Vol. 7, Issue 1, Part A (2025)

Background: Unexplained infertility occurs when a couple are unable to get pregnant after actively trying to conceive for any other reason than a specific diagnosis, where, despite numerous and extensive investigations, no discernable cause is identified. The microbiome across the human body is an area of growing research in recent years, and the uterine microbiome, in particular, has gathered attention, especially since the endometrial microbiome is vital in embryo implantation and plays an important role in the outcomes of pregnancy. Nonetheless, its contribution to unexplained infertility is still poorly characterized, although evidence is growing supporting a link between microbial diversity and fertility success.
Objective: This study aimed to explore the composition and diversity of the endometrial microbiome in women with unexplained infertility and its potential correlations with fertility outcomes, with an emphasis on assisted reproductive technology (ART) outcomes. Filling a significant knowledge gap, the research incorporated primary data collected during an analysis of fertility and reproductive health from women attending the Baghdad Fertility and Reproductive Health Center and previous studies to assess the association of microbial diversity with ART outcomes and expand understanding of the role of microbiome in unexplained infertility.
Methodology: This study included 500 women diagnosed with unexplained infertility between January 2024 and January 2025 at the Baghdad Fertility and Reproductive Health Center. Endometrial samples were collected and 16S rRNA gene sequencing used to identify the microbial bacterial species in the uterine microbiome. Alpha diversity indices: Shannon Index and Simpson Index were used to determine microbial diversity between pregnant and non-pregnant women. In addition, the relative abundance of significant pathogenic genera, including Lactobacillus, Gardnerella, and Prevotella, was compared between the groups and microbials diversity status correlated with ART reproductive outcomes including oocytes number, embryo quality and pregnancy events.
Results: Pregnant women had a significantly different microbial diversity than women with no concurrent pregnancies, with the pregnant microbiome found to be more diverse. The Shannon Index and Simpson Index of pregnant women was also significantly higher than those non-pregnant women indicating that the endometrial microbiome status may play a role in successful pregnancy outcomes. Lactobacillus was more abundant in pregnant women and Gardnerella and other possible pathogens were notably higher in non-pregnant women. Highter microbial diversity significantly correlated with ART outcomes in women, including more oocytes retrieved, higher pregnancy rates, and lower miscarriage rates.
Conclusion: Through the study, it is providing very strong evidence that a balanced and diverse endometrial microbiome is one essential factor for achieving successful pregnancy in women with unexplained infertility. Their results indicate that the presence of beneficial microbes such as Lactobacillus contributed to this, whereas microbial dysbiosis, defined as an overgrowth of pathogenic species (e.g. Gardnerella), is linked with poor fertility outcomes. These findings highlight the need for clinicians to consider the uterine microbiome in the diagnostics of infertility and as a target for treatment, providing a previously overlooked therapeutic target in ART procedures.