Infertility affects ~1 in 6 people of reproductive age and remains difficult to treat because causes are heterogeneous and diagnostics are incomplete. Recent evidence reframes the female reproductive tract as a low-biomass but biologically active microbial ecosystem. Dysbiosis, typically loss of protective Lactobacillus species (notably L. crispatus) with overgrowth of anaerobic pathobionts, is associated with implantation failure and recurrent pregnancy loss. Framing conditions such as chronic endometritis and reproducible low-Lactobacillus endometrial profiles as dysbiosis-related disorders clarifies opportunities for prevention, companion diagnostics and microbiome-directed therapies. This narrative review contrasts receptive (Lactobacillus-dominant) versus dysbiotic states and summarises mechanisms linking microbiota to fertility: microbial metabolites (lactic acid, short-chain fatty acids) support epithelial barrier function and immune tolerance, whereas dysbiosis provokes inflammation that impairs implantation. Although observational data consistently associate Lactobacillus dominance with better outcomes, evidence quality is low-to-moderate due to retrospective designs, methodological heterogeneity, and a lack of adequately powered, diagnostic-stratified randomised trials. The review highlights precision microbial therapeutics under development, single-strain next-generation probiotics, synthetic consortia, engineered live biotherapeutics, postbiotics, targeted phage/endolysins and vaginal microbiota transplantation, and proposes a diagnostic-driven roadmap that matches microbiome endotypes and clinical contexts (e.g., preconception vs. immediate embryo transfer) to specific interventions. Regulatory and safety issues for reproductive biologics are also considered. The reproductive microbiome is a promising translational frontier but currently offers a consistent signal rather than definitive proof of benefit. To translate promise into practice requires standardised low-biomass sampling/reporting, mechanistic validation in human-relevant models and diagnostic-stratified randomised trials with staged endpoints, alongside strategies to address engraftment, formulation and regulatory pathways.
Li et al. (Sun,) studied this question.