AMH and Ovarian Reserve: Debunking Myths and Clarifying Facts (Episode 595)

Full Transcript: Episode 595

Lisa Hendrickson-Jack:

This is the Fertility Friday Podcast, episode number 595.

In today’s episode, I am diving into AMH, anti-Müllerian hormone. This is an important topic for women who are trying to conceive, women who are struggling with fertility challenges, and for practitioners alike. And of course, the reason why it’s such an important topic is because there are still many misconceptions about how this information, how this number should be used in practice. And it leaves many women feeling hopeless, feeling like they’re not going to be able to conceive — all based on this number, this result. So we should really talk about what it really is, what it really measures, what the research tells us it is best used and most useful for, so that we can be providing the best and most accurate information to our clients. And if you yourself are listening to gain a better understanding of how this could apply to your fertility, then I think you’ll find today’s episode very helpful. As always, I will link the paper that I’m referring to in the show notes page, which you’ll find at fertilityfriday.com/595.

So the paper is called “Evaluation of Female Fertility, AMH and Ovarian Reserve Testing.” This is a review paper going through some of the latest research. It provides a really good summary and is intended for practitioners and clinicians to clarify some of the most common misconceptions about AMH. To start this episode, I think it’s useful to share a little bit of background in terms of how common fertility challenges are. It’s estimated that anywhere from one in six to one in eight couples are struggling with fertility issues. And as we’ve talked about many times on the podcast, although we tend to think of fertility issues as a woman’s issue, up to 30% of the time infertility is related solely to male factor, and about 50% of the time male factor is involved — it might not be the sole factor, but it is involved. Statistically speaking, when we’re looking at couples who’ve been trying to conceive for a year or more, if we were to test his sperm parameters, they’re likely not hitting those optimal levels. These topics are covered in much more depth in Real Food for Fertility — the sperm chapter is chapter 11, with over 200 citations going through what’s normal, normal sperm parameters. And in the egg quality chapter, you’ll find a detailed discussion of AMH and other ovarian reserve parameters and essentially what the research says is going on there.

Being a research paper, it’s really helpful that the authors go through some of the bigger picture challenges contributing to the rise of infertility across the world. We know there’s a trend for women to be delaying their first pregnancy. The way the researchers frame it is that there is a lack of knowledge about fertility — not the fertility awareness method, but generally awareness about fertility, how it works, and how it changes with age. Certainly one of the challenges of our modern era is that our bodies are most receptive to pregnancy and natural fertility is highest when we’re in our 20s — and even into our early 30s — but as we get into our mid to late 30s, there is this natural decline. This is something that we should be talking about, that we should be aware of, that women should be taught to understand. When we’re not taught about our fertility, but we’re kind of taught we can get pregnant at any time — that it doesn’t change as we get older — a lot of women are essentially afraid of pregnancy for most of their life, and then when they’re finally ready to start trying in their 30s, they haven’t been given this information.

And if we’ve been using hormonal contraceptives and suppressing fertility, we’re also not taught about the fact that there is a temporary period of subfertility while our body adjusts, especially if you’ve used birth control long term. In the studies they define long term as two years — which is often kind of shocking, because many women are using hormonal contraceptives for five, ten, fifteen, even twenty years. If we don’t know about that transition phase, we don’t necessarily know to come off birth control while we’re still avoiding — ideally a year or two before you’re ready to start trying to conceive — just to let your body sort itself out so that you can actually see what your cycles look like. If you come off birth control while you’re still using non-hormonal methods, and there’s an issue with your cycle, you would have time built in to sort it out. This is especially important for women who have a history of irregular cycles, hormonal disturbances, severe PMS, or severe period pain. And what I always say is that doesn’t mean you can’t get pregnant right away. It’s like car insurance — we don’t want to assume the worst, but we want a strategy in place.

Getting back to this paper: women are having children later in life and a lot of women aren’t really aware of how fertility changes with age. And interestingly enough, although AMH is being used in the clinical setting to try to predict a woman’s chances of conceiving naturally or to predict when she’s going to go into menopause, the researchers are clear that that is not actually what the research tells us. That’s not how we should be using this information. And they still maintain that a woman’s age is the most significant factor in determining whether or not she will conceive — over AMH numbers.

So let’s get into what is really going on here in terms of AMH. Anti-Müllerian hormone is a hormone produced by our ovarian follicles as they are maturing. We are born with all the eggs we’re ever going to have. As we go into puberty and move through our reproductive life, every time we gear toward ovulation, there is a small pool of primordial follicles developing at the beginning of the cycle, and the size of that pool is actually related to the total amount of eggs we have left. So over the years, researchers have identified a link between how many eggs are in that developing pool and the total number remaining — and they’ve made that connection by looking at the changes over time. When we look at a woman’s antral follicle count from when she’s younger all the way through to her 40s, we can see this gradual decline. In the same way, AMH is actually produced by this pool of follicles — so when they’re looking at that number, they are able to see the size of this pool.

How it’s used is as a proxy for ovarian reserve. Because if they look at AMH values from younger women all the way into their 40s, there’s a gradual decline. We have this correlation between the AMH and the estimated number of eggs remaining. But keep in mind — it’s always an estimate and it’s always indirect. Unlike sperm testing, we can’t just go in and count how many eggs are left. With sperm testing, they can count the sperm. But we can’t do that with women. So AMH is never a direct “this is how many eggs you have left.” It’s always an estimate.

Some of the misconceptions about AMH are that it’s going to predict if you’ll be able to conceive, that it will predict how long you have until menopause, that it’s a static number that never changes, and even that it’s genetically inherited from your parents. Based on this study, researchers estimate that about 50% of our capacity in terms of when we’ll hit menopause is related to genetic factors — based on studies showing similarity between mothers and daughters in terms of when they reach menopause. But 50% is certainly not 100. There are other studies showing that AMH is affected by obesity, by conditions like PCOS — women with PCOS have higher AMH levels because of the higher pool of follicles that’s characteristic of the condition. AMH levels are also impacted by endometriosis — women with endometriosis are more likely to have lower AMH levels due to the inflammation and complexities of the condition, but that doesn’t necessarily correlate to her ovarian reserve directly. And there was an interesting study that Lily and I shared in Real Food for Fertility where women were given vitamin D at a certain time of their cycle and it actually increased AMH levels over a period of time. The reason I point that out is because one of the common misconceptions is that it’s static, set in stone. It’s not.

So while we do have a correlation between AMH levels and ovarian reserve, it is not a direct means of predicting exactly when you’re going to go into menopause. And the other piece that’s really important is that this number is estimating your reserve — how many eggs you have left. But it’s also a quantity thing. That means that even if you have a low number, that doesn’t automatically mean the quality of those eggs is also low. When these researchers review the data and outline how the AMH number should be used, they are crystal clear: it is not actually predictive of your reproductive capacity, how likely you are to get pregnant. And it also can’t be directly used to predict when you’re going to go into menopause. I’m sure that at least some of you listening have been told the exact opposite thing. The good news is, there’s a lot of research on this — it’s not difficult to find. The conclusion is crystal clear. And that is what makes it really interesting when I hear so many clients being told, “my doctor told me I’m going to go into menopause early,” or “my doctor told me I won’t be able to have kids.” As we know, it takes up to two decades for the latest research to get into standard clinical practice. This study was published in 2022 — this is not new information.

So then what is AMH used for? What are the clinical applications? The research shows that the best use of AMH is for clients who are undergoing ART — assisted reproductive technology. If you’re going through IVF and they test your AMH, whether it’s low or high, it’s going to be an excellent predictor of how many eggs they’re likely to retrieve. There’s a really strong correlation between that AMH number and how successful that retrieval is going to be, how receptive your ovary is going to be to the stimulation. When the AMH number is low, it’s saying that the antral follicle pool is low — so if that pool is very small, the number of eggs they’ll be able to stimulate is going to be directly related to how many eggs are actually in that pool. If AMH levels are in the optimal range, you’re a good candidate for that stimulation process. Conversely, if your AMH levels are too high — commonly seen in PCOS — that can lead to a greater chance of hyperstimulation, which can be a very serious condition, and in severe cases can even be fatal. So the authors describe how AMH helps clinicians gauge dosing and approach stimulation more precisely. They say: “Serum AMH estimates ovarian reserve, helps determine dosing in ovarian stimulation, and predicts stimulation response.” And: “AMH is a good marker of oocyte quantity but does not reflect oocyte health or chances for pregnancy.”

Could we be more clear? It has real utility for these procedures — but it does not predict whether that pregnancy is going to go to term. If you are not planning to do IVF, then that AMH number is not as helpful — because it doesn’t actually tell you if you’re likely to get pregnant naturally. It actually doesn’t tell you that.

Interestingly, there are research studies where they compare pregnancy rates of women with higher and lower AMH levels, and typically, one is not related to the other. As I share in Real Food for Fertility: outside of IVF and similar procedures, AMH is similarly a poor predictor of a woman’s ability to conceive naturally. In an observational study of 87 women planning to conceive, 88% conceived within one year, and the researchers found no relationship between AMH levels and time to pregnancy. The authors of this paper go so far as to say that for women not seeking IVF treatments — a healthy woman trying to conceive naturally — AMH shouldn’t necessarily even be used because there’s no research to show it will help predict whether she’ll conceive or not. And they go on to really stress that age is still the biggest factor. As we get older, we are more likely to have chromosomal abnormalities and other changes that affect fertility. Age is the most significant factor — over AMH.

Ultimately, if you are trying to conceive naturally, it makes a lot more sense to focus on strategies to support egg quality — supporting mitochondrial health, reducing oxidative stress, supporting nutrient reserves. The example I always give is the banana: if you leave it on the counter it turns brown, but if you dip it in lemon juice it doesn’t, because vitamin C is a potent antioxidant. If we understand that these numbers are not telling us about quality — they’re just telling us about quantity — then we can focus on the thing that is likely going to make the biggest difference: supporting egg quality and sperm quality.

Another direct quote from the study: “There was no AMH level below which pregnancy did not occur.” Pregnancies have been recorded in the literature even when women’s AMH levels are undetectable. While that’s not necessarily the ideal situation, it is not a reason for hopelessness. If AMH levels are low, there is certainly room to be supporting egg quality, looking at nutrition, and looking at sperm quality as well. But the research is not showing this direct causative effect that if AMH is low, natural pregnancy can’t occur, or that it has predictive value on whether a pregnancy will go to term.

So in many ways, this is good news. It allows women to step out of the fear around this number and refocus on what’s most important. As practitioners, it’s helpful for us to have a clear understanding so that when our clients come to us with these concerns, we know how to support them. It’s a good reminder to stay current with the research. When AMH was first discovered, there was all this excitement about being able to predict when women would go into menopause — but now we have a lot more data, and it really changes how this conversation should be had. If you’re wanting to dive into the study, you’ll find it in the show notes at fertilityfriday.com/595. And if you want to go way more into depth on egg quality and sperm quality, I would certainly direct you to Real Food for Fertility. So with that said, I hope you have a wonderful week, weekend, whenever you tune into the show. And until next time, be well and happy charting.