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The topic of today is ethnic disparities and reproductive health and IVF outcomes. I am delighted to be joined by Dr. Meera Shah, a fertility doctor from Nova IVF in Mountain View, California.
Dr. Shah is double board certified in OB GYN and reproductive endocrinology. She is a Bay Area transplant, originally from North Carolina. Dr. Shah attended UC Berkeley, followed by a fellowship year at the NIH where she did basic science research in neuro endocrinology. She went to Stanford for medical school and completed a residency in OB GYN and returned to Stanford for her fellowship. During her fellowship, she published articles in areas ranging from fertility preservation to cancer, pregnancy loss, reproductive genetics, and ethnic differences and IVF. She joined Nova in 2017 and continues to engage in medical education with the Stanford community.
Dr. Aimee: Thank you for being on the show, Dr. Shah. Tell us about your practice.
Dr. Meera Shah: Thank you for the opportunity to be on your show — I have so much respect for you, and the practice that you have built!
I also practice in the San Francisco Bay area. My practice is Nova IVF and we are based in Mountain View. I have one practice partner. We specialize in personalized IVF care and providing exceptional patient care, just like you.
Dr. Aimee: Why did you go into medicine and more specifically, why fertility medicine?
Dr. Meera Shah: I took a leap of faith entering a career in medicine because I am the first person in my entire family to become a doctor. My parents immigrated to the US from India and instilled many values in me that allowed me to excel academically. This opened a lot of doors for me that really helped me succeed as a young ambitious and impressionable woman.
The year after I graduated from UC Berkeley, I went to the National Institutes of Health where I did basic science research. I enjoyed it, but it was not the right fit for me. I really liked the idea of translational research — in other words, taking bench concepts from the lab to improve human disease.
And so, I applied to medical school that year and was so fortunate to land a spot at Stanford. I met my future husband there (who is also a physician) and I found incredible mentors, who really paved the way for me to find a passion in women’s health.
I completed my OB GYN residency at UCSF and soon discovered it was a vast field and that I wanted to subspecialize within women’s health. I found the right fit in reproductive medicine, as it allowed me to be challenged intellectually and have great continuity of care with patients. The variety of procedures that we get to do day to day is incredible. And I love being able to help couples fulfill one of the most important purposes in their lives: to build their own family. It has been the most gratifying career I could have ever imagined.
My own personal path to parenthood was not straightforward. Like many of our patients, I found that there were a lot of roadblocks along the way. I had recurrent miscarriages and it challenged me to think about what it is like to be on the other side of the table as a patient. Through those life experiences, I gained a lot of perspective on what it is like to go through fertility treatment. And it has allowed me to really have an appreciation for what we do in our field.
Dr. Aimee: Thank you for sharing such a personal story about yourself as well. Your patients are so lucky to have you as their doctor. I want to go into the questions for today’s topic about ethnic disparities. What ethnic differences exist in women’s overall reproductive health?
Dr. Meera Shah: Let’s start with the beginning of the reproductive spectrum, which we define as menarche, which is the age of onset of a girl’s first period. Even as early as menarche, we do see some differences among ethnic groups.
Most girls will undergo the first period around the age of 12.5, but some studies show that African American and Hispanic girls undergo menarche at a younger age, while Caucasian girls undergo menarche at a later age. These findings might be explained by the different rates of obesity among young girls of different ethnic backgrounds.
On the other end of the reproductive spectrum, there are some differences among ethnic groups in the age of onset of menopause. Black and Hispanic women undergo an earlier onset of menopause as compared to white women. This is important because menopause is linked to cardiovascular disease and osteoporosis. So, for these ethnic groups undergoing menopause at an earlier age, they are at a higher risk for those conditions as well.
Uterine fibroids also have strikingly different incidences among different ethnic groups. Fibroids are essentially a benign overgrowth of the muscular part of the uterus. There is a 3x higher incidence of uterine fibroids in black women. We know that fibroids can affect everything from fertility to menstrual bleeding patterns, and it can affect pregnancy outcomes and increase miscarriage risk.
The last thing I wanted to talk about was polycystic ovarian syndrome or PCOS. It’s a common condition, in as much as 15% of women. It can have a wide variety of symptoms and clinical presentations. We know that it is often misdiagnosed. One of the clinical criteria is the presence of facial hair, which we know is more common in certain ethnic groups.
The severity of the PCOS can differ among different ethnic groups. One study found that Hispanic women had a more severe phenotype of PCOS as compared to Caucasian women. They also manifest some of the androgen excess symptoms and metabolic manifestations of PCOS in a much more severe form as compared to white women. There are limitations to these studies which warrant further investigation, but nevertheless these findings are interesting.
Dr. Aimee: It is interesting because sometimes you might think something is abnormal, but the reality is it is quite normal for you.
And a lot of the studies might say that it is abnormal, but maybe the population they study does not represent you precisely.
Are there also ethnic differences in men’s reproductive health?
Dr. Meera Shah: There are some small studies that suggest that there might be some ethnic differences in semen parameters, testicular architecture, and male factor infertility. There is not a lot of data out there, so we cannot make any conclusive statements.
Interestingly, when researchers were looking at using androgens as a potential male contraceptive, they found that the ability to induce azoospermia (absence of sperm) was only about 60–70% in Caucasian men, compared to 90% in Chinese men.
There might be some slight variations within the Y chromosome genetics that potentially could explain some of these differences. There also might be an underlying biological process that is explaining some of these differences.
Dr. Aimee: Do the differences you have found mean that there are differences in infertility, based on your ethnic group?
Dr. Meera Shah: This is really an important question. What we know is that infertility is a global problem. It does not discriminate against ethnicity, race, or religion. And, there are many causes for infertility. So I’d like to break that down using your creative acronym, the TUSHY method. So just to review your method:
T is for the fallopian Tubes
U is Uterine factor
S is the semen
H is for hormones
Y is your genetic profile
Let’s talk about T first, which is the tubal factor. The fallopian tubes must be healthy and open for a natural conception to occur. Many things can cause abnormalities within the fallopian tubes including prior pelvic infections and endometriosis.
Endometriosis is an inflammatory condition, in which hormonally active cells that are supposed to be inside of the uterus find themselves outside of the pelvic cavity. This can cause scarring and blockage of the fallopian tubes.
An interesting finding in the Nurses’ Health Study was a higher risk of endometriosis among white women compared to black women, and an even higher incidence in Asian women. Asian women had a 6–8 fold higher increase of endometriosis compared to white women. One of the limitations of doing any study with endometriosis is in making the diagnosis. Endometriosis is a pathological diagnosis. It is often misdiagnosed or underdiagnosed.
Overall, we do know that tubal factor is more common in Black women, and this is likely secondary to higher rates of pelvic inflammatory disease, which is primarily caused by chlamydia and gonorrheal infections.
We will move on to U, which is the uterus. Previously, we talked about Black women having a threefold higher risk of uterine fibroids, which can cause problems with getting pregnant and implantation. It can cause issues with miscarriage, specifically later onset miscarriage and other pregnancy-related complications.
We also know that obesity is negatively associated with pregnancy outcomes and pregnancy related complications. And this may be related to several different mechanisms including ovulatory dysfunction and menstrual irregularities, which can impact the uterine lining shedding process and signalling for ovulation. If the uterine lining is not shedding at regular intervals, it can cause thickening, which can over time cause endometrial hyperplasia, which is a risk factor for uterine cancer. Any woman who has irregular cycles needs to be evaluated, especially if it has been ongoing for a long duration.
Unfortunately, we know that obesity affects ethnic groups differently, and it is much more common in Hispanic and Black women. It is likely multifactorial in etiology, caused by dietary, behavioral, genetic, and socioeconomic factors, but the reality is that it is something that we need to address. It is a public health issue.
Next up is sperm factors. There may be some differences related to underlying genetic differences in the Y chromosome. As mentioned earlier, the data is inconclusive, and we need to do some more research.
H stands for the hormonal profile and as you know, one of the markers that we use a lot in assessing fertility and ovarian reserve is AMH, or anti-Mullerian hormone.
In 2013, there was an interesting study conducted at UCSF. They were looking at whether AMH differed between ethnic groups. They found that Black women had lower AMH levels at a younger age, but they experienced less of a reduction of AMH with advancing maternal age. They also found that Hispanic and East Asian women (compared to white women) may have lower AMH levels. This might indicate that they have lower ovarian reserve and might be less responsive to IVF hormones. It also might put them at risk for earlier onset menopause, which may not only have implications for their fertility window, but also implications for their long-term health as it relates to their cardiovascular disease risk and bone health.
Y stands for Your genetic profile. In our field, we do a lot of preconception screening. One of the tests that we often order is a carrier screening, and it allows us to identify whether couples are at risk for having children with specific types of recessive genetic conditions.
The American college of OB/GYN recommends ethnicity-based screenings, which are specific test panels for women and men with specific ethnic backgrounds. For example, couples of Ashkenazi Jewish descent are recommended to undergo additional screening for specific diseases that have a higher carrier frequency in that group. They would screen for diseases like Niemann-Pick, familial dysautonomia, and cystic fibrosis.
Dr. Aimee: What about miscarriage rates? Are there also differences among ethnic groups when it comes to that?
Dr. Meera Shah: There was an interesting study that looked at over 38,000 fresh cycles of IVF, and they found that Black women had a 7% higher risk of miscarriage compared to white women. Most of these miscarriages were in the second trimester.
We generally think about genetic causes of miscarriage in the first trimester. In the second trimester, we think more about systemic conditions, structural causes (like fibroids) and infection. It might be interesting to investigate this pathophysiology more to really understand these differences.
Dr. Aimee: So, what about the IVF outcomes?
I mean, you talked about miscarriage rates and that was profound, what you just shared with us, but IVF outcomes and ethnic, ethnic differences.
Dr. Meera Shah: There are some very striking differences in IVF outcomes, among different ethnic groups.
In looking at women undergoing IVF in five US registries (a large number) the study showed that women of Black, Hispanic, and Asian descent had lower clinical pregnancy rates as compared to white women.
It is important to keep in mind that they did not account for the infertility diagnosis or miscarriage rates, or obesity. They also included multiple cycles for the same patient, which may have affected their findings.
In this same study, Black women were 24% less likely to have a live birth as compared to white women with their first cycle of IVF. A follow-up study including 200,000 IVF cycles found similar results.
There also have been some studies comparing IVF outcomes in Caucasians and East Asians. These studies adjusted for the dose of gonadotropins, number of follicles, and number of eggs retrieved. They found that East Asian women, as compared to Caucasian women, had a much lower live birth rate.
Interestingly, they found that the peak estrogen levels in East Asian women was much higher per follicle. One of the potential explanations for that might be genetic variances in the receptor for FSH (follicle stimulating hormone).
I have a personal interest in IVF outcomes in South Asian women. Studies from Stanford University looked at clinical pregnancy rates, comparing South Asian women to Caucasian women. The study included women transferring a day 5 embryo (blastocyst) and adjusted for potential confounders, such as embryo quality. They found that Caucasian women had higher live birth rates in fresh cycles as compared to South Asian women.
When I joined Stanford as a fellow, I was interested in looking at whether that relationship held true in frozen cycles. One of the potential confounders in fresh cycles is that the uterine environment, specifically the endometrial receptivity, can be altered by the supraphysiologic levels of estrogen and can subsequently affect IVF outcomes. So we looked at a cohort of South Asian and Caucasian women transferring a single blastocyst in frozen cycles. We found that the differences seen in fresh cycles were eliminated in frozen cycles. Live birth rates were completely the same in both ethnic groups. We postulated that this might be explained by differences in endometrial receptivity that we see in fresh stimulated cycles which are controlled for in frozen cycles.
Dr. Aimee: And what about in donor egg IVF? Are there ethnic differences in those types of cycles?
Dr. Meera Shah: We do not have great studies to really make conclusive statements. Here’s what we know.
One study out of Spain compared Black and Caucasian recipients of donor eggs. They found a 40% decrease in ongoing pregnancies among black women. And they did adjust for things like tubal factor and uterine factor infertility. This study was limited by a small sample size and has not been corroborated in other studies yet.
Another difference relates to the ethnicity of the egg donor — One study demonstrated a lower ovarian reserve in egg donors of East Asian descent. This might go back to what I mentioned earlier linking this ethnic group to lower AMH levels. While these donors did not respond as well in terms of their oocyte yields, the actual live birth rates were similar across all ethnic groups.
Dr. Aimee: So, we know that there are a lot of healthcare disparities that exist. What are they and what can we do, especially as fertility doctors to change that?
Dr. Meera Shah: It is very unfortunate that there are very large racial and ethnic disparities that exist across the country. In general, fertility care usage is much higher among white women as compared to other minority groups. And we also know that minority ethnic groups take much longer to come and see us. They might wait a year or two longer, and that can impact treatment, and their psychological perspective on treatment. There is a lot of work to be done around de-stigmatizing infertility, especially among these minority ethnic groups.
We know that cost is a huge barrier, with the cost of IVF potentially exceeding 50% of one’s household income. We know that this is a huge barrier and it might be potentially more of a barrier among certain ethnic groups, and couples of lower socioeconomic status. Interestingly, even among states where infertility care is mandated, we are still seeing disproportionate access to care.
And I personally believe that one of the first things that we need to do is diversify our workforce. It is great to see that this new generation of fertility specialists include so many women of color and women of diverse ethnic backgrounds. Our own patients need to see doctors that look like them, that have similar cultural backgrounds, and that understand the stigma of infertility.
One of the things that I see a lot in my practice is a condition called vaginismus, which is where a woman is unable to have penetrative intercourse because it’s so painful for them. Much of that is psychological. I anecdotally find this condition to be much higher among my South Asian and East Asian patients. I think it relates directly to the taboos around sexuality and being comfortable with your sexual health.
We are doing our best to increase financial coverage for patients. We are fortunate to be in the Bay Area where a lot of tech companies provide fertility benefits, but that is not the case in the rest of the country. States really need to take that on as their responsibility to provide more coverage. Many states do, but the rest need to jump on that bandwagon.
Finally, I believe health education is really important. We can now do that effectively through sessions like these, and other social media platforms. Knowledge is power. The more we can educate women,the more they are going to feel like they can access care, understand it, and feel empowered to ask the right questions and get the information they need to make informed decisions.
Dr. Aimee: Well, I certainly feel a lot more educated on this topic after hearing you talk about all of this stuff, and I hope our listeners learned as much as I do. Thank you for coming on today’s show. So where can our listeners find you if they want to see you as a doctor?
Dr. Meera Shah: We practice that Nova IVF: https://www.novaivf.com/
I have an Instagram profile (@dr_meerashah) where I do a lot of education on women’s health and fertility topics.
Dr. Aimee: Is thereanything else you want to share with our audience before we sign off today?
Dr. Meera Shah: The fertility journey can be a long and circuitous path. Finding the right doctors and the right clinic can really help you achieve your reproductive goals, and it helps you stay positive through the inevitable highs and lows. I think you do an incredible job of that. And I unanimously hear from your patients that Dr. Aimee is one of the most positive people that they encountered on their journey.
As someone who had personal challenges on my own road to parenthood, my best advice to all of you is again, find that provider that you click with. Do not lose yourself during fertility treatment. There are things in life that should still provide you joy. Practice self-care. Self-care prevents burnout as women go through fertility treatment and can ultimately help couples find success in their journey.
Dr. Aimee: Thank you so much for that. That was a really, powerful. And thank you for all your time. Thank you for all the research that you do and that I hope people follow you on Instagram and learn as much as I do from your posts as well.
Dr. Meera Shah: Thank you so much, Dr. Aimee.
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