Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).

Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.

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Feeding a protein-bound source of sialic acid during early development enhanced learning and increased expression of 2 genes associated with learning in developing piglets. Sialic acid in mammalian milks could play a role in cognitive development.

Objective: To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes. Design: Cross-sectional study. Setting: Academic institution. Patient(s): Reproductive-aged women with PCOS (n ¼ 14) and controls (n ¼ 14) from the Centre for Reproductive Medicine. Intervention(s): Shotgun metagenomic sequencing on fecal samples from patients, and clinical parameters (including body mass index, endocrine hormone levels, and glycemia level) gathered for correlation analysis. Main Outcome Measure(s): Identification of different gut microbial strains and relativity between microbiota and clinical parameters. Result(s): We found several microbial strains were statistically significantly more abundant in the PCOS group, including Parabacteroides merdae, Bacteroides fragilis, and strains of Escherichia and Shigella, whereas Faecalibacterium prausnitzii was enriched in the control group. Metagenomic species (MGS) analysis revealed that the microbes of the PCOS group were negatively correlated with those of the control group. Of note, we observed a positive correlation between MGS relevant to PCOS and endocrine disorders, including body mass index and elevated levels of serum testosterone, luteinizing hormone, and antim€ ullerian hormone. Functional alterations, reflected by Kyoto Encyclopedia of Genes and Genomes orthologues, could imply potential mechanisms of microbial involvement in the developmental progress of PCOS. Conclusion(s): Our findings suggest an intimate association and potential mechanisms linking microbial dysbiosis and the pathophysiologic changes of PCOS. We address the importance of monitoring and modulating microbial composition and functional shifts in future clinical practice. (Fertil Steril Ò 2020;113:1286-98. Ó2020 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Context Up to 40% polycystic ovary syndrome (PCOS) patients have prediabetes, an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established. Objective To evaluate clinical efficacy of exenatide (EX), metformin (MET) or combination (COM) for prediabetes in PCOS. Design Randomized, open-label, parallel-group controlled trial. Setting Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Patients PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2-h post glucose 7.8-11.0 mmol/L on OGTT). 150 out of 183 eligible enrollees completed the study. Intervention EX (10-20 μg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks. Main Outcome Measures Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic β-cell function parameters (secondary endpoints) and potential mechanisms were assessed. Results IGT was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of MET group (32%, 16/50) (p = 0.003 and 0.027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A two-step hyperglycemic clamp study further revealed that EX had led to higher postprandial insulin secretion as compared to MET, potentially explaining the higher remission rate. Conclusions As compared to MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.

Objective To elucidate the relationship between CpG-induced activation of innate immunity and pregnancy outcome. Design An animal model-based study. Setting Academic. Animal(s) Pregnant nonobese diabetic (NOD) mice were compared with nonimmunodeficient mice. Intervention(s) We mimic toll-like receptor 9 (TLR9) activation using CpG ODN administration in pregnant wild-type (WT) and natural killer (NK) cell–deficient NOD mice. Main Outcome Measure(s) Evaluation of fetal resorption and preterm birth in pregnant mice; flow-cytometric analysis and ELISA detection. Result(s) CpG-induced fetal resorption or preterm birth was observed steadily only in NOD mice but not in WT mice. Concurrently, CpG treatment triggered amplification of uterine macrophages and neutrophils. Moreover, CpG induced a substantial increase of serum mouse keratinocyte-derived cytokine (mKC) and tumor necrosis factor-α (TNF-α) that were produced by uterine CD11b+F4/80+ cells but not by NK or CD11b+Gr-1+ cells. In addition, depletion of F4/80+ cells abrogated a CpG-induced increase in TNF-α production and improved pregnancy outcomes in NOD mice treated with CpG. Conclusion(s) These results provide evidence that CpG-driven innate immune activation may lead to activation and amplification of macrophages followed by their migration to fetomaternal microenvironment, up-regulated TNF-α production, and consequent adverse pregnancy outcomes.

Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality. Melatonin exerts its antioxidant actions as a strong radical scavenger that might affect oocyte quality directly as it is the most potent antioxidant in follicular fluid. To investigate the precise role of endogenous melatonin in IVF outcomes, we recruited 61 women undergoing treatment cycles of IVF or intracytoplasmic sperm injection (ICSI) procedures and classified them into three groups according to their response to ovarian stimulation. Follicular fluid was collected to assess melatonin levels using a direct RIA method. We found good correlations between melatonin levels in follicular fluid with age, anti-Müllerian hormone (AMH) and baseline follicle-stimulating hormone (bFSH), all of which have been used to predict ovarian reserve. Furthermore, as melatonin levels correlated to IVF outcomes, higher numbers of oocytes were collected from patients with higher melatonin levels and consequently the number of oocytes fertilized, zygotes cleaved, top quality embryos on D3, blastocysts obtained and embryos suitable for transplantation was higher. The blastocyst rate increased in concert with the melatonin levels across the gradient between the poor response group and the high response group. These results demonstrated that the melatonin levels in follicular fluid is associated with both the quantity and quality of oocytes and can predict IVF outcomes as well making them highly relevant biochemical markers of ovarian reserve.