Progestin May Reduce Conception Rates in Women With PCOS

In anovulatory women with polycystic ovary syndrome (PCOS), one-time use of progestin to induce withdrawal bleeding before ovulation induction may decrease the odds of conception and live birth, according to a new study conducted by researchers for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIHCD) Cooperative Reproductive Medicine Network (RMN).¹

Often, one of the first steps in infertility treatment for women with PCOS is a one-time dose of progestin. The hormone causes the uterine lining to thicken, and without progestin maintenance therapy, the uterine lining sloughs off and bleeding begins. The logic behind this common clinical practice is to simulate the bleeding that begins a normal monthly menstrual cycle.²

Using data from 626 women with PCOS obtained in a previous study, the researchers performed a secondary analysis to estimate whether using progestin to mimic menstruation before ovulation induction with clomiphene, metformin, or a combination of clomiphene and metformin has any affect on ovulation, conception, and live birth rates.¹ Metformin was used in the original study because women with PCOS often have insulin resistance.³ However, the original study showed that women were less likely to become pregnant and give birth than women taking clomiphene alone or clomiphene in combination with metformin.³

In this study, ovulation rates were higher after cycles involving spontaneous endometrial shedding than after anovulatory cycles with or without progestin (72% vs 30% vs 27%, respectively).¹ However, the rates of conception and live births were higher after anovulatory cycles without the use of progestin. When calculated per cycle, the live birth rates were 2.2% for women who had spontaneous menses, 1.6% for women who had anovulatory cycles with progestin withdrawal, and 5.6% for those who had anovulatory cycles without progestin. Even more significant, the live birth rate per ovulation was 3.0% for the spontaneous menses group, 5.4% for the anovulatory with progestin withdrawal group, and 19.7% for the anovulatory without progestin group.

One study author (Esther Eisenberg, MD) summarized the results as follows: “Our results indicate that a treatment with progestin before ovulation induction is counterproductive in helping women with PCOS achieve pregnancy.”²

Pertinent Point:

The common practice of progestin-induced endometrial shedding before ovarian stimulation may adversely effect the rates of conception and live birth in anovulatory women with PCOS.

References:

References
1. Diamond MP, Kruger M, Santoro N, et al. Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome. Obstet Gynecol. 2012;119(5):902-908.
2. U.S. Department of Health and Human Services, National Institutes of Health. Progestin treatment for polycystic ovarian syndrome may reduce pregnancy chances Accessed May 28, 2012.
3. Legro RS, Barnhart HX, Schlaff WD, et al, for the Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551-566.