Precision Ob/Gyn: We Need A Digital Approach To Endometriosis And Ovulatory Dysfunction
From Democratizing IVF: Using Science, Medicine, And Engineering (And Venture Capital) To Help Build Families
Twenty-first century precision gynecology will mean redefining and deepening our understanding of long-recognized but poorly characterized conditions.
One particularly frustrating example is endometriosis. Women suffer from debilitating pain, intolerable periods, and infertility from endometriosis. Strictly defined, endometriosis is the appearance of the types of cells (glands and storm) that line the uterus, cells that nurture an early pregnancy, in places other than the uterus, usually on the cells lining the abdomen and pelvis. We have no great treatment for endometriosis. We can zap it surgically with a laser or with an electrode, and we can use birth control pills or other hormone-suppressing medications that turn off the menstrual cycle, creating a temporary menopause; it seems as if pregnancy reduces or reverses endometriosis symptoms. Very aggressive surgery to find and remove endometriosis in the deep tissue surrounding the vagina and rectum has been used in severe cases as well, as has hysterectomy for particularly severe cases.
If these treatments seem small-r radical — well, they are. They do not so much treat endometriosis as they erase the reproductive system.
Painful periods? Turn them off.
Hormonally-dependent symptoms? Induce menopause.
Inflamed and scarred reproductive system? Remove it.
Not the precision medicine with which we want to define healthcare in the 21st century.
If our treatments for endometriosis are imprecise and heavy-handed, they do reflect our imperfect understanding of what we are treating. For many women, endometriosis is an enigma. We sometimes stumble upon it while doing other procedures in women who have no symptoms whatsoever. Conversely, women often present with textbook symptoms, strongly suggestive of severe endometriosis, but with no evidence of it after a thorough diagnostic workup.
Clearly, we are missing something. Is endometriosis a normal variant in some women? Is endometriosis with symptoms a disease, while endometriosis without symptoms is not?
Unfortunately, the combined doctor and patient frustration over our very incomplete understanding of endometriosis has not been channeled into clinically meaningful progress over the past few decades. Worse, one still hears anecdotes about women’s symptoms being dismissed, based on our inability to adequately explain them.
Similarly, our understanding of disorders of ovulation that result in infertility is simplistic, easy to misunderstand, mis-treat, and mis-communicate.
Menstrual cycles are typically described in three ways: as normal, or exhibiting characteristics of one of two hormonal abnormalities: polycystic ovarian syndrome or hypothalamic amenorrhea.
Polycystic ovary syndrome (PCOS) seems pretty well characterized on the surface. With PCOS, there are quite specific changes in the cycling levels of the brain hormones that stimulate the ovaries. The ovaries have a distinct appearance on ultrasound, periods can be mildly to totally irregular, and there are sometimes manifestations of high levels of testosterone and similar hormones. Recognizing PCOS is particularly important in women taking fertility drugs, when the large number of small, partially matured eggs mature all at once, creating a hormonal storm of sorts, making these woman at high risk for ovarian hyperstimulation syndrome (OHSS), a serious complication.
The other, less common type of ovulatory dysfunction, hypothalamic amenorrhea, is characterized by minimal stimulation by brain hormones to the ovaries. Women do not have periods at all with the syndrome, and need high doses of fertility drugs to “wake the ovaries up.“
The two entities appear quite distinct, hypothalamic amenorrhea and PCOS, and each needs a very different approach to the fertility drugs that we use in IVF. Hypothalamic amenorrhea needs high doses of both of the hormones with which the body stimulates the ovaries (luteinizing hormone or LH, and follicle stimulating hormone, FSH) while PCOS is best treated with light doses of FSH alone.
This all seems so easy in a textbook.
Unfortunately, our definitions and categorizations break down quickly. Physical signs, lab results and ultrasound findings can be contradictory, or a patient with “classic” PCOS fails to respond to medication or a patient with hypothalamic amenorrhea responds as if she has PCOS, developing hypothalamic amenorrhea.
In most of these cases we can pivot treatment and compensate for the imperfect assumptions that we inferred from taking a patient history, doing a physical exam, drawing blood tests and doing ultrasound scans. Over time, we develop a more nuanced understanding — and a proprietary vocabulary (“pseudo-hypothalamic” or “ovulatory PCOS” for example.) But we have not evolved our understanding to a higher, consistent standard. Relaxing the rigidity of our definitions makes them no less analog and imprecise.