LACTOBACILLUS-DOMINANT ENDOMETRIAL MICROBIOTA AND IVF OUTCOMES: A SYSTEMATIC REVIEW AND META ANALYSIS

Abstract

Background: The endometrial microbiota has been proposed as a modulator of embryo implantation. Whether Lactobacillus dominant (LD) endometrial microbiota improves in vitro fertilisation (IVF) outcomes remains uncertain. We conducted a systematic review and meta-analysis to quantify the association between LD endometrial microbiota and IVF outcomes. Methods: We searched PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, and Web of Science from inception to January 2025 for observational studies and randomised controlled trials comparing LD versus non-Lactobacillus-dominant (NLD) endometrial microbiota in women undergoing IVF/ICSI. Primary outcome was clinical pregnancy rate (CPR); secondary outcomes included live birth rate (LBR), implantation rate (IR), biochemical pregnancy rate (BPR), and miscarriage rate. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analysis (DerSimonian-Laird) was applied. Heterogeneity was quantified by I², τ², and Cochran Q. Publication bias was assessed by Egger regression and Begg-Mazumdar rank correlation. Results: Five studies (n = 627 participants) met eligibility criteria, spanning Japan, Spain/multinational, the Netherlands, and China. The LD endometrial microbiota was significantly associated with higher CPR (pooled OR 2.24, 95% CI 1.37–3.67; I² = 52%; p = 0.001) and LBR (pooled OR 3.01, 95% CI 1.42–6.37; I² = 46%; p = 0.004). Implantation rates were numerically higher in LD patients in all reporting studies. The NOS scores ranged from 5 to 7 (out of 9), indicating moderate to good methodological quality. No significant publication bias was detected (Egger p = 0.24). Sensitivity analyses excluding the smallest study did not materially alter pooled estimates. Conclusions: LD endometrial microbiota is associated with significantly improved clinical pregnancy and live birth rates in women undergoing IVF/ICSI. However, between-study heterogeneity, small sample sizes, and variability in LD definitions limit certainty. Large, prospective, standardised studies are needed before clinical application of endometrial microbiome testing can be recommended.