The increased levels of intracellular reactive oxygen species (ROS) in granulosa cells (GCs) may affect the pregnancy results in women with polycystic ovary syndrome (PCOS). In this study, we compared the in vitro fertilization and embryo transfer (IVF-ET) results of 22 patients with PCOS and 25 patients with tubal factor infertility and detected the ROS levels in the GCs of these two groups. Results showed that the PCOS group had significantly larger follicles on the administration day for human chorionic gonadotropin than the tubal factor group (P < 0.05); however, the number of retrieved oocytes was not significantly different between the two groups (P > 0.05). PCOS group had slightly lower fertilization, cleavage, grade I/II embryo, clinical pregnancy, and implantation rates and higher miscarriage rate than the tubal factor group (P > 0.05). We further found a significantly higher ROS level of GCs in the PCOS group than in the tubal factor group (P < 0.05). The increased ROS levels in GCs caused GC apoptosis, whereas NADPH oxidase 2 (NOX2) specific inhibitors (diphenyleneiodonium and apocynin) significantly reduced the ROS production in the PCOS group. In conclusion, the increased ROS expression levels in PCOS GCs greatly induced cell apoptosis, which further affected the oocyte quality and reduced the positive IVF-ET pregnancy results of women with PCOS. NADPH oxidase pathway may be involved in the mechanism of ROS production in GCs of women with PCOS.

SUMOylation function is required to protect against oxidative stress in beta cells; this mechanism is, at least in part, carried out by the regulation of NRF2 activity to enhance ROS detoxification. Homeostatic SUMOylation is also likely to be essential for maintaining beta cell functionality.

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Purpose We aimed to evaluate the regulation of miR-99a to the biological functions of granulosa cells in polycystic ovary syndrome (PCOS) via targeting IGF-1R. Methods We collected aspirated follicular fluid in both patients with and without PCOS. Granulosa cells (GCs) were isolated through Percoll differential centrifugation to detect both miR-99a and IGF-1R expressions. We further transfected COV434 cells with miR-99a mimics to establish a miRNA-99a (miR-99a) overexpression model. We explored the regulation of miR-99a to the proliferation and apoptosis of human GCs via IGF-1R in COV434. The effect of different insulin concentrations on miR-99a expression was also evaluated. Results MiR-99a was significantly downregulated while IGF-1R was upregulated in patients with PCOS. MiR-99a can regulate IGF-1R on a post-transcriptional level. After transfection of miR-99a mimics, the proliferation rate was decreased and apoptosis rate was increased significantly in COV434. Exogenous insulin-like growth factor 1 (IGF-1) treatment could reverse the effect of miR-99a. MiR-99a was negatively and dose-dependently regulated by insulin in vitro. Conclusions MiR-99a expression was downregulated in patients with PCOS, the degree of which may be closely related to insulin resistance and hyperinsulinemia. MiR-99a could attenuate proliferation and promote apoptosis of human GCs through targeting IGF-1R, which could partly explain the abnormal folliculogenesis in PCOS.

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BackgroundThe objective of this study was to carry out a systematic review and meta-analysis of embryologic and clinical outcomes following open versus closed vitrification of human oocytes and embryos.MethodsAn electronic literature search was conducted in main electronic databases up to June 30, 2018 using the following key terms: ‘oocyte’, ‘embryo’, ‘blastocyst’, ‘vitrification’, ‘cryopreservation’, ‘device’, ‘survival rate’, ‘pregnancy rate’, etc. A meta-analysis was performed using a random effect model to estimate the value of risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were carried out to further confirm the results.ResultsTwelve (Eight prospective and four retrospective) studies comparing open versus closed vitrification of human oocytes or embryos were included. For prospective studies on oocytes, no evidence for a significant difference in cryosurvival rate (RR = 0.91, 95% CI: 0.80–1.03, P = 0.14; n = 2048) or clinical pregnancy rate (RR = 1.29, 95% CI: 0.80–2.06, P = 0.30; n = 150) was observed. Additionally, there were no significant differences between the two methods concerning secondary endpoints included positive βHCG rate, implantation rate, miscarriage rate, ongoing pregnancy rate, live birth rate, cancellation rate, babies born per transferred blastocysts, or multiple birth rate (P > 0.05). The results of the retrospective studies were similar as the prospective studies.ConclusionsIt is still impossible to conclude that closed vitrification system could be a substitution for open system in human oocyte and embryo cryopreservation based on current evidence. Therefore, more well-designed prospective studies addressing these issues are still warranted.

Earlier administration of GnRH antagonist could avoid premature luteinizing hormone increases among high ovarian responders, especially those with a starting AFC of 22 or more.