Abstract
Study question
How do live birth rates differ in anovulatory women with polycystic ovary syndrome and hypothalamic hypogonadism compared to normo-ovulatory women undergoing fresh or frozen embryo transfer?
Summary answer
Live birth rates are similar among all groups undergoing fresh embryo transfer but are significantly lower in women with hypothalamic hypogonadism undergoing frozen embryo transfer.
What is known already
Conflicting data exist regarding pregnancy outcomes in patients with tubal factor infertility versus polycystic ovary syndrome (PCOS). Some studies demonstrate higher pregnancy and live birth rates for women with PCOS undergoing fresh embryo transfer, but other studies demonstrate no difference. Women with PCOS have higher live birth rates than those with tubal factor infertility when undergoing frozen embryo transfer. Fewer data are available regarding IVF outcomes in women with hypothalamic hypogonadism (HH) and tubal factor infertility. Several studies report comparable live birth rates with fresh embryo transfer, but there are no data on frozen embryo transfer outcomes.
Study design, size, duration
Retrospective cohort study of all fresh and frozen autologous embryo transfers performed for patients with oligo-anovulation (PCOS, n = 380 and HH, n = 39) and normo-ovulation (tubal factor infertility, n = 315) from 1/1/2012 to 6/30/2019. A total of 734 transfers from 653 patients were analyzed.
Participants/materials, setting, methods
Transfer outcomes, including implantation, miscarriage, clinical pregnancy and live birth rates, were assessed in fresh and frozen embryo transfer cycles. Adjusted relative risks (RR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, stimulation protocol, number of embryos transferred, embryo quality, endometrial stripe thickness and day of transfer. Poisson regression was used for counts and with an offset for ratios. Generalized estimating equations were used to account for patients contributing multiple cycles.
Main results and the role of chance
For fresh embryo transfer cycles, live birth rates are similar among patients with tubal factor infertility, PCOS and HH (29.5% vs. 37.9% vs. 35.9%, respectively, aRR 1.15 95% CI: 0.91–1.44 and aRR 1.23 95% CI: 0.81–2.00, respectively). When evaluating frozen embryo transfer cycles, patients with HH have lower live birth rates than patients with tubal factor infertility (26.5% vs. 42.6%, aRR 0.54 95% CI: 0.33–0.88) and patients with PCOS (26.5% vs. 46.7%, aRR 0.55 95% CI: 0.34–0.88). Additionally, patients with HH have higher chemical pregnancy rates and miscarriage rates than patients with tubal factor infertility (26.5% vs. 13.0% and 17.7% vs. 6.5%, respectively, RR 2.71 95% CI: 1.27–5.77 and RR 2.03 95% CI: 1.05–3.80, respectively). Point biserial correlation showed no significant correlation between live birth and endometrial stripe thickness in HH patients undergoing frozen embryo transfer (r = 0.028, p-value 0.876).
Limitations, reasons for caution
This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited.
Wider implications of the findings: Lower live birth rates for HH patients undergoing frozen embryo transfer cycles are not correlated with endometrial stripe thickness. This may be due to absent gonadotropin signaling on endometrial receptors. A prospective randomized trial of HH patients to modified natural versus programmed frozen embryo transfer would best support this hypothesis.
Trial registration number
Not applicable
Live birth after fresh embryo transfer vs elective embryo cryopreservation/frozen embryo transfer in women with polycystic ovary syndrome undergoing IVF (FreFro-PCOS): study protocol for a multicenter, prospective, randomized controlled clinical trial
