Welcome to the Huberman Lab Podcast,
where we discuss science
and science-based tools for everyday life.
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,
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 were 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.
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 will 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
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
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 do’s 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 to thank the sponsors of today’s podcast.
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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 in 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 development of body hair, facial hair,
deepening the voice, breast growth, et cetera.
You’d say, okay, 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.
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, okay?
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, right?
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.
Okay, 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.
Okay, if that doesn’t make sense to you,
just remember autosome, okay, 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.
Okay, 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.
Okay, 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, okay?
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 OBGYNs.
But right now we’re just talking about the egg cells, okay?
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, okay?
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, right?
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 in 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, okay?
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 one to 11 or 12 to 23.
That’s not the goal.
The goal is to have chromosomes one, two, three, four,
five, six, 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 menarche, all right?
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 and 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,
can’t have puberty, can’t have puberty.
And in fact, those cells are releasing
this neurotransmitter called GABA
because it’s inhibitory,
prevents the firing of those neurons.
Okay, 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 or 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,
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 hundred 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 hundred 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, right?
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
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 nine,
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 in, 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 a half 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 a half years old,
by 1940, it was down to 13 and a half 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, right?
There’s a distinction between odors that we perceive
and pheromones, which are subconscious, right?
We don’t actively perceive, but that can impact our biology.
And pheromone 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 pre-pubertal 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.
There is something about the odor and or pheromones,
or perhaps something else that occurs
when a young pre-pubertal 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, excuse me,
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?
And 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, okay?
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, right?
Estrogen or estradiol is going to have different effects
on the breast tissue than it would on skin,
although it has 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 testy,
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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Okay, 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 pair,
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 ovulatory and menstrual cycle occurs
when luteinizing hormone and follicle-stimulating hormone
have been released, and the ovulatory slash 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,
but 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 slash 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,
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 OBGYNs 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 that’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 OBGYN
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.
Okay, 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 real biology
to support the fact that the lunar cycle
can 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 conflict 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.
Okay, so we need to bring together
the so-called haploid contents,
the 23 individual strands of chromosomes from the egg
to a place in 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, okay?
So day one is when the period initiates.
It is days one through 14 approximately, right?
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, right?
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’ve 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, from Star Wars, you know,
or from any kind of a space odyssey movie
where something is ready to happen.
You know, the 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 systems 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 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,
right, 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, okay?
That deployment or the release of that one mature,
proper selected egg with the taploid,
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, okay,
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, okay?
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.
Okay, 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, a thing 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, a little bit shorter,
depending on the length of the 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,
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
or 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 and 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, right?
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
in 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 then 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 in 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 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.
You know, 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 track to 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
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 the levels of hormones.
So for instance, a more than thousand-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, that 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 OBGYNs 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,
protect 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,
do’s 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’re 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.
Okay, 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.
A good example would be the mullerian inhibiting hormone
or MIH, the gene for mullerian inhibiting hormone,
which is a hormone that prevents the formation
of the mullerian 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, right?
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,
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.
Okay, so you have karyotype, genotype, and phenotype.
Well, what we need to do is we need to bring together
that sperm, which is haploid.
It contains those 23 chromosomal strands
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’re 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, okay?
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,
and involves the activity of mitochondria,
which are involved in generation of ATP,
which is involved in all aspects of energy in 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 way it works,
to be born from their parent cells
and then mature 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 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,
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 pediatricians 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 two degrees cooler
than the rest of the body.
This is very important.
You know, 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 two 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
and 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, right?
The spermatogenesis cycle takes 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, or otherwise, rather.
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’s 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.
Okay, 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, right?
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 the, typically the egg,
but it can also occur in the sperm, okay?
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, okay?
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,
anytime 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, okay?
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 they 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, okay?
I think in high school,
we all remember this by thinking about,
it’s the vas deferens.
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 vas deferens.
I never forgot that.
I don’t know, maybe it was a 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 the 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 cell.
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.
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.
Okay, 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 cells 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, 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, right?
It is the force of the whip right at that end
that you’re, with the battle rope you’re doing
with your hand and then 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.
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, okay,
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 OBGYNs and urologists
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,
and focusing on fertilization.
But what we were talking about right up
into 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 in 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’s 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.
Okay, 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.
Okay, so puberty onward to the rest of life.
And luteinizing hormones secreted from the pituitary
acts on the testes and on a very specific cell type
in the testes called the Leydig 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.
Okay, 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 a hundred 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.
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 to 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 where I should say,
maybe sit back and just appreciate
that the exact same players, GnRH from the hypothalamus,
which causes luteinizing hormone
and follicle-stimulated hormone release 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 testicle
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, right?
Because remember, ovulation and the menstrual cycle
are really about creating
the opportunity for fertilization, okay?
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 dead,
but also quality sperm that have, for instance, one tail.
It’s not entirely uncommon to see sperm with two tails,
right, 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 zero, one, two, or three,
three being the best for fast forward progressing,
a zero is not moving at all.
One, they’re actually called twitchers, right?
Twitchers are sperm that are just twitch in place,
but don’t undergo forward progression.
Two is somewhere in between one and three, not surprisingly.
Different clinics, different OBGYNs,
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 zero, but a one, a two, or ideally a three.
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, right?
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 the process
of fertilization and differentiation of the embryo,
well, then what you get are identical twins, okay?
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 I refer 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, 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 a hundred years ago,
or maybe even 35 years ago,
the typical male ejaculate contained
a hundred 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.
And 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.
That’s not exactly what we’re talking about here,
but there are some excellent data contained
in meta-analysis 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. Shana 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 counts 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 two milliliters.
So ejaculate volume can be anywhere from 1.5
to five 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 in 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.
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, right?
Within the female,
but I will also touch on some parallel themes
as it relates to in vitro fertilization
and intrauterine insemination, okay?
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, you know, 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, okay?
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, okay?
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,
you know, that 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 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 swim as far as they possibly can,
and we’ll 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 OBGYNs 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 timeframe.
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, okay?
So again, to reiterate,
if one’s goal is to fertilize the egg,
you want to take into consideration
that most often there’s going to be a dramatic decline
in the concentration of sperm per ejaculate
anytime 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 OBGYN
who can tell us a lot more about the details
and the 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 of 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 spermaticide.
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 and 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
the very first month that they try,
well then there’s no other work to do,
at least until that child is born.
And if and only if they decide
they want to have more children.
However, many couples find that they do not conceive
in the first month of trying,
even when they apply the optimal methods
and even if their age and every other factor
related to egg quality and sperm quality is optimized.
Now, I think it’s the rare instance
in which egg quality and sperm quality are optimized.
In fact, the word optimal and optimization and optimized
is a little bit misleading in general
because no one really knows what that is.
But of course there is an ideal,
there’s a perfect standard
to which everyone would like to achieve.
But of course, we all enter the picture
with genetic variables, environmental variables,
and so forth, many of which we’ll talk about
because you can in fact adjust them
in the direction that you would like
to improve sperm and egg quality.
But most people simply will not succeed
in achieving a successful fertilization
the first month that they try.
Now, there is a truth that governs
how many tries it ought to take
in order to achieve successful fertilization
and ultimately pregnancy.
And it’s very age dependent.
And in particular, it’s dependent on the age of the mother
because the age and quality of the egg,
while it’s not the only factor,
is certainly one of the most determining factors
in whether or not successful fertilization occurs.
And as women age, the quality of the eggs
tends to diminish over time,
largely due to changes in the mitochondrial function
and the spindle that pulls the chromosomes apart,
although there could be other factors involved as well.
Now, before continuing any further,
I just want to acknowledge that this whole language
around egg quality and sperm quality
is not the greatest language
because it’s entirely subjective.
And yet the word quality in these instances
is really there to explain a broad variety of factors
that can in fact be measured.
Things like the number of follicles
that are deployed each month in a woman’s ovulation
or the number of motile sperm
or the number of morphologically,
that is correctly shaped sperm in the male and so forth.
So when we talk about egg quality or sperm quality,
we’re really referring to an amalgam of different features
related to the different aspects of ovulation
leading to successful fertilization
or the different aspects of sperm
related to whether or not they can arrive
and deliver their DNA contents and so forth.
So I will use the words egg quality and sperm quality
just as general themes
because that’s what a lot of the clinicians use.
But I do understand that it’s a little bit of a loaded term
in both instances,
and it doesn’t relate to any one specific parameter per se.
So getting back to this issue of how long couples should try
according to the age of the female
and perhaps also the age of the male.
Well, most of the data that have been collected
relate to the age of the females I mentioned before.
And what we’re about to discuss
is within the scientific literature
described as what’s called fecundability,
which is the amount of time over which a given couple
needs to attempt to conceive,
of course, by having intercourse with ejaculation
around the time of ovulation.
Okay, it assumes that all the other things
are being done correctly.
And what we know
is that there’s a strong age-dependent effect
that largely rests on the age of the egg,
that is of the female.
And what we know is that for females 30 years old or younger,
if they have intercourse with ejaculation
around the time of ovulation,
say on the day before and on the day of ovulation,
and there could be other intercourse with ejaculation
around that time as well,
on average, that will result
in a successful fertilization in pregnancy
about 20% of the time on the first month of attempting,
the first ovulation cycle.
Now, if fertilization in pregnancy occurs, great, right?
There’ll be at least a nine-month lag
until they decide whether or not
they want to try and conceive again.
However, most couples,
even if the woman is 30 years old or younger,
will not successfully conceive on that first attempt.
And that’s because the probability is not 100%, it’s 20%.
So 80% of the time, they simply will not conceive.
Which means that they hopefully will try again
the very next month.
And if they successfully conceive, great.
And if they don’t,
then they ought to try again the next month,
the next month, and so forth.
Now, the typical advice that an OBGYN would give you
is that for a woman 30 years or younger,
and leaving aside the age of the father,
but still assuming that egg quality and sperm quality
are sufficiently high to achieve fertilization,
that the couple should,
or if the woman’s trying to have kids alone,
the woman should attempt to conceive
over the period of six months.
Well, if you think about it,
if there’s a 20% chance in the first month,
and it’s unsuccessful,
well, then on the second month,
there’ll also be a 20% chance.
On the third month, also a 20% chance.
What I’m describing here
is what obviously is independent probabilities.
That is, if you were to flip a coin
and the probability of getting heads is 50%,
the probability of getting tails is 50%, of course,
you don’t expect that the previous flip
had anything to do with the result
that you’ll get on the subsequent flip.
That’s what independent probabilities are.
However, when it comes to fecundability,
we’re really talking about something
which is called cumulative pregnancy rate,
which is not really independent probabilities.
Now, why would that be?
Why would it be that if you did not successfully conceive
in the first month of trying,
that by simply trying again and again and again,
the probability of conceiving would increase?
Well, the reason for that
is that this whole business of fertilization
is not just about what’s happening with the egg,
it’s also about what’s happening with the sperm.
So there are a number of different events
related to the biology of the egg
and the biology of the sperm,
which you are now very familiar with
from everything I’ve talked about up until now.
And there are a bunch of chance events,
for instance, that the sperm won’t actually arrive
at the egg in time,
or that the egg won’t arrive at the sperm in time,
because of course, it’s a bidirectional migration
of those two cell types,
or that for whatever reason, fertilization won’t occur.
So what we’re really talking about
when we talk about the cumulative pregnancy rate over time
is the fact that there are multiple probabilities at work.
And yes, those are somewhat independent
in the sense that the biology of the sperm
doesn’t really strictly depend on the biology of the egg,
at least not until they meet and fertilize,
but the likelihood of pregnancy
depends on those independent probabilities,
which makes this a cumulative pregnancy rate.
Now, if any of that is confusing,
what it basically means is that for the egg and the sperm
to meet and to fertilize,
a number of different events
that carry some intentionality, right?
The sperm swims towards the egg and so forth,
the egg doesn’t have a personality in there,
at least not yet,
but it quote unquote wants to be fertilized, right?
It is in principle receptive to fertilization.
Well, in order for that to happen,
there are going to be some events related to chance
that could limit the ability for that to happen.
And there’ll be other events dictated by the biology
of those two cell types
that are driving that event to happen,
that are biasing the event to yes, happen.
And so what we’re talking about
when we talk about cumulative pregnancy rate
is how much of the biology of the woman
is skewed towards fertilization to be likely to occur, okay?
So to make this very simple,
all we need to know is that for women 30 years old
or younger, because the probability of getting pregnant
on any one attempt to conceive is 20%,
well, then if that doesn’t occur the first time,
then she should simply repeat that at least five
and probably six times before deciding to go to an OB-GYN
and conclude that there’s something going on
either with the egg or of course it could be with the sperm.
Okay, because 20 times five is 100,
so we’re talking about cumulative percent.
So 20, 40, 60, 80, 100,
and the six month there would take you to 120%,
which is a different thing altogether.
But in general,
that’s why OB-GYNs will tell their female patients,
look, if you’re setting out to conceive,
try for about five or six months,
and if you’re not successful, come back and see me.
Now, for women who are age 31 to 33,
the probability of conceiving in that first month
drops to about 18%.
So women in that age range and their partners
should certainly try and conceive naturally
over a period of six or seven months
in order to get to that 100% cumulative probability.
And then for women who are age 34 to 37,
the probability of conceiving in that first month
of trying, and certainly every month thereafter,
is about 11%.
So when the age of the woman starts extending out
to about 34 or 35 years old,
then the typical advice of the OB-GYN
is going to be to attempt to conceive
over a period of about nine months to a year
before deciding to take some sort of medical intervention.
And then of course, as the age of the woman increases,
so too does the quality of the eggs go down.
Now that’s not true for every woman.
There are many women who in their late 30s and 40s,
and even early 50s
have successfully conceived healthy children,
although the probability of that,
the likelihood of it drops substantially.
So for instance, for women who are age 38 to 39,
the probability of a successful conception
by natural conception, intercourse with ejaculation,
is going to be about 5%, right?
So it’s really dropped to a quarter of what it was
when that woman was 30.
Again, these are averages only.
What does that mean?
Well, it means that if you are age 38 or older,
chances are that you should probably go to your OB-GYN
right at the outset of your desire to conceive
and ask what you can do to improve egg quality.
Otherwise, if you were to extend the math out, right,
we know that if you’re age 30 or younger,
20% chance in any one given month,
that means about four to six months of trying.
Well, you can simply multiply that times four or five
for someone in their late 30s or early 40s.
And so what you’re really talking about
is several years of trying,
and of course what’s happening during those several years,
the woman is getting older, and as a consequence,
the quality of the eggs is declining even further.
So if you are, you know, 35, 36 years old,
it might not be entirely unreasonable to talk to your OB-GYN
right at the outset of desiring to conceive,
but you could also just take the approach
of trying to conceive naturally
for about a year or a year and a half
before deciding to do that,
keeping in mind that all the while you can’t stop time.
So biological time and aging
is going to occur in the backdrop.
But hopefully this description
of cumulative pregnancy rate makes sense.
Again, the idea is that while it’s true
that every single month,
there’s an independent chance
of the woman getting pregnant,
and that chance is dropping from about 20% at age 30
over time to about really one to 3%
for women 40 or older.
There’s also this notion of cumulative probability,
which involves multiple biological events
in both the egg and the sperm
that have to converge in time and space
in order for successful fertilization to occur.
Now, as long as we’re on this topic,
I think it’s only fair to address the issue of miscarriage.
And miscarriages can arise from a variety of sources.
They can arise from genetic defects.
They can arise from issues in the milieu of the uterus.
They can arise from issues with the sperm,
for that matter, right?
We really don’t want to put all the weight
and all the responsibility on the egg.
This is always an egg-sperm dynamic.
And when I say egg-sperm dynamic,
now hopefully that calls to mind
the huge library of information
that we’ve been covering up until now
about chromosomal segregation
and the coming together of these different cell types
and their genetic information.
Any number of different steps
within the process of fertilization leading up to pregnancy
can lead to miscarriage.
However, the probability of miscarriage
greatly increases as a function of the age of the egg.
And the basic numbers on this
are that for women who are 35 years or older,
about 25% of successful fertilizations
lead to miscarriages.
Now, when those miscarriages occur during pregnancy
can be highly variable.
Sometimes it’s within the first trimester.
Sometimes it could be later,
but the probability is about 25%.
That probability increases greatly over time
such that by the time women are in their early 40s,
so 40 or older,
the probability of miscarriage
after a successful fertilization
is going to be about 50%.
And this could be due to a number of factors,
as I mentioned before,
but one common reason
is that there can be chromosomal abnormalities.
And that could be related typically
to the segregation of the egg
when half of the chromosomes in that egg are removed,
taking it from diploid to haploid.
If you recall, there’s that little polar body,
which is the removal of the chromosomes
that’s ejected from the egg that will eventually ovulate.
And sometimes not all the chromosomes
that were supposed to be ejected in that polar body
and as a consequence,
there are multiple chromosomes
or duplications of chromosomes,
things like trisomies.
Sometimes too many chromosomes move away,
and they’re actually removal of entire chromosomes,
meaning both strands,
so that you have chromosomal deletions.
And in that case,
typically fertilization won’t occur,
but there are instances in which fertilization will occur.
So a woman will get a positive pregnancy test,
her periods will stop,
and the couple will think
that they’re advancing along the steps
to a successful pregnancy,
and then there will be sadly a miscarriage.
Many, many times,
those miscarriages are the consequence of the fact
that when there are extra chromosomes there,
or there are too few chromosomes present,
that embryogenesis can simply not progress in a healthy way.
There are some instances in which all of the chromosomes
and all the chromosomal arrangements are perfectly normal,
and miscarriages can still occur.
I’m going to do a future episode
about pregnancy and embryonic development,
where we will get into this more deeply,
but just understand that the frequency of miscarriages
increases dramatically after about age 34,
and then continues to increase dramatically,
extending well out until the 40s.
Now, a very important consideration
in terms of understanding and predicting fertility
this word that describes the probability
of getting pregnant on a given try and over time,
is trying to address how quote-unquote fertile a woman is,
and importantly, how quote-unquote fertile a male is.
Now, we’ll talk about the male side in a moment,
but when trying to address how fertile a woman is,
of course, age is going to be one of the major factors,
but just one factor, all right?
We already talked about how age determines
the likelihood of a successful pregnancy.
If the intercourse and ejaculation is being carried out
at the correct times and with viable sperm
capable of fertilizing eggs,
and then of course there’s the issue of egg quality,
but in general, most women would like to know
how fertile they are as a function of their age, right?
And I actually think this is one of the most important topics
in this whole space around fertility
that isn’t often discussed,
or at least isn’t often discussed
until women are in their late 30s or 40s,
when oftentimes they will look back
and wish that either they had frozen their eggs
or they had frozen fertilized embryos,
which is a whole thing unto itself.
I mean, talk about that when we have an episode
on in vitro fertilization in more depth,
but there is a fairly straightforward way or set of ways
that women can determine their basic level of fertility,
leaving aside a lot of the detailed issues
about the quality of eggs and so forth.
One thing that you already learned
is that there’s this vault,
there’s this reserve that we call the ovarian reserve,
and that each month,
a certain number of follicles leave that reserve,
and there’s the opportunity
based on the ovulation of a single egg
to fertilize that egg and for the woman to get pregnant.
And one thing that we know for sure
is that the size of the population
that’s released from that vault each month
has a very strong positive correlation
with the size of the reserve in the vault itself, okay?
So the way to think about this perhaps
is that the vault is like a bank account,
has a certain amount of money, in this case, eggs in it,
and you could imagine if someone’s reasonably logical
that if they have more money in their bank account,
then they’re going to withdraw a larger amount each month
than if they have a small amount each month
if the idea is to make that vault, that bank of eggs,
available to them over the longest period of time.
And indeed, biology is pretty smart.
It doesn’t deploy or release half the follicles
in one month and then just slowly trickle out
the remainder of follicles.
No, that’s not how it works.
What you find is that, of course, in younger women,
so say in their late teens, 20s, and 30s,
the ovarian reserve in the vault
is going to have more eggs in it,
and the number of follicles and eggs
that leave that vault each month is going to be quite high.
So one way to evaluate how, quote-unquote, fertile you are,
again, just one way, is to go to your OB-GYN
and say that you would like to know
how many follicles you have in a given month.
And of course, they’ll look at them
on both sides in both ovaries.
And for instance, if a woman has just two or three follicles
that are out each month, well, then the assumption,
again, it’s just an assumption,
but the assumption that’s pretty good
because there’s this positive correlation
that generally occurs is that that ovarian reserve,
that the number of eggs in the vault is fairly low
compared to someone who, say, has 20 follicles
or 30 follicles each month, okay?
And that’s the typical trend.
Again, these are averages,
and it’s very important to not get attached
to any one number here.
Again, these are averages.
So for instance, there are women
who only deploy five follicles and eggs each month
out of their ovarian vault,
but who find themselves to be very fertile, right?
And there could be a number of different factors
to explain that.
Other women will have 20 or 30 eggs and follicles
that leave that vault, the ovarian reserve, each month,
and they will have a harder time getting pregnant
for any number of different reasons.
But in general, the more eggs and follicles
that leave the vault each month,
the higher number of eggs that are still in reserve,
meaning the greater amount of time
over which a given woman could still attempt
to have successful fertilizations.
Now, this small collection of follicles and eggs
that are released each month actually has a name.
They’re called antral follicles.
These are small follicles.
They tend to be about two to nine millimeters across.
The way these are analyzed or measured
is woman will go into the OB-GYN office
and by ultrasound, typically there’s some local anesthesia,
but it’s not often a general anesthesia,
but by local anesthesia, sometimes no anesthesia,
they will essentially count the number of follicles
that are present in each side,
on ovary on the left and the ovary on the right,
and give a woman some sense of how many follicles she has.
And typically this is done over a series of months
to determine how many eggs
are leaving the ovarian reserve each month,
and therefore how many eggs she is likely
to still have in the ovarian reserve.
Now, there’s a non-invasive way to do this as well,
although typically an OB-GYN will do
both what I just described with ultrasound
and measure something called AMH,
which is anti-Mullerian hormone,
which is a hormone that is released
by that antral follicle population,
the population of follicles and eggs
that leave the ovarian reserve each month.
So one is a blood draw measure of a hormone AMH,
the other is a structural imaging measure
of the antral follicles directly.
Again, the typical trend is for the number
of antral follicles to decline over time.
So one might expect, for instance,
that a woman in her 20s or 30s might have 20, 30,
maybe even 40 antral follicles
that are exiting the reserve each month.
And again, that’s the total across both ovaries.
Again, these are just averages,
these are going to be distributions,
there’ll be people with far fewer,
there’ll be people with far more,
but that over time, regardless of where a woman starts out,
from one decade to the next half decade and decade and so on
that the number of antral follicles will decline
and the amount of, or the levels of AMH will also decline.
So what does this all mean?
What this means is that if you are a woman
who is in her 20s or 30s or 40s,
whatever your age,
if you are interested in conceiving in the future,
it’s very likely a good idea to go to your OB-GYN
and get either your AMH levels measured
or your follicle count measured.
And to do that several times in a given period,
and I don’t mean a menstrual period,
I mean a given period of time across several months
to determine what is the average number of follicles,
what’s your average AMH level,
thereby giving you some window into how many eggs
you are likely to still have in your ovarian reserve.
I cannot tell you how many women that I’ve spoken to
and how many OB-GYNs more importantly,
because they speak to many more women about this
than I ever have or ever will,
wish that they had done this earlier, right?
They think, oh, well, I’m in my 20s,
so I’m likely to have a ton of follicles
or they got pregnant once before.
And so they’re not so concerned about the number of follicles
or their AMH levels.
But over and over again,
I was told in researching for this episode
that the earlier and more frequent
that women do this procedure of measuring AMH
and measuring their follicle count,
the higher the probability that they will eventually
have a successful fertilization and pregnancy
when they seek to do so.
Now, the mirror image of all this, of course, is the sperm.
And there’s a kind of common misconception out there
that the sperm, you only need one
and indeed you only need one,
but actually you need many and it’s only one
that’s able to successfully fertilize the egg.
So this whole concept of you only need one
is both dismissive of the sperm,
but more importantly, dismissive of the biology
of the sperm and the egg.
Okay, it only takes one successful sperm
and one successful egg,
but that’s sort of like telling a woman,
hey, you only need one egg, right?
You need one egg of sufficient quality
in the right time and place.
And you need one sperm of sufficient quality
in the right time and place
in order to get successful fertilization
and hopefully pregnancy.
But you need a lot of sperm
in order to get a high probability
that that one sperm will be able
to successfully fertilize the egg.
So we have this image of sperm
as kind of these dumb operators
that just sort of swim mindlessly towards anything.
And if they bump into an egg, then they fertilize the egg.
And that’s really not the way it works.
As I talked about earlier,
the sperm with its head, its mid region, its tail,
chock-a-block with mitochondria in the mid region
is really an active motile cell
that indeed will just swim forward
if it’s a healthy forward-progressing sperm.
But many males out there
just simply do not have any knowledge
of how many quality sperm that they happen to have.
Now, given the fact that sperm analysis
is relatively inexpensive,
and also the fact that freezing sperm
is relatively inexpensive,
I think it stands to reason that most men
should at least get some window
into the numbering quality of their sperm.
Now, it’s a fair assumption to say
that if someone is in their late teens, early twenties,
or thirties, that they probably have high quality sperm.
But again, as with the egg
and the importance of measuring AMH
and follicle count across time,
men should really evaluate the quality
and number of their sperm.
And we talked a little bit earlier
about some of the parameters
that urologists and OBGYNs like to see
when evaluating sperm, right?
You know, there’s a minimum number
or concentration of sperm that they’d like to see
if a couple is going to use IVF in vitro fertilization.
And typically that’s going to be
about 15 to 20 million per mil of sperm or semen.
And typically they want to see
somewhere between two and five milliliters of semen overall
in a given ejaculate after a 72 to 48 hour abstinence period
because of course, the more ejaculations,
the smaller the volume of the ejaculate
in a short period of time.
But after 48 to 72 hours,
you more or less maximize the volume of ejaculate.
And then of course they want to see 50,
but typically 60% or more of motile sperm
in order to get IVF, but more is better.
And of course there is an enormous range
as I mentioned before.
Some males will have anywhere from 10 to 20 million
sperm per milliliter of ejaculate.
And some men will have 100 to 200 million, okay?
But just because they have 100 to 200 million
doesn’t mean that all of those sperm
are of high quality and can fertilize eggs.
Sometimes the more than half will be twitchers
and some will be a motile and so on and so forth.
So it’s very straightforward
what I believe most people should do
and what the urologists I spoke to
in advance of this episode said to do,
which is to simply do a sperm analysis,
refrain from ejaculation for 48 to 72 hours,
give a sperm sample, have that sperm sample analyzed.
The cost of the sperm analysis is not typically that much.
Okay, and considering that conception
and healthy conception and fertilization
is an expensive process
if you have to go the in vitro fertilization route,
it stands to reason that the cost is pretty well justified.
You also have the option to freeze sperm over time.
There is evidence that the age of the father
and therefore the age of the sperm
can dictate whether or not there’s a higher instance
of problematic pregnancy or developmental outcomes,
including autism, that is true.
You probably heard that if the father is 40 years or older,
the incidence of autism is increased significantly.
That is true, although the overall probability
of having an autistic offspring,
if somebody, if the father that is, is 40 years or older,
is still quite a bit lower than you would imagine.
It’s not as if the probability suddenly skyrockets, okay?
So we’ll have an episode on autism
and genetic and non-genetic influences on autism
and other aspects of the autism spectrum.
But the point is this, I believe,
and the urologists I spoke to
who are interested in fertility and male health
and sexual health suggest that men get their sperm analyzed
at least once every five years.
And certainly if they’re going to want to conceive children
in the distant future,
that they consider freezing their sperm
because that too is fairly nominal cost
in order to freeze sperm at a younger age.
And of course, if you can freeze and use sperm
from the time in which you were younger,
why wouldn’t you, right?
I mean, you can still opt to go for natural pregnancy later
if that’s what you want to do,
but having that in reserve is generally a good idea.
And I discussed some of the parameters that are looked for,
and perhaps most importantly,
there is the possibility of an underlying issue
whereby, for instance,
there is very little sperm in an ejaculate.
As I mentioned earlier,
the seminal fluid in the ejaculate
could have zero sperm in it,
but the volume of ejaculate could appear completely normal.
So just because your ejaculate volume is normal to you
or is in that range of, you know, two to five milliliters,
well, then it doesn’t necessarily mean
that there are any sperm there
or that there are very few sperm there.
And the few sperm that are there
or the many sperm that are there are functionally motile.
So get this analyzed.
It’s really worth doing.
And again, it’s not something you have to do every year.
It’s something that you want to do probably every five years,
at least until the point where you’ve conceived
as many children as you ever want to conceive.
So the basic takeaway here is that if you’re a woman,
to get your egg count, your antral follicle count, that is,
and therefore your reserve of eggs indirectly measured,
and of course, also get your AMH levels measured.
And if you’re a male, to have a sperm analysis
and to do that relatively early.
In fact, another incentive for doing that early
is that you have a comparison point
so that, for instance, if you are in your early 20s
and you’re not thinking about having kids at all,
or you’re thinking that you might someday have kids,
but it’s a really someday, someday, far off in the future,
well, it’s wonderful to have a reference point
from which to compare your biology in your early 20s
to your biology in your mid or late 30s or 40s
when you might happen to be interested in conceiving.
And if that doesn’t provide incentive enough,
I should mention, and this is important to point out,
and that I think both males and females are not aware of,
is that one in five couples that have issues with fertility,
the issue ends up falling on the biology,
that is the quality of the sperm
or a lack of number of sperm.
So, you know, I think there’s a misconception
that when fertility is an issue,
it’s always an issue with the eggs
and this age-dependent decline in egg quality,
again, it’s the best language we have available to us
at the moment, this age-dependent decline in egg quality
is often to blame, but not always.
One in five couples that have challenges conceiving
turns out that it’s going to be an issue with the sperm.
And of course, there are a number of different
sperm analyses that should all the other parameters
of sperm appear normal.
Now, for instance, you can get a DNA fragmentation analysis,
you can see whether or not the DNA of the sperm
are somehow disrupted.
Urologists these days are excellent at figuring out,
for instance, if a male has lots and lots of sperm,
everything looks great,
but the shape of the head of the sperm isn’t quite right,
if it’s not oval enough and it’s too rounded,
that could be a genetic defect,
under which conditions there is zero probability
of the male ever naturally conceiving, right?
Regardless of who the female partner is,
believe it or not, males can have a ton of sperm,
but if they carry a certain genetic defect,
those sperm will be incapable of depositing
those 23 chromosomes into the egg.
However, there are ways in which that sperm can be coaxed
or forced to fertilize the egg and deposit
its genetic contents by in vitro fertilization
and then implantation into the female.
So again, lots of reasons to have a egg reserve analysis
by ultrasound and AMH for females,
and lots of reasons for males to have a sperm analysis.
And of course, typically with a sperm analysis
and a ovarian reserve analysis will be a hormone analysis.
And I’m a very strong believer in people getting an insight
that is a window into their hormonal composition,
not just when they encounter problems,
but starting at a pretty early age,
even if it’s only done once every five years or so,
having a reference point to your 20s and to your 30s
and mid 30s for when you felt a certain way,
maybe as in the case for many people I know,
they actually feel better in their 40s
than they did in their 20s,
because they’re doing a lot of things
to support their health, that is possible.
But in many cases, people start feeling not as well,
or their fertility seems to be dropping off,
or any number of different parameters
that we’ve discussed today,
or related to vitality and longevity
seem to be dropping off over time.
And they want to get a insight into what could be the issue.
And hormones are sometimes, not always,
but sometimes involved in those underlying issues.
And there’s nothing as valuable as having a reference point
from a time in which things were going well
to evaluate the, for instance, the levels of hormones,
not just testosterone,
but also estrogen and progesterone and so forth.
So you need a comparison point
in order to determine what really needs to be changed.
So all of this is a strong push for people
to use your insurance,
if you’re able to put it on insurance,
oftentimes people are.
And if not, to try and find a reasonable
or reasonably priced way to do a sperm and egg analysis,
and to ideally do a hormone analysis as well,
it’s really going to set you up
for the maximum probability of being able
to conceive children when you want to,
and also to avoid a bunch of other health-related issues
that involve hormones and reproductive health,
and in general, to support your mental health
and physical health.
So I’ve been talking about a bunch of things to do.
There are a couple of things to be mindful of
to actively avoid if your goal is to be and remain fertile,
and that’s regardless of whether or not
you want to conceive children in the future or not.
Now, in the context of this discussion,
the same things that we’ve heard to be true
for other aspects of our health turn out to also be true.
So let’s just start with the basics.
Everybody should be getting approximately
six to eight hours of sleep every night.
That should be quality sleep.
Optimizing your sleep is fundamental
to balancing your hormones.
Now, balancing your hormones is kind of a catchphrase
for all things related to proper hormone regulation.
Sleep is the fundamental layer of mental health,
physical health, and performance of all kinds,
and believe it or not, fertility.
When people are not sleeping well or enough,
stress hormones, in particular cortisol,
shift to peaking later in the day,
and those elevated cortisol levels later in the day
cause a bunch of different problems
in both males and females, many of which impact fertility.
So controlling cortisol starts with controlling your sleep.
It also impacts testosterone and estrogen levels.
So of course, the proper ratios of testosterone
and estrogen will vary from males to females,
but in order to get those right,
or as right as they can be without other interventions,
you want to make sure you’re getting enough quality sleep.
How much sleep?
Most people need about six to eight hours
of sleep per night.
Waking up once, maybe twice per night
in the middle of the night and going back to sleep
is not such a big deal,
but six to eight hours of solid sleep would be ideal.
Some people need a little bit less
in order to function, five hours.
Some people need a little bit more.
Developing teenagers and babies and kids need a lot more.
People who are sick or recovering from injury
need a lot more.
We’ve done multiple episodes on sleep.
We have a toolkit for sleep available free
You go there, you don’t even have to sign up
for the newsletter, although you can if you want.
Just go to Toolkit for Sleep under the menu,
and you’ll be able to download that,
or you can even just view it on the screen
if you don’t want to download it.
It has lots of tools.
We’ve done an episode called Perfect Your Sleep
that has a lot of tools.
They’re all timestamped for you.
We’ve done a Master Your Sleep episodes,
lots of tools to get your sleep right.
Get your sleep right if you are wishing to conceive
and or to simply have healthy biology
to be fertile or otherwise.
That’s just fundamental.
Now, there are other things to not do,
and those again fall into the somewhat obvious categories,
but I think a lot of people aren’t aware
of just how striking an effect
these certain behaviors that you want to avoid
can have in diminishing your fertility
for both males and females.
So let’s talk about those.
So the first one is smoking.
And when we talk about smoking here,
we’re talking about smoking nicotine,
and we’re talking about smoking cannabis.
And indeed there are strong data,
and I will put a reference to one of the better,
larger analyses of these data.
There are strong data showing
that cannabis reduces fertility.
Now I can already hear the screams from the back,
although they’re probably fairly drawled out screams
from the back of people saying they smoke cannabis
and they had no trouble conceiving.
Certainly there will be exceptions,
but whether or not you’re male or female,
smoking cannabis is a bad idea
if you want to conceive a healthy child.
Can you still conceive a healthy child
while smoking cannabis?
Probably certain people can.
Many people will greatly decrease the probability
of a healthy fertilization and pregnancy
by smoking cannabis.
There are excellent data to support that.
As well, nicotine, both smoked or vaped,
is going to disrupt the process of fertilization
and can disrupt pregnancy dramatically, okay?
So just avoid it altogether.
How does this happen?
Well, it turns out that smoking increases
what are called reactive oxygen species.
This greatly disrupts the quality of the egg
at the level of the spindle and mitochondria
and a number of other features.
And in the sperm,
turns out that smoking doesn’t necessarily
disrupt the sperm directly,
although it can cause DNA fragmentation,
which can cause all sorts of abnormalities,
can prevent fertilization,
can lead to birth defects in the offspring.
But more importantly,
it increases what are called reactive oxygen species
in the seminal fluid,
in the semen that contain the sperm.
This very, under normal circumstances,
under healthy circumstances,
beautifully orchestrated chemistry of fluid
that allows the sperm to thrive in their trajectory
and attempt to fertilize the egg
and lead to a healthy pregnancy.
So if you are a smoker and you want to conceive,
the best advice I can give you is to quit smoking
and yes, that includes cannabis as well.
Now, I am not somebody who believes that cannabis
across the board is not useful.
There are medical applications and other applications.
I talk about that in an episode all about cannabis
for health and disease and notice health was in there too.
So you cannabis smokers don’t come after me with,
I guess, whatever it is,
with bongs and pipes or whatever it is that you want
or with vapes.
The point is that while it can be beneficial
for certain populations,
it’s certainly bad for others.
And if you’re trying to conceive,
it is bad for fertility and for a healthy pregnancy, okay?
Now that’s smoking and vaping, by the way, okay?
Vaping is included there.
Now the next category of don’ts relates to alcohol.
Now everyone has heard that drinking during pregnancy
is a bad idea.
You may have heard,
and some people have talked about the fact that
there are cultures in which they allow, if you will,
or even condone, sadly, one or two drinks while pregnant,
provided it’s just champagne
or something of that sort.
That is a terrible idea.
I did an episode all about alcohol,
both its potential health effects
of which there turned out to be zero.
And yes, that includes red wine.
It is far better to not drink at all.
And if you’re going to drink,
the limit if you’re a healthy adult
who’s not trying to conceive, not pregnant,
and you don’t have issues with alcoholism
is probably two drinks per week total.
That’s right, two drinks per week total.
And that’s the level that you really should consider
if you’re a drinker,
if you’re somebody who’s trying to conceive.
However, for a woman who becomes pregnant,
the total number of drinks
that you should allow yourself per week while pregnant
and breastfeeding is indeed zero.
There is absolutely no evidence
that one can quote unquote get away with drinking
And people say, well, I had a perfectly healthy child,
but of course you don’t know
what the health of that child would have been
had you not drank at all.
Now, I’m not here with any generally strong stance
I myself am somebody who has a drink every once in a while,
although I don’t consider myself somebody
who has a strong proclivity for alcohol.
And of course, at this moment,
I’m not trying to conceive children
and I’m certainly not pregnant.
So that’s safe for me,
but frankly, I haven’t had a drink in a very long time.
And so I don’t miss it and that’s me,
but I do realize that a lot of people enjoy alcohol.
And so it’s that two drinks per week limit
that really sets the upper limit and threshold
beyond which you start running into issues
with cellular mutation.
You start running into issues of oxidative stress,
greatly increased cancer risk,
in particular, breast cancer risk.
All of that’s covered in the alcohol episode that we did.
You can find it hubermanlab.com and timestamped
if you want to navigate to specific topics and so forth,
find out all about the data,
supporting the statements that I’m making,
so on and so forth.
Now, if you’re somebody who’s seeking to conceive
or you fall into this category
that some couples describe themselves as we’re not trying,
but we’re not not trying,
meaning they’re not using birth control,
they’re kind of letting chance run its course.
Well, then you should definitely be aware of the data
showing that even just one bout,
one bout of so-called binge drinking,
which is five to six drinks in a given night
or half day in a 12 hour period,
one bout of five to six drinks.
If you’re a woman or you’re a man,
greatly increases both the likelihood of mutations
in the embryo that would result from a fertilization.
And at the same time,
for reasons that should be obvious to you
based on all the biology we’ve talked about,
a greatly reduced probability of fertilization.
Now, that absolutely does not mean
that you should use the ingestion of five or six drinks
as a method of birth control.
That is not what I’m saying here.
What I’m saying is that if you go out on a given night
and you have five or six drinks
and you happen to become pregnant,
the probability that that pregnancy
will be disrupted in some way is greatly increased.
What the exact consequences are, no one can tell you.
But also if you’re somebody who is interested
in conceiving a child,
well, then you absolutely should abstain
from ingesting drinks more than one or two
during the time in which you’re trying to conceive.
And ideally it would be zero.
And you certainly would want to avoid
drinking multiple drinks per night.
And so this idea of going out and having, you know,
three or four drinks or four or five drinks in a given night
at a time in which you’re also trying to conceive children,
the biology tells us, the epidemiology tells us
that this is just a terrible idea.
It’s going to reduce the likelihood of fertility
and successful pregnancy.
And if there is a successful pregnancy,
the word success needs to be in quotes, right?
I mean, I think every parent,
every species for that matter,
wants to increase the probability
of having healthy offspring.
And so to my mind anyway,
and to the OBGYNs and the urologists
that are focused on fertility that I spoke to,
everyone will say, try as hard as you can
to avoid these so-called binge drinking episodes.
And again, these episodes are one night
of consuming five to six drinks.
Now, another important thing to remember in this context
is that the negative effects of consuming
five or six drinks in a given night
extend over many weeks
following the ingestion of that alcohol.
If you’re a male,
what that means is that’s going to impact
the quality of your sperm
and greatly decrease the likelihood
of successful fertilization and or healthy pregnancy
over the period of that entire spermatogenesis window,
which is as we talked about before, 60 to 90 days, right?
60 to generate the sperm
and then in some additional time for the sperm
to be transported to the point
where they could be ejaculated.
If you’re a woman and you have five or six drinks
on a given night,
well, then you are going to disrupt the quality
not of just the egg that eventually ovulates,
but indeed the entire pool of follicles
that leaves the ovarian vault and reserve
and from which the one egg will be selected.
In other words, you are reducing the quality
of all of the eggs that you happen to deploy that month.
Now, some of you who were really following
the biology earlier might say,
well, what if I have those five or six drinks
during the time in which I’m menstruating,
just in which there’s bleeding present
and therefore I haven’t yet ovulated.
Ah, but if you remember the biology
we talked about earlier specifically,
there is a subset of follicles and eggs
that leave that ovarian reserve
quite a bit before that one egg is selected for
And of course there are all the different hormonal cascades
in the general milieu of the ovary,
which are important and are being regulated
by different hormones.
And yes, indeed, the regulation of those hormones
is strongly impacted by alcohol
through a number of different pathways,
through the regulation of the neurotransmitter GABA
up in the brain.
It’s actually a lot of GABA and GABA receptors
in the hypothalamus,
the very region from which gonadotropin-releasing hormone,
our old friend from a couple hours ago in this discussion,
going to disrupt GnRH secretion.
You can disrupt pituitary function with alcohol.
Again and again, what we’re seeing is that
consuming more than one or two drinks per week of alcohol
is really detrimental to the entire process of fertility
and the entire process of healthy pregnancy.
And that’s true from both the male side and the sperm
and is true from the female side and the egg.
So my simple advice on this is if you are wishing to have
a healthy fertilization and pregnancy,
the best thing to do would be avoid alcohol together.
And if you’re going to drink,
to really limit that drinking to one or two drinks
per week maximum.
So those are the major don’ts.
Really avoid excessive stress.
And I should mention excessive stress is not just
best avoided by getting enough quality sleep at night,
although that is the primary way.
There are other ways to avoid stress.
We’ve done entire episodes about this
and we have a toolkit related to reducing stress
with very simple zero cost tools.
Again, you can find all that hubermanlab.com.
I should mention if you want to find any episode or topic
or timestamp, that website is keyword search available.
So you can just go to hubermanlab.com,
put into the search function, stress tools,
and a bunch of different links will pop up
related to those topics.
Likewise with sleep,
likewise with any number of different topics
you might be interested in.
So get enough quality sleep and thereby reduce stress
and also directly buffer stress with real-time tools
to buffer stress that I’ve talked about
in the episodes that you can access.
And there are ways to greatly reduce
your overall level of stress,
to limit any cortisol that’s released early in the day,
which is when you want cortisol released
and not have it late in the day and so on and so forth.
So reduce your stress.
And as I just told you,
by all means do not drink more than two drinks per week
and zero is better than two.
If anyone tells you,
oh, there’s all this resveratrol in red wine
and that’s good for us,
the data simply tell us that there’s not enough resveratrol
in red wine to really have any positive health benefit.
The data around resveratrol and health benefits itself
is under question nowadays.
Zero alcohol is better than any alcohol.
Two drinks per week is the limit.
Also limit or eliminate or avoid nicotine
and ideally cannabis smoking and vaping at the time
in which you are trying to get pregnant.
And certainly if you are pregnant,
avoid all of the things as best you can
that I just described a moment ago.
Now there are a couple other don’ts
that are really important.
One of the most important don’ts relates to STIs
or sexually transmitted infections.
Everyone who’s sexually active should get an STI check.
In fact, if you go to a fertility clinic
or you go for sperm analysis or you go for egg analysis,
almost always they will do an STI check
even if you happen to be in a monogamous relationship,
even if you happen to be not sexually active
and you’re somebody who’s seeking to use IVF
with a sperm donor or something of that sort.
Why would they do that?
Why is there so much concern about that?
Is it about avoiding giving birth to a child
that has something like a herpes infection or HIV?
Well, certainly that’s one reason,
but that’s a down the line reason
because at the time when someone goes into the clinic
for one of these sperm or egg analyses,
I mean, that’s well in advance of any pregnancy, right?
The reason is there are a number of STIs
in particular chlamydia
for which it greatly increases
the probability of miscarriage.
So chlamydia is one of those very insidious
and cryptic STIs because a lot of people,
both males and females,
don’t even realize that they have chlamydia
and then they can carry chlamydia
at the time in which they conceive
and then that can lead to ectopic pregnancies
and or miscarriages.
So by all means, get an STI check
if you are somebody who’s seeking to conceive children
or evaluating your fertility generally.
Chlamydia can also have damaging effects
on the epididymis and on the various other aspects
of male reproductive health.
In the future, we will do an episode all about sexual health.
This is not the time for that,
but get an STI check if your goal
is to conceive a healthy child.
Now, the other thing that can have a very negative impact
on fertility and healthy pregnancy is a viral infection.
Now, for instance,
if a male has had a severe viral illness,
and this could be any number of different viral illnesses
from flu to cold or any number of different viruses,
pick your favorite virus,
in the previous 70 to 90 days,
that can greatly diminish the number
and or quality of sperm, okay?
So that’s really important.
This is also important if you’re going to go in
and do a sperm analysis and you had a viral infection
in the previous 70 to 90 days,
well, then you need to be aware of that
because it could greatly impact the parameters
of that sperm analysis.
Likewise, for women,
if you’ve had a serious viral infection
in the previous 30 days,
does that mean you should not try and conceive?
but you should talk to your OBGYN about that.
There are data showing that viral infection,
in particular of influenza in the mother
in the first trimester of pregnancy has some correlation.
It’s not 100%,
but some correlation with negative mental health outcomes
of the offspring sometime later, including schizophrenia.
This is some of the work that was done at Caltech
a number of years ago and other laboratories as well.
Those data are still being built up over time.
Again, it’s not one for one.
It’s not causal.
So if you did get an influenza or a cold
or other kind of viral infection during the first trimester
or any trimester of pregnancy,
I don’t want to cause alarm,
but you should talk to your OBGYN about this.
The goal of course is to avoid viral illness at any time
when you’re trying to conceive or have a healthy pregnancy.
But of course, sometimes people will get ill
and the children can turn out to be perfectly normal
and fine, but it is something that you want to avoid
and it will impact your egg analysis
and it will impact sperm analysis.
And one thing I found really surprising
in researching this episode was that one in 25 men
carry a copy of a mutation for cystic fibrosis.
Now, some of you are probably familiar with cystic fibrosis
as a condition that can cause issues with the lungs,
the accumulation of fluid in the lungs or other tissues.
Cystic fibrosis, in order to express that way
of accumulation of fluid in the lungs,
you really need two copies, right?
You need two mutant copies
or you need two copies of the cystic fibrosis gene.
One in 25 men will carry just one copy
and therefore will not have any symptoms of cystic fibrosis.
But those one in 25 men will have defects
in the architecture of the vas deferens,
the duct through which the ejaculate needs to pass
in order to eventually be ejaculated out of the urethra.
And so what that means is that these men can have
what appears to be normal semen volume,
but that they won’t have normal numbers of sperm.
And that’s not because of a deficit in making the sperm,
the testes can function just fine,
the brain and the pituitary communicating
with the testes just fine,
but that literally the passageway by which the sperm arrive
within the seminal fluid and are eventually ejaculated
is disrupted by the cystic fibrosis gene.
Luckily, if somebody has just one copy
of the cystic fibrosis gene and they’re male,
and this is the issue,
the vas deferens either can be repaired by a urologist
who’s expert in the surgical repair of vas deferens
or sperm can be extracted from the testicle directly,
which might sound like a painful procedure,
but I believe nowadays in talking with various experts
on this, turns out that it can be done
with a minimum of discomfort.
And certainly if the goal is to have a healthy child,
you’re going to need those sperm.
So you’re going to want to get them one way or the other,
regardless of the discomfort.
Now, before getting into some of the things
that you can do in the positive sense
to increase your fertility,
we do need to touch on just a few other things
that you want to avoid in order to avoid
diminishing your fertility.
And this mainly relates to males,
but it will also be relevant to females.
And of course, when I say also relevant to females,
I’m referring to the fact that if it’s a woman and a man
who are trying to conceive,
then she of course is going to be interested
in her egg quality, but also the sperm quality.
And of course there are women who are conceiving
by way of sperm donor through IVF or IUI or otherwise,
but in any case, the need to understand and maximize
the quality of both the egg and the sperm is paramount.
So in order for men to maximize the quality of their sperm,
as I mentioned earlier,
does not seem to be a big difference
whether or not they use boxers or briefs
or whether or not they, quote unquote, go commando.
They don’t wear any boxers or briefs of any kind.
However, it is important to keep the testicles cool enough.
They need to be about two degrees cooler
than the rest of the body.
And there are a number of different ways to do that.
As I mentioned before,
avoid going in hot tubs during the period
in which you’re trying to conceive children.
You should also avoid going in saunas during the period
in which you were trying to conceive children.
And if you do go in the sauna,
you can bring an ice pack there
and you can put it on the testicles
in order to offset the heat of the sauna
and keep the testicles cool while in the sauna.
The other thing that you’ll definitely want to do
is avoid putting a laptop or any other hot device
directly onto your lap.
There are a number of different devices
that you can put on your lap.
You could put books or a box,
or there are these devices that are designed
to dispel the heat from the laptop.
I would say, if you’re trying to conceive,
just keep the laptop off of your lap,
just put it on a table or standing desk or whatever,
just keep it off of your lap.
Also, there are some really interesting data
showing that the amount of time that men spent sitting,
regardless of whether or not they sit
with their ankle on their opposite knee
or with knees spread, the classic man spread stance
or any other kind of seated stance
is going to increase the temperature of the scrotum.
For reasons that are somewhat obvious,
if you think about the architecture of all this,
I think both men and women,
if you put enough thought to it,
you go, oh yeah, that would increase the temperature.
Obviously avoid seat heaters in cars or otherwise,
but reducing the total amount of time that you spend seated
is really important if you want to keep
the temperature milieu of the scrotum optimal
for sperm quality and fertilization.
And as I mentioned earlier,
it’s going to be important to make sure that your legs
are not really big to the point where they are creating
a hotter than is healthy environment
for the scrotum and testicles.
So a hotter than normal environment for the testicles
can be caused by legs that are very large,
upper thighs that are very large due to obesity
or due to those upper thighs being too muscular.
So by all means, don’t skip leg day,
but be aware that if you’re somebody
who’s trying to conceive,
you want to do whatever you can
to reduce the temperature of the scrotum,
or at least not let it get too hot for too long, okay?
So I can think of all sorts of reasons now
that men are going to come up with
to do the man spread stance of their knees really far apart,
even further if they have large legs.
That’s not a discussion we want to have here.
And that’s not really what today’s discussion is about.
Really the principle is what’s most important,
which is to keep the temperature of the scrotum
and testicles lower than the rest of your body.
There’s a direct blood flow from the body to the testicle
that provides blood flow.
It’s designed in a way that that blood pathway
should be outside the body
and as far away from the body as possible
in order to get the temperature milieu
of the scrotum and testicle correct
for healthy sperm quality.
Now, a topic that is sure to be a bit controversial,
but it really shouldn’t be because the data,
at least to me, are very clear,
is this issue of phone use and sperm quality.
Now, this can open up a whole array of issues
related to things like EMFs,
and you’ve got people out there that have, you know,
ideas about 5G and all of this stuff.
That is not what this discussion is about.
The discussion I’m about to have with you
relates to the fact that the electromagnetic fields
and the heat-related effects of smartphones
can indeed have a detrimental effect on sperm quality.
And yes, indeed, on testosterone levels as well.
I’m going to refer you to a paper.
We will link it in the show note captions.
The title of this paper is
Effects of Mobile Phone Usage on Sperm Quality.
No Time-Dependent Relationship on Usage.
A Systematic Review and Updated Meta-Analysis.
This is a paper that came out in 2021
and talks about the fact that phones
emit a radio frequency electromagnetic waves,
which are called RF radio frequency,
EMWs, electromagnetic waves,
at a low level between 80 and 2,200 megahertz
that can be absorbed by the human body.
We know this, okay, this is not controversial,
and have potential adverse effects on brain, heart,
endocrine system, and reproductive function.
That has been established.
Keep in mind, there is basically no controversy
that radio frequency waves and EMFs
can have a negative impact on biological tissues.
The question is how intense
are those radio frequency waves and EMFs,
and how detrimental are those on those biological tissues?
Okay, it’s a matter of degrees,
but there is very little controversy
as to whether or not they have an effect
on biological tissues,
and I’m aware of absolutely zero data
showing that they can have a positive effect
on biological tissues.
Since what we’re mainly talking about now are smartphones,
we want to separate out the heat effects of smartphones
from the EMFs related to the fact
that they are Wi-Fi smartphones,
or they’re using cellular towers and Wi-Fi.
One or the other combination.
Okay, so there are a number of different things
in the phone that could be detrimental.
We need to separate those out.
Well, because you might have heard
that carrying your phone in your pocket
can reduce your testosterone levels and sperm count,
and guess what?
That is true.
The data contained within this meta-analysis
and other meta-analyses clearly point out
that it can reduce sperm count
and maybe testosterone levels significantly,
but certainly sperm count and motility significantly.
It reduces sperm quality.
So should you avoid putting your phone in your pocket?
Certainly your front pocket, I would suggest yes, right?
If you are somebody who is seeking to conceive, right?
I’m not somebody who is going to stop using my smartphone.
I don’t expect anyone’s going to stop using their smartphone.
The question is, should you carry it in your front pocket
if you’re a male?
I think to be on the safe side,
the answer is probably avoid doing that too much of the time.
Ideally, don’t do it at all.
Then people will say, well, what if I turn off the Wi-Fi
or I turn off the cellular access,
then is it still a problem?
Well, it’s a problem due to the heat-related effects.
And then people say, well,
I don’t actually feel the heat of the phone.
It doesn’t get that warm,
but the temperature effects of the phone, it turns out,
are enough, even under conditions
in which people don’t report it to be uncomfortably warm,
that it can change the temperature milieu of the testicle
in ways that can diminish sperm quality.
How much and how that relates to fertility
and healthy pregnancy, not clear,
but since we’re talking about things to avoid,
if your goal is to have a healthy fertilization
in pregnancy, well then, by all means,
just don’t carry it in your front pocket.
Then people say, well, what about back pocket
or what about backpack?
Look, it’s very clear that avoiding being too close
to the phone is probably better for your sperm quality
than putting the phone very close to your testicles
or anywhere else on your body,
but it’s also the reality that most people
are going to carry a phone nowadays, all right?
It’s just the reality.
I think the current estimates and it’s discussed
in this paper that 90% of the human population
has a smartphone, 90%, which is incredible,
the adult population, of course,
although a lot of kids have them as well.
So this paper goes on to detail a number
of different studies and outcomes from studies,
but basically what they find, and here I’m paraphrasing,
is that the data indicate that sperm quality declines
when people start using a mobile phone.
So from the point they start using a mobile phone,
regardless of the usage time, this is important.
It used to be thought that it was four hours a day
or more of holding your phone or having that phone
close to your body was going to diminish sperm quality.
It turns out that it’s not related to usage time.
That’s even the title of the paper.
It’s just the fact that people are using mobile phones
is reducing sperm count and quality.
That’s the reality.
Is it entirely responsible for all the reductions
in sperm quality and maybe even the reductions
in testosterone levels that we’re observing
from decade to decade going forward?
I doubt that’s the case.
Is it likely to be one of the major players?
I’ve got my bet on the fact that it is
based on the data that I’ve observed.
And so if any of you would like to peruse the data
in this meta-analysis, they’re quite good.
This study looked at 18 studies that include 4,280 samples.
They were able to separate out the radio frequency
versus the heat effects, and they were able to eliminate
this time of usage variable that previously we thought
if you were exposed to a lot of cell phone contact
that it was far worse than if you were exposed
to a little bit.
If you’re exposed to any at all,
you’re going to diminish sperm quality.
What does that mean?
Does that mean that no matter what you do,
if you own a smartphone,
that you’re going to diminish sperm quality?
I think the short answer is yes,
but that you can mitigate it.
What might you do?
Well, keeping your phone away from your groin
or as far from your groin as possible,
if you’re a male who’s wishing to conceive,
and maybe even a male who’s wishing to maximize
his testosterone levels, because it does appear
that radio frequency waves and the heat from the phone,
so both of those factors independently and together,
of course, can disrupt the Leydig cells of the testes
and the production of testosterone
and intratesticular testosterone.
It’s important for sperm production.
The exact biological variables leading to all these changes
isn’t exactly clear, but if you’re like me, you say, okay,
probably not a problem for most males to carry their phone,
but probably best to not carry it in the front pocket,
maybe even avoid carrying the back pocket as well.
Again, in the future,
we will have an episode all about Bluetooth.
We’ll talk about various aspects of EMFs.
It’s a super interesting dataset,
and it’s a dataset for which there’s a ton of controversy.
It’s really interesting, however,
and there are more and more quality data
coming out all the time, and I think going forward,
we are going to see that, indeed,
there are some negative effects of smartphones
related to both their radio frequency transmission
and the fact that they generate heat,
and in general, heat is not good for biological tissues.
So any discussion about heat and sperm
and how heat is detrimental to sperm
has to raise this issue of whether or not cold
is good for the testicle.
Okay, well, now there’s a lot of data starting to come out
about the positive effects,
the positive biological effects of deliberate cold exposure
on different aspects of brain biology,
such as the release of dopamine and norepinephrine,
and on the biology of the body, to some extent metabolism,
but more so the impact on brown fat stores,
which are good for us, so-called brown fat thermogenesis.
There’s a lot related to deliberate cold exposure,
and we’ve done entire episodes on deliberate cold exposure.
Again, you can find that at hubermanlab.com.
We did a guest episode with an expert
on the use of cold for health and performance
with my colleague, Craig Heller
from Stanford Department of Biology.
We also have a toolkit on how to apply
deliberate cold exposure for health
for both females and for males,
for sports performance, cognitive performance,
mood, sleep, et cetera.
You can find all that, again, hubermanlab.com,
totally zero cost.
Go into the menu, go to newsletter and scroll down,
and you’ll find those.
When thinking about sperm quality,
we want to remember that excessive heat is bad.
Now, does that mean that deliberate cold is good?
Well, it turns out that one of the major causes
of lowered sperm count and overall reduced sperm quality
that’s quite common is the presence
of what’s called a varicella.
A varicella is kind of like varicose veins
of the veins that innervate the testicle.
What it essentially does is it means that blood will pool
in the testicular region.
It can’t circulate back to the body quickly enough,
and therefore the temperature of that environment increases.
There’s some other things that varicellas do
which can be obstructive at the physical level,
so they’re not just temperature related.
It’s pretty clear that using deliberate cold exposure
can be healthy for the sperm because of the ways
not that cold directly supports testosterone
or sperm quality, but rather because cold reduces heat.
Okay, so you will find available online,
I think they’re actually called,
forgive me, but that’s what they’re called.
I didn’t name them called snowballs.
These are, they’re sort of like gel pack cold briefs
that you can buy and men will wear for some period of time.
I don’t think you wear them all day.
You wear them for some period of time.
A lot of people are now using cold showers and ice baths
and circulating cold baths
or going into a cold ocean or lake
for any number of different reasons I talked about earlier.
I myself start every day
with either a one to three minute cold shower
or one to three minute immersion up to my neck
in a cold bath, cold water,
circulating water or a cold shower.
I do that mainly for the psychological effects
related to the long lasting increases
in dopamine and epinephrine,
but there are other data starting to come out
showing that that sort of approach or similar approaches
can increase testosterone levels
and maybe even sperm counts
can reduce cortisol late in the evening
if the cold exposure is done early in the day,
so on and so forth.
So a lot of interesting data coming out
in really good journals that are peer reviewed
and so on in humans.
I should mention those studies are done in humans
to support the use of deliberate cold exposure.
But again, if you’re going to use deliberate cold exposure
to improve sperm quality, can it work?
Yes, indeed it can work,
either indirectly by increasing testosterone
or directly by improving sperm quality,
but both of those effects are likely to be indirect
by virtue of reducing the temperature
of the testicle overall,
not because there’s any sort of magic effect of cold
on the testicle.
Now, I have to imagine that a number of you,
in particular, the females listening to this,
are going to say, is deliberate cold exposure,
and for that matter, is deliberate heat exposure,
like sauna or hot tub, good or bad for the ovary,
for eggs and for fertility?
Now, there are fewer data to look to, unfortunately,
but what we do know is that deliberate cold exposure
done in the way that I just described,
one to three minutes a day, ideally early in the day
through cold shower or immersion up to the neck,
doesn’t have to be an ice bath,
could be cold circulating water
or even non-circulating cold water.
And people will say, well, how cold?
I should have mentioned that before.
There is no way I can tell you
exactly how cold the water should be
because for some people,
60 degrees Fahrenheit will be exceedingly cold.
For other people, 40 degrees is going to be more appropriate.
How cold should you make it?
If you’re going to embrace these practices,
you want to, according to the literature,
what you want to do is make it uncomfortably cold,
such that you really want to get out, but safe, right?
You don’t want to go into 30 degree water immediately.
You can actually have a heart attack and die if you do that.
So you want to progress gradually into the cold.
So you don’t want to shock your system too much,
although it is the adrenaline evoked by that,
that quickening or shortening or elimination of the breath
for a short period of time
when you get into uncomfortably cold water
that correlates with, or is actually the reflection of,
would be more accurate to say the release of adrenaline
and then dopamine and so forth,
which has been very well documented.
So uncomfortably cold, but safe to stay in.
And I cannot tell you an exact number
that is uncomfortably cold, but safe for you.
It’s going to differ person by person.
You want to figure that out,
just like I can’t tell you how much weight
that you should squat in order to achieve
some effective resistance training for the legs.
It’s going to differ depending on your strength
and your prior experience and so forth.
So ease into it, be safe.
But it does appear that both for men,
for reasons I talked about a few minutes ago,
and for women, that deliberate cold exposure
can be beneficial for fertility and for hormone production,
but in particular for females
in terms of regulating cortisol and for hormone production.
Now you might say, okay, getting into cold is stressful.
How can that be helpful for regulating stress?
Well, it turns out when you get into the cold,
you get a big surge in adrenaline and then dopamine,
which is very long lasting,
provided that’s done in the early part of the day.
So I would say, you know, not too close to sleep.
Then what you do is you restrict
your maximum cortisol release to a period earlier in the day
that buffers, reduces, that is the likelihood
that you would have excessive amounts of cortisol
later in the day, which not only can disrupt sleep,
but is correlated with a number of other hormonal effects
that are not good for us
and therefore not good for fertility.
So here, what I’m describing are positive
yet indirect effects of a cold on hormone levels,
both in males and in females.
So for men, we talked about increased testosterone,
improved sperm quality that was indirect, right?
You’re reducing the temperature of the testicle,
but it’s not that cold itself
is positively impacting those things.
Does that make sense?
Heat is bad, therefore reducing temperature is good.
Likewise with females, deliberate cold exposure
can be good for the overall fertility process,
not because cold is good for the ovary
or being cold is good for the ovary
or for luteinizing hormone or for follicle-stimulating hormone
or anything else like that,
but rather that using deliberate cold exposure
as a way to restrict stress in a deliberate way
to a particular time of day
increases the release of cortisol then
and indirectly reduces the amount of cortisol
that’s released at other times along the 24-hour cycle.
Okay, so these are positive yet indirect effects.
So if you’re a woman who really is interested
in exploring deliberate cold exposure
or who enjoys it or is already doing it
and you’re wishing to conceive, great, explore it,
do it safely, of course,
but explore it and continue to do it.
However, if you’re somebody who just hates the cold
and doesn’t want to go anywhere near it,
there’s no reason to think that you absolutely need it
provided that your stress, your sleep,
and other factors are all being carried out properly.
The next things that we’ll talk about
in terms of positive things or things that we can do
in order to maximize fertility for both females and males
are the things that you also generally hear about elsewhere.
Right along with sleep and avoiding alcohol
and avoiding nicotine and avoiding cannabis,
avoiding excessive heat for the testicle,
avoiding excessive stress,
is that you want to try to get enough exercise, right?
Why would exercise have anything to do with any of this?
Well, exercise, and that is both a combination
of resistance training and cardiovascular exercise
is going to improve the health of the mitochondria,
in particular, cardiovascular exercise.
And I realized that for you fitness experts out there,
anytime someone says cardio,
people kind of roll their eyes like, what is that?
You know, there’s endurance training,
there’s interval training, there’s HIIT training,
there’s sprints, there’s all sorts of different things.
Some of those overlap, some of them are separate.
Indeed, that’s the case.
But we can use a general rule of thumb here,
which is that for most people getting anywhere from 30
and ideally 45 to 60 minutes of exercise per day
for six days per week, maybe even seven,
but most people like to take a day off
or need to take a complete day off each week.
Six to seven days per week is going to be good
for mitochondrial health and function.
It’s also going to impact all the other things
like quality sleep, mood, reducing stress,
and so on and so forth.
So exercise we can handle pretty quickly
by just saying everyone should be doing it.
Now, when people are pregnant,
they might have to, of course,
change the amount of exercise
or the type of exercise that they’re doing.
There are varying opinions on that,
but certainly the type of exercise
and the amount can vary when people are pregnant.
But if you’re seeking to conceive,
getting enough exercise is good
because it’s good for the mitochondria.
The mitochondria are present in that mid region of the sperm
and mitochondria are critical for chromosomal segregation
and the spindle and other aspects
of the formation of a healthy egg,
ovulation and fertilization in the female.
One thing that I know a lot of people
are interested in nowadays is so-called intermittent fasting
or time-restricted feeding.
I mean, let’s be fair.
Everybody is restricting their feeding time
because hopefully everybody is sleeping
at some point in the 24-hour cycle
and nobody’s eating while they are sleeping.
That said, many people are employing
a so-called eight-hour feeding window
or a 10-hour feeding window or a 12-hour feeding window.
And indeed, there are some data to support the idea
that that can be a good thing
for a number of different biological and health parameters.
However, also a lot of data,
especially recently pointed to the fact
that your overall number of calories
and the quality of your food sources
is going to be the most important variable.
And some people simply find that time-restricted feeding,
intermittent fasting, as it’s also called,
is just a convenient way to ensure
that your total intake of calories
is not excessive for what you need.
Now, with all that said,
there is evidence that I’ve covered in a solo episode
and we’ll soon have an expert guest on
showing that time-restricted feeding
can have certain positive outcomes
for various aspects of organ, cellar, and tissue health.
Okay, this is somewhat controversial,
but there is growing evidence
that by restricting your feeding window
to say eight hours or 10 hours or 12 hours,
that it is better than if you were to eat
over a longer period of each 24-hour cycle.
But again, the data are still incoming.
The reason we want to talk about
time-restricted feeding, intermittent fasting,
is that a lot of people do use it
because they find it easier to not eat
at certain periods of their 24-hour cycle
than to restrict calories.
But again, keep in mind,
you have to restrict calories
if your goal is to maintain or lose weight, all right?
A discussion that we’ve covered
in that episode on intermittent fasting
and in the episode with Dr. Lane Norton
and that we will cover in other episodes in the future.
So refer to those episodes at hubermanlab.com
if you would like to learn more
about intermittent fasting per se.
For sake of this conversation,
a number of people are probably asking,
if I restrict my feeding to a certain window each 24 hours,
because that’s what’s convenient
or because I’m excited about the potential
positive effects of intermittent fasting,
is that going to disrupt the likelihood of fertility
and thereby a healthy pregnancy?
And the short answer to that is if you are a female
and you are having regular menstrual cycles,
that is a fairly consistent duration,
so maybe it’s 21 days, maybe it’s 35 or anywhere in between,
but it’s fairly consistent from month to month,
and you are following intermittent fasting
well then chances are pretty good
that it’s not disrupting your fertility
and likelihood of fertilization in a healthy pregnancy.
Of course, during pregnancy,
you need to talk to your doctor
and make sure that you’re eating in a way
that’s supportive both of you and of the developing fetus,
that’s extremely important.
I am not aware of data exploring in a regimented way
time-restricted feeding during pregnancy, okay?
So please, please, please, if you’re pregnant,
do not jump on a time-restricted feeding,
so-called intermittent fasting diet.
Talk to your OBGYN, talk to your doctor,
talk to multiple doctors for that matter
before doing anything like that
because of course you’re now eating for two
or if you have twins in there, you’re eating for three.
And very important.
If however, you’re not yet pregnant
and you want to be fertile, get pregnant,
or simply maintain a fertile potential in biology,
you’re following intermittent fasting,
it’s going to be the regularity of those periods
and regularity of cycle length
that will tell you whether or not that’s a good idea or not.
Keeping in mind, of course,
that if your total number of calories is too low,
your periods will cease.
That’s a well-known effect.
But of course, stress can also induce
cessation of menstruation.
And there are other factors that can induce
cessation of menstruation as well.
Some of them start with changes in the brain,
literally in the hypothalamus,
some occur in the pituitary.
Many of the lifestyle factors can do that,
but most typically it’s going to be
excessive caloric restriction
or it’s going to be a caloric deficit
brought on by excess physical activity.
So even if someone’s eating a lot,
if they’re not eating enough
to offset their physical activity
or they’re not eating enough of in particular fats,
the essential fatty acids and protein,
but also carbohydrates,
well then menstruation can cease.
And of course, if menstruation is ceasing,
chances are almost with certainty
that you’re not getting regular ovulations.
Now, in terms of males
and whether or not intermittent fasting
is going to disrupt somatogenesis
and testosterone production,
there’s essentially no data we can look to,
but we can look to the general logic
around the relationship
between body fat, testosterone, and somatogenesis.
And this was something that was covered
in a discussion I had on
optimization of hormone health for males
that I had with Dr. Kyle Gillette,
who’s a medical doctor and obesity specialist.
Again, you can find that episode at hubermanlab.com
if you want to learn all about hormone optimization in males.
And essentially the story is as follows.
If a male is excessively overweight,
he’s carrying too much body fat in particular,
not too much muscle,
although that can be an issue too,
but too much body fat is typically the issue.
So, you know, more than say 20% body fat,
well then losing body fat
is going to be the primary goal
for maximizing testosterone,
sperm health, and spermatogenesis.
If however, a male is already lean,
well then actually increasing calories
will increase testosterone.
So it’s a bit of a complicated story,
although not so complicated
that none of us can understand it.
Basically, if you’re overweight,
you should focus on losing weight
in order to maximize sperm quality and health.
If you are very lean,
well then restricting your calories
to the point where you are starting to lose weight
or you’re dropping even more body fat
is unlikely to increase your testosterone further, right?
Doesn’t necessarily mean it’s bad
or that you shouldn’t try and go,
for instance, from 15% to 10% body fat.
I’m not saying that that’s bad
and that will reduce your testosterone,
but in general, if you’re already very lean,
so, you know, 10% body fat, 5% body fat,
and you start restricting calories further,
your testosterone levels will drop.
So in the context of intermittent fasting,
it’s really not an issue
of whether or not your feeding window
is eight hours or 12 hours.
It’s really an issue
of whether or not you’re getting enough calories
to offset the physical demands and activities of your life,
whether or not you’re on a maintenance diet
to maintain your weight.
And of course, you have to put all that in the context
of whether or not you’re overweight or lean to begin with.
The simple thing to take away from this
is if you’re a male who’s using, because you like it,
intermittent fasting, so-called time-restricted feeding,
and you’re following an eight-hour
or maybe even a one-meal-per-day type approach,
although I don’t really recommend that
for a number of reasons we could talk about separately.
If you’re eating over the course
of eight or 10 or 12 hours per day,
because that’s what works for you,
and you are ingesting enough calories
to maintain your weight if you’re already lean,
or you are ingesting fewer calories
than you are burning in order to lose weight
because you are already overweight
and you want to lose body fat,
you’re probably optimizing for all the things
that you need to do in order to improve sperm quality
and testosterone levels.
Now, also in that episode that I did with Dr. Kyle Gillette
on optimizing hormones for males,
we talked about testosterone replacement therapy.
It’s not a topic I want to get into in any detail right now,
but I will say this.
Remember earlier when we were talking about spermatogenesis
and the fact that in order for sperm to be generated
consistently every month ongoing from the time of puberty
until essentially the time that a man dies,
you need two things.
You need testosterone production
from the Leydig cells of the testes,
and you need spermatogenesis to be supported
by that androgen binding protein
coming from the support cells from the Sertoli cells.
So you need testosterone
and you need androgen binding protein,
and you need the Leydig cells and the Sertoli cells active.
When men take exogenous,
meaning from outside the body testosterone,
either by cream or by patch or by pellets,
or more typically by injection,
the most typical TRT approach nowadays
is testosterone cypionate,
which is biologically identical
to the kind of testosterone you would make.
Well, because of negative feedback loops,
which you also learned about earlier,
the testicles themselves shut down
their own testosterone production.
Why would that be?
Okay, so you’re taking testosterone in by syringe
or by patch or any other method.
So the circulating testosterone
and the amount that arrives at the testicle
is going to be hopefully clinically appropriate,
not super physiological,
but it’ll be somewhere in the healthy reference range,
maybe a little bit higher.
Nowadays, some people are going a little bit higher.
So we’re not talking about full-blown
quote-unquote anabolic steroid use,
keeping in mind, of course, that estrogen is a steroid,
testosterone is a steroid,
but when we think about steroids,
we mean like performance-enhancing drugs,
so super physiological doses.
We’re talking about within physiological
or near physiological ranges.
So if someone’s taking their testosterone in
from an outside exogenous source,
the levels of circulating testosterone
will be sufficiently high
that the pituitary will register that
and will stop making luteinizing hormone
and generally follicle-stimulating hormone as well.
And as a consequence,
spermatogenesis is vastly reduced or eliminated.
In other words, for men who are on TRT
or who are taking testosterone from an external source,
the number of sperm that they’re going to make
is going to be dramatically reduced.
There are things that they can do to offset that,
like taking HCG, human chorionic gonadotropin,
which is just kind of a mimic for luteinizing hormone
to stimulate the testes to continue to make testosterone.
And some men will also, or instead,
take FSH to stimulate the Sertoli cells
to support spermatogenesis, excuse me,
or both, or some combination.
Some people take clomiphene, clomid.
There are any number of different ways to bypass
or offset the sperm-reducing effects
of taking exogenous testosterone.
This is a conversation that was covered
in a fair amount of detail in that episode with Dr. Gillette,
but just keep in mind that if you are taking testosterone
from an exogenous source,
your sperm counts will dramatically be reduced
unless you do something to offset it.
So if you are wishing to conceive,
you need to think about whether or not
you’re going to offset the testosterone replacement therapy
or whether or not you’re going to come off it entirely.
So you’ll need to talk to a urologist
and a chronologist about that.
And again, a number of these different themes
and ways to go about tapering off TRT
were covered in that episode with Dr. Cal Gillette.
So if you’re on TRT or you’re considering taking it
and you’re interested in having children, not just now,
but at any point,
you really want to take these things into consideration.
Now, I do want to point out
that for the number of you out there
who are taking supplements,
some of which we’ve talked about on this podcast,
I’ve talked about on other podcasts,
such as Tonga Ali.
It turns out that there are a lot of men and women
taking Tonga Ali to reduce sex hormone-binding globulin
levels to increase testosterone and estrogen,
in some cases, libido and so forth.
Those approaches, meaning supplement-based approaches
to increase testosterone or free testosterone
or some related hormones
are not going to shut down
your own endogenous testosterone production
and reduce the number of sperm that you make.
Or at least as far as we know,
it’s not going to disrupt ovulation in any kind of way,
provided that the dosages are within normal ranges.
Again, supplementation to support your hormones
should not disrupt ovulation or spermatogenesis
or testosterone production.
Quite the opposite, it should enhance it.
What I just described around TRT
is taking exogenous testosterone,
and that itself is an entirely different beast.
Now, with all of that said,
there are some supplements out there
that include testosterone as a ingredient
that’s been snuck in to various formulas
that include blends and things of that sort.
You want to be aware of that.
And we did an episode about how to develop
a rational guide to supplementation.
I highly recommend listening to that episode.
Again, it’s timestamped, available free
at hubermanlab.com in all formats,
because it talks about which supplements
are likely to be clean, quote unquote,
to contain the things that you expect them to contain.
There’s more and more evidence coming out
that a lot of supplements, including some, for instance,
supplements that contain testicle
or the extracts of testicles can contain testosterone.
Whether or not that can shut down
your own endogenous testosterone production isn’t clear.
No one’s really explored that in detail.
But based on everything we just talked about with TRT,
it stands to reason that it might either reduce it
or shut it down.
It’s just never been explored yet.
So by all means, make sure that you know
what you’re taking if you’re taking supplements.
But again, the major point here
is that for both females and males,
taking supplements to support healthy hormone production,
including things like Tonga Ali,
is not the same as taking hormones or bioidentical hormones,
which indeed can shut down
your own endogenous production of hormones
and thereby reduce both egg quality
and the chance of fertilization and healthy pregnancy
and sperm quality and the chance of fertilization
and healthy pregnancy.
Anytime there’s a discussion about fertility and pregnancy,
there seems to also be a parallel discussion
about sex determination.
That is, what factors can influence
whether or not the child that’s born is male or female?
That is, whether or not it has double X chromosomes,
so one X chromosome from mom, one X chromosome from dad,
because the egg was fertilized by a sperm
that had an X sex chromosome, that 23rd chromosome,
or whether or not the offspring is male,
whether or not it has the X chromosome from mom,
because it’s always going to be the X chromosome in that egg
and a Y chromosome from the sperm
that fertilized that particular egg.
Now, of course, there are instances out there
of people that have XXY chromosomes or XYY chromosomes,
but the vast majority of people out there
are going to have either an XX chromosome,
so we call that a female karyotype, right?
This is different than genotype and phenotype,
but a female karyotype would be XX
or a male karyotype, which would be XY, okay?
Now, despite the fact that it is the egg and the sperm
and the chromosomes that they carry
that are going to determine the chromosomes,
there’s a lot of lore and discussion
about the factors that can bias
which sperm will fertilize the egg,
and thereby whether or not you’re going to get an XX,
female, or an XY, male chromosome, and therefore offspring.
Now, not only is the lore around this whole issue
of sex determination rather prominent,
but it is also somewhat unusual
and perhaps even interesting.
So for instance, Aristotle himself proposed
that if a man is thinking about himself and his own pleasure
more than his partner and her pleasure
at the point of ejaculation,
then the offspring will be male.
Aristotle also asserted that if a man is thinking more
about his partner and her pleasure
at the point in which he ejaculates,
well, then the offspring would be female.
Of course, we have zero reason to believe
that there’s any truth to Aristotle’s theory.
There are no data to support that.
In fact, I’m not even sure how you would run that experiment
because you can’t really look at people’s thoughts.
You’d have to rely on honest self-report.
And even if people were to faithfully report
what they were thinking about at the moment of ejaculation,
this would involve, of course,
bringing people into the laboratory
and somehow measuring or analyzing their thoughts
or gathering their thoughts during the sexual intercourse
at the point of ejaculation,
then figuring out which biological sex
was the offspring, et cetera.
Just near impossible
and probably not the most important experiment
to invest our time doing.
Nonetheless, there continues to be a lot of lore
about what determines the sex of the offspring.
Most notably, there’s a lot of lore and discussion
and rumor about the idea that particular sexual positions
at the point of ejaculation during intercourse
can somehow bias the likelihood
that a pregnancy will be either resulting
in male or female offspring.
Now, again, there are zero data to support this.
And yet this whole notion of sex determination
is a really interesting one
that people seem to be somewhat obsessed by.
So much so that, again, if you go online
or if you were to talk to people in the sort of,
let’s call it holistic or peripheral health spaces
related to fertility, there is discussion about,
okay, well, you take this sexual position
at the point of ejaculation to get a boy
and you take that sexual position
at the point of ejaculation to get a girl,
or you do this in the early part of the day
or the later part of the day.
Again, all for which there is zero data
to support any kind of systematic relationship
between what I just discussed
and the biological sex of the offspring.
That said, there are now emerging methods
that people are using in order to separate out the sperm
that will indeed give rise to a male offspring
versus a female offspring.
Now, this of course is done
in the context of in vitro fertilization.
We haven’t talked too much about in vitro fertilization,
but in vitro fertilization involves, as the name suggests,
taking an egg and taking a sperm, pairing them in a dish.
This can be done a number of different ways,
but just to briefly describe the IVF procedure,
IVF involves administering supra,
meaning greater than normal, supraphysiological levels
of follicle-stimulating hormone and luteinizing hormone
during the follicular phase of a woman’s cycle.
What that causes is the maturation of not just one egg
that would be ovulated, but multiple follicles and eggs.
And then ovulation itself is suppressed
also through the administration of exogenous hormones.
And then under ultrasound guidance,
an OBGYN goes in and collects the mature eggs and follicles,
puts them in a dish,
and then sperm are delivered to that dish.
And those could either be sperm
that were frozen previously, or more typically,
or ideally it would be live sperm collected that day
that are washed through a very straightforward procedure.
And then those sperm either are allowed to compete
for those eggs and fertilize those eggs
and allow them to advance to very early embryo stage
before those embryos are frozen
and eventually implanted into a woman
in order to have them be carried to full term.
Ideally, or there’s a procedure
in which specific sperm are selected
because they have the best morphology,
motility, and so forth.
And in a process called ICSI, I-C-S-I,
in which the sperm themselves are literally forced
to fertilize that particular egg.
Now, under those conditions,
typically a couple or a woman,
if she’s doing this on her own with a sperm donor,
will get multiple fertilized embryos, okay,
that are carried to a multicellular stage
so that it’s clear that they could grow into a child
if they were implanted into a viable host,
sometimes the surrogate,
sometimes the woman who wants the child herself.
And under those conditions,
it is possible to look at the genetic makeup,
including the karyotype of those early nascent embryos,
in which case people really can select the sex
of their offspring.
They will have some embryos that are XX,
some embryos that are XY.
It’s very likely also that they will have some embryos
that have karyotypes or genotypes which are not ideal
in that they would potentially lead to a miscarriage
or some other genetic defect.
And so typically people do not select
to implant those embryos
if they have the option to implant embryos
that are of either XX or XY karyotype
and the normal chromosomal arrangements
for obvious reasons.
So the whole point here is that sex selection is possible
but only using in vitro fertilization.
The other thing that is becoming clear to us
in more recent years is that sex selection
is actually possible at the level of the sperm
even prior to fertilization.
This is an emerging dataset
and this is largely happening in clinics
outside of the United States,
but there are some clinics that have figured out methods
in which they can take a sperm sample
and they can spin that sperm sample in a centrifuge
at a rate that separates out the sperm
into what are called different fractions.
So for those of you who’ve done a little bit of biology
with centrifuges, when you spin any kind of substance
that includes multiple things in it of different weights,
when you spin them, the things of different weights
segregate out into different fractions
along the depth of the tube.
And then you can take out one fraction or the next
simply with a little pipette.
You take out the top fraction, the middle fraction
and so forth.
And what these clinics have figured out
is that if they spin the sperm sample
at the correct spin rate,
that the sperm that will give rise to male offspring
and the sperm that will give rise to female offspring
segregate out into different fractions,
allowing them to take each of those fractions separately
and to apply them to eggs if it’s in vitro fertilization
and give rise very reliably,
certainly much more than chance
to either male or female embryos.
They also, of course, can choose to do this
outside the context of in vitro fertilization.
So some people are now opting to have their sperm samples
spun out in this way,
separate out the sperm that give rise
to male or female offspring,
and then to only use the fraction
that they are interested in, right?
So if they want a boy, they’ll use one fraction.
If they want a girl, they’ll use different fraction.
And then to use those fractions in the context
of what’s called IUI or intrauterine insemination,
which is, as the name suggests,
rather than having the man deliver the ejaculate
with his penis and the sperm with his penis,
they have a device.
The devices are now commercially sold.
Believe it or not, they’re sold over the counter
and on the internet.
So people will even do this at home.
And so what they’re doing is they’ll take the sperm
and they’ll do IUI in order to bias the probability
that they’re going to get a male or a female offspring.
Again, this is something that’s now emerging.
It’s not commonplace.
Most of the time, people simply roll the dice, as it were,
by having either intercourse and just hoping for,
or not caring if, they get a male or female offspring.
Or in the instance of IVF,
selecting male or female offspring,
sometimes largely on the basis
of the chromosomal arrangements.
So of course, some people might prefer to have one
or the other biological sex as their offspring.
But of course, the healthy chromosomal arrangements
are going to be paramount for getting a healthy child.
And as I mentioned before,
unhealthy chromosomal arrangements
or abnormal chromosomal arrangements
often lead to miscarriage and or birth defects.
So selecting for healthy chromosomal arrangements
is always paramount,
but some people are selecting for biological sex.
And indeed, some couples who can conceive naturally
are opting for IUI in order to be able
to select biological sex
because of this ability to spin out the sperm samples
to different fractions and select the male or female sperm.
That is the sperm that would give rise
to a male or female offspring.
So this is a rapidly emerging theme, believe it or not.
And of course, it has nothing to do
with Aristotle’s assertions
about what people are thinking about
at the point of ejaculation,
nor does it have anything to do with body position
at the point of ejaculation.
But I do find it rather interesting
that even in this day and age,
people seem to be continually pursuing new
and different ways to understand why one sperm
or another sperm happens to fertilize the egg.
And when that information is not available,
because frankly, it’s not available yet,
we don’t know why a sperm containing a Y chromosome
or sperm containing X chromosome
is more likely to fertilize an egg.
I mean, there’s some ideas, for instance,
that older fathers tend to have more daughters
as opposed to sons.
But when you really look at the data, it’s pretty mixed.
So if you’ve heard that before,
has a particular nickname that I’m not going to describe
on the podcast, you can look it up online.
But if any of you are aware of any other kind of ideals
or lore, no matter how ridiculous or crazy,
please put them in the comment section on YouTube.
I’d be very curious to learn about those,
mostly out of interest and curiosity.
But look, sometimes these outrageous stories
such as notions of body position
and how they influence biological sex,
even though they turn out not to be true,
turn out to be interesting for other reasons.
And in fact, next, we’re going to talk about
how body position during sexual intercourse
can in fact influence fertility and pregnancy.
So another common theme around fertility and pregnancy
that you’ll hear about is that for couples
that are trying to get pregnant,
that during intercourse,
they should do whatever it is that works for them.
But then after the man ejaculates,
that the woman should try and position her ankles
above her head or somehow otherwise tilt her pelvis back
in order to increase the rate and or probability
that the sperm swim toward the egg
as opposed to the other direction.
Now, I talked to a couple of different OBGYNs
and urologists that are focused on fertility
about this topic.
And it turns out you get pretty mixed answers
as to whether or not there’s any validity
to this idea that the woman’s body position
after the man ejaculates inside of her
can somehow influence the probability of pregnancy.
One group of experts told me
that there is no reason for a woman
to need to continue to lie down, elevate the ankles,
or in any way, tilt her pelvis back
in order to increase the probability
of successful fertilization.
The other group suggested that indeed,
there is a strong reason to believe
that tilting the pelvis back,
maybe even keeping the ankles elevated
and having a woman lie on her back for about 15 minutes
with the pelvis positioned at about 20 degrees back
is ideal for optimizing fertilization.
I mean, they were really specific about the recommendation.
So I find this interesting that within the cohort
of extremely well-trained MDs, OBGYNs,
and urology fertility docs and OBGYNs,
you see a split that has nothing to do
with whether or not the physician was male or female
or their training or their institution, none of that.
There just seemed to be a sort of even split
between the two.
Now, granted, it wasn’t the largest sample size
that I could have obtained,
and yet I do find it interesting
that there’s this split in the opinion about this.
One group, the group that said,
no, pelvic position doesn’t really matter,
don’t worry about it,
it’s not going to influence the rates of fertilization,
argued that the sperm swim very quickly
and that if they are released near the cervix,
they’re going to swim very quickly toward the egg
in order to fertilize it, regardless of pelvic position.
The other group said, well, yes, sperm swim quickly,
and even if they’re released right at the entry
to the cervix, that the sperm
still have a long distance to go.
Again, if you were to scale this
according to the size of the sperm
versus the size of a human body, an entire human body,
what you’d scale it to is the distance
between Los Angeles and San Francisco,
and it needs to undergo that
basically within 24 hours or so,
although, as we mentioned earlier,
sperm can survive quite a while inside of the woman’s body,
maybe three or five days at least.
So in both cases, they acknowledge it’s a long distance,
but on the one hand, you have a group of experts
that are saying the sperm more or less know what to do
and are going to do it regardless of the position
of the woman after ejaculation inside her,
and the other group saying,
no, we want to do everything we can
to bias the likelihood that the sperm will fertilize the egg.
Okay, well, setting aside the basic argument
that tilting back of the pelvis and lying stationary or so
for about 15 minutes after sexual intercourse
and ejaculation is not an expensive, you know, endeavor,
although it requires a little bit of time,
and it forces people to remain motionless
or close to motionless,
and they’re not up and around and moving about.
Aside from that, it’s a relatively low investment.
So one argument is,
well, if it could bias the likelihood of fertilization
at all and people want to get pregnant,
why wouldn’t they do that?
Okay, so that’s a reasonable argument,
but it doesn’t really point to the mechanism.
The arguments that point to a potential mechanism
are that if you recall what we were talking about
when we talked about sperm quality,
sperm quality involves a bunch of different measures
like concentration of sperm per milliliter semen,
morphology of those sperm, how many are forward motile.
It turns out that in any one ejaculate sample,
the total number of forward motile
and yet fast forward motile sperm
that are also of the highest quality morphology
is actually quite low.
And so the idea here is that you want to get as many sperm
of the highest quality swimming toward the egg
because those sperm stand the highest probability
of fertilizing that egg.
And in fact, this relates to some of the discussion
we were having earlier about behavioral dos and don’ts
for sake of increasing the probability of fertilization.
And the one that is most important here is cannabis.
It turns out that the data on cannabis
really do support the idea
that some of you may have heard from parents and teachers.
I don’t know, I did hear this from parents and teachers
that cannabis can disrupt the swimming styles of sperm
in ways that are not supportive of fertilization,
that it can turn more of the sperm into twitchers.
Although when I learned about this,
I was not informed of the word twitchers.
What I was told is that if you use cannabis,
that the sperm don’t know which direction to go,
that they’re confused,
almost implying that the sperm themselves
are high on cannabis.
Well, that’s certainly not the argument
that I’m making here,
but it does seem to be the case
that people who use cannabis,
even once the sperm that are generated
during that particular month or two months,
during which or after which they use cannabis,
have less forward motility
and possibly altered morphology as well.
Okay, I want to be very clear.
I did not say that if you use cannabis once,
you are forever disrupting the motility
and morphology of your sperm.
I did not say that.
What I said is that if you use cannabis once,
then the sperm that are generated in the 60 days
after that cannabis use
are going to have a higher incidence of disrupted motility
and perhaps morphology as well.
Okay, remember, sperm are continually generated
every 60 days or so.
And so if you use cannabis once,
you are not forever disrupting your sperm.
But if you are using cannabis
and then you are looking to conceive in the next 60 days,
you are going to be reducing,
we think significantly so,
the number of quality forwardly motile sperm.
So the simple takeaway from this is avoid cannabis use.
Although if you are going to use cannabis,
and again, there are medical uses of cannabis
and beneficial uses of cannabis for certain populations.
It can be bad for other populations.
We talked about that in the Huberman Lab podcast,
all about cannabis.
But if you’re going to use cannabis,
you should try and abstain from cannabis
in the two months prior to the attempt to fertilize
and get pregnant.
Now, I’m not aware of any data on how cannabis use
by the woman can influence the likelihood
of fertilization and pregnancy.
And I want to couch this whole discussion around cannabis
under the umbrella of something that came up
in the episode that I did on cannabis,
which is that for about half of people out there,
male and female, okay?
So here, we’re not distinguishing by biological sex.
About half of people that use cannabis
report it as an aphrodisiac.
It makes them want to have sexual intercourse
more than if they don’t use cannabis.
And for the other half,
it actually has the opposite effect
by way of an influence on a hormone called prolactin,
which suppresses the dopamine system, the testosterone,
and the estrogenic system.
And so this whole idea that cannabis is an aphrodisiac
seems to be true for about half of the human population
and not for the other half of the human population.
So I mentioned that because I know a number of people
use cannabis as an aphrodisiac.
They like to use cannabis before intercourse.
It was actually very surprising to me to discover
when I researched that cannabis episode
that approximately 15, 1.5% of women who are pregnant
continue to use cannabis during pregnancy.
And that’s a very alarming statistic.
And everything we know is that the use of cannabis
during pregnancy is detrimental to the health,
in particular, the brain development of the fetus.
So that’s a real concern.
I highly recommend women abstain
from cannabis use during pregnancy.
Talk to your OB-GYN about it if you’re using it all
or considering using it all.
So based on what I told you earlier about the fact
that cannabis use is not good for egg quality
and the fact that cannabis use can disrupt
the motility of sperm and therefore is not good
for sperm quality, and it can disrupt the patterns
of swimming in sperm in ways that reduce
the likelihood of fertility,
I think the take-home message is clear,
which is that whether or not you want to be
a cannabis user or not,
if you are going to try and conceive,
and certainly while you’re pregnant,
you’re going to want to avoid the use of cannabis.
And that is smoked cannabis and vaped cannabis.
And during pregnancy, the consumption of cannabis,
even in edible form or in tincture form,
is also going to be detrimental to the developing fetus.
But of course, we started this conversation
in the context of body position,
in particular, at the point of ejaculation
in determining the sex of the offspring
and or the likelihood of getting
a successful fertilization in pregnancy.
And I think that given that the tilting back of the pelvis,
so again, this is elevating the pelvis by about 20 degrees,
I don’t think it has to be exact, exact,
but about 20 degrees for about 15 minutes
post-ejaculation inside of the woman,
or I suppose if people are using IUI,
since that seems to be the consensus among those experts
that believe that pelvic tilt backward can be beneficial
for increasing the probability of fertilization.
And given that it involves no cost,
but a little bit of time,
seems to me that if you want to get pregnant,
that that would be the right thing to do.
And as far as I know, there’s no information,
nor was I able to obtain any recommendations from experts
about what the ideal body position of the male is
after ejaculation if the goal is to increase
the probability of fertilization in pregnancy.
So we’ve been talking about behavioral interventions,
some do’s and some don’ts that people can do
to increase their fertility and the likelihood
that any fertilized egg
will be carried to term successfully.
And soon we’ll also talk about things
that people can take to improve their fertility.
Now, keep in mind that this entire discussion
is about fertility, but also remember,
as we discussed at the beginning of the episode,
trying to increase your fertility
is one of the best ways to think about
trying to create and maintain optimal physical health.
So for people that are trying to conceive
and for people who are not trying to conceive,
optimizing your fertility status,
whether or not you’re male or female,
it’s one of the best ways to target those approaches.
And there are now a lot of data supporting the idea
that acupuncture of all things can be very beneficial
for improving both female and male fertility.
And should a woman get pregnant
for improving the quality of outcomes,
that is the likelihood that there will be
a successful pregnancy that is carried to term,
not premature and so on and so forth.
Now, for some of you out there,
you might think, oh, of course, acupuncture.
Acupuncture has been known to work for thousands of years,
and therefore it’s not surprising
that it would assist with fertility and pregnancy.
For many of you out there, however,
probably thinking acupuncture,
that seems kind of like fringe science,
but what I can assure you is that there are now
quite a few clinical trials funded by government agencies
like the National Institutes of Health
showing that acupuncture is a very effective treatment
for a number of different things,
including fertility and pregnancy,
but for hormone status, for stress relief,
but even for chronic illnesses of different kinds,
including autoimmune illnesses.
So this is no longer considered fringe science.
In fact, one of the best laboratories in the world
working on this is a laboratory
out of Harvard Medical School
run by a guy named Chufu Ma.
Chufu’s lab has really been exploring in a mechanistic way
how the different stimulation sites
that are used in acupuncture,
so where the needles are inserted,
tap into neural pathways
that link the different organs of the body.
So for instance, they’ve found that stimulation
of a particular site on the lower limb
can reduce inflammation dramatically throughout the body
by way of neural pathways that originate in the lower limb
and extend to areas such as the kidney and the pancreas.
So all these quote-unquote ancient maps of the human body
as they relate to acupuncture
are now being parsed at the level of mechanism,
which I think is wonderful
because it not only is showing us
that so much of what has been purported and reported
in the landscape of acupuncture
actually has an underlying mechanistic basis,
and with additional mechanistic understanding, of course,
always arrive new and better practices.
That’s the idea, to evolve these fields of acupuncture,
to evolve the fields of mechanistic understanding
of our biology and health.
And so the issue of whether or not acupuncture
can assist in getting pregnant
and in carrying a child to term
and for that child to be healthy
are really starting to emerge in a major way.
And rather than go into all those data in detail,
what I can tell you is that there are clinical trials
and data supporting the fact that female fertility itself
can be supported by acupuncture through several mechanisms,
one of which is the balancing,
and I realize that’s a somewhat tricky term
and I’ll define it better in a moment,
the balancing of hormones
across the ovulatory slash menstrual cycle,
including regulating levels of FSH
so that they’re not too high nor too low
and restricting the FSH to the follicular phase
of the menstrual cycle,
as well as using acupuncture to improve things
like blood flow and the health of the ovary itself
and other aspects of the female reproductive axis.
So acupuncture can operate at the chemical level,
It can act at the mechanical level,
impacting the different tissues
through which the egg has to pass and so on and so forth.
Likewise, on the male side,
acupuncture has been shown to improve semen volume,
quality of sperm, sperm motility, et cetera,
and in large part through changes in the neural pathways
that innervate the very tissues and vascular input
to the scrotum and testicles,
because as we learned earlier,
temperature regulation of the scrotum and testicles
is so vital for getting healthy sperm
and increasing sperm quality.
In addition, there are good data to support the idea
that acupuncture can increase levels
of testosterone, free testosterone,
and the sorts of hormones that are going to support
healthy hormone production and sperm production in males.
And this is distinct from applying testosterone
from an exogenous source, right?
So when we’re talking about acupuncture
and increasing levels of testosterone,
we’re talking about increasing levels
of endogenous testosterone.
So those Leydig cells can support the Sertoli cells
and the Sertoli cells can make
that androgen binding protein,
and you get enhanced spermatogenesis.
You can find evidence for all of these different features,
both changes to the chemical milieu, that is the hormones,
and changes to the mechanical milieu,
including, for instance,
improvement of the pathways leading
from the seminiferous tubules to the epididymis
to the vas deferens,
basically clearing out the plumbing
so that more quality ejaculate can be delivered,
which of course is going to increase
the probability of fertilization.
So when you hear that acupuncture can improve
the likelihood of pregnancy,
that’s an accurate statement for which
there are now increasing amounts of mechanistic data.
If you want to learn more about how acupuncture
can be used to contribute
to improve fertilization in pregnancy,
there are a number of different excellent reviews on this,
both as it relates to females and as it relates to males.
One of the best papers that I happen to like
is one that we’ll provide a link to in the references
entitled Acupuncture and Herbal Medicine
for Female Fertility, an Overview of Systematic Reviews.
So a review of reviews.
This was published recently in 2021.
We’ll provide a link to that.
And there’s also going to be a link to a review
that relates to acupuncture for male fertility
and hormone augmentation.
I should just mention briefly
that if you’re going to look at scientific papers,
one thing that you’ll want to consider
is also looking at the references that they reference.
And now, of course, papers tend to reference
a ton of references, in particular in reviews.
So what you’ll want to do is look for the references
that are showing up most often in the introduction.
Those references often are going to be
the most prominent recent reviews
or the most important findings in recent years.
That’s not always the case, but that’s often the case.
So if you read the first couple of paragraphs
of these papers, and these are openly available
as full text, by the way, online, if you go to these links,
you’ll be able to access the best papers,
the most relevant papers,
in the context of acupuncture supporting female
and acupuncture supporting male fertility
and hormone status.
Now I’d like to discuss things that both men and women
can take in order to maximize their fertility.
And again, and again, when we’re talking about fertility,
we’re talking about people who want to conceive
and have children, but also we’re talking about
a basic measure of overall health status.
So if you’re somebody who does not want to conceive children,
I still encourage you to think about whether or not
you would want to do certain things or not do certain things
in order to maximize your fertility as a means
to maximize your vitality and longevity,
because that’s really what maximizing fertility is about
for a lot of people.
That said, I know a lot of people would like
to conceive children, perhaps not right away,
but in the future, and what I’m about to describe
are some tools and interventions that is things
that one can take in order to improve their hormone status,
but also in particular, the quality of their eggs
and the quality of their sperm in the short and long-term.
The first on the list of things that people can take
in order to improve egg quality or sperm quality
L-carnitine is present in various foods,
in particular in red meats,
but again, it’s going to be very hard
to get sufficient levels of L-carnitine
to improve egg quality and sperm quality,
unless you’re going to take it in supplement form.
The typical recommendation based on peer-reviewed studies,
they’ve shown significant improvements in egg quality,
that is chromosomal arrangements,
that is the likelihood of fertility or pregnancy rather,
the likelihood of sperm being forward fast swimmers
as opposed to twitchers or emotile
and having proper morphology.
All those measures has been demonstrated
to be significantly improved by the ingestion of L-carnitine.
How much L-carnitine?
Well, that depends on how you’re obtaining the L-carnitine.
If you’re obtaining it in capsule form,
one to three grams per day of capsule form L-carnitine
is what’s been suggested to improve egg quality
and sperm quality.
Now, one to three grams per day can be taken all at once
or spread out throughout the 24-hour cycle.
It can be taken with or without food,
does not seem to matter.
And when taken for a period of 30 to 60 days,
does seem to significantly improve all the parameters
that have been discussed for egg quality and sperm quality.
Now, the mechanism for that effect is pretty clear.
L-carnitine is involved in the processing of lipids, fats,
in terms of mitochondrial function.
And as we talked about before,
mitochondria are vital for the organization
and action of the spindle that pulls apart the chromosomes,
taking that cell within the female from diploid to haploid,
which is essential.
You really want just the 23 individual chromosomal strands.
You don’t want chromosomal repeats.
It’s also involved in the actual fusion of the egg
as it exits the ovary and enters the ovulation cycle.
Mitochondria are also important, as we talked about before,
for the forward motility of sperm
because of the enrichment of mitochondria
in that mid region just behind the head
that caused the whipping flagellation of the tail,
allowing for forward movement,
as well as other aspects of cellular morphology.
So it makes a lot of sense
as to why L-carnitine supplementation would be beneficial.
Again, it’s one to three grams per day
over a period of about 30 to 60 months.
If you’re hoping to conceive in the upcoming months,
recommend taking it for at least 30 days prior to that.
Of course, based on the data we talked about before,
the cumulative probability, fecundability, et cetera,
there’s no reason to not continue to try for pregnancy
before taking L-carnitine.
But L-carnitine is going to improve egg and sperm quality.
And so you might actually take the stance
that even if you don’t have any problem getting pregnant,
wouldn’t you want to maximize the quality of the egg
that gets fertilized and the quality of the sperm
that fertilizes that egg?
So that’s additional rationale for taking L-carnitine.
One important note,
if you are going to take L-carnitine in oral form,
in capsule form, it can increase something called TMAO.
TMAO can cause stiffening of the arteries.
You don’t want TMAO levels to go too high.
One way to offset the increases in TMAO
caused by oral L-carnitine
is to take 600 milligrams of garlic per day.
I suppose you could eat cloves of garlic.
That would work just as well
because garlic contains something called allicin,
which can offset the increase in TMAO.
But 600 milligram capsules of garlic are going to be,
or garlic extract rather,
is going to be the most probably cost-effective
and simplest way to do this.
And also they are going to create that garlic smell.
Some people like the smell of garlic, some people don’t.
So if you’re going to take oral L-carnitine,
I suggest also taking 600 milligrams a day
of garlic extract.
And you can do that at any time throughout the day.
It doesn’t have to be with the L-carnitine.
The next item on the list of compounds
that have been shown to improve egg quality
and sperm quality, and quite robustly so, is coenzyme Q10.
Coenzyme Q10 is something that you can actually
measure levels of in your blood.
Most physicians will say that they want to see
your levels of coenzyme Q10
to be somewhere between 0.5 and 2.5.
It’s going to depend on the units.
Most people, I realize, are not going to run off
and get their CoQ10 measured.
It’s not included in most standard blood tests,
but if you were to measure your CoQ10,
that’s the range that you want to look for.
That said, many people opt to supplement with CoQ10,
and you’ll find that many fertility docs, OBGYNs,
and urologists that are trying to assist their male patients
with fertility will suggest CoQ10,
because again, it supports the health of mitochondria.
Mitochondria are so vital to so many aspects
of the formation and fertilization of the egg and sperm
that, of course, fertilizes the egg.
The coenzyme Q10 dosages that are most often suggested
and that you’ll observe in the peer-reviewed research
literature on humans, I should add,
is 100 to 400 milligrams per day.
And the coenzyme Q10 is taken generally with a meal
and ideally a meal that contains fat.
And there’s even some idea that taking coenzyme Q10
with your dinner, assuming that dinner includes some fat,
you don’t have to add additional fat,
is going to be more advantageous
than taking coenzyme Q10 early in the day,
although that’s probably a detail
that’s getting a little too far down in the weeds.
So again, 100 to 400 milligrams of coenzyme Q10 per day,
whether or not you’re a man or a woman,
for improving the likelihood of fertility
by way of improving egg and sperm quality.
And again, if you’re somebody who just doesn’t have
any problem getting pregnant,
or if you’re already producing many sperm
of quality morphology,
this is another case in which you could take a step back
and just say, well, why wouldn’t I want
to further optimize the quality of the egg and the sperm?
Because the quality of the egg and the sperm
ultimately are going to determine
not just whether or not you have a successful pregnancy,
but are going to determine, admittedly,
in ways that will forever remain cryptic to you,
but nonetheless are going to be important
in determining the qualities of the brain tissue
and body tissue of your offspring.
The third item on the list of compounds
which are commonly suggested or prescribed
by fertility docs nowadays for men and women
wishing to conceive and or optimize their fertility
as a basis for general vitality and health is inositol.
Now, inositol has many uses.
So you’ll hear about the use of inositol
for reducing anxiety or improving mood,
or even for the treatment of depression.
We talked about inositol
in previous episodes of this podcast.
For instance, I talked about inositol,
and in particular, taking 900 milligrams
of myoinositol prior to sleep,
which is something that I do along with
the other supplements that I take and recommend for sleep,
such as magnesium threonate, apigenin, and theanine.
If you’re curious about those,
you can see our newsletter on sleep
or our Perfect Your Sleep episode
or the Master Your Sleep episode
talks about behavioral and supplementation-based tools
for improving sleep.
But myoinositol is not just suggested or prescribed
for people that are wishing to get pregnant
and for general health,
but myoinositol is often recommended
for people that want to improve egg and sperm quality
because of the way that it can positively
impact insulin sensitivity.
Insulin sensitivity might sound like a bad thing
to people out there,
but it turns out that you want to be insulin sensitive.
The last thing you want is to be insulin insensitive.
Insulin insensitivity is associated with type 2 diabetes,
with obesity, and even for people
who are not challenged with obesity.
You want your cells to be insulin sensitive.
You don’t want a lot of insulin
floating around in your system
with your cells unable to use that insulin.
That’s really what insulin insensitivity is about.
Myoinositol at dosages of one to five grams per day,
it’s pretty high, one to five grams per day,
keeping in mind that 1,000 milligrams is one gram,
has been suggested to improve
egg quality and sperm quality.
Now, one point of, I wouldn’t say caution,
but of note is that myoinositol can reduce anxiety
and it can be a slight sedative,
which is why some folks, including myself,
take almost a gram, 900 milligrams prior to sleep.
If you’re going to take five grams of myoinositol,
you would want to restrict that to the late evening
or second half of your day.
And I don’t suggest starting that high.
I would start with one or two grams
and then working your way up,
seeing what you can tolerate
in terms of the level of anti-anxiety
and drowsiness that it produces.
One to five grams per day of myoinositol
is what’s suggested for both men and women
wishing to improve egg health and sperm health.
But for women, it’s also often suggested to include also,
okay, so to take myoinositol,
but to also take d-chironositol.
D-chironositol has elements in it
that can be both pro and anti-androgenic.
Androgens are things like testosterone
and related molecules.
There are a number of different causes of infertility
and disruption to egg quality,
age being the most significant factor.
But another significant and very common factor,
even among young women who are of fertile age,
is having too many androgens
and as it relates to something called
polycystic ovarian syndrome.
And we’ll do an entire episode about menopause and PCOS
and a number of other things that relate to fertility
because it’s an entire and very interesting other discussion
that we need to have.
But the recommendation is that women take
one to five grams of myoinositol,
but also d-chironositol because of the ways
that it can balance androgens
and offset some of the negative effects
of polycystic ovarian syndrome,
or even for women who do not have
polycystic ovarian syndrome,
because of the ways that d-chironositol
can balance androgens in ways that are beneficial.
The dosages of d-chironositol that are recommended
tend to be 125th to 140th of the myoinositol dose.
So you have to get out your calculator.
Remember, 1,000 milligrams equals one gram.
So figure out if you’re taking one gram
of myoinositol per day or two grams,
you’re going to want to convert that to milligrams.
So let’s say you’re taking two grams
of myoinositol per day, that’s 2,000 milligrams.
Then you’d want to divide that by 25.
And that’s how many milligrams of d-chironositol
you would want to take as well.
Or you could go with the lower end dose
and divide it by 40 and take that number of milligrams
of d-chironositol along with the inositol.
Again, probably taking it later in the day
is going to be good.
And it’s not clear at all that taking it with food
or without food makes any difference whatsoever.
So I would suggest you do either.
Keep in mind as I’m discussing these recommendations,
I may call them prescriptions,
but none of these are prescription drugs.
And of course you should always discuss any supplements
that you’re planning to take or stop taking for that matter
with your physician.
I don’t say that to protect me, I say that to protect you.
You know, anytime you’re going to add or change something
in your overall health regimen,
you want to discuss that
with your trusted healthcare professional.
Typically, I would hope a board certified MD.
The fourth item in the list of commonly suggested supplements
for men and women wishing to optimize egg
and sperm quality respectively is omega-3 fatty acids.
And now here we’re talking about something
that could be obtained from food
and can be obtained from food.
So if you’re consuming fatty ocean fish,
things like sardines, anchovies, salmon with the skin,
chances are you’re going to get some quality omega-3s.
Omega-3s are also available in plant-based sources.
It’s also available in krill for that matter.
But most people find it difficult
to reach the threshold required
for optimizing mental health and physical health.
That is the threshold of the EPA essential fatty acids.
And so for that matter,
I’ve suggested before in this podcast
and many fertility docs will suggest
that their patients take omega-3 fatty acids
in supplement form.
It could be taken in liquid form or in capsule form,
but enough of those so that you’re getting
at least one gram per day of the EPA form of omega-3s.
Okay, so at least one gram per day
and as high as two or even three grams per day
of the EPA form.
So you’ll need to look at the packaging
because oftentimes you’ll say high potency omega-3s.
You’ll say, you know, 1,500 milligrams of omega-3s,
but that’s not 1,500 milligrams of the EPA form.
You look on the back of the label and you’ll say,
each serving contains 750 milligrams of EPA.
You want to get above that one gram dosage per day
and as high as three grams per day of the EPAs.
The most cost-effective way to do that
is going to be liquid form omegas,
but that’s a little bit inconvenient for many people
and some people don’t like the taste.
That’s why they rely on the capsule form omegas.
And of course there are compounds
that can impact fertility status, quality of eggs,
quality of sperm, not by adjusting mitochondria
or insulin sensitivity or creating a general milieu
of support for the egg and the sperm production
and function such as the compounds
that I just listed off to,
but rather compounds that influence the hormones involved
in the generation of sperm and the generation of the eggs
involved in the ovulatory cycle
and the spermatogenesis cycle that is.
Now, these are going to come in different forms
and I want to just emphasize that the supplements
that do this, that adjust hormones in these ways
that can be beneficial are distinct from hormone therapy
or bioidentical hormones, okay?
Distinct from hormone therapy or bioidentical hormones
because as we discussed earlier,
when you take a hormone like testosterone
or even estrogen for that matter
from an exogenous, an outside source,
you’re going to disrupt the feedback pathways
inside of your body and you’re going to shut down
your own endogenous production.
The supplements I’m about to describe do not do that
and yet can adjust levels of hormones in more subtle ways
that can be beneficial for the process
of maximizing fertility for males and for females.
The first of which on this list that I’d like to discuss
has been discussed in previous podcasts as well,
which is a substance called Tongat Ali.
Tongat Ali also goes by other names,
but when taken at 400 milligrams per day,
sometimes separated into two dosages,
but typically taken as once a day, early in the day,
because it can be a little bit stimulating,
although not anxiety provoking, I’ve never heard of that,
can be a little bit stimulating,
but 400 milligrams a day of Tongat Ali
has been shown to increase free testosterone
by way of reducing something called
sex hormone-binding globulin.
It’s also been shown to increase luteinizing hormone,
the net effect of which has been described
as a subtle but significant increase in libido
and some of the other parameters associated
with increased androgens like free testosterone
in males and females.
So a number of people out there
are taking Tongat Ali in this way.
400 milligrams per day,
restricted to the early part of the day
with or without food.
People always ask, do you need to cycle Tongat Ali?
I’m not aware of any need to cycle Tongat Ali.
In fact, it tends to work better,
meaning the effects on libido
and some other hormone profiles
tends to increase over time.
Again, Tongat Ali is an option,
as certainly none of these things are requirements.
We’re simply listing off options,
but many people, both males and females,
seem to benefit from and like Tongat Ali,
even if they’re not seeking to conceive.
There’s no reason to think that Tongat Ali
directly improves egg or sperm quality,
except in males, the increase in androgen
created by Tongat Ali supplementation
can indeed lead to improved spermatogenesis.
So there’s a growing amount of data
in this research literature on Tongat Ali.
Many people find it beneficial.
And so it’s something that both men and women
wishing to conceive and or optimize their fertility
just as a general health parameter might want to explore.
The other supplement that’s been shown
to improve both egg quality and sperm quality,
and there I’m referring to a number of different parameters
related to egg quality and sperm quality,
as well as to increase libido fairly substantially
is a substance called Shilajit.
Shilajit spelled S-H-I-L-A-G-I-T.
Shilajit is actually a compound
that’s used in Ayurvedic medicine,
but there’s some really good research studies
exploring the supplementation with Shilajit
at about 250 milligrams twice per day.
And this has been looked at in males and in females.
It does seem to significantly increase two hormones.
One is testosterone
and the other is follicle stimulating hormone.
And for that reason, Shilajit is often considered a tonic
that people use both as an aphrodisiac to increase libido,
as well as to increase fertility.
Now, one note of caution,
if you’re a woman and you’re considering taking Shilajit
in order to increase testosterone
and follicle stimulating hormone,
keep in mind that the ovulatory cycle
is this very tightly regulated cycle
in which you want low but elevated levels
of follicle stimulating hormone
early in the follicular phase,
then it peaks right before ovulation,
and then low levels of follicle stimulating hormone
in the second half of your cycle.
For that reason, using Shilajit chronically
around the entire course of your ovulatory cycle
could be a little bit risky.
And I’d recommend that you talk to your OBGYN
prior to doing that, or if doing that at all.
For males, it’s a little bit less of an issue
because as I mentioned earlier,
sperm are constantly being generated
and the presence of FSH
is going to increase spermatogenesis.
Now, Shilajit is not FSH itself.
Shilajit stimulates the release of FSH
and it stimulates the release of testosterone.
So again, there’s no reason to think
that it would shut down your endogenous testosterone
or FSH production.
Although there are a limited amount of data
that really explore that in detail.
Many people use Shilajit
in order to increase their testosterone, FSH,
their libido, and various aspects of sperm health.
Again, the dosages of Shilajit
are about 250 milligrams, two times per day.
One issue with Shilajit is it often comes as a tar.
It was a little hard to measure out the dosages.
Yes, a tar, it’s this kind of thick gummy substance
that you’re supposed to dissolve in water.
And the recommendations are you take a little bead
and dissolve it in water.
It is available in capsule form
where the ability to control the dosage
is made a little bit easier.
But of course, as with any supplement,
I recommend starting with the lowest possible dosage.
So you might want to start with a small,
very small bead of Shilajit dissolved in water,
taken once per day,
and then increase the dosage as needed
in order to obtain the effects that you want.
Things like Shilajit start to bring us into the realm
of what can only be described
as a little bit unwieldy, right?
Here we’re saying you can’t really control the dosage.
Now you’re talking about hormones
that need to be tightly regulated,
at least for females across the ovarian cycle.
For males, yes, it has been shown
to increase testosterone and FSH,
improve sperm motility and sperm count pretty significantly.
No reason to think that you couldn’t do that chronically
And yet I do want to acknowledge that Shilajit
as this black tar substance
contains a lot of different things.
In fact, it comes from a mineral pitch.
What is that?
Literally the dirt and plants
that have been compressed by rocks in the Himalayas.
So it’s pretty esoteric stuff
when it really comes down to it.
But the biological effects of Shilajit
in both males and females seem to be related
to the fact that it is highly enriched
in something called fulvic acid.
And fulvic acid is involved
in a lot of different cellular processes,
not the least of which, at least in this context,
is the transport of molecules across cell membranes.
And for hormones to have their effect,
they need to cross cell membranes on the outside
and the inside of the cell.
So maybe that’s how it’s having its effect.
Again, the mechanisms of exactly how Shilajit
increases testosterone and FSH
and thereby libido, egg quality and sperm quality
aren’t entirely clear.
But for the more adventurous of you out there
who want to experiment with Shilajit,
whether or not you’re trying to conceive or not,
it might be something to consider.
But of course, do talk to your physician.
The next compound that I want to discuss is zinc.
And then this discussion mainly pertains to males,
although I, of course, should point out
that females should get the recommended daily allowance
of zinc each day.
Males, on the other hand, seem to benefit
from having additionally high levels of zinc intake.
Now that can be obtained through foods.
You know, you’ll often hear,
oh, you know, oysters are enriched in zinc
and oysters are an aphrodisiac.
You know, I don’t know who’s doing the marketing
for oysters, but it’s really terrific.
I think that seems to have persisted.
And maybe it’s true, oysters are enriched in zinc.
What does zinc do for fertility?
Well, in males, we know,
based on a really nice set of studies,
that zinc dosages that are pretty high,
of about 120 milligrams taken twice per day,
and that’s quite a lot, with meals,
can significantly increase testosterone
And this probably shouldn’t come as a surprise to us.
It turns out that zinc is highly enriched in human testes
and in the testes of other animals,
including fish and other mammals.
And it was actually in 1921 that it was observed in fish
that zinc levels skyrocket in the testes of fish
during their breeding season.
So zinc is correlated with increases in breeding,
but you never know which direction
that correlation is running.
Turns out that zinc in both animals,
including fish, other mammals, and in humans,
strongly impacts the enzymatic functions in the testes,
including the function of androgen binding protein.
So it seems that high levels of zinc
can increase spermatogenesis
and testosterone levels very significantly.
This was explored in a really nice study
that I’ll provide a reference to.
It’s an older study, I really like it.
It’s called Effective Zinc Administration
on Plasma Testosterone, Dihydrotestosterone,
and Sperm Count.
This is but just one study among many now.
This dates back to 1981,
but there’ve been studies subsequently
that point to the fact that supplementation with zinc
at those high levels can really be helpful
in terms of increasing sperm count, testosterone,
and even testicular size of all things.
So one important point about taking zinc,
this 120 milligrams of zinc two times daily
definitely needs to be done with meals.
If you’ve ever taken zinc on an empty stomach,
even if you just take 15 or 30 milligrams of zinc,
you can feel very nauseous, not well for a few hours.
So make sure that you’re taking zinc with full meals.
So this would mean that you’re taking
in at least two full meals per day.
I should also mention that zinc supplementation
did not appear to impact
gonadotropin-releasing hormone or prolactin.
So it seems to be a fairly targeted effect
on the testosterone and related pathways in males.
As far as I know,
there have not been systematic explorations
of the effects of high levels of zinc administration
I would hope that those studies would soon be done.
But meanwhile, if you’re a male
and you’re interested in improving sperm quality
and your testosterone levels overall for whatever reason,
zinc likely is a good candidate.
And that pretty much summarizes the compounds
that men and women should take
in order to maximize egg quality,
sperm quality, and fertility.
And then of course, we start to enter the landscape
of other things that men and women can take
in order to improve fertility.
And those other things generally are prescription drugs.
And so I just want to mention what a few of those are.
But of course, these are things
that you would absolutely have to obtain prescriptions
for from your MD.
And your MD would, without question,
would want to take blood tests
prior to prescribing these things.
So for instance,
if men have been taking exogenous testosterone
through the use of anabolic steroids
like performance enhancing drugs
or even testosterone replacement therapy,
their endogenous testosterone levels
are going to be very low
and their sperm counts are going to be very low
unless for instance,
they are prescribed and taking something like HCG,
human chorionic gonadotropin,
which mimics LH and would stimulate the testes
to produce testosterone
and through some indirect pathways,
although not to the same degree
as if people are not taking exogenous sources
Some men, even if they’ve never touched TRT
or exogenous testosterone of any kind
will be prescribed to take HCG
because of its ability to stimulate the testes
to produce more testosterone in sperm.
So they’re just taking HCG alone.
Other men will take or will be prescribed rather FSH
in order to stimulate spermatogenesis or HCG and FSH
or clomiphene, which can regulate all sorts of things
in the both testosterone and estrogen related pathways
at the level of brain and pituitary and gonad, testes.
Likewise for women, if they’re low in FSH,
they might be prescribed FSH.
If they are low in luteinizing hormone,
they might be prescribed HCG.
If they’re low in testosterone,
they might even be prescribed testosterone
and if their testosterone is too high
and they’re dealing with PCOS,
they might be prescribed antiandrogens
and androgen blockers and on and on and on.
There are so many different hormones
that can impact the different aspects
of the ovulatory and the spermatogenesis cycle
that the OBGYNs and the urologists
focus on male fertility nowadays
really have an excellent handle on which levers
and buttons and threads to pull and push and so forth
in order to set in motion a proper ovulatory cycle
and a proper spermatogenesis cycle.
You know, everything we talked about up until now
and in the early phase of this episode,
especially about how the brain commands the pituitary
and the pituitary commands the gonads
and then the gonads, the ovary or the testes
send feedback signals to the pituitary
to then influence the pituitary.
All of that incredible orchestra,
that dance is so tightly regulated
in a way that really provides the OBGYNs
and the fertility docs concerned with male fertility
exceptional tools to, for instance,
figure out if a man is not producing any sperm
but his testosterone levels are well within normal range.
Well, then there’s some very clear sets of explorations
and potential treatments, some of which are mechanical,
making sure the epididymis and vas deferens are clear,
allowing the sperm to enter the ejaculate
and the ejaculate to enter the urethra
and obviously to enter the female,
as well as for a woman who’s not ovulating
to adjust her levels of FSH
or maybe even to apply acupuncture in conjunction
with supplementation and various prescription hormone
therapies to adjust fertility and ovulation
and the probability of successful pregnancy.
So there’s a vast landscape of prescription drugs
and surgical interventions of varying degrees
of invasiveness and some are, for instance,
outpatient procedures, some require general anesthesia,
et cetera, in order to maximize male and female fertility.
What I’ve tried to do today is to provide you
with a deep dive understanding
of the ovulatory and menstrual cycle.
We talked about the brain, the pituitary, the ovary,
the fallopian tubes, and in fact,
the whole female reproductive axis
as it relates to fertility and reproduction.
I also described the male reproductive axis
as it relates to the brain, the pituitary, the gonad,
the testes, and the various ducts,
the pathways out of the testes that allow the sperm
to be enriched within the semen,
and then the semen and the ejaculate
to exit through the urethra.
I did all that as a way to frame the various tools
and interventions that can really assist
in increasing fertility, egg quality, and sperm quality.
So when we discuss mitochondria in the context
of the development of an egg or the development of sperm
and its ability to swim quickly forward,
now it should make sense as to why a given intervention,
whether or not it’s L-carnitine
or whether or not it’s exercise
or whether or not it’s getting enough sleep
and limiting stress, why all that should matter
and why in fact mechanistically
those interventions can work.
Because indeed there are many interventions
that we can all do and use to support our fertility.
And again, as a more general theme today,
I really wanted to A,
teach you about the human reproductive axis.
I do find the biology of the ovulatory and menstrual cycle
and spermatogenesis to be absolutely fascinating to me.
And again, if you’re somebody who’s interested
in conceiving or if you’ve already conceived children,
and even if you don’t want more children,
this is really the aspect of our biology
that allowed us to be here.
It’s the aspect of our biology
that determined whether or not we are male or female.
It’s the aspect of our biology that determines so, so much.
And yet I think that most of us
generally are not taught this in school
or at least not at the depth that we discussed it today.
So hopefully that information was in and of itself
interesting and perhaps useful as well.
And I do think that even if people are not wishing
to conceive more children,
that the information related to fertility
and optimizing egg and sperm health
is a value in the sense that optimizing egg and sperm health
can be used as a proxy
for optimizing our body and brain health generally.
In other words, and here I’m admittedly taking
words out of the mouths of the various wonderful doctors,
the OBGYNs and urologists that helped inform me
in anticipation of this episode,
what is good for the woman is good for the egg
and for fertility and for pregnancy.
And what’s good for the man
is good for the quality and production of sperm
and for fertility and pregnancy.
Put differently, whether or not we are male or female,
the things that we can do to optimize our fertility
are the exact same things that we should all be doing
to optimize our vitality and our longevity.
And I realized today’s episode was so much the deep dive
and fairly broad as well,
that it ended up being fairly long and extensive.
And yet we still have not touched on
any of the important themes
that I know a number of people want to know about.
So for instance, menopause, andropause, PCOS,
and other themes related to hormones
and reproductive function and biology.
And I promise that we will have episodes,
both solo episodes and episodes with expert guests
in the future to cover all of those topics in detail.
Meanwhile, the information discussed in today’s episode
should serve as a basic foundation
for those discussions going forward.
And hopefully we’re of interest to you in their own right.
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Thank you once again for joining me for today’s discussion,
all about the biology surrounding this incredible thing
that we call fertility,
including the ovulatory cycle, spermatogenesis,
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