Endometriosis: Are stem cells to blame?

Endometriosis and fertility

Endometriosis is found in 20% to 50% of infertile women. We theorize that it affects fertility by impairing oocyte development and/or quality, sperm penetration or fer-tilization, tubal function, and implantation. Without treatment, spontaneous monthly fecundity rates are between 2% and 3%.

Forget hormonal therapies. But that said, do not attempt medical suppression of endometriosis in women who hope to conceive. Hormonal therapies, such as danazol, progestins, and GnRH agonists, are ineffective despite their suppressive effect on endometriosis implants. They prevent ovulation and only further delay fertility.15,16 Surgery for endometriosis-associated infertility can modestly increase the monthly fecundity rate to under 5%.

Refer early to fertility specialists. Ovulation induction using clomiphene, coupled with intrauterine insemination, increases monthly fecundity rates to 9% and gonadotropin-controlled ovarian hyperstimulation further raises monthly fecundity rates to about 15%. In vitro fertilization has the highest monthly success rates in patients with endometriosis-associated infertility, reaching pregnancy rates of 30% to 50% per cycle, depending on age. Clearly, patients with endometriosis-associated infertility can benefit from early referral for infertility treatment.

Future directions

Why do current medical and surgical procedures fail so often? And why do drugs fail to restore fertility? As we begin to understand more about the molecular and cellular defects in endometriosis, we have begun to explain these phenomena. The stem cell theory explains how endometriosis can be found remote from the peritoneal cavity, resist some treatments, and occasionally even occur after hysterectomy. Endometriosis has also found ways to avoid the normal hormonal restraints that we use to control it. By ex-pressing its own aromatase, endometriosis can make high local concentrations of estrogen and resist treatment with GnRH agonists. We have recently learned that in women with endometriosis, the progesterone response is blunted or undetectable, indicating a resistance to progesterone. Patients who fail conventional medical treatment likely have progesterone resistance. In the future, treatment options for endometriosis may need to target progesterone resistance.

Finally, we’ve recently shown that endometriosis induces epigenetic changes in the uterus that inhibit implantation. These changes involve DNA methylation and persist even after the endometriosis is removed. This finding helps to explain the continued infertility even after complete surgical resection of endometriosis. An understanding of the scientific basis of this enigmatic disease has and will continue to lead to novel and superior treatments for endometriosis.

Two important messages to keep in mind when treating patients with endometriosis: (1) recognize the treatment goal for each woman, whether it’s pain management or preserving or restoring fertility; (2) impress upon her that endometriosis is a disease that can be chronic and incurable. Fortunately, a broad and expanding armamentarium is available to treat these women.

DR. KULP is Instructor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT.

DR. TAYLOR is Professor of Obstetrics, Gynecology and Reproductive Sciences, and Director of Reproductive Endocrinology and Infertility at the Yale University School of Medicine. He is also Professor of Molecular, Cellular and Developmental Biology at Yale University and a recipient of eight National Institutes of Health research grants. Dr. Taylor is on the Speaker’s Bureau at Wyeth.

By: Jennifer L. Kulp, MD, Hugh S. Taylor, MD
Contemporary OB/GYN


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