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Anti-Mullerian Hormone (AMH) and Fertility

In this video, Dr. Barad explains what anti-mullerian hormone is, how it relates to fertility, what AMH levels mean, and how CHR treats women who present with low AMH levels while trying to conceive.

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One of the tools that have become useful in helping to evaluate a woman's ovarian reserve is AMH. Now, AMH is the initials of the term, "Anti-Mullerian Hormone,"(also called "Mullerian-Inhibiting Substance" or "Mullerian-Inhibiting Factor"). Now, those long terms are not really very helpful in understanding what it is because they were named in other contexts, actually having to do with embryological development, so we're going to call it AMH. AMH is produced by small follicles in your ovaries, actually, those small antral follicles that we mentioned a little while [ago], which are the stage of the follicle in which the egg develops before it actually enters the ovulatory cycle and starts growing, and getting bigger, and ready to ovulate. So, you can think of them, these antral follicles, as those that are sort of "on deck," ready to come into the next cycle. And those antral follicles are around for about four to six weeks before they enter the ovulatory cycle in which they might ovulate. So, at that stage, when they're just detectable with an ultrasound (meaning maybe they're from about three millimeters to ten millimeters in size), they produce this hormone, AMH. So, each little developing follicle produces some AMH. Now, it's not reflective of all the follicles in your ovaries because there are thousands of follicles that are in earlier stages of development than this that won't produce AMH and that you won't see if you do an ultrasound or try to measure AMH. So, the AMH reflects the antral follicles that are preparing to enter your next ovulatory cycle (what we call your functional ovarian reserve) because these are the follicles that are going to be available to you in the next month or two when you try to make some eggs. I tell my patients that if each follicle is producing some AMH, then the more AMH that you can measure, the more such follicles you have. It's as though you were trying to guess how many kittens are in the next room. You might guess by the number of meows that you hear or something like that. So, it's an indirect way of telling how many follicles are available to come in. Now, our AMH assays (the tests we use for measuring AMH), have improved greatly over the last ten years. But, even now, there can be people who have some follicles, but the amount of AMH they produce is below our ability to detect it. So, even if you have undetectable AMH, doesn't mean you have no follicles, but it probably means you have very few follicles. The other thing about AMH is that some people have claimed that AMH levels don't change through a cycle, or from cycle to cycle. To some extent this is true, but it's not entirely true. For instance, a young woman who's just had a baby will have nearly undetectable AMH because her ovaries have been somewhat suppressed by the hormones that are produced by her pregnancy and there will be very few antral follicles. In other words, she has very decreased functional ovarian reserve immediately after she delivers and her AMH will look like the AMH levels that we'd see in the menopausal woman. This is why it may take a month or two (actually six to eight weeks) or more before a woman resumes normal menstrual function after she has a baby because there are no small little antral follicles ready to come into the next cycle. If there are no antral follicles, there won't be any AMH. The same thing is true if somebody uses a strong birth control medication. We published this in a paper several years ago. So, certain oral contraceptives or implantable contraceptives (like the Norplant, or the Norgestimate that you insert into your arm, some of the contraceptive patches or the contraceptive rings that women use intravaginally) have strong hormones in them that will suppress the formation of antral follicles in the same way that pregnancy does. In those cases, you can see a diminished AMH as well, which will recover if the birth control hormones are stopped. So, it depends on what you've been exposed to recently when you're doing these AMH levels and what you information you can take home. Another thing that people are unaware of is that going through a cycle of ovulation induction, which you take out 20 eggs or something like that. Immediately after your retrieval, because you've kind of swept all of the antral follicles to the more mature stage by taking the gonadotropins, your AMH levels may be lower because you've sucked up all those actual follicles to be developing follicles and it may take a little while for them to replenish. This can be especially true in older women (especially after they've done a few cycles in a row), so although in older women we find we can actually increase the number of eggs that they produce if they do back-to-back cycles, that may only be true for five, six cycles in a row. After a while, you can kind of create a bit of vacuum on the back end, fewer antral follicles replenishing, and therefore a lower AMH. So, bottom line-- AMH is not a constant level. There are various things you can do that can influence it. So, if AMH is an important thing to measure, what is a normal AMH level? And, the fact is that as people change, as they go through life, as the number of eggs that are entering your ovulatory cycles (number of follicles entering your ovulatory cycles) change in each decade, as you go through life, the expected AMH level you have will change as well. For example, among a woman in her 20s, we'd expect to see an AMH of around four to five nanograms per milliliter. And, a woman in her 30s, the same kind of healthy woman, might only have a level of two to three. And then, when you get to be 40, you'd expect it to be around one. Now, we've produced at CHR some nomograms. Some other people have produced similar graphs that show what the expected AMH is at each age. And, what you want to know when you're evaluating your ovarian reserve is, is your ovarian reserve similar to your peers or not? If you are 25 and your AMH is only one or two, you've already got evidence of diminished ovarian reserve relative to your peers who would otherwise have levels of four or five. And that may be important information going forward that could help you in terms of your family planning, or your planning in terms of when to have children because it raises the question, "Are you still going to be in good shape (good reproductive shape) 10 years later or not?" So, if your AMH appears to be less than expected for your age, especially if you're somewhat younger and you're trying to achieve a pregnancy, What can we do to try to bring you back to be comparable to your peers? At CHR, we do use supplements like dehydroepiandrosterone (DHEA), which helps increase the number of follicles that survived to the antral stage, and therefore. helps raise your AMH again. We also would probably use more medications in ovulation induction than you would have if you had higher levels of AMH. You can kind of think of it the same as if you're trying to drive up a slippery hill, you might step on the accelerator harder to keep the car moving in the direction that you want to go. So, there are things that we can do to try to restore you to a better level of function.

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