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BackgroundEvidence suggests that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes. This systematic review and meta-analysis was conducted to determine whether levothyroxine (LT4) supplementation would improve pregnancy outcomes among infertile women with SCH and/or TAI who underwent in vitro fertilization (IVF) or intracytoplastic sperm injection (ICSI).MethodsWe searched databases of PubMed, EMBASE, Web of Science, Cochrane Controlled Trials Register databases, and Clinicaltrials.gov up to April 2018 to identify eligible studies. Studies that focused on the treatment effect of LT4 on pregnancy outcomes of women with SCH and/or TAI who underwent IVF/ICSI were included in the data synthesis. We only included randomized controlled trials (RCTs). Relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model to assess the results of pregnancy outcomes, including clinical pregnancy rate, miscarriage rate, live birth rate and preterm birth rate.ResultsFour published RCTs including 787 infertile couples undergoing IVF/ICSI were included in this meta-analysis. Notably, the study observed no significant associations of LT4 treatment with the clinical pregnancy rate (RR = 1.46, 95% CI: 0.86–2.48), live birth rate (RR = 2.05, 95% CI: 0.96–4.36), or preterm birth rate (RR = 1.13, 95% CI: 0.65–1.96). However, patients receiving LT4 supplementation had a significantly decreased miscarriage rate relative to those receiving a placebo or no treatment (RR = 0.51, 95% CI: 0.32–0.82). A further sub-group analysis showed that LT4 supplementation did not improve the miscarriage rates among patients with SCH (RR = 0.67, 95% CI: 0.39–1.15) or TAI (RR = 0.28, 95% CI: 0.07–1.06).ConclusionsGiven its potential to reduce the miscarriage rate, LT4 supplementation is recommended for infertile women with SCH and/or TAI who are undergoing IVF/ICSI. However, additional population-based RCTs are needed to confirm this recommendation.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0410-6) contains supplementary material, which is available to authorized users.

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, whereas the pathogenesis is still not fully understood. Systemic and ovarian oxidative stress (OS) imbalance is a pivotal feature of PCOS. Humanin, a mitochondria-derived peptide, has been reported to function as an antioxidant in cardiomyocytes, pancreatic beta cells and other cells, but how this function is regulated remains unclear. In this study, we investigated whether humanin expression differs in the granulosa cells (GCs) of PCOS patients versus controls, and whether humanin alleviates OS in PCOS ovaries. Sixteen PCOS patients and 28 age- and BMI-matched controls undergoing IVF were recruited, and their serum, follicular fluid and GCs were collected for humanin analysis. Dehydroepiandrosterone-induced rat PCOS models, and vitamin K3-induced OS COV434 cell lines were applied to investigate the mechanism. Humanin expression was significantly down-regulated in the ovaries of PCOS patients relative to those of non-PCOS patients. Exogenous humanin supplementation significantly attenuated body weight gain, ovarian morphological abnormalities, endocrinological disorders and ovarian and systemic OS in PCOS rat models. Our study further demonstrated that this attenuation effect was involved in the modulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. In summary, this study reported for the first time that decreased expression of humanin in the GCs was associated with oxidative imbalance in PCOS. Humanin alleviates OS in ovarian GCs of PCOS patients via modulation of the Keap1/Nrf2 signalling pathway.

ObjectiveThis meta-analysis was aimed to evaluate the association between maternal physical activity before IVF/ICSI cycles and reproductive outcomes.MethodsWe searched databases of PubMed, EMBASE and Web of Science electronic databases, and ongoing trials up to November 2017 to identify studies that focused on the relationship between maternal physical activity before IVF/ICSI cycles and reproductive outcomes, including implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate. Odds ratio (OR) with 95% confidence intervals, were calculated to assess the results of each outcome.ResultsEight published studies encompassing 3683 infertile couples undergoing IVF/ICSI treatment were included into the analysis. There was an increasing, but not statistically significant, trend in implantation rate for physically active women when compared with physically inactive women (OR = 1.95, 95% CI 0.99–3.83, I2 = 77%). No significant difference was found in miscarriage rate between physically active women and physically inactive women (OR = 0.76, 95% CI 0.41–1.44, I2 = 49%). However, rates of clinical pregnancy and live births in physically active women were significantly higher than those in physically inactive women (OR = 1.96, 95% CI 1.40, 2.73, I2 = 42% and OR = 1.95, 95% CI 1.06–3.59, I2 = 82%, respectively). Subgroup analysis helped to confirm these results.ConclusionsFemale physical activity before IVF/ICSI cycles was associated with increased rates of clinical pregnancy and live births, whereas only a small but not statistically significant increase was found in implantation rate, and no effect was shown on miscarriage rate.

This study aimed to investigate the role of microRNA (miRNA) in heat stress-induced spermatogenic impairment. Testes from 15 adult ICR mice subjected to testicular hyperthermia at 43°C for 30 min and from 15 control mice were collected and pooled into 3 samples. Isolated RNA from these samples was subjected to small RNA high-throughput sequencing, and differentially expressed miRNAs were identified and validated using RT-PCR. The identified miRNAs were further subjected to Gene Ontology and KEGG analyses, which revealed significant enrichment for pathways potentially involved in heat stress-induced spermatogenic impairment. Additionally, a correlation analysis of the relative levels of validated miRNAs with germ cell apoptosis was performed. Of the 11 miRNAs identified as differentially expressed, 8 were validated as consistent with sequencing data. Further analyses suggested that the target genes of those miRNAs were involved in various pathways (e.g., ribosomal, HIF-1, MAPK) that may be critical to heat stress-induced testicular damage. Some identified miRNAs, including miR-449a-3p, miR-92a-1-5p, miR-423-3p, and miR-128-3p, correlated closely with germ cell apoptosis. The study results reveal a detailed miRNA profile of heat stress-induced testicular damage and highlight new and potentially important candidate targets in the process of male infertility.