Even before starting medical school, Hugh Taylor, MD, HS ’92, FW ’98, chair and the Anita O’Keeffe Young Professor of Obstetrics, Gynecology and Reproductive Sciences, knew he would build a career as a physician-scientist. The Connecticut native studied molecular biophysics and biochemistry as an undergraduate at Yale, and planned to use basic science research to investigate the intricacies of cancer biology. Those plans changed on his first day of clinical rotations as a third-year medical student on the labor and delivery floor. On call that night, Taylor rushed to the emergency department, where he joined surgeons and staff operating on a woman with a life-threatening ruptured fallopian tube caused by an ectopic pregnancy. In the same shift, an obstetrician guided Taylor as he helped deliver a baby. “I loved the sense of urgency and immediacy of it all,” he says.
After finishing his obstetrics and gynecology residency at Yale New Haven Hospital, Taylor buried himself in work studying genes that influence the development of Drosophila flies. That background helped years later, while his lab worked toward a discovery that Hox genes drive the differentiation process that separates the female reproductive tract into the uterus, cervix, fallopian tubes, and vagina. Early in his career, he and his team also contributed to the field’s understanding of how endocrine disruptors like bisphenol A (BPA) might be harmful to fetuses and children.
Taylor’s interest in fundamental developmental biology led him to an unsolved mystery—endometriosis—a disorder that affects an estimated 1 in 10 U.S. women, and likely more because the condition is underdiagnosed. The painful condition causes tissue that usually lines the uterus to grow outside it. “It’s a really troubling disease—we don’t know how this happens, but we are doing research to find out why,” says Taylor, who will become president of the American Society for Reproductive Medicine in 2021. “Yale Medicine Magazine” caught up with Taylor to learn about the latest research in endometriosis and what’s on the horizon in fertility preservation.
What are some of the latest findings from your lab on endometriosis?
First, we’ve historically thought of endometriosis as a condition that happens when a little bit of uterine tissue flows backward out of the fallopian tubes during menstruation, and implants and grows in the wrong direction. We’ve created a new theory for the etiology of endometriosis. Because we occasionally see endometriosis in the lungs or the brain—places it just cannot get from flowing out of the fallopian tubes into the abdomen—we believe there’s a stem cell component to it.
In our animal studies, we’ve found that endometriosis affects things like metabolism and weight and can cause inflammation. Women with endometriosis are more likely to be depressed or anxious and have a lower pain threshold. This means it has an impact on multiple organ systems outside of the pelvis, and so we are doing a push to describe it as a systemic disease. I’ve been on my own personal mission to make sure people know these are effects of the disease. Far too often, we hear that women with endometriosis are complainers. But no, they are not complainers. The disease sensitizes them to pain and makes them more anxious. We want to try to reverse some of these stigmas.
And endometriosis currently can be diagnosed only by a surgical procedure called a laparoscopy, which involves passing a tube with a tiny video camera through a small incision in the abdomen to examine the ovaries, fallopian tubes, uterus, and other organs, right?
That’s right. However, we’ve created a blood test that detects levels of certain microRNAs (which are short noncoding RNA fragments that regulate gene expression) that we are testing in clinical trials. We hope that this will enable anyone to diagnose endometriosis at its very earliest stages.
Now a woman lives with the disease for an average of 10 years before it is diagnosed. There are a lot of reasons for that. One is that menstrual pain and cramping is some of the only pain in medicine that’s considered normal, so people tend to dismiss it. Pain is usually the first sign of endometriosis. If we could recognize the disease earlier, I think we could provide treatment earlier, and prevent some of the long-term complications of the disease like infertility and scarring.
What’s an important issue in fertility today?
One issue is the woman’s biological clock. We know that somewhere around age 40, most women will stop producing high-quality eggs. Up until recently, once women reached that barrier, they had to rely on donated eggs. But these days, more women are choosing to freeze their eggs. With egg freezing, the biological clock is less relevant. The uterus, the ability to become pregnant, doesn’t change as much with age. Of course, there are diseases that can impact pregnancy at any point. But a woman could come back in her 40s, and if she has eggs in the freezer, that could allow for a successful pregnancy. Of course it’s not a guarantee. But if you are healthy and have good eggs, there is a possibility.
In the far future, what is something that could happen in the field of fertility?
We haven’t looked at this in humans at all yet. But it’s possible to make egg and sperm cells from stem cells. We could make eggs long after a woman reaches menopause and make sperm from female cells. This means that women would not need a man—the sperm could be produced outside the body. Whether that would be safe—it’s a big unknown.