Introduction: The Genital Microbiome and Its Association with Infertility in Men and Women
The human genital tract harbors a dynamic and complex microbial ecosystem—collectively referred to as the genital microbiome—that plays a vital role in maintaining reproductive health. This community includes a wide array of microorganisms such as bacteria, fungi, viruses, and archaea that colonize the reproductive tracts of both males and females. A balanced genital microbiome is essential for homeostasis, protection against pathogens, immunomodulation, and optimal reproductive function. Conversely, disturbances in microbial composition and function—referred to as dysbiosis—have been increasingly associated with subfertility and infertility.
Female Genital Microbiome
In women, the vaginal microbiota is predominantly composed of *Lactobacillus* species, particularly *L. crispatus*, *L. jensenii*, *L. gasseri*, and *L. iners*. These beneficial bacteria contribute to reproductive health by producing lactic acid, hydrogen peroxide, and bacteriocins, which maintain a low vaginal pH (approximately 3.5–4.5) and inhibit the colonization of opportunistic pathogens. A *Lactobacillus*-dominated vaginal microbiome has been linked to better fertility outcomes, improved endometrial receptivity, and a reduced risk of infections and inflammatory responses.
However, disruptions in *Lactobacillus* dominance—often characterized by increased abundance of anaerobic bacteria such as *Gardnerella vaginalis*, *Atopobium vaginae*, *Mobiluncus* spp., and *Prevotella* spp.—result in bacterial vaginosis (BV). BV has been implicated in various adverse reproductive outcomes, including pelvic inflammatory disease (PID), tubal factor infertility, recurrent miscarriage, preterm birth, and decreased success rates in assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and embryo transfer. Inflammatory responses triggered by altered vaginal and uterine microbiota can compromise endometrial receptivity and impair embryo implantation.
Emerging studies utilizing next-generation sequencing techniques, including metagenomics and 16S rRNA gene profiling, have revealed that the upper female reproductive tract—including the endometrium, fallopian tubes, and even the peritoneal cavity—also harbors distinct microbial communities. While previously believed to be sterile, the uterine microbiome is now understood to play a regulatory role in immune activation, angiogenesis, and hormonal modulation—processes critical for successful implantation. Dysbiosis within the uterine microbiota has been associated with chronic endometritis and implantation failure, potentially contributing to cases of unexplained infertility.
Male Genital Microbiome
The male reproductive system also hosts a unique microbiome encompassing the urethra, prostate, epididymis, and testes. A healthy male genital microbiota is essential for maintaining optimal semen parameters, including sperm count, motility, morphology, and DNA integrity. Studies have demonstrated that the presence of pathogenic bacteria such as *Escherichia coli*, *Enterococcus faecalis*, *Staphylococcus aureus*, and *Ureaplasma urealyticum* is significantly higher in the semen samples of infertile men compared to fertile individuals. These pathogens can induce local inflammation, promote the production of reactive oxygen species (ROS), and trigger oxidative stress, ultimately leading to sperm DNA fragmentation and reduced fertilizing capacity.
Chronic infections of the male reproductive tract—including epididymitis, prostatitis, and urethritis—are frequently associated with microbial dysbiosis and may result in obstruction, autoimmune reactions, or testicular damage. The inflammatory milieu resulting from such dysbiosis not only affects spermatogenesis but also alters the immunological and nutritional composition of the seminal plasma, further compromising fertility.
Methods: Mechanisms Linking Microbiome Dysbiosis to Infertility
Several biological mechanisms have been proposed to explain how imbalance in the genital microbiome contributes to infertility:
* Chronic Inflammation: Dysbiosis induces persistent inflammation that interferes with ovulation, sperm function, fertilization, and implantation.
* Oxidative Stress: Pathogenic microbes enhance ROS production, damaging gametes and reproductive tissues.
* Toxin Release: Certain bacteria release metabolites and toxins that are cytotoxic to oocytes, sperm, and embryos.
* Altered pH and Nutrient Environment: Disruption in microbial metabolism alters the reproductive tract’s biochemical conditions, impairing gamete viability and embryo development.
* Immune Dysregulation: Abnormal microbial populations may compromise maternal immune tolerance mechanisms essential for embryo implantation and pregnancy maintenance.
Results: Clinical Implications and Future Perspectives
Growing awareness of the genital microbiome’s role in fertility has led to novel diagnostic and therapeutic approaches. Microbiome profiling using high-throughput sequencing techniques may serve as a biomarker for reproductive potential and ART outcomes. Restoring microbial balance through targeted antibiotic therapy, vaginal or seminal probiotics, fecal microbiota transplantation (FMT), and dietary interventions is a promising area of research.
Moreover, individualized modulation of the genital microbiome could be integrated into personalized medicine strategies for infertility treatment. As the evidence base expands, future clinical guidelines may incorporate genital microbiome assessment as part of routine infertility evaluation.
Conclusion: Conclusion
The genital microbiome is a critical, yet often overlooked, component of reproductive health. Disruption of this microbial balance is increasingly recognized as a contributing factor to infertility in both sexes, via mechanisms involving inflammation, oxidative stress, and immune dysfunction. Continued research into microbial composition, host–microbe interactions, and therapeutic interventions holds great promise for advancing the prevention, diagnosis, and treatment of infertility in the context of precision reproductive medicine.
Keywords: Genital microbiome
Infertility
Dysbiosis
Female reproductive tract
Male