ObjectiveTo study the characteristics and relationship of the gut microbiota in patients with polycystic ovary syndrome (PCOS).MethodWe recruited 45 patients with PCOS and 37 healthy women from the Reproductive Department of Shengjing Hospital. We recorded their clinical indexes, and sequenced their fecal samples by 16S rDNA full-length assembly sequencing technology (16S-FAST).ResultWe found decreased α diversity and different abundances of a series of microbial species in patients with PCOS compared to healthy controls. We found LH and AMH were significantly increased in PCOS with Prevotella enterotype when compared to control women with Prevotella enterotype, while glucose and lipid metabolism level remained no significant difference, and situations were opposite in PCOS and control women with Bacteroides enterotype. Ruminococcus gnavus, Prevotella stercorea, Dialister succinatiphilus and Bacteroides fragilis were more abundant while Christensenellaceae spp. were less abundant in the PCOS group. P. stercorea was significantly more prevalent in PCOS-not insulin resistance (NIR) compared to control-NIR and PCOS-not overweight (NOW) patient groups compared to control-NOW groups. Kyoto Encyclopedia Genes and Genomes reflecting pathways related to lipopolysaccharide biosynthesis were more abundant in the PCOS group.ConclusionOur study found gut microbiota that had different abundance in patients with PCOS compared to healthy controls. An intimate relationship was shown between the gut microbiota and pathological changes in PCOS. We suggest the gut microbiota should be taken into consideration in the treatment of symptoms of PCOS via drugs and diet.

The essence of enterotypes is stratifying the entire human gut microbiome, which modulates the association between diet and disease risk. A study was designed at the Center of Reproductive Medicine, Shengjing Hospital of China Medical University and Jinghua Hospital of Shenyang. Prevotella and Bacteroides were analyzed in 407 samples of stool, including 178 men with enterotype B (61 normal, 117 overweight/obese) and 229 men with enterotype P (74 normal, 155 overweight/obese). The ratio between Prevotella and Bacteroides abundance, P/B, was used as a simplified way to distinguish the predominant enterotype. In enterotype P group (P/B ≥ 0.01), obesity was a risk factor for a reduced rate of forward progressive sperm motility (odds ratio [OR] 3.350; 95% confidence interval [CI] 1.881–5.966; P < 0.001), and a reduced rate of total sperm motility (OR 4.298; 95% CI 2.365–7.809; P < 0.001). Obesity was also an independent risk factor (OR 3.131; 95% CI 1.749–5.607; P < 0.001) after adjusting follicle-stimulating hormone. In enterotype P, body mass index, as a diagnostic indicator of a reduced rate of forward progressive sperm motility and a decreased rate of decreased total sperm motility, had AUC values of 0.627 (P = 0.001) and 0.675 (P < 0.0001), respectively, which were significantly higher than the predicted values in all patients. However, in enterotype B group (P < 0.01), obesity was not a risk factor for asthenospermia, where no significant difference between obesity and sperm quality parameters was observed. This study is tried to introduce enterotypes as a population-based individualized classification index to investigate the correlation between BMI and asthenospermia. In our study, overweight/obese men with enterotype P were found to have poorer sperm quality. however, sperm quality was not associated with overweight/obese in men with enterotype B. Thereof, BMI is a risk factor for asthenospermia only in men with enterotype P, but not in men with enterotype B.

Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective cross-sectional study recruited 147 patients undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) (70 with no pregnancies and 77 with clinical pregnancies). The association between SCFAs levels and clinical pregnancy outcomes was evaluated using univariate and multivariate logistic regression analyses. The association between SCFAs and metabolic parameters was analyzed using a linear regression model. Receiver operating characteristic (ROC) curve analysis was used for assessing the efficiency of SCFAs to evaluate the clinical pregnancy outcomes. Fecal propionate levels were significantly higher in the no pregnancy group than in the clinical pregnancy group (p < 0.01). Fecal acetate and butyrate levels were not significantly different between females with and without clinical pregnancies (p > 0.05). There were positive relationships between fecal propionate levels and fasting serum insulin (FSI) (r = 0.245, p = 0.003), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.276, p = 0.001), and triglycerides (TG) (r = 0.254, p = 0.002). Multivariate analyses determined that fecal propionate (OR, 1.103; 95% CI, 1.045–1.164; p < 0.001) was an independent risk factor for no pregnancies. The area under the ROC curve (AUC) of fecal propionate was 0.702 (p < 0.001), with a sensitivity of 57.1% and a specificity of 79.2%. High fecal propionate concentration has a negative association on clinical pregnancy outcomes and is positively correlated with FSI, TG, and HOMA-IR.

ObjectiveThis study assessed the impact of the cervical microbiome on reproductive outcomes in frozen embryo transfer (FET) patients.Study designThis cross-sectional study included 120 women (aged 20–40 years) undergoing FET. A cervical sample obtained before embryo transfer was analyzed using 16S full-length assembly sequencing technology (16S-FAST), which detects full length 16S rDNA.ResultsWe found that &gt;48% of the identified Lactobacillus species were novel. The cervical microbiome was clustered into three cervical microbiome types (CMT): CMT1, dominated by L. crispatus; CMT2, dominated by L. iners; and CMT3, dominated by other bacteria. CMT1 had a significantly higher biochemical pregnancy rate (P=0.008) and clinical pregnancy rate (P=0.006) than CMT2 and CMT3. Logistic analysis showed that compared to CMT1, CMT2 and CMT3 were independent risk factors for biochemical pregnancy failure (odds ratio [OR]: 6.315, 95% confidence interval [CI]: 2.047-19.476, P=0.001; OR: 3.635, 95% CI: 1.084-12.189, P=0.037) and clinical pregnancy failure (OR: 4.883, 95% CI: 1.847-12.908, P=0.001; OR: 3.478, 95% CI: 1.221-9.911, P=0.020). A L. crispatus-dominated group as a diagnostic indicator of biochemical and clinical pregnancy positive had area under the curve (AUC) values of 0.651(P=0.008) and 0.645(P=0.007), respectively. Combining the cervical microbiome with embryonic stage optimized the diagnostic performance for biochemical and clinical pregnancy failure with AUC values of 0.743(P&lt;0.001) and 0.702(P&lt;0.001), respectively. Additionally, relative abundance of L. crispatus predicted biochemical pregnancy positive with AUC values of 0.679(P=0.002) and clinical pregnancy positive with AUC values of 0.659(P=0.003).ConclusionCervical microbiome profiling using 16S-FAST enables stratification of the chance of becoming pregnant prior to FET. Knowledge of the cervical microbiota may enable couples to make more balanced decisions regarding the timing and continuation of FET treatment cycles.

Background Diminished ovarian reserve (DOR) is a type of reproductive endocrine disease associated with infertility and premature menopause due to the decline in the number and quality of oocytes. In recent years, studies have been conducted on the relationship between gut microbiota and reproductive health, our objective was to find a solid relationship between gut microbiota and DOR. Methods After rigorous inclusion criteria, 34 women with DOR and 30 normal ovarian reserve controls were recruited at the Reproductive Medical Center of Shengjing Hospital of China Medical University from March to December 2021. Serum levels of AMH, basal sex hormones, AFC, gut microbiota and short-chain fatty acids were measured in two groups. Results Quantitative polymerase chain reaction (qPCR) sequencing technology and gas chromatography was introduced to find a significant difference of the composition and metabolites of gut microbiota between DOR and healthy individuals. After careful comparison of Prevotella/Bacteroides frequencies, we found that individuals with Prevotella /Bacteroides > 0.01 had a higher possibility with DOR. In addition, receiver operating characteristic and spearman correlation analysis were applied to identify butyrate and isobutyrate as a mark to predict the risk of DOR. After canonical correlation analysis, we found that in patients with Prevotella enterotype, Akkermansia muciniphila and Enterobacteria could be considered as harmful bacteria. Based on the above results, an intervention was conducted on six patients who suffered from DOR. After 28 day intervention, the concentration of Enterobacteria and isobutyrate were significantly reduced, meanwhile the amounts of Bifidobacteria were significantly increased. Finally, the concentrations of antral follicle count (AFC) were increased and two thirds of them were successfully pregnant. Conclusions In summary, we defined population with Prevotella/Bacteroides > 0.01 as Prevotella enterotype and found that Prevotella enterotype was closely related to DOR. Akkermansia muciniphila, Enterobacteria, Bifidobacteria, butyrate, and isobutyrate could be used as biomarkers to predict the ovarian reserve in two enterotypes. And different dietary interventions for two enterotypes and have demonstrated significant clinical effects.