Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome.

BACKGROUND: DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS. METHODS: Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR. RESULTS: Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (-443, -431, -403, -371, -331, -120, -49, -5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose-dependent relation. CONCLUSION: Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.

Optimum oocyte retrieved and transfer strategy in young women with normal ovarian reserve undergoing a long treatment protocol: a retrospective cohort study.

PURPOSE: This study aimed to investigate the relationship between the number of oocytes retrieved and clinical outcomes in young women with normal ovarian reserve who were undergoing their first in vitro fertilization and embryo transfer (IVF-ET) cycle. The transfer strategy based on yielded oocytes was also discussed in this article. METHODS: A total of 1567 patients who underwent first long protocol of IVF treatment in our reproductive medical center between January 2010 and June 2014 were categorized into five groups based on the retrieved oocyte number, namely, 4∼6, 7∼9, 10∼12, 13∼15, and ≥16. Baseline parameters were similar among the groups. Primary outcome was defined as the cumulative live birth rate (CLBR), and secondary outcomes included the rate of patients with high risks for ovarian hyperstimulation syndrome (OHSS). RESULTS: It was found that the CLBR increased with the number of oocytes, as well as the rate for high risks of OHSS. In fresh cycles, 10∼12 oocyte group demonstrated the highest implantation rate (53.32 %), clinical pregnancy rate (CPR) (73.13 %), and live birth rate (LBR) (61.14 %), with no significant differences. Moreover, both cumulative CPR (CCPR) and CLBR became significantly higher in the 10∼12 oocyte group, compared with 4∼6 and 7∼9 groups. However, when the retrieved oocytes increased to 13∼15 or ≥16, the cumulative results did not have a significant increase. Also, the high risk rate of OHSS was much lower in the 10∼12 group (11.53 %) than that in the 13∼15 group (29.97 %) and ≥16 group (77.30 %). Unconditional multivariate logistic regression analysis showed that when ≥10 oocytes were retrieved, the CLBR increased significantly (P < 0.01). When oocyte number exceeded 16, the CPR of frozen embryo transfer cycle was much higher than that of fresh cycle (P < 0.05). CONCLUSIONS: For young women with normal ovarian reserve, retrieving 10∼12 oocytes might result in optimized pregnancy outcomes in a fresh cycle with low OHSS risk and would not compromise cumulative outcomes. When ≥16 oocytes were retrieved, a "freeze-all" embryo strategy might be preferable.