BACKGROUND: Infertility treatments are continually evolving, with vaginal probiotic supplementation before embryo transfer (ET) being explored as a potential method to improve clinical outcomes. So, this systematic review evaluated the effect of vaginal probiotics on pregnancy rates following ET. METHODS: Studies were identified through PubMed, Scopus, Web of Science, Cochrane, and clinical trial registries up to October 17, 2024. We included prospective interventional studies (RCTs or quasi-experimental) focusing on pregnancy outcomes post-ET. We excluded non-prospective studies, non-vaginal routes of probiotic administration, and studies with insufficient methodological or statistical details. The data was extracted from each qualifying study by two reviewers and recorded using an electronic form. Results were synthesized using a random-effects model, with Mantel-Haenszel (MH) risk ratio (RR) and 95% confidence intervals (CI) calculated for ET outcomes. Also, subgroup analyses were done to explore the history of recurrent implantation failure (RIF) as a probable source of heterogeneity. RESULTS: We included six studies with 850 participants (419 in intervention and 431 in control groups). Vaginal probiotics showed a non-significant increase in clinical pregnancy rates compared to the control group (157 per 419 [37.47%] versus 136 per 431 [31.55%], respectively
RR: 1.19
P = 0.07), with similar findings in women with and without a history of RIF. No significant differences were found in biochemical pregnancy (RR: 1.04
P = 0.74) or ongoing pregnancy rates (RR: 1.09
P = 0.53). A non-significant reduction in miscarriage risk was observed (RR: 0.67
P = 0.12). CONCLUSIONS: Vaginal probiotics may offer a non-significant increase in clinical pregnancy rates and a slight non-significant reduction in miscarriage risk. However, considering the potential limitations of the included studies, findings should be interpreted with caution. Further research is needed to explore the potential of personalized probiotic therapy. PROSPERO REGISTRATION CODE: CRD42024550798.