Cumulative live birth rate after ovarian stimulation with freeze-all in women with polycystic ovaries: does the polycystic ovary syndrome phenotype have an impact?

RESEARCH QUESTION: Do cumulative live birth rates (CLBR) differ between polycystic ovary syndrome (PCOS) phenotypes when a freeze-all strategy is used to prevent OHSS after ovarian stimulation? DESIGN: A single-centre, retrospective cohort study of 422 women with PCOS or polycystic ovarian morphology (PCOM), in whom a freeze-all strategy was applied after GnRH agonist triggering because of hyper-response in their first or second IVF/ICSI. Primary outcome was CLBR; multivariate logistic regression analysis was used. RESULTS: Phenotype A (hyperandrogenism + ovulation disorder + PCOM [HOP]) (n = 91/422 [21.6%]); phenotype C (hyperandrogenism + PCOM [HP]) (33/422 [7.8%]; phenotype D (ovulation disorder + PCOM [OP]) (n = 161/422 [38.2%]); and PCOM (n = 137/422 [32.5%]. Unadjusted CLBR was similar among the groups (69.2%, 69.7%, 79.5% and 67.9%, respectively; P = 0.11). According to multivariate logistic regression analysis, the phenotype did not affect CLBR (OR 0.72, CI 0.24 to 2.14 [phenotype C]; OR 1.55, CI 0.71 to 3.36 [phenotype D]; OR 0.84, CI 0.39 to 1.83 [PCOM]; P = 0.2, with phenotype A as reference). CONCLUSIONS: In women with PCOS, hyper-response after ovarian stimulation confers CLBR of around 70%, irrespective of phenotype, when a freeze-all strategy is used. This contrasts with unfavourable clinical outcomes in women with hyperandrogenism and women with PCOS who underwent mild ovarian stimulation targeting normal ovarian response and fresh embryo transfer. The results should be interpreted with caution because the study is retrospective and cannot be generalized to all cycles as they pertain to those in which hyper-response is observed.

Live births after in vitro maturation of oocytes in women who had suffered adnexal torsion and unilateral oophorectomy following conventional ovarian stimulation.

PURPOSE: To report the first successful application of in vitro maturation (IVM) of oocytes resulting in live births in two anovulatory women who had suffered oophorectomy following ovarian torsion after stimulation with gonadotropins. METHODS: Data abstraction was performed from medical records of two subfertile women with excessive functional ovarian reserve. Both women had previously received gonadotropins for ovulation induction or ovarian stimulation, resulting in ovarian torsion. They were offered IVM of oocytes retrieved from antral follicles after mild ovarian stimulation, insemination of mature oocytes using ICSI, and embryo transfer. Outcome measures were the incidence of complications and live birth after fertility treatment. RESULTS: Transvaginal retrieval of cumulus-oocyte complexes from a unique ovary was conducted. One patient had a singleton live birth after vitrified-warmed embryo transfer in the second IVM cycle. The other patient had a singleton live birth after transfer of a fresh blastocyst in her first IVM cycle. CONCLUSIONS: Although approaches have been developed to prevent ovarian hyperstimulation syndrome (OHSS) and to increase the safety profile of fertility treatment in predicted high responders, women with an excessive functional ovarian reserve may have a non-negligible risk of ovarian torsion. For these patients, IVM should be considered as a safer alternative approach.

Outcome of in-vitro oocyte maturation in patients with PCOS: does phenotype have an impact?

STUDY QUESTION: Does the phenotype of patients with polycystic ovary syndrome (PCOS) affect clinical outcomes of ART following in-vitro oocyte maturation? SUMMARY ANSWER: Cumulative live birth rates (CLBRs) after IVM were significantly different between distinct PCOS phenotypes, with the highest CLBR observed in patients with phenotype A/HOP (= hyperandrogenism + ovulatory disorder + polycystic ovaries), while IVM in patients with phenotype C/HP (hyperandrogenism + polycystic ovaries) or D/OP (ovulatory disorder + polycystic ovaries) resulted in lower CLBRs (OR 0.26 (CI 0.06-1.05) and OR 0.47 (CI 0.25-0.88), respectively, P = 0.03). WHAT IS KNOWN ALREADY: CLBRs in women with hyperandrogenic PCOS phenotypes (A/HOP and C/HP) have been reported to be lower after ovarian stimulation (OS) and ART when compared to CLBR in women with a normo-androgenic PCOS phenotype (D/OP) and non-PCOS patients with a PCO-like ovarian morphology (PCOM). Whether there is an influence of the different PCOS phenotypes on success rates of IVM has been unknown. STUDY DESIGN, SIZE, DURATION: This was a single-centre, retrospective cohort study including 320 unique PCOS patients performing their first IVM cycle between April 2014 and January 2018 in a tertiary referral hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Baseline patient characteristics and IVM treatment cycle data were collected. The clinical outcomes following the first IVM embryo transfer were retrieved, including the CLBR defined as the number of deliveries with at least one live birth resulting from one IVM cycle and all appended cycles in which fresh or frozen embryos were transferred until a live birth occurred or until all embryos were used. The latter was considered as the primary outcome. A multivariate regression model was developed to identify prognostic factors for CLBR and test the impact of the patient's PCOS phenotype. MAIN RESULTS AND THE ROLE OF CHANCE: Half of the patients presented with a hyperandrogenic PCOS phenotype (n = 140 A/HOP and n = 20 C/HP vs. n = 160 D/OP). BMI was significantly different between phenotype groups (27.4 ± 5.4 kg/m2 for A/HOP, 27.1 ± 5.4 kg/m2 for C/HP and 23.3 ± 4.4 kg/m2 for D/OP, P < 0.001). Metformin was used in 33.6% of patients with PCOS phenotype A/HOP, in 15.0% of C/HP patients and in 11.2% of D/OP patients (P < 0.001). Anti-müllerian hormone levels differed significantly between groups: 12.4 ± 8.3 µg/l in A/HOP, 7.7 ± 3.1 µg/l in C/HP and 10.4 ± 5.9 µg/l in D/OP patients (P = 0.01). The number of cumulus-oocyte complexes (COC) was significantly different between phenotype groups: 25.9 ± 19.1 COC in patients with phenotype A/HOP, 18.3 ± 9.0 COC in C/HP and 19.8 ± 13.5 COC in D/OP (P = 0.004). After IVM, patients with different phenotypes also had a significantly different number of mature oocytes (12.4 ± 9.3 for A/HOP vs. 6.5 ± 4.2 for C/HP vs. 9.1 ± 6.9 for D/OP, P < 0.001). The fertilisation rate, the number of usable embryos and the number of cycles with no embryo available for transfer were comparable between the three groups. Following the first embryo transfer, the positive hCG rate and LBR were comparable between the patient groups (44.7% (55/123) for A/HOP, 40.0% (6/15) for C/HP, 36.7% (47/128) for D/OP, P = 0.56 and 25.2% (31/123) for A/HOP, 6.2% (1/15) for C/HP, 26.6% (34/128) for D/OP, respectively, P = 0.22). However, the incidence of early pregnancy loss was significantly different across phenotype groups (19.5% (24/123) for A/HOP, 26.7% (4/15) for C/HP and 10.2% (13/128) for D/OP, P = 0.04). The CLBR was not significantly different following univariate analysis (40.0% (56/140) for A/HOP, 15% (3/20) for C/HP and 33.1% (53/160) for D/OP (P = 0.07)). When a multivariable logistic regression model was developed to account for confounding factors, the PCOS phenotype appeared to be significantly correlated with CLBR, with a more favourable CLBR in the A/HOP subgroup (OR 0.26 for phenotype C/HP (CI 0.06-1.05) and OR 0.47 for phenotype D/OP (CI 0.25-0.88), P = 0.03)). 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 and misassignment of the PCOS phenotype. Moreover, the sample size for phenotype C/HP was too small to draw conclusions for this subgroup of patients. WIDER IMPLICATIONS OF THE FINDINGS: Caucasian infertile patients with a PCOS phenotype A/HOP who undergo IVM achieved a higher CLBR than their counterparts with C/HP and D/OP. This is in strong contrast with previously reported outcomes following OS where women with PCOS and hyperandrogenism (A/HOP and C/HP) performed significantly worse. For PCOS patients who require ART, the strategy of OS followed by an elective freeze-all strategy remains to be compared with IVM in a prospective fashion; however, the current data provide support for IVM as a valid treatment option, especially in the most severe PCOS phenotypes (A/HOP). Our data suggest that proper patient selection is of utmost importance in an IVM programme. STUDY FUNDING/COMPETING INTEREST(S): The clinical IVM research has been supported by research grants from Cook Medical and Besins Healthcare. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.