The implication of the vaginal microbiome in female infertility and assisted conception outcomes

Background : Infertility rates are on the rise, presenting a complex array of causative factors. Recent advancements in human microbiome and associated techniques have shed light on the potential impact of vaginal microbiota disruptions on female fertility. Our study aims to investigate differences in vaginal microbiome between fertile women and those experiencing infertility. Additionally, we aim to investigate how microbial composition in infertile population may affect the success of assisted reproduction technology (ART). Methods: We enrolled 194 women diagnosed with infertility at the Reproductive Medicine Center of Shanghai Changzheng Hospital between November 2018 and November 2021, along with 102 healthy women undergoing routine physical examinations at the hospital’s Physical Examination Center. Vaginal secretions were collected from both groups, and polymerase chain reaction (PCR) was used to amplify the bacterial 16S rRNA V4-V6 conserved region for microbial analysis. A machine learning model was built based on the genus abundances to predict infertility. Additionally, we employed the PICRUSt algorithm to predict the metabolic pathway activities, providing insights into potential molecular mechanisms underlying female infertility and ART outcomes. Results: Women with infertility exhibited a significantly different vaginal microbial composition compared to healthy women, with the infertility group showing higher microbial diversity. Burkholderia, Pseudomonas, and Prevotella levels were significantly elevated in the vaginal microbiota of the infertility group, while Bifidobacterium and Lactobacillus abundances were reduced. Recurrent implantation failure (RIF) within the infertile population showed even higher diversity of vaginal microbiota, with specific genera such as Mobiluncus, Peptoniphilus, Prevotella, and Varibaculum being more abundant. Overgrowth of Mobiluncus and Varibaculum emerged as independent risk factors affecting ART outcomes. Eleven metabolic pathways were associated with both RIF and infertility, with Prevotella demonstrating stronger correlations. Conclusions: The present study provides insights into the differences in vaginal mircobiome between healthy and infertile women, offering a new understanding of how vaginal microbiota may impact infertility and ART outcomes. Our findings underscore the significance of specific microbial taxa in women with recurrent implantation failure, suggesting avenues for targeted interventions to enhance embryo transplantation success rates.