Synchronized dysbiosis of the vaginal-gut microbiota is associated with reduced live birth rates in infertile women undergoing frozen-thawed embryo transfer

Background The interplay between vaginal and gut microbiota and their collective impact on live birth outcomes remains poorly characterized. This study investigated the association between vaginal and gut microbiota and live birth outcomes in women undergoing frozen-thawed embryo transfer (FET). Methods Vaginal and fecal samples were collected from 137 infertile women (64 controls, 73 with polycystic ovary syndrome (PCOS) undergoing FET and analyzed by 16S rRNA gene sequencing. Machine learning models based on genus-level abundance were used to predict live birth outcomes, and PICRUSt2 was employed to infer functional profiles of microbial communities. Results Significant differences in microbial composition, β-diversity, and functional profiles were observed between live birth (LB) and non-live birth (NLB) groups (all p < 0.05). NLB cases exhibited synchronized dysbiosis across both niches, with opposing patterns between subgroups: control-NLB showed increased β-diversity, whereas PCOS-NLB showed reduced β-diversity in both vaginal and gut microbiota. Notably, the combined signature of vaginal and gut taxa outperformed single-niche biomarkers for predicting live birth outcomes. In controls, vaginal Ralstonia and gut Escherichia-Shigella achieved an AUC of 0.888. Strikingly, in PCOS patients, we identified a robust, disease-specific interaction: vaginal Streptococcus and gut Bacteroides not only showed high combined predictive performance (AUC = 0.905) but also exhibited a strong positive correlation ( r = 0.782, p < 0.001), suggesting a PCOS-associated microbial interaction network. Conclusions These findings reveal synchronized dysbiosis of vaginal and gut microbiota in NLB outcomes, with vaginal microbiota showing a more direct association with live birth. In PCOS, a specific vaginal Streptococcus- gut Bacteroides axis suggests a disease-specific microbial interaction network associated with reproductive failure in PCOS. Assessing both microbial ecosystems prior to FET may improve risk stratification and guide therapeutic interventions targeting the vaginal-gut axis.