Understanding Age, Fertility, and Ovarian Reserve Testing

Why can't I have better egg quality than I do ? And I think that this is extremely pertinent because we know that one in four female physicians has a diagnosis of infertility , and also that , especially because of our training , right , for instance , you know , like to be an REI .

You go through four years of college , four years of medical school , four years of residency and three years of fellowship . I always like to joke they let me loose in my mid thirties , right . And so everyone's journey is a little bit different .

But I think that when we think about how long our training is to be able to do the things that we do , the options really are , you know , either have a kid during training , which can be very stressful , or freeze eggs with the hopes that they're going to pan out later , and we know that many times they do , but not always , you know , or , you know , many

people also don't decide to start trying until they are in their late thirties and early forties and that can come with some really stressful implications for the fertility journey as well . And you know COVID I think COVID delayed a lot of childbearing as well for obvious reasons , because people just didn't know what the risks were .

And it was a very stressful time and people kind of emerged several years older and really were faced , and still are being faced , with age-related concerns . So let's talk a little bit about physiology .

We know that we're born with all the eggs that we'll ever have and that over time we lose them , and so it's actually thought that we have the most eggs that we ever have as females , like when we're 20 weeks of a fetus . We actually lose them before we're even born . Weeks of a fetus . We actually lose them before we're even born .

And then we continue to lose them over time until menopause , when we maybe have about like a thousand eggs left and the sort of average age of menopause , at least in the US , is about 51 . However , we know that the egg quality changes and the physiological changes happen about 10 to 15 years before menopause . And so where does that put us .

That puts us in the mid to late thirties in terms of egg quality and fertility concerns . So there's this very sad graph that I think you know .

It truly makes me sad every single time I see it , and I think it's very useful for counseling patients , because in the mid to late thirties you start to see that the pregnancy rates per cycle go down and the miscarriage rates go up and that starts to cross around 36 , 37 , somewhere around there .

And so the thing that happens is we just get more inefficient as we get older . And so what's happening on the cellular level ? And so what's happening on the cellular level ?

Basically , our eggs are very large cells and they have mitochondria in them basically to power the energy of the cells , and I think of the eggs and the sort of infrastructure ofal shuttling that needs to happen to yield an egg that is sort of has the correct number of chromosomes to start , and then also , as the egg undergoes the embryo , undergoes the cell

divisions , how to get the right number of chromosomes to the right place . And so eggs need a lot of energy and as we get older , truly the eggs get tired in terms of not having the same energy sources that they had when we were younger .

And this is a really , really hard problem to fix , because at least at this point in time we can't just give the eggs more energy .

What happens is we find that , you know , say , like in the IVF cycle , sometimes , you know , even for somebody who is , say , 40 years old , maybe 20% of the embryos at best will be chromosomally normal and 80% will be abnormal .

And so in a sense it's like sort of how can we get to a good egg , how can we get to a good embryo , understanding that physiologically our egg quality is getting worse as we get older , and so there is egg quality concerns .

And then there's also the ovarian reserve markers , which help us to understand what's going on in terms of that physiology , what that means .

It's taken me a long time to understand the nuances of egg reserve testing and how it can be used when thinking about somebody's chances and maybe why somebody doesn't respond to a certain protocol but maybe might respond better to a different protocol , say an IVF or even sort of you know , lesser involved therapies .

And so I think of ovarian reserve testing in three main buckets . I think of the sort of the blood test , the anti-emullarian hormone , and so what that is , is that's basically a quantitative assessment of how many eggs you have left in your body , norms that we can go by .

But in general it is a test that helps us understand response to medications more than anything else . And it's not a test . You know , I always say I'm a fertility specialist but I truly have no test for infertility , because it doesn't tell me if somebody is infertile even people with undetectable AMHs conceive .

It just tells me , you know , how is the egg number doing in a person's body and how might this person respond to medications . So it is a quantitative test , not a qualitative test . It does not speak to egg quality and it's something that we can track over time .

You know , sometimes if I see a young woman in my office and say she's in medical school , it is not a screening test in any way . However , if we can sort of look at it , somebody has an AMH of like under one is when we start to get concerned . So say , somebody has an AMH of 0.6 and they're , you know , 20 years old .

That's somebody whose timeline might be a little bit shorter , and so perhaps we choose to freeze eggs in that person preferentially over somebody whose AMH is three or four . Obviously all of the things being equal like values , priorities and everything like that .

But in terms of sort of helping me to counsel somebody in the office , somebody with an AMH of three or four probably has a longer reproductive timeline than somebody whose AMH is less than one , if that makes sense . What sorts of things affect the AMH level than one ? If that makes sense , you know what sorts of things affect the AMH level .

Clearly , smoking or a history of smoking can decrease the AMH . So if that's an all part of somebody's story , I say , you know there's so many things we can't control , but this is one thing we can control . And so let's really , you know , get out the toxins and see what we can do . You know , weight can actually affect AMH as well .

You know it's a little bit confounded because there are people with PCOS who have higher than expected AMHs who also , you know , carry some extra weight as well . But when you look at the data overall , people who are heavier , you know , can have lower AMH values .

And so what I counsel my patients to do is to really invest in weight optimization if they have time toH values . And so what I counsel my patients to do is to really invest in weight optimization if they have time to do that .

Obviously , if somebody is 34 or 36 , it's different if they're 42 , but that's part of the conversation of things that are potentially modifiable in terms of AMH .

And then the other thing that I think about is long-term suppression on , say , a birth control pill , because we know that people who have been on OCPs long-term , their AMH can really reflect that and it can take two , three months for that value to bounce back to what it would be and there is a ceiling effect for everybody .

But at least if it can recover a little bit to a point where it's a little bit more robust , then maybe somebody will do better , say , in an IVF or a neck freezing cycle . So that's AMH in a nutshell . It's a blood test you can get at any point in your cycle . That's one of the nice parts about it , and our assays are getting better .

They're not perfect , but there are some better assays out there than there used to be and it's something that can be trended over time . The next set of values is actually a pair of tests and it's blood tests as well , and it's the follicle stimulating hormone and the estradiol .

So these are like a seesaw in a person whose axis is intact , with negative feedback when one goes up , the other goes down . So why do we check them at a certain point in the cycle ? We know that estradiol values fluctuate throughout the cycle . We also know that FSH values say when the estradiol rises , the FSH should fall .

And so , you know , a very smart endocrinologist once told me , you know , if you're hoping that something is , you know , going to be low , right , but you're worried it might be high , you check it when it should be low to kind of stress the polarity of the system .

And so if somebody comes to see me on day three and their estradiol is under 50 and their FSH is under 10 , that generally means that that axis , that hypothalamic pituitary ovarian axis , is swimming along . The ovaries and the brain are always in a conversation with each other , and so what happens is like the ovaries are making estrogen .

They send a message to the brain . They're like we're doing fine down here . You know the FSH is like , okay , keep chugging along . And then the FSH starts to rise and captures the dominant follicle and then there's that ovulation event and life goes on right . That's kind of an ideal situation .

But as we get older , what happens is we have alterations in this physiology . So as the ovaries are having a harder time doing their job , they send a message to the brain and they say help us out , we're really struggling to do our job .

So when the ovaries are having a hard time making estrogen , the pituitary and response actually works harder , on overdrive to then stimulate that system . So I think about it kind of like a thermostat .

I live in upstate New York slash Vermont , and so when I have a sweater on in the winter time and my thermostat is set to , say , 70 or 72 degrees , I know that something is wrong with my thermostat system . Right .

Then I might hear , temporarily the system revs up , right , for an hour or two as it's working harder to get the room to the desired temperature . And then what happens is then the room is the desired temperature and I'm like , okay , great , I can take off my sweater , all is well in the world and life goes on .

Now you may want to wear a cute sweater in the winter . This is no judgment here . I love my sweaters , but it's just sort of . It's a nice way to think about , just sort of what the brain is doing . It's a compensated state . It's temporarily working a little bit harder to tell the ovaries to do their job .

And so what you can see on , like day three , when the estrogen is , you know , should be low under 50 , you can sometimes see an FSH that's 11 , 12 , 13 , 14 , even higher , because it's like cracking the whip on the ovaries to work a little bit harder .

So that's one scenario , with the FSH and the estradiol , and you know , I don't love to see that scenario clinically , even though we can't really control it .

I don't love to see it because what it means is that if the ovaries are always seeing a fair amount of follicle simulating hormone from the physiology right , when we try to give FSH from the outside world , or we try to give medications that raise the body's FSH , like letrozole or chlamyd , the ovaries might be like what's the big deal ?

We see this all the time , like we , you know , we don't care , and so that's why some people don't really respond as well as we hope that they would is because their body lives in a sea of FSH in this compensated state , and so when the you know , when the we try to give our treatments , they often don't have the same impact because the change of FSH is

just not that great . So that's sort of how it clinically matters . What I will say is sometimes people actually have an elevated day three estradiol , like 80 or 90 . I don't really love that scenario either because and this is kind of complicated so stay with me but most of you who listen to this podcast went to medical school , so it'll make sense .

So if the estradiol is 80 on day three and say that the follicle stimulating hormone is like nine , right , and you might look at that and be like , oh , the FSH is under 10 . It's fine .

But if you rewind maybe two or three days , like before you got that value to , when the estradiol was probably like 30 or 40 , that FSH because it's like a seesaw that FSH might've actually been 14 or 15 .

And so what that's telling me is that you know people who have elevated day three estradiols often have shorter cycles because their dominant follicle is getting selected on the sooner side . And that tells me that there was probably a crummy luteal phase before the follicular phase , right From the previous cycle .

That luteal phase was not great and the sort of the hormones from the corpus luteum were probably not as robust the estradiol and the progesterone and also that inhibin that comes from the corpus luteum , which is the primary negative regulator of FSH . That probably wasn't doing its job and so there wasn't enough of it around .

And so , because there was not as much negative feedback from that corpus luteum , from that previous luteal phase , the FSH actually starts to rise even before somebody has their period right . So a lot of times people will see me , on like day four , day five , day six , they already have a dominant follicle .

It's not that that follicle just like popped up all of a sudden , it's that that process has been ongoing even in the previous luteal phase . To make that process Like , again , the brain is trying to crack the whip on the ovaries and sometimes the result of that is a very short molecular phase , right , and then somebody ovulates early in their cycle .

And then , you know , luteal phase should in a normal situation be preserved around 12 or 14 days , but we don't always see that either if the hormones are less optimal . So that's another scenario where the FSH and the estradiol can really matter and sometimes people can be fooled to think that they have a normal FSH .

Um , you know , I've even seen , like , you know , some physicians don't know this information . I love to share the word because , um , the physiology is complicated . You have to really think about it . Don't be fooled by a quote , unquote normal FSH , unless you have an estradiol to compare it with , because those two have to be interpreted together .

And if the day three FSH excuse me , the day three estradiol is elevated , that probably tells you something about the person's physiology , or maybe it's even your physiology , where the body is really struggling to do its job .

And in those situations the body also generally sees a lot of FSH in general and may have some FSH resistance when it comes to IVF stimulation protocols and such . And so the third value that we have for ovarian reserve is the AFC or the andropholic account ultrasound .

And the way that I like to think about this is that our body doesn't go through one egg at a time . It actually goes through groups of eggs at a time , cohorts , and I think of it like a big pyramid scheme where you have the one dominant follicle at the top and then you have all the little guys below who are supporting this dominant follicle .

Now I think of eggs as like social creatures , and eggs like to be surrounded by other eggs , and so if you have a dominant follicle at the top , you know it does better if it has a robust cohort behind , because actually , if you look at it on a cellular level , those cells all communicate with each other .

They send each other messages through like gap junctions , and you know if you only have a group size of like two or three eggs that that that dominant egg is not as supported .

So in general it is nice to have a larger ant , you know , um antral folic account , compared to a smaller one , just because it sort of speaks to the relative number of eggs that you have left in your system and also sort of the health of the cycle .

Now , as we get older and our egg reserve dwindles , as happens with our physiology , our body conserves , and so maybe in the past , when we were 25 , we went through a group of 20 or 30 eggs every month . That is very typical .

But as we age , maybe our body has decided to get a little bit stingy and goes through eight follicles in a month , or maybe it goes through six follicles in a month , sometimes even like two or three , and so what that number tells me is that you know what is the ceiling effect of eggs that I could expect in a given cycle .

So if I sort of hit the ovary hard with IVF medications and a person's antral follicle count is eight , for instance , maybe at best I could get eight plus or minus two eggs from that cycle .

Now , again , this is not sort of literal , because there are people who have an AFC of like 12 and at best we can get four or five eggs every time and that probably related to FSH resistance . That continues to be . One of the growth edges of our field , of course , is how can you maximize the number of eggs and also the egg quality as well .

But it just gives a general sense of the size of the cohort and you know also , if somebody is freezing eggs , I might say , okay , your follicle count is six , you know that might be the most that we can get every cycle .

And so if you're hoping for , for instance , 20 eggs in the bank , then you might have to go through several cycles to get there , whereas someone who is lucky and has a very good egg reserve , you might get there in one to two cycles . So that's sort of what the androphalic count tells me .

I don't really believe in scanning people from cycle to cycle and be like oh , your AFC is good this month , we should proceed . Oh , it's not good this month , we shouldn't proceed .

But we also do know that people who have been on OCPs birth control pills for long-term suppression sometimes can see a temporary drop in their FOLK account , which then can come back after they don't have as much suppression anymore .

So again , even though our guiding documents say that you just need one ovarian reserve value and not the trio , I think that they all tell us different pieces of information that help with the nuances of how to help somebody with their journey . And so if you're looking at your test results and you're like what does this mean ?

I hope this elucidates it I will say that we do know that the values can change over time , so the FSH value can certainly change month to month .

What I will say is something I learned in fellowship which is also proven true is that please don't be reassured by a normal FSH when you've also had a very abnormal FSH , because the abnormal FSH is probably closest to the truth in terms of the physiology .

And so if somebody has an FSH of 25 and it's well-timed and estrogen is low , I'm going to trust that the most , even if they happen to have a good month when the FSH is normal . So I just wanted to say that there can be fluctuations month to month in the FSH values . Shorter cycles we look at cycle length .

If somebody has consistently had 28-day cycles and all of a sudden their cycles dropped to 23 , 24 days consistently , that can be a sign of you know egg reserve issues as well , and then we figure out what to do from there , right , so we can't really create eggs from no eggs .

There are some data that the supplement CoQ10 can be helpful with that egg energy that I was speaking to before in terms of just helping people with low egg reserve . So what I tell my patients , is my clients , is 200 milligrams three times a day . No brand is better than another .

I'm not a huge supplement person but I do really believe in this one because I do think it can . There's animal and human data that it might , you know , affect , even at the level of the mitochondria , the , the ability of the ovaries to , you know , make more and possibly even better eggs . So those are some of my thoughts about age and egg reserve .

I think we don't talk enough about age and I think that my general um , you know sort of guidance is that doing treatment on the sooner side is generally better than doing treatment later . Freezing eggs on the sooner side is generally better than freezing eggs later .

Um , and then also , if somebody is like , well , how many IUIs do I do before moving to IVF , and all those things , that is a very tailored conversation .

But I will say it also depends on your age and how many children you want and what your F-reserve is and those sorts of things , and so hopefully , again , this orients you to sort of what people talk about in the field in terms of how these values matter and then also how they're used in terms of prognosis and helping to guide people with their next right

thing .

As always , I love you , I love this session , I love talking about physiology , even though this particular topic does make me quite sad , but it's one of those things where knowledge is power , and the more we know , the more we can act on it , and what I want is that people get to their best possible outcome , you know , and also with their emotions intact .

So with that , I love you and until the next time , bye .