BackgroundPer- and polyfluoroalkyl substances (PFAS) exposure is associated with various health risks. However, limited research has explored their potential connection with congenital heart disease (CHD).ObjectiveThis study aimed to investigate the relationship between different types of PFAS and childhood CHD using a mixed analysis approach.MethodsA hospital-based case–control study was conducted involving 282 children with CHD and 282 control participants. Plasma samples were analyzed for 19 PFAS congeners. Logistic regression, Bayesian kernel-machine regression (BKMR), and weighted quantile sum (WQS) models were employed to assess the association between individual PFAS and PFAS mixtures with CHD risk.ResultsAnalysis of 564 subjects revealed higher plasma concentrations of various PFAS compounds in the CHD-group. Logistic regression identified significant associations between CHD risk and specific PFAS, notably 6:2 Chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) (OR = 1.65; 95%CI: 1.40–1.94), 8:2 8:2 Cl-PFESA (OR = 1.69; 95%CI: 1.69–2.19), Perfluorobutanoic acid (PFBA) (OR = 2.68; 95%CI: 2.28–3.15), Perfluorobutane sulfonic acid (PFBS) (OR = 2.38; 95%CI: 1.77–3.22), Perfluorohexanoic acid (PFHxA) (OR = 2.62; 95%CI: 1.99–3.45), and Perfluorotetradecanoic acid (PFTeDA) (OR = 2.18; 95%CI: 1.81–2.63). BKMR analysis confirmed these findings. WQS analysis emphasized PFBA, 8:2 Cl-PFESA, PFHxA, and PFTeDA as key contributors to the association between PFAS mixture exposure and CHD risk.ConclusionExposure to PFAS mixtures was associated with an increased risk of CHD in children, with 6:2 Cl-PFESA, 8:2 ClPFESA, PFBA, PFHxA, and PFTeDA playing significant roles.

Background: Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic disorders in PCOS remain elusive, hampering therapeutic development. Enhanced metabolic health correlates with increased microbiota gene content and microbial diversity. We aimed to explore the impact of gut microbiota and serum steroids on PCOS regulation associated with androgen excess.Methods: The fecal samples of patients with hyperandrogenic PCOS (n = 14) and control group with PCOS (n = 14) were analyzed by 16S rRNA gene sequencing. The peripheral venous blood of all subjects was collected to detect serum hormones. The association between gut microbiota and serum hormones was analyzed with the R language.Results: Our findings reveal that the hyperandrogenic PCOS group exhibits lower richness and diversity of gut microbiota compared to the control group. Characteristic genera in PCOS patients with hyperandrogenism include Bifidobacterium, Enterobacteriaceae_unclassified, Streptococcus, Saccharimonadaceae, Enterococcus, and Eubacterium_nodatum_group. Five hormones, including 5β-androsterone, deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and cortexolone, emerge as potential serum biomarkers for identifying patients with hyperandrogenic-PCOS (HA-PCOS). Furthermore, a lower vitamin D3 level may act as a susceptibility factor, suggesting that vitamin D3 supplementation could serve as a potential intervention for PCOS with hyperandrogenism.Conclusion: Specific fecal microbiota and serum steroids may be used as characteristic markers for clinical diagnosis of hyperandrogenic-PCOS. This research enhances our understanding of the intricate interplay among hormones, gut microbiota, and hyperandrogenemia in patients with PCOS.

Abstract Objective This study investigated the risk factors of assisted pregnancy outcomes in infertile men receiving assisted reproductive treatment and established a risk prediction model. Methods A cross-sectional survey was conducted on 1037 infertile men who underwent ICSI-ET assisted pregnancy at the Reproductive Medicine Center of Obstetrics and Gynecology Hospital Affiliated to Tongji University from March 2023 to September 2023, and the clinical information of 403 gestation cycles (study group) and 634 non-gestation cycles (control group) were compared. Logistic regression was used to analyze the risk factors of assisted pregnancy outcomes in infertile men. The R software was used to draw the histogram and receiver operating characteristics (ROC) curve. Results Single factor results showed that there were differences between the two groups in age, BMI, smoking, drinking, drinking tea, daily sleep time, daily exercise time, anxiety, depression, stress, insomnia, forward motile sperm rate, inactive sperm rate, sperm DNA fragmentation index, sperm survival rate, chlamydia infection and other 16 factors (P < 0.05). Multivariate regression showed that age, BMI, smoking, drinking, daily sleep time, daily exercise time, anxiety, depression, insomnia, forward motility sperm rate, sperm DNA fragmentation index and sperm survival rate were independent risk factors for assisted pregnancy outcome of infertile men (P < 0.05). The nomogram and the area under ROC curve show that the risk prediction model has good performance. Conclusion The assisted pregnancy outcome of male infertile patients is affected by many factors, and the medical staff can make a predictive plan according to the predicted results.

Background: Aromatase inhibitors (AIs), such as anastrozole, have shown effectiveness in treating oligoasthenozoospermia due to abnormal testosterone to estradiol (T/E-2) ratio (T/E-2 < 10). However, its efficacy in subfertile men without abnormal T/E-2 ratio (T/E-2 > 10) remained unevaluated. This retrospective study aimed to investigate whether patients with T/E-2 ratio > 10 could also benefit from anastrozole treatment. Methods: One hundred and five subfertile patients treated with 1 mg anastrozole daily were included, in which 62 patients had a T/E-2 ratio of < 10, and 43 patients had this ratio > 10. Semen parameters and sex hormone levels (including FSH, LH, PRL, E-2 and total T) were measured before and after a three-month treatment. T/E-2 ratio and total progressive motility sperm count were calculated from these results. Results: Patients in both groups (T/E-2 ratio < 10 and > 10) showed significant increase in sex hormone levels (FSH, LH and total T), T/E-2 ratio and semen parameters (semen volume, sperm concentration, total sperm count, progressive motility and total progressive motility count). The changes of these parameters between two groups were comparable. A subgroup analysis comparing the effect of anastrozole on overweight and normal patients also showed no significant difference. Improvements in semen parameters were seen in some azoospermic and cryptozoospermic patients. Conclusions: The majority of subfertile men with and without abnormal T/E(2 )ratios responded to anastrozole treatment with significantly improved semen parameters and sex hormone levels. Anastrozole showed potential effectiveness in male subfertile patients with T/E-2 > 10, to be confirmed by future prospective, randomized, controlled studies.

Exposure of females to fine particulate matter ≤2.5 μm in diameter (PM2.5) prior to pregnancy could produce adverse impact on fertility and enhances susceptibility of the offspring to a variety of diseases. In the current study, female C57BL/6 mice (6 weeks of age) were exposed to either concentrated PM2.5 or filtered air (average PM2.5 concentration: 115.60 ± 7.77 vs. 14.07 ± 0.38 μg/m-3) using a whole-body exposure device for 12 weeks. Briefly, PM2.5 exposure decreased anti-Müllerian hormone level (613.40 ± 17.36 vs 759.30 ± 21.90 pg mL-1, P＜0.01) and increased reactive oxygen species (ROS) level (45.39 ± 0.82 vs 24.20 ± 0.85 arbitrary unit in fluorescence assay, P＜0.01) in oocytes. The exposure increased oocyte degeneration rate (21.5% vs 5.1%, respectively (P＜0.01) and decreased the 2-cell formation rate (71.9% vs 86.0%, P < 0.01). Transcriptome profiling using RNA sequencing showed wide spectrum of abnormal expression of genes, particularly those involved in regulating the mitochondrial respiratory complex in oocytes and metabolic processes in blastocysts. The exposure decreased litter size (6 ± 0.37 vs 7 ± 0.26, P＜0.05) and weight (1.18 ± 0.02 vs 1.27 ± 0.02 g, P＜0.01). In summary, PM2.5 exposure decreased female fertility, possibly through increased ROS production in oocytes and metabolic disturbances in developing embryos. The cause-effect relationship, however, requires further investigation.

The zona pellucida (ZP) is an extracellular matrix universally surrounding mammalian eggs, which is essential for oogenesis, fertilization, and pre-implantation embryo development. Here, we identified two novel heritable mutations of ZP2 and ZP3, both occurring in an infertile female patient with ZP-abnormal eggs. Mouse models with the same mutations were generated by CRISPR/Cas9 gene editing system, and oocytes obtained from female mice with either single heterozygous mutation showed approximately half of the normal ZP thickness compared to wild-type oocytes. Importantly, oocytes with both heterozygous mutations showed a much thinner or even missing ZP that could not avoid polyspermy fertilization, following the patient's pedigree. Further analysis confirmed that precursor proteins produced from either mutated ZP2 or ZP3 could not anchor to oocyte membranes. From these, we conclude that ZP mutations have dosage effects which can cause female infertility in humans. Finally, this patient was treated by intracytoplasmic sperm injection (ICSI) with an improved culture system and successfully delivered a healthy baby.

Objective: To develop a unique approach using polarization microscopy (PM) to determine whether the presence of a spindle can be used as an indicator associated with fertilization failure 5 hours after short-term insemination.Design: Observational study.Setting: Assisted reproduction center.Patient(s): Eighty-five patients undergoing short-term insemination.Intervention(s): Oocytes imaged via PM at 4, 5, and 6 hours after standard insemination.Main Outcome Measure(s): Spindle visualization and fertilization rate, with rescue intracytoplasmic sperm injection (ICSI) results determined by rates of normal fertilization, abnormal fertilization, and good-quality embryo formation.Result(s): After standard insemination, comparisons of spindle visualization at three time points indicated that the predictive accuracy rates were 84.30% at 5 hours, 86.80% at 6 hours, and 62.20% at 4 hours, with the rates at 5 and 6 hours statistically significantly higher than at 4 hours. A spindle was present in 242 of the 788 metaphase-II oocytes 5 hours after insemination, and there were 204 failed fertilizations on day 1. The positive predictive value was 0.84. After rescue ICSI, the abnormal fertilization rate of the polar body group (assessed using the polar body visualization method) was statistically significantly higher than that of the PM group (assessed using the spindle visualization method) and the regular ICSI group (9.37%, 5.88%, and 4.87%, respectively).Conclusion(s): The presence of a spindle 5 hours after insemination in in vitro fertilization is an accurate indicator of unfertilized oocytes. Spindle imaging combined with rescue measures effectively prevents fertilization failure and decreases the polyspermy rate. (C)2017 by American Society for Reproductive Medicine.