Hello everybody and welcome to the vP life podcast,

brought to you by vitalityPRO.

My name's Rob and I'll be your host on today's episode.

Today, we're sitting down with Dr.

Ahmet Ozyigit.

Dr.

Ozyigit holds a PhD in economics and is also a board certified embryologist.

During today's discussion, Dr.

Ozyigit and I talked about all things related to women's health, including how

the female endocrine system works, what the HPGA axis is, how he treats women

with fertility issues, the direction the industry is headed and so much more.

Today, we encountered several issues with audio quality during the session.

However, the information is still gold and definitely worth a listen.

It's also worth noting that all links and resources mentioned in today's

episode will be available in the show notes, which you can find linked

in the video description below.

Good morning, Dr.

Ozyigit, thank you for joining us today.

Would you just quickly like to introduce yourself?

Tell us who you are, what you do, your story, that sort of thing.

Uh, good morning.

Yes, absolutely.

Yes.

Thanks for having me.

Uh, it's, it's my pleasure to be here.

Uh, my name is Ahmet Ozyigit and I was born in Cyprus.

1981.

I grew up here and got my high school degree and everything and kind

of, um, headed to the, the States for college and I studied there.

Uh, initially I got my degree in economics, I got my master's

degree in economics and then got my PhD in economics.

So kind of went down the whole economic pathway and then, you know,

um, medicine started intriguing me and, you know, I kind of got into it.

Because of my parents, essentially, because of their, um, their field,

their hospital of infertility.

So, I got into it, I initially started helping out with them

with patient coordination and, um, you know, infertility always

was something of a passion.

So I had my master's degree in clinical embryology and I have a

postgraduate diploma in endocrinology.

Now I'm a, uh, I'm doing my fellowship in anti ageing and metabolic medicine with

the A4M, the American Anti Ageing Academy.

So it's, it's, it's, I do come from an eclectic background, let's say.

Yeah, definitely.

What drew you to functional medicine?

Cause obviously A4M has got a very strong functional medicine

sort of component to it.

Um, and, and what, I suppose it's one could argue that anti ageing medicine

and functional medicine are, are root cause medicine at the heart in any case.

So what drew you to that specifically?

Well, um, you know, like when you go to medicine, when you

go to medical school, you go through medical school, you do your research,

you do your studies, you do everything, and then you're taught a certain way.

And then you look at research, you look at data, you look at, um, you know, like,

um, how things work in real life as well.

And you're kind of like, okay, you know, like, maybe not everything that I learned

in medical school is exactly what it is.

And maybe there are certain other things that could be incorporated.

It doesn't have to be either this or that, you know, like, there are

certain components of this, there are certain components of that.

So functional medicine is something that, that does work and.

I do believe there are quite a lot of things that we can incorporate

into our lives without compromising the medical field as well.

So, you know, that kind of drove me into it because, yes, there are certain things

that we can do to improve our lives.

And we don't have to, you

know, take sides like 100

percent on the medical side or 100 percent on the functional side.

You know, it's, it's always a mix between things.

And so.

You know, as long as there are components that help, uh, help us live healthier

lives, better lives, then I'm all for it.

Yeah.

No, definitely.

I think that there's too much of a divide between sort of quote unquote, Western

and functional medicine or traditional medicine and functional medicine.

At the end of the day, it's just medicine and biology that works

and one is just looking maybe more.

Yeah, just at the root cause slightly deeper looking at the reason why something

is happening opposed to just trying to treat the issue pharmacologically

with some sort of drug intervention.

And you know what, like at the end of the day, you know, like the first

thing of medicine is do no harm, right?

It's like, as long as you don't do any harm, as long as you are within the safety

margins of things, there are things that work, there are things that are safe.

So as long as you are being safe.

Safe as long as you're not doing any harm.

I think that kind of, you know, like there are things that work that are safe.

There are things that have the potential to work and they're still safe, so

you can kind of experiment with them.

But there are things that can potentially cause you harm, so you

don't really wanna experiment with them.

So that's kind of where I am.

And then you are sort of your foray or your, your move into sort of

broadly speaking fertility medicine.

Was that just a direct res, uh, result of your parents being in that field?

That is correct.

That is correct.

Yes, absolutely.

Because initially I was helping out with the patient international patient

coordination and I was helping out with, you know, like coordinating the patient's

treatments and so on and so forth.

And, you know, like, the more you get into it, the more you delve

into it, the more things you see, you know, like, it's fertility is

like this very, very broad fields.

So, yes, I, I.

You know, like I, I got interested and I started reading up on it.

I started doing my own research and then I said, you know, why not, you

know, like do a proper study on it.

Yeah.

Fair enough.

And today's topic, we're obviously going to be talking about, uh, oocyte ageing

and female infertility specifically.

To start off with, I think we should maybe just look at what's, as you well

know, the, the hypothalamic pituitary gonadal axis and how that sort of starts

to really set the scene for fertility in general, especially in women.

Um, would you like to just give the audience a brief

overview of, of that system?

Absolutely.

Um, yes, I'll, you know, like, um, I hope you're not overemphasizing the word brief.

This can, you know, this can take a bit more than a brief, but

yeah, I'll, I'll try to be brief.

Okay.

So, um, when you're talking about the whole, um, hypothalamic pituitary

gonadal access, um, you're talking about the, the female endocrine system,

and you're talking about how the hormones work, how they interact and.

When you're talking about female fertility, one thing, um, there is

one crucial point that we all need to understand, and this is that

women are born with all the eggs that they will ever have, right?

Um, there's no, um, there's no reproduction of that.

There's no, they don't, these eggs, these follicles, they don't grow in number.

And it is kind of what it is.

So you're just born with a finite set of reserves and you just keep using them up.

And I think that's very crucial to understand female fertility.

So women are born with all the eggs that they will ever have.

And another interesting point is that ovarian reserve actually

reaches its maximum level.

Um, which is about 6 or 7 million follicles, and this is reached

at, um, 16 weeks of gestation.

So, a girl actually has her highest level of ovarian follicles before she

is even born, and that's surprising.

because, um, you know, you're, you're still a fetus and at the

time of birth, an average female will have about 2 million follicles.

So you go from six to seven.

in the womb down to 2 million when you're born.

So you're actually, you've used up more than half of your

follicles before you're even born.

So there's quite a lot of wastage.

And I just want to clarify here that I sometimes use them interchangeably,

but follicles are these small cysts that contain the eggs.

So sometimes we use them interchangeably, but not every follicle may contain an egg.

So technically they're not the same thing when it comes to, um, numbers.

So, um, you have.

2 million follicles at the time of birth, and that's when things come to a stall.

So at the time of birth, there's obviously no potential for pregnancy.

There's no activity of these oocytes.

There's no potential for pregnancy until the girl hits puberty.

And before puberty, these follicles, they exist as primary follicles,

and they're just in a solid state.

They're just frozen in a solid state.

So once you reach puberty, then there is going to be a series of events that

initiate all the hormonal activity and pituitary glands in the brain is

responsible for propagating these changes.

And your pituitary glands, what it does when you hit puberty is

it initiates the secretion of hormones known as gonadotropins.

And these gonadotropins, these are, um, the follicle stimulating hormone and

luteinizing hormone, the FSH and the LH.

And these gonadotropins, they initiate certain physiological changes.

These involve production of sex hormones by the ovaries and, and then

when, that's when you start seeing an increase in, uh, the level of estrogen.

Sorry to interrupt you.

What triggers the onset of puberty?

Uh, when In a, in a girl's maturation, will she start to see that increase

in FSH and LH, if that makes sense?

What triggers that, that signaling to start occurring?

It's kind of abrupt.

So it's not really well known what it is exactly.

It's kind of, it, it just, it just changes and it, and these signals,

it probably depends on a lot.

Okay.

You know, the interaction of the hormones kind of depends on the level of maturity.

I am not 100 percent sure what it is exactly.

So I do believe it's kind of abrupt and it just happens and it starts.

Yes.

So, you know, you start getting the, these boosts of FSH and LH and the

FSH and LH, which we're going to talk about it in a little bit, but.

You know, with these FSH, um, you, you start secreting estrogen.

Your, your ovaries are, you know, they're, they are getting

ready to release a follicle.

They're getting ready for ovulation.

So there's going to be more estrogen.

So estrogen secretion will help with breast development and the

maturation of the reproductive organs, the vagina, the ovaries and

the uterus and so on and so forth.

So, yeah.

Once you complete these changes, you will have reached sexual maturity, and

that's when you are able to get pregnant.

That's when you are able to ovulate.

So, yes, maybe, um, you know, like, I wasn't able to completely

and perfectly answer your question of what kind of triggers it, but,

you know, like, I do believe it's, it's kind of an abrupt change.

So, um, what this starts happening around the age of 12,

um, which is called menarche.

So the first period of a girl, um, is around the age of 12.

And that's, uh, that's called menarche.

And consider, uh, we just talked about your ovarian reserve having

2 million follicles at birth.

And considering that you start having a period around the age of 12, so

that's when your menarche sets in and menopause, you reach menopause

at the age of 51, approximately.

So that gives you about 39 years of menstruation, right?

So I actually did the math for my book.

So bear with

me.

That's fun.

On average, it comes down to having, being, menstruating

about 468 times over your lifetime.

Right?

That's

incredible.

So given, right?

And given you have 2 million follicles at birth.

And given you only, um, ovulate about 468 times, so statistically speaking, each

follicle, each one of these 2 million follicles, they have a chance of about 0.

02 percent of reaching ovulation.

So it's, it's quite a wasteful process.

We don't really necessarily know why there is so much wastage, but there is

on average, um, we know that a woman loses about 1000 follicles a month.

And only one of these follicles will reach ovulation and give us an egg.

So, uh, one in 1, 000 will reach ovulation, will have

the potential to fertilize and that's, that's pretty much it.

So, um, this is just a brief overview to understand what an ovarian reserve

is and why we're limited with a finite, finite set of reserves.

So a woman is born with it.

There is so much wastage along the way, and I know we're going to talk

about oocyte ageing in a little bit, but you know, I think it's really

important for our listeners to appreciate that oocyte ageing, yes, it is a

problem, but the wastage in ovarian reserves, it's even more of a problem.

So combining that with oocyte ageing, you know how difficult it

becomes for women to get pregnant.

Definitely.

Just to interject very quickly while we're sort of talking.

discussing this, uh, preemptively.

Do you think Girls are sort of hitting menarche that or entering puberty

earlier on than they were and do you think that's sort of cause for concern?

Generally speaking is that an environmental issue potentially just

sort of more Xenoestrogens floating around those affect the onset of puberty.

I do believe so Yes, because there is a trend towards it, right?

You know, like it, it used to be around 13, 14.

The, the age of menarche used to be about 13, 14, then, then 12,

and then we're seeing 11, 10, 9, 8-year-old girls hitting puberty.

And that, that is definitely a problem because you haven't really developed,

you haven't completed your development.

When you're eight years old or nine years old, you're not ready to have

a period when you're eight or nine.

So, yes, and an early onset of puberty is becoming a problem.

And yes, um, we're, we're blaming a lot of things, environmental factors, where

lifestyle changes because, you know, um, obesity and what we're eating, um, you

know, um, steroid chickens, I do believe that, you know, like it does, it does have

a lot, a lot of roles, what we're eating.

And people are becoming more and more sedentary.

Children are not really playing outside, you know, like they're, they're

playing on their tablets all the time and there's more sedentary lifetime.

There's less exercise for sure.

And there's more hormonal way of feeding your children.

You know, um, there's a lot of things that are infused with, with hormones.

and junk food.

So yes, of course, I think lifestyle is definitely the main factor here.

That's driving it.

Yeah.

Yeah.

Sorry to, to interrupt you.

I just thought, uh, I said, okay, that was

perfectly fine.

Yeah.

If you want, um, I can just go ahead and, um, you know, that kind of perfect.

Yes.

About what happens in a normal menstrual cycle and how the

hormones interact with each other, what this FSH and LH do and how estrogen, you

know, increases and so on and so forth.

Yes, please continue.

Um, so let's say you've, um, you know, as, as a female,

you've just had your first periods, you know, like you've, you've hit a

menarche and you started ovulating and you started having your period.

So what happens?

in this normal menstrual cycle.

So it's called a menstrual cycle.

It's composed of two components, the ovarian cycle and the endometrial cycle.

The ovarian cycle is kind of what happens that helps grow and mature those oocytes

and that makes them ready for ovulation.

And the endometrial cycle is what happens in your endometrium, kind of prepare the

environment for the embryo to implant and, you know, be able to survive.

So, at the beginning of this menstrual cycle, Uh, the, your

follicles are still quite small.

They're at their baseline.

And that's one thing that we're going to talk about further down the road.

I think when, when it comes to testing for ovarian function, for

ovarian activity and why we test certain hormones at certain times.

So at the beginning of a menstrual cycle, your follicles are quite small and they

have not developed and they only release a very, very small amount of estrogen.

And during this stage, when the follicles are quite small, they rely

very heavily on follicle stimulating hormone, as the name suggests.

Follicle stimulating hormone is released from the pituitary gland to, um, stimulate

the follicles so that they can grow.

So FSH is one of the gonadotropins that we just, um, talked about briefly.

FSH during this follicular phase.

This stage is called follicular phase when the follicles are small and they start

growing and FSH is produced in very large amounts and the follicles are quite FSH

dependent for their growth at this stage.

As the follicles become larger, they develop a little bit more, they do

secrete greater amounts of estrogen.

And in the meantime, you do have this other enzyme called

aromatase, which is activated when FSH levels are slightly higher.

So, that also kind of helps with estrogen synthesis as well.

So, around mid follicular phase, around day 7 or 8 of the menstrual cycle,

there's going to be a sharp increase in estrogen because the follicles are now

growing, they're developing, they're secreting more and more and more estrogen.

So this elevated estrogen inserts a negative feedback on the FSH.

So the brain senses that there's enough estrogen, meaning your follicles

are developing, everything is order.

So it kind of needs to slow down the FSH secretions because you

just don't need them anymore.

So your FSH starts to decline from that point onward because it's no

longer needed for follicle development.

It's still there, you know, it's not, it doesn't go down to zero, but you

know, like the, it's, the follicles are not as FSH dependent as, as, as

they were within the first few days.

It's a bit like a dimmer switch.

It's been sort of turned down because the need's not there.

Absolutely.

Absolutely.

What happens next is one of your follicles.

This is this is not an IVF cycle.

This is not a medicated cycle.

This is what happens in a natural menstrual cycle.

So what happens next is one of your follicles.

This is called the dominant follicle, and it will reach an ideal size,

you know, like before ovulation around the around 15 millimeters in

size, 15 or so millimeters in size.

With the level of estrogen being released, you're going to end up having a surge in

the level of your luteinizing hormone, LH.

This is another signal that the body can now start preparing for ovulation.

And then you start seeing an increase in progesterone and so on.

So, we start out with a very small follicle, FSH dependent.

So, with large secretions of FSH, the follicle starts growing and developing.

And then it starts secreting more and more estrogen.

And as it's, uh, secretes more estrogen, what you're going to see is an LH surge

when the estrogen level becomes a critical at a critical point, you're going to

have an LH surge, which will bring on another cascade of events, um, you know,

that will prepare you for ovulation.

So this is pretty much the series of events that happen in a menstrual cycle.

So, um, how do you know that it's, everything is working well?

I guess, you know, this kind of brings us to the testing, right?

Yeah, definitely.

I kind of briefly mentioned earlier that there is a specific

time for testing for the hormones.

And, you know, like we also need to know that, you know, like standard

testing with like, not every woman is just going to go out there and get

tested for their ovarian activity.

If there's no problem, you know, if you are able to get pregnant, there's no

reason for you to get tested frequently, you know, from time to time you might get

tested just to see your ovarian activity.

Just to see your ovarian reserve, just to make sure that everything is

working perfectly from time to time.

You know, like you do need your checkups.

You, you do need to have your health screenings.

But most of the time when women need the feel, the need to, um, get tested is if.

Something's going wrong.

You know, if not, everything is going right.

Let's say, you know, you've actively trying to conceive for about a year

and you're not getting pregnant and, you know, like you think something's

not right, then you that's when you usually go and get tested.

So this one year period is not just a random number, you know, there's a lot

of evidence, there's a lot of research into it, and it shows that, you know,

most women, most couples, when they try to conceive, they will be able to

conceive within a year of actively trying.

I was just going to ask, when do you sort of start looking at the, the

male partner versus a female partner?

Is there sort of an order of operations there?

Or do you, do you generally start with the male?

Because obviously it's easier to figure out, or do you just

generally go to the female first?

Yeah, well, you know, like, um, tech, like, Normally, rationally

speaking, yes, um, you know, like, uh, the, the male side is easier to test

because it's just, you know, like, manually producing the semen and then

just seeing the testing the semen.

So it doesn't involve any blood work.

Doesn't involve anything invasive or anything like that.

So that's usually that does need to be the 1st thing, but

usually when couples come in and.

They're concerned they're not able to get pregnant.

It's usually everything at one go.

So you do female testing and male testing at the same time.

That's usually what we do, but you're right, you know, like in, in

terms of, you know, where you would start, you, you might want to kind

of, you kind of want to start with the obvious ones, the easier ones.

If there is a problem with the female patient, you know, if there's an obvious

problem, if there if, if she has, if she's having irregular cycles, right?

If she's just having very short cycles, if she's having certain, um,

symptoms and signs that give you.

You know, um, an indication for testing, then that's probably where you start,

but you test the male as well, just to be on the safe side, because you

also don't want to skip any testing because, you know, you, you might

think, yes, it's a female problem because she's having very short cycles.

Yes, it's a female problem because she's having very long cycles.

She's having, you know, like, there might be something there, but there might be

something else on the other side as well.

You don't want to skip that.

You don't want to miss that.

So.

It would need to be a complete testing in, in my opinion.

Okay, perfect.

You know, I think that when, when we define infertility,

we define it as actively trying to conceive for about a year.

And I think that applies to women.

younger than 35 years of age, because when you're younger than 35 years of

age, you do have a year to wait, you know, like you can stand to wait a year

to just to see what what's going on.

And maybe you're going to get pregnant naturally.

And you know, most of the time, women do.

And so if you're about 28 years old, 30 years old, 31 years old,

and you know, like you, you've been trying for a few months and

it hasn't worked, then, you know, there's usually no cause for concern.

So you can, you can wait up to a year and see if you do get pregnant

naturally, then that's fine.

If you don't, then that's when the testing should start.

But if you're about the age of 38, 39, 40, and your biological clock is already

ticking, you know, and we know that you're all already born with a very,

very limited ovarian reserve, you're quickly, um, losing those reserves.

So, yeah, you don't want to wait a year when you're 41, and then you

become 42, and it's gone, right?

So you don't want to wait for a year.

You do want to wait for maybe a few months.

And then after a few months, if things aren't working out, then you

do get tested and just see what your options are going to be from there.

Those tests going forwards, I think we'll chat about next.

So what are the first steps in sort of really breaking down?

Where the issues are and yeah, how do you sort of figure out which tests

are best to run for the obviously the woman specifically in this case?

Well, we usually start out with the basic panel to be honest, the

basic panel would involve just to see how ovulation is, you know, work, like

how your hormones are interacting, what your baseline hormone levels are.

Are they suppressed enough?

Are they elevated?

Are they, you know, like, who's, who's.

They all mean different things.

If your hormones are at their baseline levels on around day two or

day three of the menstrual period, we start testing the hormones.

So if your hormones are at their baseline levels where they should be, fine.

If their hormones are elevated, there might be a problem with the

feedback mechanism signaling that your ovaries may not be working fine.

So you kind of your starting point would be with the semen analysis on the

male side, because that's just easy.

You just get it out of out of the way for females at the starting point

would need to be day 2 or day 3.

So day 2 or day 3 of the menstrual period, day 2 or day

3 FSH, LH and estradiol levels.

So these will show us.

What the baseline levels of FSH, LH, and estrogen are, and these

are the hormones that are directly involved in the feedback mechanism.

So, at the beginning of the menstrual cycle, while they're still bleeding,

while the follicles are still quite small, these hormones are expected

to be at their baseline levels.

These are relatively, um, low because follicle development hasn't started yet.

So you just want to establish a baseline and see where the hormones are.

But at the same time, you do have this gold standard testing for

ovarian reserve, which is called AMH, the anti malarian hormone.

And the reason why it's a gold standard test is because the AMH

is secreted directly from the cells that surround the follicles.

These are called the granulosa cells.

So these cells, they directly secrete the AMH.

So AMH is not subjected to any feedback mechanism like FSH or LH.

So FSH and LH, they are subjected to a feedback mechanism.

They could be affected by other hormones.

They could be affected by other things, and it could take time for them To show

changes, you know, that you might get a delayed response with FSH and LH.

With AMH, you don't have that problem.

It's secreted directly from the cells that surround the follicles.

So this is a more reliable indicator of your, um, of your ovarian reserves.

And it can be done independently from the day of the menstrual cycle, because it's

not involved in the feedback mechanism.

And it's more or less, um, same throughout the cycle.

So AMH testing is one of our gold standards.

It could be measured in nanograms or picamoles, you know, it just depends

on where you get the test, but, you know, we will be able to interpret

the test based on the levels.

And you also want to, um, get tested for certain other hormones that are

not directly involved in ovulation, but also, you know, they might be involved

in how FSH and LH, um, are secreted.

It could potentially mask them.

It could potentially, um, elevate them.

So you do want to measure prolactin levels for instance, and thyroid

function for instance, because these are also derangement.

These hormones also can potentially affect female ovulation.

Sorry to interrupt.

What specifically does the, how does the thyroid or potentially a hypothyroid

or hyperthyroid state affect fertility?

Because obviously that is a hormone that a lot of people tend

to struggle with, I'd imagine.

So what are the, maybe the mechanics there, specifically?

. Dr Ozyigit: Um, well, okay, that's a good question.

One of the things is because hyper or hypothyroidism, because you know,

like we, thyroid is the gland that modulates your metabolic activity, right?

And metabolic activity is not like when we talk about metabolism, um, a lot

of people think it's just, you know, like a way of burning your calories.

It's not just that there's a lot of metabolic pathways.

There's a lot of me metabolic activity.

And you know, as a biochemist, you.

Definitely know all these different pathways.

So, um, you know, hyper or hypo thyroidism in terms of your metabolic activity.

If it's not working fine, it could potentially interfere

with your other hormones also.

They are being secreted from the same glands, so TSH, um, is secreted from

the same gland that secretes FSH.

So they are both being secreted from the pituitary, so some sort of interaction

is bound to happen at that level as well.

In terms of prolactin, I am not exactly sure the pathway.

Oh, that's fine.

Oh, it masks, but elevated prolactin levels, they do.

I'm not exactly sure about the biochemical pathways that are involved,

but elevated prolactin levels, they do tend to elevate FSH levels as well.

Okay.

And that would have a, would that then overproduce potentially follicles

or sort of drive too much follicle formation if there is an excess in FSH?

It's kind of the opposite, to be honest.

It's the, it's the opposite.

It's drives it down a little bit.

You know, like when in, when in menopause, when a woman enters menopause, there's

a lot of FSH production because there is no feedback coming from the ovaries.

So, um, some sort of along the way, something goes wrong and you're

not getting that ovarian response, but your FSH still gets elevated.

Oh, okay.

I'm with you now.

All right.

Now that makes sense.

So then continuing from where we were, um, we've got the, the LHA, the LH

and the FSH being, uh, secreted and that causing the cycle to continue.

And, um, you know, like with, with terms in terms of FSH and

LH testing, you know, like one of the, one of the benchmarks of, for example,

uh, polycystic ovarian syndrome used to be, you know, LH greater than FSH.

And so that kind of ratio used to signal to us that, you know, um,

there could be PCO and that's still.

You know, in the clinical sense, it is still still a relevant ratio

that we do that we might look at.

But obviously, there are other testing now with the AMH testing

and you do an ultrasound scan and you are able to see PCO.

And if there's any signs and symptoms of PCO as well, but essentially

these tests, they do give you a pretty good idea of where we're

standing in terms of ovulation.

FSH, LH, estradiol, AMH testing, prolactin levels, and TSH, and 3T4, just to see

if there is any other interactions that could be jeopardizing the ovulation.

These would be the initial tests, these would be the standard tests that you

would be going through if you do suspect there's a problem somewhere along the way.

And an ultrasound scan, baseline ultrasound scan, is also quite important

to visualize the preantral follicles, the preantral follicle count, how

many follicles you have in each ovary that are getting ready for ovulation.

That is quite a good indicator of your ovarian activity as well.

And we know that, you know, um, antral follicle count, does correlate

very well with the AMH level.

So when you're testing the AMH, and when you're looking at the antral

follicle count as well, you know, then you do have a pretty good idea.

And sometimes there are other things that could be a Affecting your AMH level, that

could be affecting your antral follicle counts, taking hormonal supplements,

taking the birth control pill or vitamin D deficiency, even vitamin D deficiency

could potentially mask your AMH level.

So, sometimes you might see a very low AMH level and then you go and check

the antral follicle count is actually higher than what's suggested by the AMH.

So, All of these clinical correlations, all of these things, you kind of

cannot just do one measurement of FSH and LH and say, Oh yeah,

you're, you're perfectly fine.

You're ovulating.

You're, you're fine.

No, you can't.

So all of these other things that could be potentially interfering, you

do need to see a complete picture.

So the standard testing would definitely need to involve your hormones, the FSH,

LH, estradiol, AMH, um, your thyroid function, your prolactin levels, because

that could also get in the way, but also an ultrasound scan just to see

if there's, if, if everything is okay in the ovaries, if the ovaries look

okay, if, if you do see a certain level of antral follicles, if, if there are

any cysts, you know, if there are any pathologies, if there are any endometrial

polyps, if the uterus looks okay, you know, see these types of things could

also potentially cause infertility.

So it doesn't always have to be the hormones.

Um, we usually, you know, like the hormones are, are usually the first

suspects, but there are with men.

It's, it's much easier because you just check the sperm and that's it.

That's, that's the contribution of the male side.

But with the females, there's so many things that could potentially go wrong

that you kind of, yes, you start with the standard testing with the hormones,

you look at the ovaries, you look at the uterus, and then there's so

much more that you can actually do.

You know, like if things are still not working out, if there's

nothing that you can explain there.

They might even go through an IVF cycle or one or two, and then you

say, okay, well, this is not working.

There might be something else.

Is it an immune system issue and overactive immune system?

Is it something else?

You know, then, then you start looking into other things as well.

Okay.

And from immune system standpoint, maybe we should briefly just touch on that.

Are you just looking for an overactive immune system and you're looking

at markers such as CD57 and those sorts of markers specifically?

Yes, well, you do, you do check CD57, sometimes the natural

killer cells, but then again, you know, some of the markers that you test.

Yes, they will potentially, um, point to inflammation, potentially, or they could

potentially point to an elevated level of activity, but it doesn't necessarily mean

that that's the problem with the uterus.

That's the problem with your, you know, like, um, with the natural

killer cells, we, we do have that problem because natural killer

cells, yes, they have been tested.

Yes, they do correlate with, um, implantation failures.

Um, but the natural killer cell population in your blood does

not necessarily correlate with the natural killer cell activity.

in the endometrium.

So when you test the natural killer cell activity in the

endometrium, you're not going to have the same results as the blood.

So you don't necessarily know what's causing the issue.

You don't necessarily know that all the tissues are subjected

to the same inflammatory levels, inflammatory, inflammatory markers.

So that's also a problem.

Yes.

Yes.

inflammation is a problem.

Yes.

Immune system is a problem.

But where does it start?

Where does it end?

How, how much do you actually test these people and how much

of that test is actually going to pinpoint the problem that's going

on in the reproductive system.

And sometimes you just do certain , you just take certain prophylactic

measures against the possibility of an overactive immune system.

Rather than going through and doing an extensive panel of immune testing.

So sometimes that's just a wiser method because otherwise you're

going to end up spending tens of thousands of dollars or euros and just

maybe have nothing to show for it.

So, you know, it kind of needs to come down to a cost benefit analysis

sometimes what you are able to identify with these tests and how much.

What you identify, how much that can be interpreted in terms of

the reproductive function and how much it actually helps you.

And sometimes, you know, taking some certain prophylactic

measures could potentially, um, just overcome the problem.

Okay, perfect.

Should we move on to oocyte, oocyte ageing now?

Uh, specifically,

absolutely.

Yes, absolutely.

So oocyte ageing, um, you know, like, obviously we all age, we were born,

we're ageing, we're going to die.

That's, you know, that's, we, we know that, right.

And our cells also age, but ageing becomes a more of an issue because

it's, we know that there are.

Finite set of X, and we don't want them to age prematurely, but we

know that they do age as well.

We just don't want them to age prematurely.

We just don't want them to, you know, like, stop working

when they should be working.

So, um, we all age, our cells age, oocytes also age.

That's just a biological fact.

And only so much that we can do about it in terms of lifestyle interventions,

supplements, and, you know, like, better living, healthier living in general.

But in terms of oocyte ageing, we can look at, look at it through, um, two different

pathways or two different dimensions.

And, you know, like, they're not necessarily independent, these dimensions,

they're not necessarily independent from each other, but they're like distinct,

distinct things that are happening.

And first, You have increased frequency of errors during chromosome segregation,

segregation during the process of meiosis.

So you have meiosis one, meiosis two, which happens

at the time of fertilization.

During both processes, you could have things go wrong.

But as we are ageing, the frequency of errors happening during chromosome

segregation, they do tend to increase.

So incorrect chromosome segregation during cell division gives you

chromosomal errors, and these errors are known as aneuploidies.

And you do observe this in the clinical setting as well.

You do observe this when we're doing an IVF cycle.

If the patient wants to do a pre implantation genetic analysis, pre

implantation genetic testing, PGT.

And when you do PGT on a woman who is, um, you know, like 27, 28, um,

just for screening or maybe for gender selection for whatever purposes.

When you do the screening, you see that most of these embryos are quite healthy.

Most of these embryos, but when I say healthy, obviously, I'm talking

about chromosomal aneuploidy is that you can actually see with PGT.

So, when you do, when you run tests on these embryos, you do see that maybe.

80 percent 90 percent of these embryos are free of main chromosomal aneuploidy

is, but when you're doing the same thing on a 40 year old woman, you

see 60, 65, almost 70 percent of the embryos having some sort of a genetic

problem and monosomy, a trisomy, um, you know, trisomy of 13, 18, 21.

You know, Patao, um, Edwards syndrome, Down syndrome, things like that.

You do start to observe these in a more frequent manner.

So yes, this is a problem.

So it's not just a research talk.

It's not just, um, something that we are saying technically,

this is what's going to happen.

No, this is what we see in, in the clinical setting.

This is what we see when we test these embryos.

As you age, the eggs do age and chromosomal errors become more prevalent.

So, chromosomal segregation, errors of chromosomal

segregation become problematic.

And, um, you just have higher margin of errors.

And this obviously increases the rate of infertility.

And this also causes more miscarriages.

This causes pregnancies with babies with chromosomal errors.

So then that's your standard ageing process.

There's nothing new, right?

That's your standard ageing process.

And that's what we would expect.

That's why you see a lot of women miscarrying at the age of 40, 41, 42,

but that rate is going to be much smaller in people in their 20s or early 30s.

And you also have another issue with advanced maternal age.

And that's the fact that ageing alters the presence and activity of certain

genes that are involved in cell cycle regulation, the spindle formation,

integrity of the organelles that are found in your cytoplasm, such as the

mitochondria, and the gene regulation.

And then, obviously, when you have these problems, and you're going to have other

problems potentially going downstream in terms of your oocyte integrity.

So, Keep in mind, oocyte is just like another cell, right?

So if you do have problems, if you do have mitochondrial issues, if you do have

problems with the cell cycle regulation, then it's not going to be a viable cell.

And that will show in terms of the reproductive capacity of the person.

But also, it just doesn't mean, just because we're talking about

advanced maternal age, it doesn't mean that this is always the case.

We also have Issues that are not associated with advanced maternal age.

And that's when you have environmental toxins, chemicals, oxidative stress,

these kind of come into play.

And we know from scientific evidence, we know from the research that we're

reading, that oxidative stress and inflammation tend to go hand in hand.

And when there is an oxidative stress in the body, there is an imbalance

between free radical formation and how capable your cells are to clear them.

So you do have the free radical formation, but you don't necessarily

have the means to clear them out.

So you do have that the antioxidant

potential is not there.

Yeah.

And you know, like Initially, we all thought, you know, like more antioxidants,

you know, like the more the merrier.

That's when the hype was back in like 10, 10, 15 years ago, you must remember

this, you know, like, we thought, like, antioxidants were like the,

the solution to everything because we have this oxidation, oxidative damage.

We have this oxidative stress.

So we're antioxidants, but.

Also, you know, like we, you know, like we, that's not how things work.

You can't just like keep infusing people with antioxidants and expect

that everything will be resolved.

Because some of the, um, some of the processes in our bodies, they

rely on that oxidative stress.

They rely on the free radicals.

So your immune system works better.

So things that actually, you know, like you'd have the drive for your body to make

more effective use of the immune cells.

So you cannot just have all antioxidants and, you know, no oxidants whatsoever.

So you have to, you have to have a nice balance between them, but obviously

it doesn't mean that your oxidative, this oxidative stress cannot be bad.

Uh, there are quite a lot of studies.

I made some notes of some of these studies here.

And cause I obviously I can't remember them all, but oxidative, there are studies

that studied, um, oxidative stress.

And the relationship between oxidative stress, the inflammatory markers

and premature ovarian insufficiency.

Another study found that interleukin 6 and 21 were significantly higher in women

with premature ovarian insufficiency.

These being pro inflammatory cytokines, correct?

Absolutely.

Yes.

And, um, also there's another study that found, um, higher tumor necrosis

factor receptor two levels in women who've entered menopause prematurely,

uh, compared to the, the, the, the other subject compared to the healthier women.

Let's say healthier in quotation marks.

So all, all of these compounds, these molecules, for maybe people who

don't understand more, either what are called protranscription factors

or inflammatory cytokines that are driving an inflammatory process that

is then damaging the oocyte in these older, should we say, individuals.

Is that correct?

Absolutely.

Absolutely.

Because you know, like with, with the pro-inflammatory markers, you, you,

you got, you kind of have to have, you know, like pro-inflammatory cytokines.

You need to have the post-inflammatory cytokines as well, just to clear them out.

But sometimes in oxidative stress, in chronic low grade chronic

inflammation, you do have these pro-inflammatory cytokines that are

slightly elevated there that are.

Higher than what they should be and they're chronically higher,

so there's nothing to stop them.

You know, like, normally, when you have an injury, you have those pro

inflammatory cytokines reaching, you know, reaching out and helping with

the inflammation, but also when, when, you know, the damage is being repaired,

you do have the cytokines, you do have the other inflammatory cytokines.

Okay.

Post inflammatory or corrective cells that come in and kind of help clear out that

inflammation, you know, so you have the pre inflammatory markers and the markers

that help clear out this inflammation, but in chronic inflammation, we're

finding out that, you know, like the clearing system is not necessarily there.

So when you have this low grade inflammation, when you have these pro

inflammatory cytokines there chronically, they do affect your oocyte quality, they

do affect your oocyte count as well.

And, you know, like, they also can, you know, like, they're also

associated with a lot of other things.

You know, like, if you have inflammation, you know, like, there's a more

recent term called metaflammation.

It is used for chronic inflammation that affects your metabolic function as well.

And you know, like the, the risk factors for this are usually obesity,

insulin resistance, type two diabetes, and these are all risk factors and

with chronic adiposity, the adipose tissue kind of changes its form, starts

creating pro inflammatory cytokines and this inflammation, it doesn't, it

doesn't get resolved, it's persists for a prolonged period of time.

And you know, like you, you see a lot of people.

Struggling with weight loss, infertility, fatigue, just name it, you know, like,

so yes, inflammation in the body does affect a lot of organ systems and the, the

reproductive system is just one of them.

And the function, you know, mitochondria, the powerhouse, the energy producer of

the cells, um, the number of mitochondria and their efficiency also tend to decline.

Both with age and also with unhealthy lifestyle choices.

You know, like we know the usual suspects to fast food.

not exercising enough, excessive alcohol consumption, cigarette

smoking, you know, exposing yourself to toxins, drugs, things like that.

So yes, um, unhealthy lifestyle choices, um, they do affect how

mitochondria are functioning as well.

But not just the mitochondria.

Um, keep in mind that if you're not getting enough nutrients, if you're

not getting enough protein in your diet, if you're not getting the healthy

fats, then you're compromising your health in other departments as well.

And your body is all connected.

It's not just one thing, right?

Your body is, is, is a connected machinery.

So a problem in one side does potentially affect how other

parts are working as well.

For example, there are studies that show poor sleep quality is also

associated with low estradiol levels.

And when you have lower estradiol levels, you know, like you do run the

risk of having an infertility issue.

So even sleep, even poor sleep contributes to infertility, so you cannot think of

the reproductive system as being this independent system from everything else

and, you know, just say, Oh, you know, like, if you, if you, if we were talking

about this, um, 40 years, 50 years ago.

We would probably say, you know, like, yes, women are born with a finite set

of reserves and, you know, as age, they age, they, they decline in numbers.

So that's that, you know, whatever, but now we, with research, with

more evidence, with more research being done in the field, a lot of

things in our systems are connected.

And a lot of lifestyle factors are affecting our

health at the cellular level.

And, you know, that's why we're talking about New and shiny supplements that

come out, you know, like, because we want to improve our cellular health, but we

need to know there's not just one pill.

You take a pill and it makes it go away and makes things.

Okay.

You have to establish your baseline as well with healthier lifestyle choices.

So, yes, in terms of.

oocyte ageing looking at something that does come with age.

We're looking at the genetic defects.

We're looking at the accumulated DNA damage.

We're looking at things that can go wrong in terms of ageing in general.

But we're also looking at things that we all accumulate in our lives,

environmental toxins, chemicals.

things that we do to our body in terms of creating an inflammatory

response, creating inflammation in our bodies through our lifestyle choices.

So it's all interconnected.

And one hormone can potentially affect the other hormones, you know, one organ

system can potentially affect the other organ systems, your immune system, your

exercise has a lot of roles in, in your immune modulation, how you eat has a

lot of roles in your immune modulation.

So good quality of sleep has a lot of value on immune modulation.

So, yes, we are, Talking about something that's just connected.

That's a lot of information.

Maybe for the listener, it would be easier if we could work through a

sort of a hypothetical case study.

So if you have a, someone who is struggling to conceive, they are.

Or they've hit that 36 year mark, maybe they're 36 to 40.

What is your sort of process for taking them through a potential

fertility treatment to try and obviously help them to conceive?

Obviously you will do the initial testing to sort of identify a problem, but from

then onwards, what, what are your most consistent sort of treatment options or

how do you sort of work that process?

Maybe it's the best way of asking it.

Yeah, yeah, yeah, absolutely.

Well, you know, like not every, not every person is going to be the same.

So each patient is unique.

So you kind of like need to get a very, very detailed history.

First of all, you know, like, um, their, uh, social history, their medical history,

you know, like if they had a pregnancy, if they had a miscarriage before, What

other issues they might have, what other health conditions they might have.

So you do need to.

You know, like a good medical history is always, always number one.

You do need to understand the medical history of that person.

You need to understand, um, you need to see that person as an

individual and see other possible connected things that might go wrong.

So a good medical history is where you start.

And, you know, this would include social history, medication history,

previous surgeries, previous accidents, exposures to, you know,

like radiation and toxins and so on.

And then, yes, the next thing would be testing that we just kind of discussed.

You, you do want to see that, you know, the standard testing is there.

Just you, you do want to have a basic understanding.

It is a basic understanding of what you're dealing with because, you know, like.

Just looking at just the hormones, looking at the, um, ovarian activity,

looking at how many antral follicles you see in the ovaries doesn't

necessarily mean that you get the whole picture and you understand everything.

Because all of these things that we just discussed, you know, like, it's

like a world of information out there.

And it's quite a lot of things that are all connected in your bodies.

So, yes, it's not going to give you a very thorough understanding

of what you're dealing with.

But it will give you a very basic understanding of the

potential causes of infertility.

If you do see a very highly elevated of FSH.

And if you do see a very, very low level of AMH, that's going to point

to you that, yes, there is a problem with the ovarian function here.

You know, like, we have, we're looking at very, very highly

depleted ovarian activity.

And, you know, like, if that also correlates with the antral follicle

counts, you know, if you're only looking at an antral follicle

count of 1 with an AMH level of.

less than 0.

1 nanogram and, you know, FSH highly massively elevated forties, fifties, then

you start thinking, you know, this is probably premature ovarian insufficiency.

If we are dealing with a patient who is 36 years of age or 37 years of age, if

everything looks okay, you know, like you look at the antral follicle count.

You see, you know, 9, 10 antral follicles.

The AMH also correlates.

Well, you're looking at an AMH level of 1 nanogram per ml.

And, you know, like, everything kind of correlates together, FSH and LH are

within the expected values as well.

Then you start thinking, okay, you know, like, this is, you know,

like, don't really seem to have an apparent problem with the hormonal

feedback and the hormones and how well the, the all sites appear.

But also, you know, like you have the male side, so you kind of turn to the

male side just to see the semen analysis and see if the semen parameters are

within the values that would allow the patients to fall pregnant naturally.

Because, you know, like if you have less than 15 million sperm cells in

the ejaculate per ML, then, you know, like that's, that's, that's a problem.

If you have 20, 25%, if the morphological numbers are quite low, you know, if,

if, if there is a normal morphology is less than four, then that's it.

You do it, start suspecting DNA damage in the sperm as well.

So, you kind of need to take one thing at a time and kind of analyze

what, what you have at hand.

And if all looks well, then it might be the case of, um, unexplained infertility

because we do have a lot of that as well.

Diopathic.

Yeah.

Because you don't necessarily always find something.

There quite a lot of patients in their 30s, they do, the

tests look perfectly fine.

The semen analysis looks perfectly fine.

You look at the angiofollicular count quite good.

You know, the patient has regular natural cycles, no appearance

of PC or polycystic ovaries.

So you don't suspect any problems, but they're still not pregnant.

Then what that's where other things could get in the play.

So what you would do in that case is even though yes, you're not able to explain

it if the patient is quite young, and they do still have some time to, you

know, try things a little naturally.

Yes, you do go down the path of these alternative methods, for example, you

know, when I say alternative methods, I'm not talking about, you know, like, um,

voodoo and magic spells, but, you know, like when you're, when we talk about

health in general, we know that there are quite a lot of things that are associated

with poor fertility outcomes, and one of them is vitamin D, vitamin D deficiency,

you know, lower than normal vitamin D levels are linked with fertility problems.

And one of the research that I was reading about it, you know, like they talk

about vitamin D being the main regulator of this transcription of Hoxa10 gene.

And this gene is the key target gene associated with implantation of an embryo.

On the endometrium.

So for embryo implantation, you do need a proper transcription

of this gene and vitamin D is one of the regulators of this gene.

So if you are insufficient, if you have deficiency of vitamin D, Then

that's, that's when you have problems.

So, even something small, it could potentially, um, impair your fertility.

And also, um, Magnesium.

Magnesium levels.

If you are Magnesium deficient, and sometimes, you know, with

Magnesium it's interesting because only about less than, 0.

9 or something.

Percent of magnesium is actually in your bloodstream.

The rest of the magnesium is either in your bones and it's either intracellular.

So only 1 percent of the magnesium is going to be in your in your bloodstream.

So when you're testing your magnesium levels, you only have an indication

of what's in your bloodstream.

So, maybe you do have a deficiency and you're, you know, like, your bloodstream

is pulling out of this, this magnesium from yourselves just to compensate for it.

And then you test your blood blood

magnesium levels, and then you see everything is fine.

And you think, okay, you know, like, I'm not magnesium deficient

where in reality, you might be magnesium deficient in your cells.

Are you looking at specific types of nutrient testing?

Are you looking at sort of red blood cell testing for some of these markers?

Are you looking at maybe organic acids?

How are you testing for these nutrient deficiencies generally?

Just, just the basic panel, to be honest, just the basic serum markers.

They're not detailed tests.

Okay.

So you just look at.

Just the serum markers of vitamin D and serum markers of magnesium.

Okay.

And when you're looking at sort of specifically, we chatted about

mitochondrial health earlier.

Are you doing anything specifically to improve mitochondrial health?

Looking at some of the.

The processes within the Krebs cycle, so sort of NAD production, are

you, uh, those sorts of molecules, are you looking at improving

function in that respect as well?

Um, yes, we do a little bit, you know, like again, you know,

like these things, you know, like from, from time to time, you do get these, um,

new supplements that are new and shiny and you, they, they promise the world

and then, you know, sometimes they, they might be not delivering everything

they promise, but sometimes there are certain things that do work and I

think, um, NAD boosters are one of them.

And I do, like, I do use NMN myself, the vitalityPRO brand, actually.

I do, I do use NMN myself.

I, I get my, I get my patients to use them.

I get my parents to use them because I do see results with NMN.

I do believe in NMN.

And I do see quite a lot of good results with it, and there's a

lot of research on it as well.

You know, like, it does work.

It does improve certain parameters.

It does help improve certain parameters that could be tested as well, you know,

like, in terms of your energy levels, in terms exercise endurance and things like

that, especially in elder age brackets.

Okay.

I know that NMN in, in younger age brackets may not necessarily

be something that you need.

And there is no need for you if you're 20 years old and healthy and working

out and this and that, you know, like, why would you take NMN anyways?

But, you know, if you're concerned about ageing, if you're concerned about

your cellular health at the age of, you know, like, 40s, 40 plus, then yes, it

is something that you want to look into because, you know, like, you probably

accumulated some damage to your health along, along the way with some excessive

alcohol or tobacco smoking or cigarette smoking or, Environmental toxins and this

and that so your mitochondria, you know, like they might not work efficiently.

They might be, you know, like lesser in number as you age.

And, you know, like, they may not be able to handle the, the, the,

the ROS damage, the reactive oxygen species damage so well as you age.

And the same thing applies to oocytes as well, you know, that oocytes are

also cells and you know, like, um, yes, ageing affects those cells as well.

Ageing affects your telomere length, ageing affects your mitochondrial

function, ageing affects a lot of parameters inside your cells and how

well your cells are handling themselves.

So, yes.

In terms of NAD, I'm, I'm not sure because there is a lot of,

you know, like, it's, it's still new, so we still don't know a lot.

Yeah, definitely.

I believe.

We still need a lot of research.

So, um, yes.

NAD IV injections, like IV infusions of NAD.

I've, I've tried them out myself and I do like to use IV infusion of NAD, for

example, a few days before egg retrieval.

Just, you know, like, just as something that could help with possible.

Yeah.

And that's something that could help with in terms of cellular energy,

because, you know, like, meiosis 2 takes place at the time of fertilization.

So whatever you can give to those all sites before the time of fertilization.

You know, that's something that can potentially help them with the

genetic integrity of the oocyte, with the development prospects

of the oocyte and then the zygote and then the embryo, obviously.

But yes, so with IV infusions, I do a lot of IV infusions before egg retrievals

so that I can still give those cells a little bit more to handle themselves.

And also NMN, I get my patients to use NMN for about at least three months

before An IVF cycle because I do believe, you know, like oogenesis, it's, it's

an ongoing process, the Genesis going from primordial follicles to ovulation.

It's, it is something that takes about 12 weeks.

So, whatever you do to try to affect those primordial follicles, you're going

to have to do it for about 12 weeks so that you can actually see a change.

So, you can actually see an improvement in those oocytes when they ovulate.

So, yes.

NMN, I do use it.

So sort of almost an epigenetic maturity.

There is enough time for a genetic change to actually transcript over.

Absolutely.

And, and the same for men as well.

As we we're talking predominantly about women, about oocyte ageing

here, but for men as well.

You know, like whatever you do, you know, like if you stop smoking like

five days before you provide the sperm sample, it's not gonna do anything.

You know, if you, you know.

If you stop drinking like a day before you produce a sperm sample,

nothing is going to happen.

If you start, you know, eating healthy three days before the sperm temple, it's

not going to work because spermatogenesis is an ongoing prop process.

You know, like spermatogenesis, the sperm development and maturation,

this is the term we use for sperm development and maturation.

And it takes about 70, 75 days.

So spermatogenesis from day zero to, um, you know, entering the ejaculate

as, as, as, as a mature, mature sperm cell takes about 70, 75 days.

So whatever you want to do to affect that sperm cell that came

out on the other end, 75 days later.

You do want to do something, you do want to start doing something way

before those 75 days so that you can actually have some time for those cells

to be affected at the cellular level.

Sure, yeah.

And just while you mentioned the male side of it, do you do anything

to support the male fertility?

Do you use any sort of LH analogs like HCG or anything like that?

Is that not really in your, in your purview as such?

Not too much, not too much.

But, um, you know, like if you do have an issue with the sperm analysis, you

know, like if you do see, if you have azoospermia, patients with azoospermia,

Obstructive, non obstructive, depending on the etiology of the azoospermia, then

there might be things that you can try.

You can try HCG, right?

You can, you can try a number of things, but the success is quite

limited with those most of the time.

Fair enough.

And then just getting back to IVF, uh, quickly, when you really sort

of look at an IVF protocol for, a couple who are trying to conceive,

what sort of other, uh, vectors have you really ruled out at that point?

Did you find that that's generally a last ditch effort or are you sort of

finding that you are utilizing that earlier on in a protocol perhaps?

Look, usually, um, when we're involved in, in, in

things, because like, you know, I guess we do have an IVF hospital.

And, you know, like when we're involved with things, it's usually these patients

who've tried it naturally, who've tried maybe other IVF, IUI cycles, IVF

cycles, and like nothing's working.

So most of the patients that we get is going to be patients who've tried

it elsewhere, it's not working, you know, like they do want to

take a new approach on things.

So it's quite rare for me to see a patient who hasn't really done anything.

From time to time, I do see patients who, who just starting out.

Thanks.

But most of the patients that we do see are, you know, like patients who sometimes

quite experienced with IVF cycles as well, but as a general rule of thumb, when the

patients come in and you see them, you know, like, you do try to correct certain

micronutrient deficiencies as well.

You know, like, if you do see, if you do suspect certain lifestyle changes

can help them, if you do suspect that certain certain supplements can help them.

You know, vitamin D, magnesium supplements, you give them NMN, you know,

there are certain other things that, you know, like we're experimenting with like

quercetin, for example, you know, like it's, it's new in the pipelines as well.

There's some research, there's glycine and acetylsustane that

we, I do like to use them.

There's quite a lot of research on elder population, but there's some

newer research animal studies that show that glycine and acetylsustane

combination can improve all sites.

Quality as well.

So, yes, anything that can potentially help because, like, as we said, you

know, as long as the safety, as long as the safety is there, then you're not

too concerned about maybe not getting the optimal results that you're hoping

for, as long as it's safe, because, you know, like, you do, like, you do

see this patient struggling, you do want to try something with them, and

you do try the one, the things that have been shown to help, you know,

But, you know, like whatever we're talking about is not going to be magic.

Like vitamin D deficiency.

Yes.

Deficiency is associated with poor outcomes.

But it doesn't mean that the higher your vitamin D levels, the higher

your fertility levels, right?

There's no correlation like that.

If you are insufficient, then yeah, addressing that could potentially help

you a little bit, but it doesn't mean that the higher the better, right?

So, well, in, in general, I like my vitamin D levels higher, but

anyway, that's not the thing, but, um, yeah, same with magnesium, right?

Like magnesium levels, you supplement them, you, you try to help that

pathway as well, but it doesn't mean that you're going to correct

all the problems with that vitamin.

So what you try to do is you do try to eliminate the potential deficiencies and

that could be causing the infertility.

So if the patient you believe is deficient in micronutrients,

you go there, you do that.

And then, you know, like if the patient is also suffering from chronic weight

issues, you know, inflammation, chronic inflammation, chronic weight issues,

insulin resistance, type two diabetes, these types of things could also

impair your ability to get pregnant.

So you do want to address those as well.

You know, like if you're looking at a chronic weight problem, then, you

know, like before you, um, go for an IVF cycle or before you decide.

That again depends on the age of the patient.

If you're talking about a 30 year old patient, who is, you

know, um, whose BMI is elevated.

And they do, they can wait a year or two maybe, just to

you know, see how things go.

Then maybe addressing the weight issue is more important than the fertility

issue at that point, because addressing the weight issue might actually

resolve their fertility issue as well.

And so many other things along the way.

So GLP 1 analogs in that case would be my go to and try to.

kind of get that, get them down to a healthier range of BMI and then

address the rest of it accordingly.

So that's one thing.

So like every patient is going to be unique.

So there are certain things that you can do with them and

supplements are definitely something.

That I love and, you know, like, the more research that comes out,

I, I try to follow them can't possibly follow every single thing.

And, you know, but in terms of, um, seeing results, potential results, if

something has a potentially efficacious outcome and the safety product, the safety

profile is, is there, then I will try it.

Definitely.

Dr.

Ozyigit thank you very much for your time.

Would you like to sort of point people to where they could find you?

Oh, yeah, sure.

Absolutely.

Um, you know, like they can Google my name.

Uh, but I work at Elite Hospital, Elite Research and Surgical Hospital in Cyprus.

And that's where my office is.

And Low Cost IVF.

net is our website.

That's brilliant.

Well, thank you very, very much for this.

It's been truly insightful.

And we look forward to having you on again in the future.

Thank you very much.

Thank you for having me.