Abstract

Abstract Study question Do cumulative live birth rates (CLBR) differ between PCOS phenotypes when a freeze-all strategy is used to prevent OHSS after ovarian stimulation (OS)? Summary answer When conventional-dose OS resulted in high response, a CLBR of ∼ 70% was observed after “freeze-all” in women with PCOS, irrespective of their phenotype. What is known already Previous observational studies have shown that CLBR in women with PCOS who undergo assisted reproductive technologies (ART) may depend on their phenotype. When OS was performed with caution to avoid ovarian hyperresponse, CLBR was lower in women with a hyperandrogenic PCOS phenotype. However, when women with PCOS do exhibit hyperresponse and a freeze-all strategy is used, the impact of the PCOS phenotype on the clinical outcome of the ART cycle is unclear. Study design, size, duration This is a single-centre, retrospective cohort study including 422 women with polycystic ovary syndrome (PCOS) as defined by Rotterdam criteria or PCO-like ovarian morphology-only (PCOM) in whom a freeze-all strategy was applied after GnRH agonist triggering in the context of hyperresponse defined as ³19 follicles of ³11mm in their first or second IVF-ICSI cycle between January 2015 and December 2019 in a tertiary referral hospital. Participants/materials, setting, methods PCOS phenotype was based on hyperandrogenism (H), ovulatory dysfunction (O) and PCO-like ovarian morphology (P). Ovarian stimulation was performed with rFSH or HPhMG, adjusted to BMI. The primary outcome was cumulative live birth rate (CLBR) resulting from the transfer of all cryopreserved embryos from the same IVF-ICSI cycle. Patient and cycle characteristics and laboratory and clinical data were analysed. Data were analysed by multivariate logistic regression adjusting for covariates. Main results and the role of chance In total, 91/422 (21.6%) patients had PCOS phenotype A (HOP); 33 (7.8%) had phenotype C (HP), 161/422 (38.2%) had phenotype D (OP) and 137/422 (32.5%) had PCOM (n = 137). BMI, AMH and AFC were significantly different between phenotype groups (p < 0.001), and highest in PCOS phenotype A. The type of gonadotropin used, as well as the mean daily and total stimulation dose were comparable for all groups. The mean number of retrieved oocytes was comparable among groups (22.4±10.8 for phenotype A, 21.4±7.1 for phenotype C, 20.4±7.8 for phenotype D and 22.2±9.7 for PCOM; p = 0.46). The mean number of embryos available for vitrification differed significantly (4.4±3.7, 5.7±3.4, 5.7±3.4 and 5.2±3.6, respectively; p = 0.005). Following the first frozen embryo transfer, LBR was comparable among groups (41.5%, 43.3%, 49.3% and 38.5%, respectively; p = 0.31). Unadjusted CLBR was also similar (69.2%, 69.7%, 79.5% and 67.9%, respectively; p = 0.11). The multivariate logistic regression model adjusting for age, BMI, number of oocytes and embryo stage (cleavage vs. blastocyst stage) confirmed that the PCOS/PCOM phenotype did not have any impact on CLBR (OR 0.80, CI 0.28-2.29 (phenotype C); OR 1.40, CI 0.67-2.90 (phenotype D); OR 0.65, CI 0.31-1.34 (PCOM); p = 0.1, with phenotype A as reference). Limitations, reasons for caution These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. The results cannot be generalised to all ART cycles in women with polycystic ovaries as they pertain to those cycles where OS leads to hyperresponse. Wider implications of the findings In subfertile women with PCOS eligible for ART, hyperresponse after OS confers excellent cumulative live birth rates when a freeze-all strategy is used, eliminating unfavourable clinical outcomes that had previously been observed in hyperandrogenic PCOS women after mild OS targeting normal ovarian response and fresh embryo transfer. Trial registration number not applicable

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