Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary Syndrome

Abstract

Objective-To estimate whether progestin-induced endometrial shedding, prior to ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS).Methods-A secondary analysis of the data from 626 women with PCOS from the National Institutes of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed).Results-While ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live birth per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; p<0.001). The difference was more marked when rate was calculated per ovulation (live birth per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; p < .001).Conclusion-Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared to anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin prior to ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS.

To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt?

“…Physicians are commonly asked by their patients whether ovarian stimulation may bear any carryover effect on a subsequent treatment (16), and FETs are frequently postponed in an attempt to minimize any conceivable residual effect that ovarian stimulation may have on endometrial receptivity (17). However, the literature on this matter is rather scarce (18,19). For this reason, although this empirical decision may be based on the best of intentions, the elective deferral of FETs may unnecessarily frustrate couples who wish to become pregnant as soon as possible.…”

The stair-step approach in treatment of anovulatory PCOS patients

“…In addition, inducing a menstrual bleeding with progestin before CC therapy in anovulatory women has been shown to be unnecessary 8 and has been associated with a lower conception and live birth rates compared with women in whom CC was started in the follicular phase remote from spontaneous or induced menses. 9 Recently, Jones and colleagues 10 completed a retrospective study of women who remained anovulatory with the initial starting CC dose of 50 mg.…”

“…Taking these novel findings [7][8][9][10][11][12] into account, we sought to further simplify OI treatment in CC resistant PCOS patients and apply the same therapeutic approach during the transition phase between CC treatment and gonadotropin therapy. Instead of inducing progestin withdrawal bleeding before initiation of gonadotropin therapy, we began the administration of gonadotropins using the chronic low-dose protocol once it was clear that the highest CC dose that was used failed to induce ovulation.…”

SGI 2012: What'S New in Obstetrics/Gynecology and Reproductive Medicine: An Update from the Society for Gynecologic Investigation

“…Among other clinical reports, a number of abstracts were related to infertility in general and to polycystic ovary syndrome in particular. Among these, a presentation by Michael Diamond (Wayne State University, MI, USA) representing the Reproductive Medicine Network and recently published in the Green Journal Vas incredibly intriguing [2]. This study of 626 women with polycystic ovary syndrome represented a secondary analysis of a previously published trial comparing clomiphene citrate alone, metformin alone or clomiphene citrate plus metformin [3].…”