SART Fertility Experts - Understanding Ovarian Reserve

What an alphabet soup of terms exists to describe ovarian reserve! In this episode, infertility specialist Dr. Kawwass explains markers of ovarian reserve and what they can tell us about fertility treatment outcomes. She also discusses the concepts of eqq quality and quantity.

Hello, my name is Brooke Rossi and I am a reproductive endocrinologist working out of Columbus, Ohio. Today we will be talking with Dr. Jennifer Kawwass about ovarian reserve testing. Dr. Kawwass is the Associate Professor at Emory University.

She is also the Medical Director of Emory Reproductive Center. And we're so happy to have her here today to talk about a very important issue and a question that a lot of our patients have, which is how to interpret and understand ovarian reserve testing. So thank you so much Dr. Kawwass for joining us today.

Thanks Dr. Rossi for having me. I'm looking forward to the conversation. Yeah, I think this is a great topic because I feel that we spend a lot of time, at least in my practice, we spend a lot of time talking about ovarian reserve and I think it's really confusing.

So maybe you can just start us out by just telling us what is ovarian reserve? That's a great place to start. So I agree, it can be confusing and a little bit intimidating when your doctor sort of talks to you about this thing called ovarian reserve. One thing to keep in mind is that ovarian reserve is not a measure of fertility.

So it is a measure of egg count and residual quantity of eggs, but it is not a measure of the quality of one's eggs and it is also not predictive of whether someone will be fertile or infertile. So it's really a way of quantifying how many eggs an individual may have remaining in their ovaries. What do you think about the idea that ovarian reserve measures the quantity of the eggs that are left, but maybe age tells us more about the quality of the eggs we have left? Yeah, that's exactly what I tell my patients.

We tend to think that quality is primarily a function of a woman's age and quantity is what we're measuring with ovarian reserve and ovarian reserve can vary pretty significantly from one individual to another. So there's some women that are young with a low reserve or a high reserve. And similarly, there can be older individuals whose reserve is either higher or lower than one might expect for their age.

Great. Okay. What are the different ways that we can measure ovarian reserve? Because there are several of them.

Yeah. So there are several ways to measure ovarian reserve. And it's important to remember that no one way is perfect.

And that's part of why reproductive endocrinologists often will measure ovarian reserve in maybe more than one modality. Generally speaking, we tend to think of there being three ways to measure ovarian reserve. One of them is visual and it can be done with an ultrasound.

It is often shortened as AFC or BAC for antral follicle count or basal, baseline antral count, I guess, or baseline antral follicles. Each practice might have a different acronym. Underlying concept here is that you can look visually at the ovaries and measure these things called antral follicles that are reflective of the total remaining pool of eggs.

Right. It can be super confusing because you might get a number that's 5, 10, 15, 20, and that doesn't mean there's only 5, 10, 15, 20 eggs left, but rather that those are the eggs that are available each month, not the total number that's available in the ovaries. Correct.

Yeah. And that can only be done. I mean, that's supposed to be done at a specific time of the cycle, which is maybe some reason why some people may not have had that done in the past.

Correct. In an ideal world, we would try to do that while someone is at the beginning of their cycle, between days two and five. So there's another test that's cycle specific.

This is a hormone test. It's a blood draw. It is called FSH or follicle stimulating hormone.

And it's typically drawn with something called estradiol, which is another hormone that helps us interpret that follicle stimulating hormone. It essentially is a reflection of the signal that the brain is sending your ovaries to sort of make them develop an egg every month. In this case, you want the signal to be relatively low.

So under 10 in an ideal world, which is sort of reflective of normal ovarian function. You can sort of think of it as the signal gets higher. It's kind of like your brain is a little bit screaming at your ovaries to try to get them to answer.

That's always what I say too, is like the ovary, the brain is screaming at the ovary to work harder and make more eggs. It has to yell it louder. Yeah, exactly.

The tricky thing about the FSH and estradiol is that the perfect time to draw them again is in between day two and five, ideally day two and three of your cycle. And also there's certain things that can suppress your FSH. Like if you're on birth control pills, the FSH is not a reliable test.

Whereas the antral follicle count is something, you know, it might be a little bit lower if you're on birth control pills, but it still can give you a better sense at least than that FSH. And then there's also, you know, one of the more recent tests that people have been doing in the last, I don't know, 10 years or so has been anti-mullerian hormone. Yeah.

So that is the third way we shorten that to AMH or anti-mullerian hormone that conveniently can be drawn anytime in the cycle. So I think more and more physicians and clinics probably order this more frequently with increasing frequently over time. And that AMH is kind of a reflection of the total pool of residual eggs.

So the more antral follicles you have, the higher your AMH is going to be. And again, there's sort of values that we think are within a normal range for each given age. It's normal for that AMH to get lower and lower as an individual ages.

Right. And so sometimes I think this can be confusing for patients because, you know, a high FSH may indicate low ovarian reserve, while a low AMH may indicate low ovarian reserve. And I think it's also, as you were saying, patients need to also understand that everyone's AMH level probably goes down as they get older.

So it's reasonable to see a drop over time. And so it also sounds like you're saying that what measure of ovarian reserve that's done may depend on where they're at in their cycle, if they're taking any other medicine, their doctor's preference, what their insurance company might say that they need, but any of those may be acceptable ways to measure ovarian reserve. Yeah, exactly.

What do you think, and it's not very typical, but do you have any thoughts about, you know, if you've ever seen a patient who's had maybe a normal, like a normal FSH, but a low AMH, what that might indicate, or if the levels are discrepant at all? Yeah, there actually was a publication. It might've been two years ago in fertility and where they tried to say like, which one matters the most. I think in truth, we don't know.

And it kind of, sometimes the truth comes out when you try to do a IVF stimulation and you sort of just see what the ovaries do, unfortunately. I do think we take all of the values into account when we're making treatment decisions. And sometimes, you know, you might, let's say, increase your starting dose a bit.

You kind of take both into account and it's hard to know which of the, I don't know that it's agreed upon, which is the absolute, there's no absolute truth. You just kind of consider it another factor in your counseling and decision-making. Right.

And also sometimes I've seen, you know, maybe somebody had an AMH done two years ago and it was 1.2 and then they have it checked and now it's 1.7 and they ask, well, has my ovarian reserve gone up? Right. And I, and there's some variation probably from one assay to another, one clinic to another, but doesn't necessarily mean that their ovarian reserve has gone up.

Right. So what would be some reasons patients may have ovarian reserve testing completed? Sure. Certainly if you're visiting a fertility clinic and you're trying to assess where your ovaries are starting and how it might guide your treatment decisions, that would be an appropriate time to have ovarian reserve testing.

So if you have infertility, that's a clear indication. Patients that are coming to see a reproductive endocrinologist for something like egg freezing that don't have infertility might do ovarian reserve testing. And that is a topic we might want to elaborate on in a bit.

That can be tricky when you find out things about your ovarian reserve and you're not infertile or someone who has a new medical diagnosis for which they're going to do take some treatment or medication that is going to harm their ovarian reserve. You might get a baseline before, let's say taking a chemotherapy medication or something to that effect. What kind of things, you know, aside from age, is there anything that you know affects ovarian reserve, makes it worse? Yeah, that's also a great question.

One thing for which we have pretty good data is smoking. So there's good data that cigarette smoking decreases ovarian reserve over time and can lead to earlier menopause. Additionally, if you have surgery on your ovary and some normal ovarian tissue sort of tends to get removed at the same time as whatever the pathology or thing you're aiming to remove, that can lower your ovarian reserve.

That might be for let's say a cystectomy or endometriosis or something like that. And then like we mentioned before, there's some medications that can temporarily sort of mute your ovarian reserve numbers, but don't actually change your fertility over time. Right.

One of the questions that I think is complicated when we're talking to patients about ovarian reserve is what it actually tells us about fertility, about their outcomes, and what it doesn't tell us. So maybe you could talk a little bit about what information ovarian reserve testing reliably can tell us and what questions are, what questions still remain after having the testing completed. Yeah, I completely agree with you.

I think this is somewhere where there's a lot of misinformation, even potentially among practicing general OBGYNs that maybe don't spend their days thinking about ovarian reserve testing. So the important piece here is that ovarian reserve testing in and of itself, like we sort of mentioned at the beginning, is not predictive of fertility, meaning it's not predictive of whether or not someone is going to conceive spontaneously. It is predictive of how an individual might respond to fertility medication, what protocol might be ideal, what kind of egg yield and embryo yield they may get from treatment if doing IVF.

So a good example of this would be someone that comes in to freeze eggs, doesn't know yet, has never tried to get pregnant, doesn't know yet if they're fertile or infertile, finds out that their ovarian reserve is lower than anticipated for their age. And this can be quite panic-inducing. But the thing to remember is that it really, it doesn't mean that that individual is going to have a hard time getting pregnant.

It just means that if they ever need fertility treatment, it's not going to be very efficient. I mean, I've had many a patient that come to me very early in their journey of trying to conceive, have been told by someone that their ovarian reserve testing is very low. And we'll say, well, just try to get pregnant for like three months on your own.

Don't do anything else. Let's just try for three months on your own. We know it's low, but you know, you're relatively young.

Just try for three months and then we'll see what happens. And I'd say, you know, more than a handful of times, those individuals will get pregnant without ever needing fertility treatment because again, they have low reserve, but not necessarily infertility. And there was a great paper.

I think you might, I don't know, you might have, I think it was in JAMA, Dr. Steiner was the first or last author. Do you remember if she was I can't remember anyway. There was a nice paper that got published in JAMA that highlighted this very well, that essentially showed that there is, there are many women with very low ovarian reserve that have normal fertility.

Right. And I think, you know, and this gets, you know, gets to the point that we'll talk more about, which is that, I mean, FSH and AMH are really tests that should be done in an infertile population. And it's hard to know how to interpret them in a potentially fertile population.

So like you're saying, you know, if a woman comes and she hasn't tried for that long, maybe she doesn't need to worry. But I will tell you, you know, back to the, you know, when you said that AMH predicts response in IVF patient today and on the SART website, there is a prediction calculator and she was a younger patient about 33 and her AMH level was a little low for her age. It was 1.0. So I plugged in all the information into the calculator and her chance of getting pregnant, I think was about 44% with IVF.

And I said, well, let's just look and see what it would be if your AMH was 2.0, which is kind of what it should be at her age. It was about 15% higher. Like it really, you know, I think because patients might get less eggs, they might get less embryos, they might get less chances.

It is an impact when we go to actually do IVF, you know? Yeah, I agree. Does it AMH predict anything else like risk of miscarriage or menopause? If someone has low ovarian reserve, will they go through menopause earlier? I would say a lot of this data is a bit controversial. There are papers showing potentially an association with miscarriage and there are also papers that show that there isn't.

I don't know that we have the, that we know the truth. I'd be curious to hear what you think. I agree with you.

I mean, I don't think the data are very clear. I usually tell patients that because we don't know and there isn't really anything you can do about it. I don't, I, you know, it doesn't really help to worry about it when there's nothing you can do about it.

So I would usually say no, but you know, I think that's maybe the other thing about using ovarian reserve to kind of plan. You know, I don't, I don't try to get too nervous about it when someone might have a low level, but I, I do kind of use it to say to myself and to them, maybe we shouldn't wait a long time before moving through our treatment or let's try to go through things a little bit. Efficiently.

Yeah, six months off, let's just keep going, you know? And, and sometimes it's not really so much because they're trying to have their first kid and their AMH is a little bit low, but you know, I've tried to always think about how am I going to help this person have their whole family? And if their AMH is a little bit low at 36, what will it be when they're trying to have their second kid at 38? So just this kind of sense that we need to keep moving a little bit with treatment. Yeah, I totally agree. Yeah.

What do you think about the association with age and antimalarian hormone level or age and ovarian reserve? And I think what I mean by that is what would you say about maybe a person less than 35 who has a low ovarian reserve number versus a patient who's over 40 who has a high ovarian reserve number? Yeah, I think some of that gets back to where we started about quality versus quantity. Yeah. You know, embryo for embryo, a young person's chance, even without genetic testing of the embryo, a chance of a live birth per transfer is going to be high, right? The difference is that person with a low AMH is going to have fewer embryos to choose from, but if they get to have an embryo age is going to trump everything.

So the, the battle is, is getting an embryo or getting two embryos. But once you have the embryo, we think that age kind of trumps everything. The other extreme that you're asking about is kind of an older individual that has lots, maybe a higher AMH than you'd expect.

And again, the sort of rate you're going to, you may have more embryos to choose from, which is certainly a luxury, but that rate of aneuploidy or the rate at which those embryos will be abnormal is, you know, as you get older, can get quite high, but certainly the more embryos you have to choose from, the more lucky you might be to find one that is genetically normal. And then you can have again, a higher chance of pregnancy. Yeah.

Yeah. I do find, I think when somebody gets the, you know, gets the report that they might have low ovarian reserve, it worries them. And so I do feel like I spend a good amount of time reassuring patients who are younger, exactly what you said that, you know, if we can just get a few embryos, you're likely to be okay because there's a better chance that they will be genetically normal and we have a higher chance of giving us a baby in the end.

So I agree with you. We talked a little bit about, you know, ovarian reserve and sort of the impact on in vitro fertilization, maybe the amount of response and eggs and embryos that patients may, may achieve with IVF. Does it tell us anything else about general infertility treatment or does it tell us about anyone's chance of success with other treatments such as insemination? That's a great question too.

I would generally speaking say no. I mean, I, I would incorporate it the way you were saying, right. You wouldn't maybe take six or 12 months of trying something else first, cause you don't want to dilly dally.

Right. But we've got pretty good data that, you know, three months delay of IVF isn't going to change someone's outcome, even if they have diminished reserve. So it tends to not change the order in which I would move through things.

Again, assuming sort of the tubes are open and the sperm counts, okay. And the other, there aren't other factors that are forcing your hand. Generally speaking, even with a low ovarian reserve, you might try some inseminations first.

The caveat is again, what you pointed out to if someone is trying to bank embryos for future fertility, you might say, all right, have a lower threshold to go to IVF to generate embryos earlier. But if someone's really only focused on the first and you're, if you're just really saying, I just want one child and I'm focusing on the present, I don't know that there's any reason again, assuming the tubes are open and the sperm count is reasonable not to try other less invasive techniques first. Yeah, I agree with you.

You know, you know, I live in a state where most of my patients don't have IVF coverage and, you know, it's not uncommon for us to have a patient show up and say, oh my gosh, my AMH level was low. Do I have to do IVF right now? And the answer often is no, like let's try something else. And especially if the patient has gotten pregnant before with on her own or with some other treatment.

So I, I always want to make sure that patients understand that, you know, that this number doesn't dictate their whole life, their potential, their chance of having another child. Like you always have to put in context of everything else that's going on with them. Right.

Totally agree. So we've been Dr. Kawwass, we've been, we've gone around and around and let's just, let's just talk about it now, which is what do we do with ovarian reserve testing in women who don't have infertility? So if we define infertility as, you know, less than 35, trying for 12 months or 35 or older trying for six months, what about all the patients who might just be curious about their quote fertility potential, or maybe their friend did an AMH level and they want to do it too. Like what happens if we have a patient who is 34, hasn't really tried, got an AMH level checked and now is, wants to figure out if she should do IVF, should she freeze eggs? You know, what do we, what do we think about that? Yeah, this is a great question, particularly in the setting of these home tests that people are getting data, right.

Without necessarily having a lot of counseling before they get the data, which can be tricky. I think it really requires a consultation with the reproductive endocrinologist to understand sort of someone's individual goals, how they feel about alternatives to having a biologic child, the cost of egg freezing. I mean, certainly egg freezing is something that comes into the conversation, but again, it's with the knowledge that it might not be necessary, but you don't really know.

And so it depends on where are they in their life? How likely are they to partner soon? When do they think they want children? How many children do they want? Do they have coverage for IVF egg freezing? Do they not? And how do they feel if they were to have infertility in the future? How do the alternatives feel? How adoption donor egg, right. You know, I think it's really a personal decision, but it's important in that discussion, of course, to say, just as we've said, this low egg count, you might go and meet someone tomorrow, have unprotected sex and get pregnant. Like this number in and of itself does not mean that you're going to have trouble, but it does mean that if you come see me in seven years, because you're having trouble, we're likely going to have limited options or limit lower chances of success.

Yeah, I agree. It's you know, one of the things I think we want to help patients understand is, you know, all of these tests that we do, whether it's for ovarian reserve or a semen analysis or anything in medicine, you know, for a test to really give us the right information, it has to be done in the right population, right? And so, and when it's not, then it doesn't give us as much good information about the meaning of the result. I definitely believe in patient education and women, you know, understanding their fertility, which is why I think that if people have the test done that, you know, they understand all the options, you know, which may include egg freezing, donor insemination, waiting, not waiting, you know, donoring in the future, whatever it is, but that they do have a chance to talk with a provider who understands, you know, the context of what they, you know, what they wanted from, you know, from their family building and sort of the tests that they've done and their history, right? Like what if somebody had cancer and has a low AMH versus had ovarian surgery and had a low AMH, right? Has had nothing and has a low AMH, you know? So I think- And some people like choose to get pregnant right away, right? Sometimes it changes someone's reproductive planning.

I don't know. Which can be good for some. Yeah.

Maybe somebody wouldn't have chosen to do that had they not known. So I agree with you. I think it's a great option for people to have within a context of really being able to sit down with someone and talk to them about what it all means.

I totally agree. Do you have any other last thoughts or any other things you wanted to add about ovarian reserve testing? I think I would just sort of reemphasize a lot of the things that we said. A lot can be gained by meeting with a reproductive endocrinologist in terms of understanding what the testing means, if you've already had it done, and knowing what sort of your options are.

No matter what result you get, I would try not to panic. The nice thing is that we do tend to have options, no matter what the results are. And I don't know, what would you say? I think, you know, it's funny because even though you're half a country away from me, I feel like we say the same things to our patients.

You know, I do often, back to the whole, you know, sometimes if a patient has a low AMH level, it may encourage us to move through treatment more rapidly. I would say the other side of that is true too. Meaning that if I have a woman who's maybe over 40, who has a high AMH, I also want to remind her that she doesn't have the ovaries of a 30-year-old, even if she has a high AMH level.

And so, you know, she also needs to understand that her age is most important and trumps everything, as you say. And that, you know, she still needs to think about what her plan is and moving ahead with treatment and that sort of thing. Yeah, I agree.

It is nice that two people that didn't train together or practice together give the same advice. That's very reassuring. That's good.

But I think ovarian reserve testing, you know, it's important that patients have a good understanding of it because sometimes, you know, it can be done by their primary care doctor or their OBGYN doctor. And it's totally fine for that to be done by those providers. And then the patients, hopefully, by, you know, looking for information or listening to a podcast like this, that they can better understand what that information means.

And then if they then feel like they want to seek further information from a reproductive endocrinologist or a reproductive health, you know, provider, that they can do that. So, I think that your insight for our patients will be very much appreciated. And SART thanks you for joining us as well.

Of course, it was fun. Great. So again, my name is Brooke Rossi, and this is the SART podcast series.

And today we were talking with Dr. Jennifer Kawwass from the Emory Reproductive Center discussing ovarian reserve. Thank you so much. Thank you.

The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates. These are provided as a source of general information and are not a substitute for consultation with a physician.