Investigating the Gut-Vaginal Microbiome Axis

Recurrent implantation failure (RIF) represents a significant barrier to successful in vitro fertilization (IVF), defined as the inability to achieve a clinical pregnancy despite the transfer of multiple high-quality embryos across repeated cycles, and affects nearly 10% of women undergoing assisted reproduction. While anatomical abnormalities, hormonal dysregulation, and immunological dysfunction have been well established as contributing factors, emerging evidence highlights the critical influence of microbial communities on reproductive health. Both the vaginal and gut microbiomes are increasingly recognized as central to modulating systemic immunity, hormonal balance, and endometrial receptivity, yet their combined role in implantation failure remains poorly understood. Vaginal dysbiosis often characterized by the depletion of Lactobacillus species and the expansion of anaerobes such as Gardnerella and Prevotella has been linked to hostile uterine environments and reduced conception rates, while gut microbiome imbalances can influence estrogen metabolism, inflammatory pathways, and immune tolerance, thereby indirectly affecting reproductive outcomes. However, the gut–vaginal axis in the context of RIF has not been systematically studied, particularly within Middle Eastern populations. This pioneering study at King Faisal Specialist Hospital and Research Centre aim to recruit women aged 18–45, comprising RIF patients and healthy IVF patients as our control, and will collect both vaginal swabs and stool samples during the early follicular phase to minimize variability. For the RIF group, additional samples were collected on the day of embryo transfer.

This study aims to preform Next Generation Sequencing (NGS) targeting 16S rRNA, followed by comprehensive bioinformatics analysis to characterize microbial composition and diversity. In parallel, STDs test will be employed to screen for 11 common sexually transmitted pathogens, including Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma spp., and HPV, in order to account for potential confounding co-infections. As the first study in Saudi Arabia and one of the few globally to investigate both gut and vaginal microbiomes in the context of RIF, this research fills a critical knowledge gap and has the potential to uncover microbial biomarkers predictive of implantation success. Expected outcomes include novel insights into the microbial underpinnings of RIF, improved diagnostic tools, and the foundation for microbiome-targeted strategies such as probiotics, dietary modulation, or vaginal microbiota restoration, ultimately offering new avenues to enhance IVF success rates and provide hope to women facing persistent infertility challenges.