Guest blog by Dr. Christine Palma, L.Ac, DACM, one of NYC’s top fertility acupuncturists.
The American Society for Reproductive Medicine (ASRM) has declared that creation of a family is a basic human right. Infertility is a global problem affecting all ethnic, racial, and religious groups. It’s fairly easy to find articles that have data to suggest this problem is due to lack of access to treatment. The majority of those that have access to treatment are white1. But what if these worse outcomes aren’t only due to lack of access, but to the entire reproductive medicine paradigm being developed solely around white women?
What if I told you that most drugs are tested primarily on white people? What if I told you that most of the information in gynecology or reproductive endocrinology medical textbooks comes from studies that were primarily on white women? And why is this important to me? I’m Latina. If someone from the Latinx community does a 23andme or Ancestry DNA analysis, it will show a unique combination of Spanish, Native American and African DNA. 23andme can predict where in the Spanish speaking world you are from based on these ratios and which Native American ancestry you have. It’s pretty fascinating. We can be prone to genetic problems that arise from these 3 different populations. You would think we’d be recruited more in clinical trials due to our genetic complexity and especially since we are almost 20% of the US population.
Why is this important to you? The Society of Reproductive Medicine, SART, has examined racial disparity and noted some interesting findings. They discovered Asian women required a longer duration of stimulation, had fewer eggs retrieved and had fewer surplus five day embryos to freeze compared to white women. Asian women also had a significantly lower clinical pregnancy rate and live birth rate compared to white women. Black women were also markedly worse when compared to white women. The clinical pregnancy rate was significantly lower and the spontaneous abortion rate was significantly higher. Most important, the live birth rate among black women was almost half that of white women (16.9% vs. 30.7%)1,2.
The majority of patients in my NYC acupuncture clinic are Southern European, Latina, Middle Eastern, Indian (from India), African American and Jewish. Many are told they are poor responders. Maybe it’s not them. These fertility drugs have not been tested on these populations and maybe there are other reasons why they don’t work. Everything we know about ovarian reserve is based on white women and the paradigm of reproductive medicine is based on this data.
While I was working as an engineer over a decade ago at one of the top medical device manufacturers, Boston Scientific, there was such an awareness of the need for diversity in clinical trials3. The majority of clinical trial participants are white. For a company whose business is heavily invested in heart disease, they knew how important it was to recruit more minorities so that our products work on everybody. This awareness of the need for diversity is absent in fertility medicine.
First, let’s look at the most critical and expensive fertility drugs, Follistim, Gonal-f, and Menopur. Some of the best clinical data you are going to get is what was used to get FDA approval. FDA approval is the primary goal of any pharmaceutical or medical device company. The US market typically is top in sales and has the most difficult regulatory process. The company trying to get FDA approval is spending millions of dollars with an army of engineers, statisticians, clinicians, and scientists behind this effort. Anything coming out afterwards is a bonus, not the primary focus. You can figure out what clinical data the manufacturer of the drug used for FDA approval by looking at the prescribing information that is inserted with the drug.
Follistim used the ENGAGE study to get FDA approval for ovarian stimulation4. The ENGAGE study randomized 1509 women between Follistim and another drug. They used 14 centers in North America, 17 centers in Northern Europe and only 3 centers in Southern Europe. No centers in South America, Africa, the Middle East, Australia or anywhere in Asia were included (this is typical and unfortunate). We can see straight away how the majority of Caucasians are of Northern European decent. Now let’s look at the breakdown. Asians comprised 2.8% of participants, African Americans 3.7%, Caucasians 86.7% and “Other” was 6.8% of the clinical trial. I wish I can tell you what other was. White alone in the US is 60%, African American 13.4%, Native American 1.3%, Asian 5.9%, Latinx 18.5%, multi-race 2.8% and Native Hawaiian/Pacific Islander 0.2%. This is such a disconnect to be happening as late as 2008, when this study was conducted.
The clinical studies Gonal-f used to get FDA approval did not record participant race5. Since I couldn’t get racial information from the FDA submission data, I went digging through other clinical trials. One trial with a good sample size was “Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial6”. There were 1,329 women in this trial. For Gonal-f, 93.6% of participants were White. 1.8% were Black, 4.4% were Asian, ZERO were Latina, and surprisingly 0.2% were American Indian. These results were published in 2016. This is almost insane the lack of minorities in this study considering this study was published not long ago. Another good clinical trial I found was “Randomized, controlled, open-label, noninferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa7”. White women were 96.6% of the participants. 96.6%!!! This was also published a few years ago.
Menopur is an old drug from the 1970s. A quick glance at the Menopur insert shows the FDA approval came from testing in Europe and Israel8. That’s not going to be racially representative of the US but at least they can say this happened in the 1970s, before when we should have known better. I went digging around for other phase 3 or 4 trials. There’s actually not much there for either Menopur, Follistim or Gonal-f. One trial I thought was interesting was “Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS)9”. PCOS is usually excluded in clinical trials for these drugs and IVF studies in general so this is a nice data point. There were 110 women split between Menopur and Follitropin beta. Those groups were split again between progesterone in oil and using progesterone inserts. Combining all the Menopur data, 69% of participants were white, 2% were black, 11.5% were Asian, 17% were Hispanic. Asian and Hispanic representation was not bad. Black was terribly low. This data is pretty interesting. Do we finally see more minority representation because this problem might affect minorities more than whites?
Second, let’s look at the parameters used to determine the likelihood of fertility success. Ovarian markers such as AMH, antral follicle count, FSH, and even the number of eggs we are born with, all come exclusively from studies on white women. Yen & Jaffe’s Reproductive Endocrinology10 has this nice graph showing how ovarian markers change with age.
This data comes from a study that was done EXCLUSIVLEY on white women11. Two very popular textbooks, Speroff’s Clinical Gynecologic Endocrinology & Infertility12, and William’s Gynecology13 reference the same study for the number of eggs a woman is born with and how that number declines with age. That data comes from cadaver studies done exclusively on white women14. Reproductive Endocrinologists get their baseline knowledge from these summary texts. No one has time to fact check thousands of references. You just assume when you read one of these books that someone has done that for you. We should be getting our data from all races.
Racial disparity in fertility goes beyond lack of access to care or stigmas within certain communities. The entire fertility paradigm was developed studying the disease and testing treatments primarily on white women. In other specialties of medicine, like cardiology, they know how important it is to study the disease and treatments on all races. I hope my blog can bring a new awareness to the field of reproductive medicine and in the future, we can begin to do studies that include all races.
Dr. Christine Palma, L.Ac, DACM, is one of NYC’s top fertility acupuncturists. She has successfully helped women struggling with infertility caused by endometriosis, polycystic ovarian syndrome, premature ovarian failure, advanced maternal age, thin endometrial lining, irregular menstrual cycles, and recurrent miscarriage. Her clinic, Fire Over Water Acupuncture, is located in the Manhattan neighborhood of the Upper West Side.