Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome

Abstract

STUDY QUESTION: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?SUMMARY ANSWER: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.WHAT IS KNOWN ALREADY: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.STUDY DESIGN, SIZE, DURATION: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS:At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.MAIN RESULTS AND THE ROLE OF CHANCE: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth. LIMITATIONS, REASONS FOR CAUTION:The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relative...

Comparing the risk of adverse pregnancy outcomes of Chinese patients with polycystic ovary syndrome with and without antiandrogenic pretreatment

“…Recently, a prospective study by Wei et al reported that menses induction by COC before IVF was associated with higher pregnancy loss rate and lower live-birth rate (36). This study cannot be compared with our study: First, their study endpoints were pregnancy loss rate and live-birth rate, which were not discussed in our study.…”

Fresh versus Frozen Embryo Transfer in PCOS: Arguments for and Against

“…However, a secondary analysis of our data collected in the randomized trial revealed that oral contraceptives for such purpose had an adverse effect on outcome of fresh embryo transfer in terms of the rates of pregnancy and live birth. 6 In contrast, such effect of oral contraceptives was greatly diminished by performing freeze-all and frozen embryo transfer. 6 Thus, in those cycles with oral contraceptive scheduling, frozen embryo transfer may be a better choice than immediate fresh embryo transfer to achieve live birth, though further studies are needed to obtain a confirmed conclusion.…”

“…6 In contrast, such effect of oral contraceptives was greatly diminished by performing freeze-all and frozen embryo transfer. 6 Thus, in those cycles with oral contraceptive scheduling, frozen embryo transfer may be a better choice than immediate fresh embryo transfer to achieve live birth, though further studies are needed to obtain a confirmed conclusion.…”

“…Second, due to oligo-/anovulation and unpredictability of menses cycle, oral contraceptives or progestin are frequently used to schedule the start of infertility treatment. 5,6 Third, endocrine and metabolic alterations such as hyperandrogenism and insulin resistance are commonly present in patients with PCOS. 7 Even singleton pregnancies resulted from IVF in patients with PCOS have higher risks of obstetric complications, including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, and large-for-gestational-age infants, than that in non-PCOS controls.…”

Effects of oral contraceptive pretreatment on IVF outcomes in women following a GnRH agonist protocol

“…Recent studies have investigated the effects of oral contraceptive pretreatment prior to different ovarian stimulation protocols on cycle outcomes, and it has been reported that oral contraceptives used for menses induction prior to the GnRH antagonist protocol are associated with poor outcomes after fresh embryo transfer, including a lower live birth rate, a lower pregnancy rate and a higher pregnancy loss rate (Farquhar et al, 2017;Griesinger et al, 2008;Wei et al, 2017). However, there is still insufficient evidence for the effect of oral contraceptive pretreatment on cycle outcomes in women undergoing the GnRHa long protocol or the GnRHa short protocol.…”