Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole. And today, our discussion focuses on Anti-Müllerian hormone or AMH's impact on ovulation for PCOS treatment. Joining me today is Dr. Allison Komorowski. She's an Assistant Professor of Reproductive Endocrinology and Infertility in the Department of Obstetrics and Gynecology at Northwestern Medicine.

Dr. Komorowski, it's such a pleasure to have you join us today as we get into this topic, it's really interesting, can you explain a little bit about AMH, what it is, how it's measured, and what the observed levels are for women with PCOS?

Dr. Allison Komorowski: Yes. Thank you so much for having me today. AMH is a glycoprotein in the transforming receptor beta family. It is measured by a simple serum blood test for women, and it can be done at any point in the menstrual cycle with pretty minimal variability depending where they are in their cycle. In women with PCOS, we often see higher levels of AMH compared to other women of the same age.

There are differences in AMH, dependent on the assay and the lab where it's done. So, it's important to look at both the age and lab-specific reference values when interpreting the values. But in general, women with PCOS do have higher AMH levels, and this can drive up the average AMH levels by age, which is why we tend to look at the median AMH values when trying to understand where a woman's ovarian reserve or supply of eggs lies in relation to other women her age.

Melanie Cole, MS: So then, Doctor, your study found that higher AMH levels are linked to lower chances of ovulation with ovulation induction with clomophine, metformin, and clomophine and metformin. So, how can doctors use this information to improve treatment for women with PCOS? Tell us a little bit about your study.

Dr. Allison Komorowski: Yes. That's exactly right. So, we found that women who had higher AMH levels, particularly in the range of 4-8 nanograms per milliliter, and those with ultrahigh AMH are greater than 8, were much less likely to ovulate with all the methods of ovulation induction in this study, which were clomophine, metformin, or the combination of clomophine and metformin.

So, those women who had higher AMH levels were less likely to ovulate with all three treatment arms. We also found that women with higher BMI levels were less likely to ovulate than women with lower BMI levels at the same level of AMH, indicating that the women with higher BMI also had more resistance to treatment.

Melanie Cole, MS: Wow. So, do you see AMH levels becoming a useful tool, Doctor, for diagnosing PCOS? How would this compare to the current criteria, which we know can sometimes be unclear and a little bit difficult to diagnose?

Dr. Allison Komorowski: Yes, I think there's a lot of value in checking AMH levels in women with PCOS and women with infertility in both helping with the diagnosis and guiding treatment in the future. So, the 2023 international guidelines for PCOS started to incorporate AMH a little bit more, and AMH can be used as a surrogate marker for ultrasound, where we're looking at polycystic morphology of the ovary.

And I think AMH can be a little bit easier to interpret since it's just a single blood draw, gives you one value, whereas ultrasound is a little bit more reliant on the individual performing the ultrasound, and then also someone interpreting that ultrasound. These guidelines say that AMH should not be used as the only diagnosing factor for PCOS, and it's not necessary to meet the diagnosis of PCOS, particularly in a woman who has irregular cycles or elevated androgen levels, other factors that are associated with PCOS. But I definitely think there's value in this marker, particularly if there's limited access to ultrasound.

One other area with caution would be using AMH levels in adolescence just because there really aren't normal ranges established for that population. So, I would use caution in adolescents, but I think there's a lot of value in the adult population of the AMH check.

Melanie Cole, MS: Certainly there is. And you've mentioned BMI, and I'd like you to speak about lifestyle factors like age and BMI. Should doctors consider these things when looking at AMH levels in women with PCOS? How does it differ in someone with a higher BMI or a more advanced age?

Dr. Allison Komorowski: Yes, we know that age impacts the supply of eggs in the ovarian reserve, which AMH is the marker of that ovarian reserve. So, we expect lower AMH levels in women of older ages. So, we always want to compare levels based on kind of the population specific ranges by age. And with BMI, we generally see that higher BMI is associated with lower AMH values. And so, particularly if there is an older woman or a woman of elevated BMI, who has a high AMH that could be suggestive of PCOS.

Other potential factors: tobacco smoking is known to have a negative impact on AMH levels. Also, hormonal birth control, like oral contraceptives are known to have a negative relationship with AMH levels as well.

Melanie Cole, MS: Those are important points for other providers. And why is it important to create this personalized treatment plan for women with PCOS? And do you feel that testing with AMH Levels can help to inform the best treatment options for these women?

Dr. Allison Komorowski: Yes, I think it's really important to understand the individual's reproductive goals when determining an individualized treatment plan for moving forward, and particularly understanding an ideal family size for that woman and when she's hoping to have children. For some women, that might be a reason to potentially do things like egg freezing to preserve fertility for the future. And I think AMH can help guide those treatment decisions somewhat in understanding what the woman's supply of eggs in the ovary looks like in relation to other women her age. And particularly for women with PCOS who have infertility, AMH levels can help us understand how likely they are to be successful with less invasive treatment options like oral ovulation induction medications, and particularly for those women with the ultrahigh AMH levels above 8, that may indicate that they are less likely to have success with the oral medication treatment and may need more invasive treatment in the future, like in vitro fertilization.

Melanie Cole, MS: So, I'd like you to expand for just a second on what you were just saying, and take us from bench to bedside here, Dr. Komorowski. How do you see this research affecting clinical practice? And what do you think your research means for the future of reproductive health, especially for women facing infertility as a result of PCOS?

Dr. Allison Komorowski: I think the most important thing to better understand is how to help patients who achieve their family building goals. And I think our study provides one kind of clue into that, that these women with higher AMH levels are less likely to have success with these less invasive treatment options. So, women with high levels are women who may benefit from earlier referrals to reproductive specialists in fertility, so Reproductive Endocrinology and Infertility specialists particularly, because they may need more invasive treatment like IVF in the future.

Additionally, these women with higher BMI, and if they have high AMH levels as well, we know that those are both two factors that contribute to less odds of success with the lower invasive options. So, they are women who definitely would benefit from future kind of referrals to the REI clinic.

Melanie Cole, MS: It could be a real game changer, Doctor. So, what are the next steps in studying AMH related to fertility and PCOS? Are there any new studies that you're excited about? Let other providers know where you think this is headed. What you would like to see happen in this field going forward?

Dr. Allison Komorowski: I'm really interested in better understanding whether we can identify women who are kind of on the more subclinical end of the PCOS spectrum, who may not be experiencing irregular cycles yet, but have elevated AMH that might be a clue that they may experience PCOS type symptoms in the future.

Additionally, there's some newer data out there regarding AMH as a proxy for the severity of the cardiometabolic risk factors involved with PCOS. So, there was a new study this year about women who are Indian with PCOS, and found that AMH levels correlated with their cardio-metabolic factors like their lipid profile and other anthropometric markers. So, I think that it's possible that AMH will also provide a key clue into the metabolic health of women in the future. And I think it would be amazing if there was just one blood test that could give us clues not only about fertility, but also about kind of lifelong health factors that many of the women with PCOS might face in the future.

Melanie Cole, MS: It certainly would. Very exciting time in your field. Doctor, thank you so much for joining us today and sharing the studies and your expertise. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/obgyn to get connected with one of our providers. That concludes today's episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.

Dr. Allison Komorowski: Thank you for having me.