump together

but aren't always the same-- for instance,

there are a lot of things that we

can do to increase our vitality that actually

can harm our longevity.

But there are a subset of biological rules and mechanisms

that, when aligned, allow us to maximize both

our vitality and our longevity.

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

and tools are housed in the discussion

around maximizing fertility.

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

In other words, if you want children

or if you don't, if you already have children

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

occurs in the brain and body will

allow you to maximize your vitality and longevity.

And of course, today's discussion

will provide an understanding of the biology

and many actionable tools that will also help you conceive

children, if that's your wish.

So of course, as is characteristic of this podcast,

we will discuss science-based tools,

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

will discuss nutrition-based tools and supplementation-based

tools and some other practices, including things like

acupuncture, which have quite good data to support them

in terms of improving fertility.

And we will discuss why those certain practices can work.

And we will discuss prescription drugs

that your doctor can prescribe to you if, for instance, you

have a deficit at the level of hormone production

or neurotransmitter production at the level of the brain

or the pituitary gland--

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

or the gonads, the ovary and the testes in females and males

respectively.

Again, by the end of today's episode,

you will have a lot of knowledge and actionable tools related

to maximizing fertility, and you will

have a lot of knowledge and actionable tools related

to maximizing vitality and longevity.

Before we begin, I'd like to emphasize

that this podcast is separate from my teaching and research

roles at Stanford.

It is, however, part of my desire and effort

to bring zero cost to consumer information

about science and science-related tools

to the general public.

In keeping with that theme, I'd like

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Let's talk about fertility.

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

"fertility" and ask, what is fertility and fertilization

really all about?

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

But more importantly, it's about producing offspring

that contain the genetic components of both parents

and indeed contain half of the genes from one parent

and half of the genes from another parent.

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

The most common types of cells in the body

are called somatic cells.

So these would be all the cells in your body

except the egg in females and the sperm in males.

The egg in females and the sperm males

are part of what's called the germline.

And again, it has nothing to do with infection.

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

be modified by the behavior of the individual that houses

those genes.

What do I mean by that?

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

mitochondrial function, you can change hormones

by reducing stress, you can reduce cortisol

by hitting puberty, for instance, you

will have the secretion of hormones that then change

gene expression in other cells, leading

to the development of body hair, facial hair,

deepening the voice, breast growth, et cetera,

you'd say, OK, great.

Yeah, that all makes perfect sense.

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

The germ cells or the germline cells--

that is, the egg and the sperm--

are a very unique and protected set

of cells that are generated in a particular way

and whose genetic components are not modifiable by experience.

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

you say, oh, that's right.

There's no reason to think that exercising

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

And you say, of course not.

Well, why is that?

Well, that's because there is a barrier

between the genes of the germline cells and behaviors.

They cannot be modified by behaviors and the various

things that you do in your lifetime.

Now, I suppose there's an exception

in the negative direction.

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

be exposed to a chemical that could mutate the DNA

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

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

an extra chromosome, for instance--

we'll talk about this a little bit later--

well, then, of course, you could end up

with offspring that have modified

DNA that don't faithfully represent half of the genes

from mom and half of the genes from dad.

But that's not the same as specific behaviors

modifying the genes of those cells--

the sperm and the egg cells--

in a way that improves the offspring.

So the key first thing to understand today

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

is the vast majority of cells in your body,

and the so-called germline cells, which

are the egg and the sperm.

The egg and the sperm are these highly protected populations

of cells that, in females, actually come

to be during embryogenesis.

So for all females out there, you

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

You have a vault of eggs that are your germline.

Those eggs all contain all the chromosomes of your DNA.

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

know, there are 23 chromosomes, and chromosomes exist in pairs.

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

and you have 22 so-called autosomes,

and then you have one sex chromosome.

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

they have two X chromosomes.

So in each one of the eggs that a woman has

and that she's had since she was an embryo

and that's contained in this vault,

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

She hasn't undergone puberty yet.

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

And those cells are going to contain

23 pairs of chromosomes.

This is very important--

23 pairs of chromosomes.

The chromosomes are essentially the wrapped-up DNA

that contains all the genetic information

to create any cell type in the body

and actually to create an entirely new individual.

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

are called autosomes.

If that doesn't make sense to you,

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

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

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

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

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

chromosomes.

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

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

and how it relates to chromosomal segregation

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

and that perhaps were opaque to you.

But I promise to make them clear.

But just understand that, within each of those eggs,

they have 23 pairs of chromosomes.

And for those of you that like nomenclature,

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

They're called the diploid, and that

means that they have 23 pairs of chromosomes,

as distinguished from cells that are

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

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

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

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

in the reserve, in this vault, that she'll

have for her entire life.

She's not going to make any more.

But they are very, very immature.

So when a woman is in embryogenesis,

she develops these very immature eggs.

Today we're also going to talk about follicles,

and we will be careful to distinguish follicles

from eggs.

They're often talked about interchangeably, online

and elsewhere and even by fertility docs and OB/GYNs.

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

themselves, which are cells.

Now, the goal of fertilization is

to bring that egg cell into close enough proximity

that it can be fertilized by a single sperm cell.

And that sperm cell will bring 23 chromosomes, as well,

that include--

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

chromosome.

And in the male, that sex chromosome

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

to female offspring, or a Y chromosome, which would

give rise to male offspring.

And today we're not talking about sexual differentiation.

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

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

chromosomes can actually accomplish

that sexual differentiation, both of body and brain.

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

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

that Y chromosome contains genes that suppress, for instance,

the development of female genitalia

and thereby give rise to male genitalia.

So rather than the formation of a clitoris,

it's the formation of a penis.

And rather than the formation of ovaries,

the formation of a testes.

So that's more directed towards sexual differentiation.

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

We'll get into that in a future episode.

But even if you're only tracking about 10%

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

If you're tracking more than 10%, well,

then you're doing terrifically well,

because the essence of fertility and fertilization is to bring

together that haploid cell that is the sperm that only has 23

chromosomes-- but not pairs of chromosomes

because that's the DNA from dad--

together with the egg, which, as I told you already,

has 23 pairs of chromosomes.

So part of the fertilization process

has to be to get rid of one half of those 23 pairs

in the female.

You got to get rid of it, and you

have to get the egg and the sperm in proximity

so that the egg can potentially be fertilized

by the sperm bringing the DNA, the 23

single strands of chromosomes from dad,

into a cell that has 23 single strands from mom.

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

but I want everyone to understand this

because it really frames up fertility and reproduction

in the proper way.

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

has 23 pairs of chromosomes.

We need to get rid of one set of those pairs

so that there's only 23 chromosomes.

We need to get rid of half of those chromosomes.

And then we need to bring that cell together physically

with the sperm cell that contains the 23

chromosomal strands from dad.

And we need to bring those together so that you

get 23 chromosomal pairs from dad

and 23 chromosomal pairs from mom.

And in doing so, you create a cell, which

then becomes multiple cells.

That's going to be the developing embryo that

has half the genes from mom and half the genes from dad.

So I hope that's clear.

That is the biological logic, which I realize

is a bit of a tongue twister.

But forgive me.

It is the most accurate way to describe this process.

We're trying to bring together the 23 single strands

of chromosomes from dad and the 23

single strands of chromosomes from mom into the same cell.

Now, that requires a literal physical contact

and pairing of the two cells.

But as I mentioned before, all these eggs in mom

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

So the ovulatory cycle and the menstrual cycle

are really about first eliminating

half of the chromosomal pairs in that 23 sets of chromosomes

and not getting rid of, for instance, half--

just going 1 to 11 or 12 to 23.

That's not the goal.

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

6, all the way up to 23, but only to have

half of the chromosomes there and to bring that cell together

with the sperm cell, physically, then allow

them to fuse and allow the chromosomes from dad

and the chromosomes from mom to fuse within a single cell

and duplicate into cells that contain half of the chromosomes

from dad and half of the chromosomes from mom.

That's what the ovulatory and menstrual cycle

are really all about.

So when thinking about it that way,

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

on the female component, or the egg component,

of fertility and fertilization.

As I mentioned before, a female has all the eggs,

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

that she's born.

Now, puberty will happen at some point

and will allow the ovulatory and the menstrual cycle

to commence.

Now, one question that you perhaps are asking

is, what controls the onset of puberty?

And there are a number of different results,

each of which could be an entire episode

of a podcast on its own.

But I'll just highlight a few things

that we know about the onset of menses or menstruation,

or it's sometimes also called a menarche.

One thing that you'll notice about today's discussion

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

online and put them into a search function

that you would see a lot of different language used

for the same thing.

So for instance, some people will

talk about the egg and the follicle as the same thing,

even though they are not.

I'll explain the difference soon.

Some people will talk about menses or menstruation

or menarche as the exact same thing.

And in fact, they are not the exact same thing,

but oftentimes these words are used interchangeably.

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

but rather to use the most commonly used terms

for the different aspects of fertility and fertilization.

But when it comes to the onset of puberty,

first of all, most of you have probably

heard that the onset of puberty is

happening much earlier in females now

than it was some years ago.

And in fact, that is the case.

And I'll talk about some statistics related

to this which are pretty striking

but don't necessarily point to anything detrimental.

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

What do we know for sure?

Well, we know that there are a number

of signals that come both through the brain

and through the body--

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

in females.

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

We know, for instance, that the entire process

of the ovulatory menstrual cycle is initiated from the brain.

We're going to get into this in a lot

more detail in a few minutes.

But there's a certain number of hormones and neurotransmitters

that are communicated from the brain,

a structure called the hypothalamus,

which roughly sits above the roof of your mouth,

and that communicates with a gland, an endocrine

or hormone-releasing gland called the pituitary gland.

The pituitary gland looks like a stalk that essentially

extends out of the brain.

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

And that has two sort of small marble

or grape-sized protrusions, the anterior pituitary

and the posterior pituitary.

And they release different hormones into the bloodstream.

Puberty is in part controlled by the fact

that, up until puberty, there are

neurons in the hypothalamus that release

a neurotransmitter called GABA, which is inhibitory,

and that prevents the neurons in the hypothalamus

from releasing a very important hormone called

gonadotropin-releasing hormone, or GnRH.

So the first thing I'd really like everyone

to know and commit to memory today is very easy--

GnRH stands for gonadotropin-releasing hormone.

This comes from the brain and will

communicate to the pituitary to release certain hormones.

Prior to puberty, in both males and females,

there are neurons in the brain that are actively suppressing

the neurons that release GnRH.

It's like no puberty, no puberty, no puberty.

You can't have puberty.

You can't have puberty.

And in fact, those cells are releasing this neurotransmitter

called GABA because it's inhibitory.

It prevents the firing of those neurons.

So puberty is actively suppressed up

until a certain point.

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

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

that means the ongoing release, around the clock--

of a hormone called melatonin.

Later in life-- in fact, after puberty--

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

and around the time that one goes to sleep.

But in children and in particular

in children prior to puberty, melatonin

is released more or less constantly.

Now, melatonin isn't the only source

of suppression of puberty.

It's also these neural mechanisms involving GABA.

But it is certainly a great candidate for one

of the reasons why puberty doesn't generally

tend to happen at, say, age four age five.

That would be very unusual.

Another component of suppression of puberty

is that typically in children they have relatively low body

fat stores.

Why is this important?

Well, we know that one of the things that can trigger

the onset of puberty-- in particular in females--

is that when enough body fat accumulates,

that body fat releases a hormone called leptin,

and that hormone leptin travels in the bloodstream,

across the blood-brain barrier, and goes to the hypothalamus

and can trigger the onset of puberty

by activating the neurons that release

gonadotropin-releasing hormone.

So many people believe that one of the reasons that puberty

is happening earlier and earlier in females

is because of the accumulation of more body fat at younger

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

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

oh, this must relate to the obesity crisis.

And indeed, there is a crisis of obesity.

Obesity is something that is causing all sorts of problems

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

and that is far more frequent today

than it was even 20 years ago.

So it is indeed a crisis because it

has enormous detrimental effects for so many aspects

of brain and body health and longevity.

But this whole process of thinking about body fat

signaling leptin to the hypothalamus and the onset

of puberty doesn't necessarily have

to do with the obesity crisis.

It might relate, but it could also relate to, for instance,

improved nutrition, which is allowing body

fat stores to accumulate maybe not to the level of obesity

but to accumulate earlier and at younger ages

in females, which is then causing

earlier puberty in females.

To just highlight how that might be possible,

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

menstruation-- that is, puberty--

in females according to country and according

to age over the last 100 or more years.

So what are the general trends in terms

of the onset of puberty in females?

Well, that's an easy one to answer.

Over the last 100 years or so, the onset of puberty

has been occurring much earlier with each passing decade.

It's really an incredible set of statistics.

I will provide a link to these data

since I know a number of you are listening and not

just watching on YouTube.

This is from a study in which the onset of puberty

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

in certain countries, there are data on that--

out to the 1970s and in other countries

starting at about 1900, extending out to about 1990.

These are ongoing collections of data.

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

in a couple of different countries,

just to give you a flavor--

but for those of you listening and for those of you watching,

the essence of all of these findings

is that puberty is happening much, much earlier

with each passing decade.

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

the average age of menarche, the onset of puberty, in females

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

So that's a pretty significant, we can say,

acceleration of the onset of puberty.

Now, of course, these are averages.

So there will be exceptions.

There's a distribution of data.

Today, still, there will be young females who

will undergo puberty at age 11 or 10 or maybe even 9

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

even 16 or 17.

However, if we look at, for instance,

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

have excellent record-keeping-- to 1850, what we see

is that the average age of the onset of female puberty in 1850

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

13 years old.

So this is a dramatic acceleration

of the onset of puberty.

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

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

they have a smaller data set, meaning it only

extends back to about 1940.

But the average age of the onset of puberty in the UK in 1940

was 13 and 1/2 years old.

Again, this is just for females.

And in 1970, it was closer to 13,

with a trend towards declining even further.

Unfortunately, they didn't continue

to collect data out to 2022.

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

in Germany and Finland, the average onset

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

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

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

regardless of location in the world, which is important,

because when you start to think about the obesity crisis,

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

believe it or not-- or perhaps not surprisingly.

And maybe it has to do with the obesity crisis.

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

Something is happening, however.

It could be increased body fat stores

due to overeating and obesity.

However, it could also be-- unrelated to obesity,

it could be, for instance, improved

nutrition and the availability of quality nutrition, which

can signal the maturation of the brain

and body mechanisms that trigger the onset of puberty,

ovulatory cycle, and menstruation.

So we want to be very careful about leaping to conclusions

about what these trends mean, but the trends themselves

are very, very apparent.

And as a final point, I should also

mention that there are a number of different behavioral

and psychosocial, as they're called, interactions that

can influence puberty as well.

This has been most strikingly observed in animals.

And so I don't want anyone to be alarmed

or to leap to any great conclusions about the onset

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

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

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

not necessarily the pheromones.

There's a distinction between odors that we perceive

and pheromones, which are subconscious.

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

and pheromones effects in humans are very controversial.

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

and there's some evidence from humans

that if you take a young prepubertal female

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

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

as a few hours, and she is also not

regularly being exposed to the scent of her father,

that she can undergo puberty earlier.

That's right.

There is something about the odor

and/or pheromones, or perhaps something else, that

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

in regular contact with.

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

is around a lot that his smell is registered

by her biological systems.

That-- I don't want to say protects

because it kind of skews the valence of the conversation,

but that offsets or buffers the otherwise observed effect,

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

if it's present often enough or perhaps intensely enough,

that it can trigger the onset of puberty in that female.

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

and we think also that is not biologically related to her

can trigger earlier onset of puberty.

And that effect can at least be partially buffered

by her being in the presence of the scent

from her biological father.

Now, some of you are probably already leaping

to conclusions about what this means.

Should you not allow your daughter

to be exposed to any males who are

of reproductive age, et cetera?

That's certainly not what I'm saying.

There's a huge number of considerations

that go into that calculation for everybody

and circumstances, et cetera.

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

in particular, closely related-- and non-related individuals,

can shape the neural systems and the hormone systems that

can trigger the onset of puberty or suppress

the onset of puberty.

So whether or not we're talking about onset

of puberty at this age or that age

and whether or not biologically-related male

or non-biologically-related male scents around,

et cetera, the thing I want everyone to know

is that at some point during development,

typically nowadays between the ages of 11 and 15

or so-- again, there's variability there.

The suppression of gonadotropin-releasing hormone

released from the hypothalamus is removed,

and then gonadotropin-releasing hormone

can activate cells within the pituitary.

And if you really want to know, it's

the anterior pituitary in particular.

And then the anterior pituitary gland,

which sits at and kind of bridges the brain and the body

because it allows the release of hormones into the bloodstream,

that anterior pituitary is going to release

two key hormones that everyone should know the name of

and what they do.

And when I say everyone, I mean males and females

need to know about these hormones

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

And of course, you should want to know

and should know about the biology of everyone

on the planet, in my opinion, because it tells you

a lot more about humans than if you just

focus on your own biology.

But those two hormones are called

luteinizing hormone, which is abbreviated LH,

and follicle-stimulating hormone, which

is abbreviated FSH.

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

is gonadotropin-releasing hormone from the brain,

from the hypothalamus in particular,

is causing the release of luteinizing

hormone and follicle-stimulating hormone, GnRH stimulates

LH, luteinizing hormone, and follicle-stimulating hormone,

FSH.

LH and FSH travel in the blood and can access all the cells

and tissues of the body.

This is one of the incredible things about hormones is that

many hormones-- and LH and FSH are included in this group--

can travel into cells, and they can actually

change the genetic expression of those cells.

They can change which genes are turned on

and which genes are turned off.

And they can also attach to the surface of those cells

and make those cells take on different properties.

So they can mature those cells.

So for instance, a good example of this outside

of the context we've been talking about

is the hormone testosterone can travel to the hair follicle

and can stimulate changes in the genes of the cells of the hair

follicle that can make hair grow.

A different hormone, estrogen, can

travel to the cells of the breast tissue

and activate genes that control enlargement of the cells

of the breast tissue.

Prolactin, a different hormone, can travel to the mammary ducts

and control the production and the secretion of milk.

And in males, that can actually happen, in certain cases,

although it's rare.

But prolactin can also travel to areas of the brain

that control libido, for instance.

And just so you'll never forget it,

males' elevated levels of prolactin

are actually what set the refractory period

after ejaculation and prevent erection

for some period of time.

So you'll never forget prolactin.

The point being that different hormones

have different effects on different cells,

depending on what cells those are.

Estrogen or estradiol is going to have different effects

on the breast tissue than it would on skin,

although as effects on both.

Similarly, when LH and FSH, luteinizing hormone

and follicle-stimulating hormone, travel in the blood

to the gonad and the gonad is an ovary,

it will have a certain set of consequences.

And when luteinizing hormone and follicle-stimulating hormone

travel in the blood to a gonad and that gonad

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

of biological implications.

So let's focus now on what happens when

LH and FSH arrive at the ovary.

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

has already undergone puberty, or perhaps we

could even frame this in the context of a female who

is about to undergo puberty.

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

undergoing puberty.

But the same set of processes, essentially,

would occur for any point from puberty onward until menopause,

which is the depletion of that vault, that ovarian reserve

of all those immature eggs.

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

and menstruation, and let's just remember

what this is all about.

This is all about creating the potential for an egg

to be fertilized, and that egg needs

to have half of the chromosomal pairs, so no pairs,

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

And we need to position that egg so

that the egg can be met by the sperm

and that sperm can penetrate that egg

and donate its 23 individual strands of chromosomes

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

and the DNA of mom.

So the obligatory menstrual cycle

occurs when luteinizing hormone and follicle-stimulating

hormone have been released.

And the ovulatory/menstrual cycle--

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

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

the female reproductive cycle, but that includes underneath it

both the menstrual cycle, as it's sometimes called,

and the ovulatory cycle.

So you decide.

I'm going to interchangeably discuss the ovulatory cycle

and the menstrual cycle.

The problem is, when you say menstruation,

people often think about just the period, the shedding

of the uterine lining when fertilization has not occurred.

So if I start saying ovulatory cycle,

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

Now, this is probably also a good opportunity

to say that if you heard that the ovulatory/menstrual cycle

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

but that's not always true.

It's, on average, 28 days long.

There are some females for which the ovulatory cycle will be

shorter-- it can be as short as 21 days--

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

Shorter than 21 days and longer than 35

days is rare, although it does occur.

One of the key things when thinking about fertility

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

I have in anticipation of this episode,

they'll tell you that whether or not

your cycle is 21 days long or 35 days long

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

happening to become much shorter or much longer

in a kind of erratic way.

So if you're somebody who's consistently

had 23 day long cycles and all of a sudden

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

an indication of anything bad.

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

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

falling within that 21 to 35 day long cycle

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

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

because that could indicate a number of different things.

Which things could it indicate?

Well, that will become clear as I spell out

the biology in a bit more detail.

But this idea that the menstrual cycle/ovulatory cycle

is always 28 days, that's just false.

That's just not true.

I should also mention that there is a common misconception that

because the average menstrual cycle is 28 days-- indeed,

the average is 28 days--

and the lunar cycle is 28 days--

and of course, there is a real biology

to support the fact that the lunar

cycle can't, in fact, impact certain aspects

of human behavior.

It does, and we'll talk about lunar cycles

in a future episode.

But there is zero data to support the idea

that the menstrual cycle and the lunar cycle

are linked in any kind of causal way.

Sorry to break it to you.

The lunar cycle and the tidal cycles at the ocean

are definitely linked in ways that are super interesting

related to the tilt of the Earth and the pull of gravity

of different planets, and it's an incredible story

into itself.

But the lunar cycle and the menstrual cycle,

despite having some weak correlation in terms

of their duration or their so-called periodicity--

no pun intended--

well, there's no causal relationship whatsoever

between the lunar cycle and the menstrual cycle.

If any of you are aware of any real data

that conflicts with what I just said,

please put that in the comment section on YouTube.

But this is pretty well established as far as I know.

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

the 23 individual strands of chromosomes from the egg,

to a place and a position where it could potentially

be fertilized by the male.

So what happens?

Luteinizing hormone and follicle-stimulating hormone

travel to the ovary.

These hormones are able to access the ovary.

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

And FSH and LH arrive at the ovary.

The ovary has this vault, this ovarian reserve

of immature cells.

They reside within what are called follicles.

The follicles are little spherical packages

that can potentially provide a nice environment for those eggs

to mature.

And when FSH, in particular, arrives at the ovary,

a small number of those follicles

will split off from the reserve, they will exit the vault,

and they will undergo maturation.

And the key player here is follicle-stimulating hormone.

And the first 14 days of the menstrual/ovulatory cycle

is referred to as the follicular phase because

of this relationship between FSH triggering the maturation

of a subset of follicles.

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

ovulatory/menstrual cycle, day one

is designated as the first day of the period,

of the shedding of the uterine lining

from the previous ovulatory menstrual cycle in which

fertilization did not occur.

So day one is when the period initiates.

It is days 1 through 14, approximately--

because here we're just considering

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

It could be shorter.

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

phase, FSH, has triggered the departure

of a subset of these follicles that contain immature eggs.

And it is triggering the maturation of those eggs.

Luteinizing hormone is also present, but also

at relatively low levels.

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

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

So inside of those follicles, the egg is developing.

It's growing.

It's maturing.

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

This, I think, is one of the most elegant aspects

of the ovulatory menstrual cycle that, in a few minutes,

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

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

because of my training, still just blows my mind that you

have one hormone, follicle-stimulating hormone,

triggering the maturation of some eggs

inside of some follicles and then those follicles themselves

making another hormone that furthers the process

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

the second half of the process.

Just a beautiful symphony of expression of different genes

and different hormones to make everything

work as optimally as possible.

So as these different follicles mature, somehow--

and we still don't know exactly how--

one of those follicles containing an egg

gets selected.

It's either because it matures the fastest

or there's something about it that

is still not completely understood

that allows it to be selected.

And all the other follicles that are maturing

degenerate and die.

And they're gone.

They don't go back into the ovarian reserve.

They are now depleted from that bank account

that is the ovarian reserve.

They die off.

But that single egg that, keep in mind,

contains 23 pairs of chromosomes--

we haven't gotten rid of one half of those 23

sets of chromosomes yet.

But that one will continue to mature.

And then, at some point, that egg

will start to undergo a process in which those chromosomes are

pulled apart by little components

within the egg called spindles.

They literally have a physical pulling

of the chromosomes apart.

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

at the middle like they were before,

like two beads of strings--

or I should say, 23 short strands

of beads that were at once connected to one another

now are pulled apart so that you have

23 chromosomes on each side, but they're

pulled apart from one another.

So that diploid cell is now starting

to become a cell in which half of the chromosomes,

half of those 23 pairs, are physically

pulled away from the others.

And then the egg actually starts to form its own

what we call an involution of membrane

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

So you sort of got an egg with two parts

where the two sets of chromosomes,

two sets of 23 chromosomes, are now separate

from one another inside of the egg.

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

and the name of that thing that gets ejected--

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

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

where some thing is ready to happen.

A little Hubble pod shoots out of the ship.

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

It's called the polar body.

And that's going to degenerate.

It's going to go away.

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

diploid-- it had 23 pairs of chromosomes-- and making

it haploid.

And now what you've got, in ideal circumstances,

is a beautifully pristine egg that was selected for

and has 23 single strands of chromosomes, 22 autosomes

and one sex chromosome.

And that sex chromosome is going to be an X chromosome

almost with certainty, because female--

mother-- is creating that egg.

So then the egg that contains just the appropriate 23

single-stranded chromosomes is going

to fuse with the wall of the ovary, and that egg

will be released and will travel into the Fallopian tube.

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

But that process, which represents the first half

of the ovulatory menstrual cycle, again,

was triggered by FSH and to some extent luteinizing hormone.

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

the production of estrogen, which allows that whole process

to occur.

And you could say, why?

Well, the answer to the why is a very important

biological principle that we are going

to return to in a number of different contexts today,

both as reference to female and male fertility.

And the principle is a so-called negative feedback.

So when estrogen is present at relatively low levels

in females in the ovary, as it is

during the development of these eggs, some of that estrogen,

of course, is going to exit the ovary.

It's going to go into the bloodstream.

And it's going to travel back to the pituitary.

Now, the pituitary can release things

like follicle-stimulating hormone and luteinizing

hormone.

But the way I'd like you to think

about the pituitary for sake of feedback loops

is that it's sort of like a thermometer

that you would put into a pool, like a backyard pool, that

is attached to the heater.

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

that you would like to keep at 70 degrees

and the temperature of that pool is 60 degrees,

well, then that thermometer ought

to trigger some sort of mechanism

where the pool would heat up until the temperature

of the pool hit 70 degrees, and then it

should trigger that thermometer to turn off the heating system.

That's kind of a negative feedback

system that would keep the temperature more

or less correct.

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

and also testosterone and these different things

like luteinizing hormone and follicle-stimulating hormone

work as well.

Typically, when the level of a hormone is too high,

then it shuts down the production

of the hormones that would trigger further production

of that hormone.

I know that's a mouthful.

It's a lot to think about.

And some of you are probably thinking, whoa,

I'm getting dizzy now with biology.

But I promise you, you can understand this.

In females, when estrogen is relatively low--

but not zero but is relatively low

during that first follicular half of the ovulatory cycle--

it actually triggers negative feedback on LH and FSH

so that not too much is produced.

But then just prior to ovulation,

the levels of estrogen and the levels of some other hormones

from those eggs--

you have the eggs producing estrogen themselves--

gets high enough that it actually

triggers a positive feedback loop on the pituitary.

So the pituitary is essentially observing

the amount of estrogen in the bloodstream produced

by the ovary, and the amount of estrogen

towards the end of the second half of the menstrual cycle

has increased and triggers a positive feedback loop.

It triggers the pituitary to release more FSH and LH,

and that helps trigger ovulation, that deployment

or the release of that one mature proper selected

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

into the Fallopian tube.

So let's just back up really quickly and just

kind of summarize what's happened.

Gonadotropin-releasing hormone from the hypothalamus

triggers the release of follicle-stimulating hormone

and luteinizing hormone.

That travels to the ovary-- triggers

the release of a subset of immature follicles

with immature eggs.

Those immature follicles and immature eggs

start to mature, start to grow because

of the presence of follicle-stimulating hormone.

The growth of those eggs themselves increases estrogen.

As the estrogen starts to accumulate in the environment,

some of that travels back to the pituitary.

And when levels of estrogen arriving at the pituitary

are relatively low, the pituitary

says, oh, we don't need to release

any more follicle-stimulating and luteinizing hormone.

However, at some point just prior to ovulation,

enough estrogen has been produced by that one

single selected mature egg and some

of the other follicles around it that were maturing but then

since died off that the estrogen triggers a positive feedback

loop.

The pituitary says, OK, and releases

more follicle-stimulating hormone

and luteinizing hormone.

And bam, the egg, which has the proper genetic components,

sets off out of the ovary and into the Fallopian tube.

So-called ovulation has begun.

That itself, what I just described,

constitutes the first half of the ovulatory/menstrual cycle,

which we call the follicular phase.

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

but we can really think about it as marked by FSH

from the pituitary and by estrogen, or estradiol, made

within the ovary.

Then comes the second half of the ovulatory/menstrual cycle,

which I personally think is one of the coolest mechanisms

in all of biology, which is that--

remember the follicle that housed

that one egg that was the selected

egg that became the mature egg?

And that follicle, which no longer contains the egg

because the egg took off and ovulated,

is called the corpus luteum.

And the corpus luteum starts making three hormones, which

include estradiol, I think called inhibin,

but the most important hormone, the one that you really

need to know about, is that it starts

producing very high levels of progesterone.

Progesterone levels start to increase

about the time of ovulation, although just

prior to ovulation.

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

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

a little bit longer or a little bit shorter,

depending on the length of cycle.

Levels of progesterone in the second half

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

compared to what they were in the first half

of the ovulatory cycle.

So again, if we were to characterize

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

say is that FSH and estrogen mark

the initial part the first half, the so-called follicular phase,

and that the estrogen and FSH set in motion ovulation,

and they prime the system for the production

of a corpus luteum, which produces progesterone.

And the second half of all of this

is called the luteal phase.

The second half of the ovulatory/menstrual cycle

is the luteal phase because of corpus luteum,

this otherwise discarded tissue that produces progesterone.

What does progesterone do?

Well, progesterone impacts the uterine lining,

so-called endometrium or the lining,

the mucous lining of the uterus where that egg that's ovulated

is potentially going to implant if it's fertilized.

And so in a kind of perfect way-- or I

should say, in a seemingly perfect way--

the egg is off on its way.

It might get fertilized.

The remnants of the compartment that let go of that egg

produce a hormone that then prepares the endometrial lining

of the uterus for the potential implantation of that egg.

It's basically making the bed for the fertilized egg

to potentially embed in, to implant in, and then

achieve all the nourishment that it needs to grow, eventually,

into a healthy embryo and child.

Just an amazing set of biological mechanisms,

if you ask me, because what you're observing here

is an incredible economy of function

whereby the same cellular components that

are producing the egg, well, some of them

are being discarded, but they're not being

discarded without purpose.

They're being discarded in a way that

triggers the onset of hormonal expression

that then prepares the fertilized

egg to be in an enriched environment in which it

can thrive.

Now, I realize that was a lot of detail.

But we have a couple of key themes.

We've got the hypothalamus, GnRH.

We've got the pituitary with LH and FSH,

and those hormones travel to the ovary.

The ovary has eggs in a vault, basically immature eggs

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

of FSH and LH each month.

And one of those eggs will be selected and will ovulate.

The remnants of the follicle and egg

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

disappear in the polar body.

And the corpus luteum gives rise to progesterone and sets

in motion the second half of the ovulatory menstrual cycle,

which is the luteal phase, which is essentially

the potential for that fertilized egg

to embed in a nice, nourishing environment.

And of course, we should all be thinking,

if the egg is fertilized and then it lays down

in the nice, comfy uterine lining

that's been prepared by progesterone

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

But what if fertilization doesn't occur?

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

If fertilization does not occur for whatever reason,

that uterine lining is going to shed.

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

It's the actual removal--

or the departure, rather--

of the thickened endometrium lining

of the uterus when fertilization has not occurred.

And of course, if that happens, we

need another ovulatory menstrual cycle.

So how does that happen?

Well, the hormone inhibin is also made by the corpus luteum

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

But it kind of tracks that increase in progesterone

that occurs in the second half of the ovulatory cycle.

But then, if fertilization does not occur,

inhibin levels start to drop.

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

Inhibin, in concert with other hormones like estrogen,

feed back to the hypothalamus and prevent the further release

of follicle-stimulating hormone and luteinizing hormone.

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

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

You want to hold on to the ones in the vault.

You don't want them to mature.

And hormones like inhibin and, again,

working with other hormones are going

to prevent the secretion of things like FSH and LH.

Now, typically, people are not getting pregnant every month.

In fact, that's not possible.

And part of the reason it's not possible

is that if the fertilized egg implants,

there are a number of different hormone cascades

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

in ways that prevent further maturation of follicles

and a follicular phase.

But in the instance where fertilization doesn't occur

and menstruation occurs--

and I should mention that the duration of menstruation,

the actual bleeding, typically is anywhere from one

to five days.

The, quote, unquote, "heaviness,"

the lightness or heaviness of that bleeding will depend on--

you guessed it-- the amount of progesterone that is secreted

from the corpus luteum.

That's one of the key players there.

And if menstruation occurs, well, then inhibin levels

also drop.

Progesterone levels also drop.

And when that occurs, there's a positive feedback

signal up at the level of the pituitary.

The pituitary literally can register

how much inhibin and progesterone and estrogen

is present in the bloodstream.

And if those levels are sufficiently low, well,

then GnRH gets secreted again, FSH gets secreted again,

and LH gets secreted again.

And the first half the follicular phase

of the menstrual cycle initiates all over again.

It's hard to overstate how beautifully orchestrated

this entire system is--

The number of feedback loops and feed-forward loops.

I think if you can just generally understand

that the first half of the menstrual/ovulatory cycle

is marked by the maturation of the follicles and FSH

and that the second half is marked

by the accumulation of progesterone

and the thickening of the uterine lining

should fertilization and implantation occur,

I think that you will certainly understand

the female reproductive cycle better than most people

out there.

It will also help you understand a number of things

that are sometimes associated with the female reproductive

cycle.

For instance, there are data showing

that, in many, not all, but in many women, in the four

to five days prior to ovulation, there is

a dramatic increase in libido.

That dramatic increase in libido is

triggered by a number of things, but some of those things

include the spike in FSH that occurs,

the spike in LH that occurs, and some associated increases

in androgens, things like DHEA and testosterone,

which, just as in males can be related to libido,

in females trigger libido.

You can imagine why this would be an effective mechanism

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

of the egg, perhaps not of the woman as a whole,

but if the goal is to fertilize the egg--

so increases in libido just prior

to the onset of ovulation.

There's also been a lot of discussion and interest

and, frankly, data exploring the malaise

that it can occur at certain portions

of the menstrual cycle.

And there's a lot of misconception about this.

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

around the time of bleeding.

But there are actually stronger data

to support the fact that some, again, some, not all women

experience a kind of malaise sometimes associated

with anxiety, sometimes not, that's associated with the mid

to second half of the luteal phase

of the ovulatory/menstrual cycle.

And that, despite what people commonly think,

is not associated with elevated levels of estrogen.

It's actually associated with the depletion in estrogen

levels that can occur during certain portions

of that second half of the luteal phase

of the menstrual cycle.

So again, this is highly variable.

For some people, they might not experience

any malaise at any point during their menstrual cycle.

Other individuals also, for instance,

might not experience any variation in their libido

at any point during their menstrual cycle.

Again, highly variable, and yet there

are some statistically significant trends

that have been observed that tracked

very specific hormonal components

within the menstrual cycle.

Again, this will all be very contextual.

And of course, this can play out in a number of different ways.

So for instance, some women experience very heightened

levels of sensitivity to caffeine

at certain portions of their menstrual cycle.

Other women experience more cramping than others

at different portions of their menstrual cycle.

Tremendous variation from individual to individual.

One of the--

I view it as an advantage.

But one of the things that many females can really do

and experience because they have cycles that occur every month

that are fairly dramatic in terms of their levels

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

in progesterone during the luteal phase of the menstrual

cycle and, I should also mention,

a 200-fold increase in estrogen during the period just prior

to ovulation.

That's why they always say estrogen primes progesterone.

That's what you learn in kind of basic endocrinology

when you're learning the menstrual cycle.

Estrogen in the first half of the menstrual cycle

primes progesterone in the second half

of the ovulatory/menstrual cycle.

Well, those estrogen increases just prior to ovulation

are in part responsible for the increases in libido.

But it's also the presence of increased androgen just prior

to ovulation.

So there's a lot of complex interplay.

I think what we will do is we will reserve

the discussion about libido, per se,

and some of the other aspects related

to sexual differentiation that we

were talking about earlier for a future episode.

But hopefully now you have in mind

what the ovulatory/menstrual cycle is.

It is a signal from the brain, from the hypothalamus,

which then triggers a signal from the pituitary,

an endocrine gland, which then signals the release of hormones

that travel to the ovary and that control

two things, maturation of eggs and the identification of one

egg in particular and then preparation of the milieu,

the environment in which that fertilized egg could

potentially land and mature into a healthy embryo and child.

So if you have that framed up in your mind

and even if you just extracted maybe 10% to 15%

of the hormones and different aspects

that I described up until now, I would consider you far more

knowledgeable about this entire process than 99% of people

out there, certainly not the OB/GYNs and urologists,

but the 99% of individuals out there.

It also frames up for us the second half

of this whole story about fertility and fertilization,

which is the generation of sperm and how the sperm eventually

arrive at the egg and how certain sperm are selected

to potentially fertilize that egg,

whereas others never really stand a chance.

So next we're going to talk about sperm.

We're going to talk about what sperm are,

where they are generated, and how they are generated,

and how they need to travel both within the male

and within the female in order to allow fertilization

to potentially occur.

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So we've covered the ovulatory cycle in females.

And I confess, it was a lot of information

with a lot of biological nomenclature.

But I promise you that many of those same themes

and indeed the same names and nomenclature

will show up in the discussion that we're

going to have now, which is about the generation of sperm.

Now, sperm are similar to eggs in the sense

that they are part of the germline.

They are these protected cells, protected in the sense

that the activities of an individual

are not going to change the genetic makeup of those cells.

Now, again, there are instances in which

mutagens, such as chemicals, could disrupt

the genomes of the germ cells in males, just

as it could in females.

But in general, the activities, the things

that we do, the experiences we have,

doesn't tend to change the genome of those cells.

However, there are a lot of lifestyle factors--

dos and don'ts, nutrition and supplements and prescription

drugs, et cetera-- that can indeed modify the quality

of the sperm.

And we'll talk about what sperm quality means.

But the point is that the sperm cell, much like the egg cell,

are both germline cells.

They are not like somatic cells.

They are unique populations.

And let's just remember what the job of the sperm cell is.

The job of the sperm cell is to deliver the genetic material

from the father and to do that in the form of a haploid cell.

So that means 23 chromosomes, 22 autosomes,

one so-called sex chromosome--

again, not sex the verb, at least not in this case.

Sex, the verb, is a discussion we're

going to have in a few minutes, but sex the noun.

The sex chromosome can either be an X chromosome or a Y

chromosome.

So 22 autosomes and then one sex chromosome

is going to be contained within the sperm

because it's a haploid cell, not a diploid cell.

Remember, the egg was diploid, then it became haploid.

The sperm cells are cells that are

created through the division of other cells.

But after that division occurs through a process called

meiosis, the sperm cell is going to contain 23 chromosomes,

consisting of 22 autosomes and one sex chromosome.

And the sperm that manages to deposit its DNA contents

into the egg, to fertilize the egg,

will either have an X sex chromosome or a Y sex

chromosome.

And the Y sex chromosome has a number

of different genes on that chromosome that

will suppress, for instance, the development

of the female reproductive axis.

One good example would be the Müllerian-inhibiting hormone,

or MIH.

The gene for Müllerian-inhibiting hormone,

which is a hormone that prevents the formation of the Müllerian

ducts, which is part of the female reproductive structure,

well, that gene controls the prevention of the development

of the female genitalia and in doing so promotes

the development of the male genitalia.

And there are other examples of genes

that are on the Y chromosome that give you

a what we call male phenotype.

You have genotype and phenotype.

By the way, in case you haven't heard this in a while

from your high school biology--

or if you never heard it, no big deal--

karyotype is the complement of chromosome--

XX or XY.

And there are individuals out there

that are XXY or XYY, a discussion for our episode

on sex differentiation.

That's karyotype with a K.

Then there's genotype, which are the genes that you have.

And then there's phenotype, spelled P-H-E-N-O-T-Y-P-E,

phenotype.

And the phenotype is how the genes,

which then code for RNA, which code for protein,

how those are expressed in terms of things like eye color.

So eye color is a phenotype.

Height is a phenotype.

Hair color is a phenotype.

So you have karyotype, genotype, and phenotype.

Well, what we need to do is we need to bring together

that sperm, which is haploidd it contains those 23

chromosomal strandes--

with either an X or a Y. Sex chromosome

is the 23rd chromosome.

We need to get that cell to the egg.

And so when we talk about spermatogenesis, of course,

we are talking about the generation of sperm cells.

But what we're really talking about is the generation

of cells whose job is to deliver the genetic material from dad

to the egg within the female in a way that increases

the probability that not only will that egg be fertilized

but that it will progress in a healthy way with each set

of chromosomes from mom and from dad--

each set of 23 chromosomes, that is--

will progress in a healthy way, will implant in a healthy way,

and will maintain and grow in a healthy way to a healthy embryo

and child and eventually adult. That's the job of the sperm.

So as we talk about spermatogenesis,

let's just remember that and why they're there

in the first place.

Now, a few things about sperm that are interesting,

besides the fact that they're haploid

and besides the fact that, as you all know, they swim.

They have a head and a tail.

They actually have a head, a mid region, and a tail,

and that mid region turns out to be very important.

It's something we'll come back to again and again.

That mid region is really key for the ability for sperm

to engage in forward progression to swim forward.

It involves the activity of mitochondria,

which are involved in generation of ATP, which

is involved in all aspects of energy and all cells.

But let's just remember that the sperm are swimming cells.

And in order to create a really good swimmer

or set of swimmers, you need a couple of things.

First of all, within the testes is where the sperm develop.

And unlike in females and unlike in the ovary,

there's no vault of sperm.

The sperm are continually being generated.

It takes about 60 days for sperm to be

born from their parent cells--

because cells actually give rise to other cells,

that's the it works-- to be born from their parent cells

and then matured to the point where they

can be a really good swimmer.

Now, that doesn't mean that a bunch of sperm

are made on day one, and then 60 days later, all those sperm

are deployed in the form of ejaculate,

and then the cycle starts over again.

So it's a little different than the ovulatory menstrual cycle.

Rather, at any given point in time-- like right now,

if you have testes, you have some sperm in your testes that

are immature and cannot swim, cannot deliver those contents

to--

those genetic contents, rather-- to the female egg.

And you have some sperm that are mature,

and you very likely have some sperm that are so mature

that they are dying off or that they're dead.

Almost certainly, also, regardless of your age,

you have some sperm that are healthier than others, that are

better swimmers than others.

This is just the way the system works.

Now, the process of spermatogenesis

involves a couple of things, but a lot of the players

are the same as the process of developing

the so-called oocyte, the immature egg.

We've got GnRH from the hypothalamus.

That's going to be a player.

We have FSH, follicle-stimulating hormone,

although the name's a little bit of a misnomer in the context

of spermatogenesis, because in the context of spermatogenesis,

there is no follicle.

What we're really talking about is

FSH for stimulating the maturation of the sperm cell,

so not egg follicle but sperm cell.

But we still have GnRH, FSH, LH, and rather

than the ovary being the target of those hormones,

it's going to be the testes.

So most everybody should know that the testes and the ovaries

are the so-called gonads.

The testes, of course, reside outside of the body.

There are instances where the testes fail

to descend during development.

Certainly, if the testes don't descend

on time, that's something that doctors need to be made aware

of, the pediatrician should be made aware of,

because that can prevent fertility.

Why would that be?

Well, it turns out that the testes

reside outside the body in the scrotum

because the temperature conditions

under which spermatogenesis can occur

and under which healthy sperm can be maintained

are very restricted and is approximately 2 degrees cooler

than the rest of the body.

This is very important.

I think this is something that used to be discussed a lot more

but isn't discussed so much these days.

But keeping the testes cool enough--

doesn't necessarily mean keeping them cold, although there

is a place for using cold exposure,

deliberate cold exposure, to improve

sperm quality and number and perhaps even

testosterone levels.

We'll talk about that a little bit later.

But keeping the testes about 2 degrees

cooler than the rest of the body is absolutely key.

If sperm get too hot, they die.

And if spermatocytes, the cells that give rise to sperm,

get too warm, well, then oftentimes the sperm

that develop are not healthy, not healthy

in a number of ways.

Either they can't engage in fast forward progression--

that is, swimming-- or they will lack the ability

to deposit their DNA contents within the egg.

So again, whatever is contained in the ejaculate

is going to be a mixture of different sperm qualities.

And sperm of different ages will impact the quality, but also

the temperature under which those sperm developed is

going to impact their quality.

And so we're going to get into tools a little bit

later, as I mentioned, but just to give you a simple takeaway.

If you are hoping to conceive in the next 90 days--

the spermatogenesis cycle take 60 days,

but then the sperm actually have to migrate from the testicle

into the so-called epididymis, which is a related structure,

and then into the vas deferens and then

into the urethra, where it can be part of the ejaculate.

In order for sperm to do all that properly,

undergo that maturation and then exit in ejaculate in a way

that's healthy or that the sperm is healthy,

if you plan to conceive children or to try and conceive children

in the next 90 days, you definitely want to avoid

exposing your testicles-- that is, your scrotum--

to elevated temperatures.

So that means definitely avoiding hot tubs,

definitely avoiding hot baths.

Now, a brief hot bath or hot tub or hot shower

isn't going to be a problem, although if you're

really interested in conceiving, I would avoid hot tubs

and hot baths as much as possible.

Hot showers are probably fine.

But if you're going to go into a sauna, for instance,

you might want to rethink that decision.

And if you do decide to, you almost certainly

would want to bring a cold pack in that you could-- well,

hopefully put some material between the cold pack

and the scrotum so you don't get a cold burn.

But put something there, but keep the scrotal tissue cool.

Keep it cold to cool because heat exposure can really

mutate and disrupt the developing sperm,

and it can kill sperm.

And so, again, that would be for an entire 90 days

leading up to your attempts to conceive.

Again, we'll get into more tools later, but a number of people

also have probably heard of the boxers versus briefs

controversy, I guess it is, or whether or not people call

it going commando with no underwear of any kind-- boxers,

briefs, briefs, or otherwise rather.

It turns out that the data on that point to the fact

that there isn't really a big difference in terms of sperm

quality if people wear boxers or briefs

or don't wear anything under their jeans or shorts at all.

The scrotum has the ability to move the testicles far enough

away from the body in order to achieve lower

temperatures if it needs to.

It achieves that through a muscle

called the cremaster muscle, which

is a really interesting muscle, believe it or not.

I was reading up on the biology of the cremaster

muscle, something I never thought

I'd spend too much time on but that I ended up spending far

too much time reading up about.

And it's really fascinating.

What you have is a muscle that is a smooth muscle

tissue, unlike skeletal muscle, which is striated muscle,

that is temperature dependent.

So it has certain nerve endings, and it has certain receptors

on it that allow it to respond to local temperature

and then to relax in order to essentially let

the testicles to descend further from the body or to contract

and bring the testicles closer to the body

in order to try and maintain the optimal temperature range.

And it turns out the cremaster muscle can achieve that

whether or not people are wearing boxers or briefs.

Although it stands to reason that any kind of--

there's no other name for it-- undergarments-- you know,

I don't know why that word just seems kind of antiquated--

but undergarment that allows some movement of the scrotum

and the testicles should be sufficient to allow

these temperature variations to occur and keep things in range.

That said, a little bit later, we'll go into some detail,

really--

because it's important-- as to why,

for instance, if you are somebody who has big thighs,

believe it or not, that it actually

can lower sperm count substantially, whether or not

the big thighs occur because you're very muscular

or the big thighs occur because you are overweight.

It can increase the temperature.

If you're sitting a lot, increases

scrotal temperature, for sure.

And there are some other things that can increase scrotal

temperature, seat heaters in cars, for instance--

terrible idea, just terrible idea if you're hoping

to conceive in the near future--

and again, hot tub, things of that sort.

So temperature modulation of spermatogenesis and sperm

quality and function is key.

That relates a little bit more to tools.

But what happens?

How does the actual sperm develop?

Well, contained within the testicle,

you have the cells, the so-called spermatogonia,

which differentiate into so-called spermatocytes.

You don't have to remember all this.

And the spermatocytes undergo this process of meiosis.

Meiosis is a form of cell division, which

reduces the chromosome number to those 23 individual strands as

opposed to pairs.

So it makes them haploid as opposed to diploid.

Very, very important for reasons that we talked about earlier.

And the meiosis process in these primordial sperm cells,

these immature sperm cells, is similar to the meiosis process

that occurs in eggs when the chromosomes segregate in

that it involves these spindle-like structures

within the cell.

Now, why do I keep bringing up the spindles?

Well, it turns out that the function

of the spindle in the egg and the sperm

is heavily dependent on mitochondrial function.

And later when we get into tools for improving egg and sperm

quality, you're going to hear about a lot of tools

for improving mitochondria.

And it's not just because the mitochondria

are involved in energy-demanding aspects of cell biology.

But it's also because the mitochondria in this context

are very, very important for the removal of or the separation

of one set of chromosomes to give you

these two sets of haploid cells, the egg and the sperm.

And this is so important because many failures at fertilization,

many failures at implantation, many, many miscarriages,

and many birth defects that do survive after birth that

are very detrimental, such as trisomies and things like that,

occur because the spindles don't effectively pull apart

the chromosomes in typically the egg,

but it can also occur in the sperm.

So the spindles and the fact that mitochondria

are rich on the spindle are very important for generating

these haploid sperm-- again, 23 individual strands

of chromosomes.

That's occurring inside of the testes.

So there's not as much long-distance migration

of the spermatocytes and the sperm cells

as there is the egg just when you

think about the overall architecture of the uterus

and the Fallopian tubes compared to the testicles,

but there's still a lot of movement.

So within the testicle, if you were

to look at the testicle in cross-section--

and I prefer to call it that rather than cut

the testicle in half.

Any time you talk about anatomy, you actually

talk about slicing things.

That's what you would do with a cadaver is what I teach

and we do in my laboratory and, frankly,

in biological laboratories all over the place.

But when you talk about it, you talk about if you were to take

a visual cross-section through the testicle,

what you would find is that there are a lot of different

little tubes, a lot of ducts, D-U-C-T-S, ducts.

Those are pathways.

And the main ducts that are important for this discussion

are called the seminiferous tubules.

So it's a mesh-like or network structure

of tubes in the testicle.

And the immature sperm sit on a little compartment

along the edge of those tubes.

And as they mature, they move towards the center

of those tubes.

And then when they are mature enough,

those sperm cells actually drop into the hollow of the tube,

and then can travel through those tubes

to a structure that's along the side of the testicle called

the epididymis.

The epididymis, again, is a series of ducts.

And then the epididymis converges with something

called the vas deferens.

I think in high school, we all remember this

by thinking about it's the vast difference.

I don't know who came up with that.

I think it was a young girl sitting

to the left of me that was like, oh, it's

like the vast difference.

I never forgot that.

I don't know.

Maybe it was the topic matter.

Maybe it was her.

Maybe it was some combination of the two.

But in any case, the sperm go from the seminiferous

tubules to the epididymis and then

to the vas deferens and then are contained in the ejaculate,

along with seminal fluid.

Now, the seminal fluid is the carrier fluid

for the sperm themselves.

This is important because it turns out

that a lot of things that can both negatively or positively

impact the quality of the sperm relates not just

to the sperm cells themselves and the temperature

of the environment that they were matured in,

but also to the semen quality.

For instance, if you are a heavy drinker, if you are a smoker,

or if you are a regular user of cannabis,

especially if you smoke cannabis or vape cannabis,

you create a lot of reactive oxygen species

that disrupt the chemistry of the seminal fluid, which

disrupts the sperm cells.

So it's not a direct action always on the sperm cell

itself, although it can be.

So for instance, in the form of smoked tobacco or cannabis,

there are a lot of carcinogens and mutagens

that actually mutate the DNA, can cause DNA fragmentation,

and debilitate sperm.

But there are also a lot of things created by smoking

in particular, regardless of what's being smoked,

that can create elevated reactive oxygen species

and disrupt the seminal fluid that the sperm are contained

in in the so-called ejaculate, the semen.

Now, this will also become a relevant conversation later

when we briefly talk about vasectomies.

Vasectomies are literally a cutting

of the vas deferens, which leads to a situation,

provided the surgery was done correctly,

where men can still achieve all the other aspects

of intercourse.

They can still achieve erection.

They can still achieve orgasm.

They can still ejaculate.

But when they ejaculate, the seminal fluid is released,

but there are no sperm contained within the seminal fluid.

And it turns out that vasectomies

are a very effective form of birth control.

And they always check to see if zero sperm

and confirm that zero sperm are being

released in the ejaculate.

They are reversible.

And that is, vasectomies are reversible, but not always.

There are a subset of cases where it's not reversible,

in which case if people still want to have children,

you have to go in and actually surgically extract sperm

from the testicles.

But it's a process in which the vas deferens is altered

or severed in a way that the sperm can't actually

exit the testicle.

They can get into the epididymis, usually,

but not into the vas deferens and so on and so forth.

So if you've ever wondered what a vasectomy is,

that's what a vasectomy is.

And I mentioned vasectomy now because it illustrates

the difference between the seminal fluid, the semen,

and the sperm that the semen contain.

So 60 days to generate the sperm, another two weeks

or so for the sperm to travel through the various ducts

to the point where they can be contained in the ejaculate.

Let's talk about the sperm cells themselves.

The sperm cells, again, have these 23 pairs

of single-strand chromosomes.

They're haploid.

They have either an X or a Y sex chromosome

as the 23rd so-called sex chromosome.

And as we all know, they have a head.

The head tends to be oval in most cases.

The head contains very important enzymes and proteins

that are designed to fuse with the much larger egg

and to actually take the membrane of the sperm cell

and combine to actually mesh with the egg cell's membrane

and then deliver the genetic contents to the egg cell,

in other words, to fertilize the egg cell.

Now, just behind the head is a region called the mid region.

That mid region is a slightly thickened region.

And here, of course, I'm talking about healthy sperm cell

morphology.

Morphology simply means shape.

A mid region-- that mid region has a bunch

of things related to cell motility

and to the forward progression of the cells.

First of all, it is chock a block full of mitochondria.

In fact, if you were to look just

behind the head of the sperm, what you'd see

is that it is completely surrounded by mitochondria.

There are mitochondria elsewhere in the cell, but most of them

are contained in this mid region compartment

just behind the head of the sperm.

And that thick region is where the tail movement of the sperm,

the flagellation back and forth, is actually generated from.

Much like if you were to hold a rope, like a battle

rope in the gym, and you were to whip the battle rope,

the whip at the one end of the rope

is what allows for the sort of-- let's just call it

what it is-- the curves in the rope,

the oscillations, the rising and falling

of the rope all the way out to the end.

It is the force of the whip right at that end that with

the battle rope you're doing with your hand--

and with the sperm, that is occurring just behind the head

of the sperm--

that is actually going to dictate how fast

and how well that sperm can swim.

And indeed, the sperm has to swim very far.

How far?

Well, on a relative scale--

and again, these are estimations because they're going to be--

how should we say?

There will be differences in the distance

from the head of the penis and where the ejaculation occurs

to the cervix, depending on the relative size

of the vaginal canal and the penis that

delivers the ejaculate to the vaginal canal.

But once the sperm arrive at the cervix, which

is at the back of the vaginal canal

just at the opening to the uterus,

once the sperm arrive there, the distance

from the cervix to the egg, of course,

will vary depending on where that egg is

in its ovulatory trajectory, its pathway.

But it is akin, if you scale for size,

to the distance between Los Angeles and San Francisco,

which is many, many hundreds of miles.

So those sperm have to swim very far.

Now, of course, if the sperm are delivered in the vaginal canal

somewhat further away, they will have further to go.

If they're delivered right at the cervical opening,

they will have less far to go.

The very effective swimming sperm swim very fast.

So they are able to accomplish that distance

in just a few days.

And this relates to a discussion that we

will get into in a lot more detail

later as to how often couples should have intercourse

if they're trying to conceive.

Many people might think, well, it's every day.

However, the more frequent the ejaculation, the lower

the concentration of sperm in each ejaculate.

So this is not a discussion about how often

to have intercourse depending to your preferences,

for pleasure or bonding or whatever reason.

This is a discussion about how often to have intercourse

in order to optimize the probability of fertilization

of the egg.

There's some general rules that, of course, come to mind,

which is ejaculations close to ovulation-- both before,

during, or sometimes after--

are obviously advantageous.

But you will also hear OB/GYNs and urologist

suggesting intercourse every other day

leading up to the day of ovulation,

starting about three to four days out

from the day of ovulation.

So we got a little bit sidetracked,

albeit I think appropriately so, in focusing on fertilization.

But what we were talking about right up until the point

of that is the anatomy of the sperm itself,

which is the head, the mid region that

contains all those mitochondria, and then the tail.

Now, what we haven't discussed is the actual generation

of the sperm.

So if you're a male or if you're a female,

I think it's really important to understand

how spermatogenesis works.

Spermatogenesis works in much in the same way

that the generation and maturation of eggs work,

although, as I mentioned before, it's

going to occur ongoing throughout the cycle

of the male's life after puberty.

We already talked about puberty, and I'll just

cover this in two or three sentences

as it relates to males.

And it's essentially the same thing.

The hypothalamus, up until the point of puberty,

is providing suppression of the release

of gonadotropin-releasing hormone.

Then some biological clock, which is still not clearly

understood-- it's probably not leptin coming from body fat.

Again, unlike in the female, it's probably not leptin

coming from body fat.

But some other signal arrives to the hypothalamus,

removes that inhibition, and GnRH,

gonadotropin-releasing hormone, is now

released onto the pituitary.

A bunch of hormones are deployed from the pituitary

as a consequence.

The two most important ones for the context of this discussion

are follicle-stimulating hormone and luteinizing hormone.

Follicle-stimulating hormone and luteinizing hormone

travel to the testes, and they're

going to do two main things.

One, they're going to trigger the production of testosterone.

And they're going to trigger the production

of the sperm themselves.

They're going to set in motion, for essentially

the rest of the life of the male, the production of sperm.

They're going to initiate the spermatogenesis cycle,

and that cycle is going to be ongoing

at various stages for different sperm

for the rest of the man's life.

This is very different than the triggering of development

of oocytes and eggs in females, where there's an existing

vault. That vault can be depleted to the point of zero

where it can't occur again.

Men can generate sperm their entire lifetime.

Of course, there's a diminishment

of sperm production in very, very late age,

say, 80s and 90s or 100s.

But believe it or not, there are still sperm being produced.

The quality of those sperm is another question.

So everything we're going to talk about now

is essentially puberty onward.

Prior to that, testicles are present,

but they're not generating sperm.

Ejaculation isn't possible, or if it is possible,

it's very unlikely and unusual, and it's not

going to contain sperm.

Everything we're going to talk about now

is puberty forward, so puberty onward to the rest of life.

And luteinizing hormone secreted from the pituitary acts

on the testes and on a very specific cell type

in the testes called the Leydig egg cells, or Leydig cells,

L-E-Y-D-I-G, the Leydig cells.

The Leydig cells of the testes are what produce testosterone.

Testosterone is going to have two major effects.

And here I mean really major because it

has many, many hundreds of effects on different tissues

of the body.

In fact, that's the definition of a hormone, really.

It's a substance that acts in an endocrine fashion.

It can act on the very tissue that generated it.

So for instance, testosterone made by the Leydig cells

within the testes will act on the testes,

as we'll talk about in a moment.

But it can also act on other tissues.

It can act on the pharynx and larynx

and deepen the voice, as it does during puberty.

It can act on the hair follicles and generate facial hair.

It can act on the musculature and generate protein synthesis

and development of muscle, bone, et

cetera, all the things we associate

with puberty and with testosterone typically.

Restricting the conversation to the effects of testosterone

on the testicle itself and on spermatogenesis,

the Leydig cells make testosterone.

And keep in mind that some of that testosterone

will travel elsewhere in the body

and do its thing for gene expression

and the more acute effects of testosterone on the brain

included.

But the testosterone within the testes

is at extremely high concentration.

In fact, the concentration of intratesticular testosterone

is at least 100 times higher than the concentration

of testosterone anywhere else in the body,

even though it's being secreted into the rest of the body.

And that's because there are a number

of different so-called binding proteins and enzymes

that sequester the testosterone within the testes.

So the Leydig cells are making testosterone,

and a lot of that testosterone is acting on

and is restricted to the testes.

And that turns out to be very important because testosterone

within the testes acts in concert

with a different biological program that starts with FSH,

follicle-stimulating hormone, that also travels to the testes

and acts on a very specific set of cells that are called

supporting cells or, more specifically,

the Sertoli cells.

The Sertoli cells are the cells that

generate something called ABP, or androgen-binding protein.

And it is the combination of testosterone from the Leydig

cells and ABP from the Sertoli cells

that is necessary for spermatogenesis.

It's necessary for those spermatocytes

to become what will eventually be healthy, mature sperm that

have really nice shaped oval heads, have a mid region,

chock a block through mitochondria,

and can generate a fast whipping motion of the tail

to swim from the cervix, or up the vagina into the cervix,

and from the cervix to the egg to fertilize the egg.

So it's really a basic set of chemical players that are

involved here and so basic, in fact,

that if you were to disrupt any one of these chemical players--

either the luteinizing hormone, the FSH,

the testosterone from the Leydig cells,

or androgen-binding protein--

you would observe pretty marked disruption

in spermatogenesis or the elimination of sperm entirely.

We'll get into a few deficits in sperm development

and sperm number and sperm function a little bit later.

But just keep in mind--

or I should say, maybe sit back and just

appreciate that the exact same players generate

from the hypothalamus, which causes luteinizing

hormone and follicle-stimulating hormone released

from the pituitary, which travels to the gonad, which

in this case is the testicle, which triggers

the release of testosterone from Leydig

cells, which triggers the action of the supporting cells,

the Sertoli cells, which make androgen-binding protein.

Testosterone and androgen-binding protein

combine and create a chemical and actually

a structural milieu in which those little spermatocytes

can go from the walls, from literally

the walls of the tubes of the seminiferous tubules,

can mature into healthy, well-developed sperm,

and can hop into those ducts, those little tubes,

and then head off to the epididymis, where they will

reside-- the epididymis is the tissue nearby the testicles

or surrounding one portion of the testicle--

and then eventually fuse with the vas deferens,

can combine with or be contained with, rather,

the seminal fluid, and then can be ejaculated via the urethra

into the female, where then they can

swim very quickly, effectively the distance, for them anyway,

from Los Angeles to San Francisco,

over the course of a very short period of time,

and fertilize the egg.

So that's the process of spermatogenesis, the maturation

of sperm, which is ongoing throughout the lifespan

from puberty onward.

And in doing so, we talked about some of the hormonal elements--

coming from the hypothalamus and coming from the pituitary,

and within the testes themselves the Leydig cells, which

produce testosterone, the Sertoli cells,

which are the support cells that allow spermatogenesis to occur.

With that in mind, next I'd like to think

about what's actually contained in the ejaculate in terms

of numbers of sperm and what's really being selected

for in terms of the sperm that actually successfully

fertilizes the egg and what sorts of elements

come into play in dictating whether or not fertilization

will or won't occur.

And the major themes that we're going to discuss

are frequency of ejaculation, but really

that's just kind of a proxy for talking about maximizing

sperm concentration and quality of sperm arriving at the egg--

because, remember, ovulation and the menstrual cycle

are really about creating the opportunity for fertilization.

And we are also going to talk about how

the vaginal duct, the vagina, and

the milieu around the cervix and some other elements

within the female herself contribute to

and support the sperm in their journey to the egg

and in the likelihood that they will fertilize the egg.

So really what we need to talk about first is sperm quality.

And we should also probably talk about ejaculate quality,

because, as odd as that theme might seem,

really the ejaculate quality, which

has a number of different parameters,

including the number of mature sperm

that are not so mature that they're swimming slower

or are dead, but also quality of sperm.

They have, for instance, one tail.

It's not entirely uncommon to see sperm

with two tails because they just didn't form properly

or sperm that are not moving very much.

In fact, sperm motility is scored along a scale of 0,

1, 2, or 3, 3 being the best, fast forward progressing.

0 is not moving at all.

1, they're actually called twitchers.

Twitchers are sperm that sort of just twitch in place

but don't undergo forward progression.

2 is somewhere in between 1 and 3, not surprisingly.

Different clinics, different OB/GYNs, different urologists

will throw out different numbers.

But in general, it is hoped that more than 50% of the sperm

should be motile in some way or another, so not scoring a 0,

but a 1, or 2, or ideally a 3.

The concentration of sperm--

of course, if it's higher within the ejaculate, the total number

of sperm per milliliter of ejaculate, if that's higher,

then there's a higher probability

that one of those sperm will fertilize the egg.

One thing I didn't mention before when

discussing the production of eggs and ovulation--

and I probably should have, so I will

now-- is that most often only one

ovary gives rise to an ovulating egg.

It happens, but it's somewhat rare for two mature eggs, one

from each ovary, to be deployed during a single ovulation.

There's a name for that when it occurs and both are fertilized.

It's called fraternal twins.

If a single egg--

that, of course, comes from a single ovary--

is fertilized and the egg splits--

and that's something that happens further along

in the process of fertilization and differentiation

of the embryo--

well, then what you get are identical twins.

There are other instances that are quite uncommon in which

you can get fraternal twins through other circumstances.

But in general, that's the way it works.

But essentially what happens is one egg

from one ovary-- that's the most common occurrence.

The sperm, once ejaculated into the vaginal duct,

are going to pass through the cervix

and then are going to swim toward the egg.

The egg could be at varying locations

along the female reproductive axis.

Now, this is actually a very important thing

and actually gets right down to the safety of both the

potentially developing embryo and the mother.

There is something referred to as ectopic pregnancy,

and that's when the pregnancy actually occurs

within the Fallopian tubes.

So the precise location in which fertilization

between the sperm and the egg occurs can vary somewhat.

But ideally, the fertilized egg implants into the endometrium

or the endometrial lining of the uterus

and develops there as opposed to within the Fallopian tubes,

which is so-called ectopic pregnancy.

Now, where the sperm and the egg meet exactly

can vary, as I mentioned before.

But in general, the faster swimming sperm

and the more far along the ovulatory trajectory the egg

are, the higher the probability of a successful fertilization

because of the proximity to the implantation zone

of the uterus.

So basically it's all a probabilities game.

It's a probabilities game related

to the number of sperm cells that encounter the egg

and where the egg is in terms of its ovulatory cycle

and also its position where it is in the ovulatory cycle.

The sperm parameters-- or I should

say the semen parameters-- and ejaculate parameters

that most clinicians want to see,

if you were to give a sperm sample,

would be somewhere in excess of 15 million sperm per milliliter

of ejaculate.

Now, there's a lot of discussion nowadays.

It seems to be a very popular news theme

to talk about diminishing sperm counts, the idea that 100

years ago or maybe even 35 years ago, the typical male ejaculate

contained 100 million sperm per milliliter,

and nowadays it's down to 15 to 20 or 50.

And indeed, sperm counts do seem to be declining.

And the exact reasons for that are not clear.

I confess I'm a little bit reluctant to talk about this

because there have been a lot of back and forth discussions

about the safety of EMFs, of electromagnetic fields,

and it's not exactly what we're talking about here.

But there are some excellent data

contained in meta-analyses and reviews

that I will provide links to and that we'll talk about

in more detail in a minute that correlate

the advent of smartphones and in particular caring

of smartphones in the pocket with diminishing sperm counts.

Although there are certain to be other factors that

can explain diminishing sperm counts as well.

Dr. Shanna Swan, for instance, has done beautiful work

describing how the phthalates and the BPAs

and so-called endocrine disruptors

might be disrupting some of the milieu

of the seminiferous tubules.

So this would be reductions in testosterone and/or disruptions

to the Sertoli cells and androgen-binding protein

brought about by endocrine disruptors such as phthalates

contained in pesticides and contained on printed receipts

and things of that sort.

There are some data that that is negatively

impacting sperm counts.

How much so is still debatable.

There are also quite good data pointing

to the fact that both the heat-related

and the non-heat-related impact of smartphones and laptops

contained on the lap are impacting sperm count

and in a negative way.

Again, there's going to be tremendous variation

in the concentration of sperm from one

individual to the next.

It will vary according to age and a number of other factors

that we'll talk about a little bit later.

But in general, if somebody is wishing to conceive,

then clinicians like to see a ejaculate volume

of more than 2 milliliters.

So ejaculate volume can be anywhere

from 1.5 to 5 milliliters.

And that will strongly be determined

by how frequent ejaculation is occurring.

There's a lot that goes into evaluating the quality

of ejaculate and sperm.

But basically these huge variations that are observed

of anywhere from 15 million sperm per milliliter

or, in some males who are not producing sperm for whatever

reason-- we'll talk about those reasons in a little bit--

as low as 5 million sperm per milliliter,

all the way up to 100 or maybe even

200 million sperm per milliliter.

Huge variation-- the cause of which is not always clear

but is certainly determined in part

by the frequency of ejaculation.

So because there are so many variables

impacting why one male versus another male or even

the same male across the lifespan

might have variations in his concentration of sperm

within the ejaculate, let's talk for a second about frequency

of ejaculation as it relates to the goal of fertility,

per se, because that's really what today's episode is all

about.

So what I'd like to talk about next

is how people can increase the probability

of a successful fertilization, focusing

both on the components from the male side

and from the female side.

And I'm mainly going to couch this discussion in the context

of the so-called natural method of sexual intercourse

and ejaculation in vivo, within the female.

But I will also touch on some parallel themes

as it relates to in-vitro fertilization

and intrauterine insemination.

So the idea here is that we want the maximum number

of high-quality sperm-- that is, rapidly forward,

motile sperm that are of the correct morphology--

that is, shape.

That's going to require a lot of mitochondria

in the mid region, a well-shaped head--

so it's going to be an oval-shaped head.

The tail is going to be a single tail, not multiple tails.

These aren't going to be the twitcher type of--

or immotile type of sperm that are either twitching in place

or aren't moving forward.

All of those components are going

to be essential for increasing the probability

of fertilization.

But of course, there's the female side of it,

too, which is that ovulation occurs

on just one day during the menstrual ovulatory cycle.

And that egg will be available for fertilization

for approximately 24 hours.

Now, keep in mind that the sperm can survive

within the vaginal duct and within the area

around the cervix and within the uterus

and along the female reproductive tract for anywhere

from three to five or it's even been

described as up to seven days.

But generally, it's going to be about three to five days.

Now, most women can figure out the day of their ovulation

by counting the total number of days of their typical cycle.

And this is where it's really useful

to have a cycle that's of more or less regular duration

or, rather, of more or less regular length.

So as we talked about earlier, if somebody's cycle

is 21 days or 25 days and it's 21 or 25 days consistently

or even 30 days consistently, that's

going to be a far better scenario to favor fertilization

than if it's 20 days one month and then 21

days the next month, but then suddenly 30 days and then

suddenly 35 days.

Those varying durations of the ovulatory cycle

make it very hard, obviously, to time

and understand when ovulation is going to occur.

So regular duration ovulatory cycles

are the ideal circumstance, and they're the ideal circumstance,

because even though the egg is only

available for fertilization for a few days,

those sperm can survive for some period of time, which

leads to the issue of how often should couples

be having intercourse.

And here, I'm referring specifically

to intercourse with ejaculation.

How often should couples be having intercourse

around the time of ovulation if the specific goal is

successful fertilization of the egg and the creation of a baby?

This is leaving aside all issues, which, of course, are

interesting issues, related to how often people are having

intercourse, whether or not there's ejaculation

every time they have intercourse or not, for sake of pleasure

or for sake of pair bonding and pleasure

or for sake of any number of other potential goals

of intercourse.

Here I'm only referring to intercourse

as it relates to the goal of fertilization of the egg.

So knowing what we know about spermatogenesis and the fact

that ejaculate is going to contain a certain concentration

of sperm but that within that ejaculate some of the sperm

will be older and less healthy and some will be optimally

mature and some might even be a little bit

immature-- although there's a tendency for the immature sperm

to not have yet exited the seminiferous tubules, gone

into the epididymis and vas deferens.

But given that the ejaculate contains

sperm of varying ages and therefore varying quality

and given that with each successive ejaculation

in a short period of time there's

going to be a decrease in the concentration of sperm

per milliliter of semen, of ejaculate,

we can make some good arguments as

to how often couples should have intercourse

with ejaculation around the time of ovulation

if the goal is to fertilize.

If ovulation occurs on, for instance,

day 14 of a cycle-- and here we're

using the kind of standard average

of 28 days of the cycle.

But for some people with a 30-day cycle,

it could be day 15, or with a shorter cycle,

it could be day 12, for instance.

But given a 28-day average cycle,

let's say ovulation occurs on day 13 or on day 14.

And typically, it would occur on day 14 of a 28-day cycle.

Well, then, given how long sperm can survive inside

of the woman, you might think that the optimal strategy would

be to have as much intercourse with ejaculation in the three

or four days leading up to ovulation, hope

that those sperm have swam as far as they possibly

can and will encounter the egg just as soon as possible

after it ovulates.

It turns out that's not the optimal strategy.

The optimal strategy is really to maximize the concentration

of healthy sperm within each ejaculate

and to really center that around the day of ovulation.

So what this involves generally and what

the typical recommendation is is to abstain from intercourse

with ejaculation about two or three

days out from ovulation and then, on the day

prior to ovulation and on the day of ovulation,

to essentially introduce as much semen

and ejaculate into the reproductive pathway

of the female as possible.

Now, that's the general recommendation

that the OB/GYNs and the urologists that I spoke to

gave.

But you will also hear a different strategy.

It's only slightly different.

But the different strategy involves

trying to maximize the concentration of healthy sperm

within each ejaculate with the understanding that,

with each subsequent ejaculation over about a 24-hour period,

that there's going to be a dramatic reduction

in the concentration of sperm.

What that means is that if a couple, for instance,

were to have intercourse with ejaculation many times

on the day prior to ovulation, yes,

that will introduce a lot of sperm

into the reproductive pathway of the female, but what it means

is that, on the day of ovulation if they were

to have intercourse, the number of high quality sperm

that will be available to the egg will be greatly diminished.

And if none of the sperm that were introduced

in the day prior managed to fertilize that egg,

well, then essentially chances are off

that there will be fertilization or they're greatly diminished.

Rather, if they're having intercourse with ejaculation

once or twice on the day prior to ovulation

and then a maximal number of times with ejaculation

on the day of ovulation, that itself

can maximize the probability of fertilization.

So which strategy is optimal?

Should couples have as much intercourse

with ejaculation on the day prior to ovulation

and on the day of ovulation?

Or should they have intercourse on the day prior to ovulation

but not so frequently that it diminishes the concentration

of sperm and then allows for intercourse

with the maximum number of ejaculations

on the day of ovulation?

You really hear it both ways.

And what this really boils down to is,

frankly, that nobody knows.

And the reason nobody knows is that there's

tremendous variation among males in terms

of the absolute concentration of sperm per milliliter

of ejaculate and the amount of sperm per milliliter

of ejaculate within a given time frame.

But what everyone agrees on is that a period of abstinence

ranging from 48 to 72 hours prior to an ejaculation

increases the concentration of high-quality sperm

within that first ejaculation to occur after the abstinence

period.

So again, to reiterate, if one's goal is to fertilize the egg,

you want to take into consideration

that most often there is going to be

a dramatic decline in the concentration of sperm

per ejaculate any time those ejaculations are occurring

within a short period of time, say,

within 12 to 24 hours of one another.

Now, all of this, of course, also

relates to the female biology and the extent

to which the woman can precisely identify the day

and timing of her ovulation.

Some women feel as if and indeed are very accurate

at estimating their time of ovulation

to within a couple of hours or some women even

report being able to feel their actual ovulation,

whether or not they are feeling the ovulation

itself, the deployment of the egg or not, isn't clear.

I certainly wouldn't know.

I've never produced eggs, nor have I ovulated,

and I'm certainly not going to contest the idea

that women can do that.

I mean, it makes sense that some people

have a very keen so-called interoceptive

awareness, an awareness of the sensory events

within their body.

And while, of course, the ovaries are not

thought of as an organ that we want

to be able to sense what's going on in there in terms of feel,

there are sensory endings within the ovary.

And so the notion that one could literally sense changes

within their ovary, including the deployment of the egg,

is not outside the bounds of reason and, in fact,

could likely be the case.

Now, that said, there are a number of different ways

that women will track their ovulation.

One is the temperature method.

So they'll actually measure intravaginal temperature.

They're looking for changes in temperature

that are consistent around the time of ovulation.

We're going to have an expert guest on, an OB/GYN, who

can tell us a lot more about the details and nuances

of the temperature method.

You'll see a lot of information about this online,

but there's a lot of misunderstanding about it,

as well.

Other women will use apps that take into account

either the temperature information

if they're acquiring temperature information--

that'll be entered into the app--

as well as marking the onset of menstruation,

the onset of bleeding, therefore,

the start of the ovulatory cycle,

because, of course, as we mentioned earlier,

that marks day one of their cycle.

And then, again and again, you can

see how regularity of cycle duration

or relative regularity of cycle duration

really favors this whole process of being able to predict

when one ovulates.

And fortunately, if the goal is fertilization,

there are some margins for error that are introduced by the fact

that the sperm can survive within the female reproductive

tract for some period of days, thereby reducing

the need for absolute certainty about the time of ovulation

and so on.

In fact, it's pretty well known that around the time

of ovulation a couple of things happen.

Earlier, we talked about one thing,

which is there's an increase in libido just prior to ovulation.

This relates to, in part, an increase

in some of the androgens, things like DHEA,

but also testosterone and some related androgens

that can increase libido both in males and females and changes

to the reproductive pathway, the female in particular,

a change in the pH-- that is, the relative acidity

versus basic nature of the mucosal lining near the cervix

and also vaginal secretions, such that,

around the time of ovulation, the entire milieu of the vagina

and the cervix and the locations in which fertilization can

occur and certainly in which the sperm are swimming

towards the opportunity for fertilization

is shifted to support sperm motility and health.

In other words, one of the best environments for sperm

to survive is going to be within the female reproductive pathway

itself.

And as long as we're talking about vaginal secretions

and mucus, it's important to point out

that a number of commercially available lubricants

can actually be detrimental for sperm health,

even if they don't contain spermicide.

So this is something that you'll want

to discuss with your OB/GYN or, certainly if you're male,

you could also discuss this with your urologist

and your partner's OB/GYN.

A lot of the commercially available lubricants

contain chemicals that, while they may favorably

change the consistency or the viscosity

of the vaginal pathway for purposes of intercourse,

certainly may not be the most favorable for maintaining

the health of the sperm and the motility of the sperm.

So again, here we're talking about intercourse only

in the context of trying to maximize fertilization.

And I should mention that there are

certain lubricants that are more conducive to the sperm

environment.

But it's something that you'll really

want to talk to your OB/GYN about

or at least read up about if your interest is

in trying to fertilize and develop an embryo.

So we covered the optimal strategies

for how often couples should have intercourse

with ejaculation around the time of ovulation

in order to maximize the probability

that successful fertilization and ultimately pregnancy will

occur.

What we haven't covered yet, however,

is how long couples should apply that method over time in order

to achieve successful fertilization in pregnancy.

Now, of course, if a couple decides

that they want to conceive and they

apply that method or any other method, for instance,

and they achieve fertilization and a successful pregnancy