O-024 Does a vaginal lactobacilli probiotic treatment improve an unfavourable vaginal microbiome before fertility treatment? A randomised, double-blinded, placebo-controlled trial

Abstract

Study question: does treatment with lactobacilli-loaded vaginal capsules improve an unfavourable vaginal microbiome associated with a lower implantation chance before fertility treatment? Summary answer: probiotic treatment did not improve the vaginal microbiome compared with placebo. However, spontaneous improvement of the vaginal microbiome was observed in 34.2% of all participants. What is known already: studies have shown that the vaginal microbiota composition is predictive of IVF treatment outcome and suggest that dysbiosis in the reproductive tract negatively affects the chance of pregnancy through as yet unclear mechanisms. Tests designed to assess different components of endometrial function are entering clinical practice and with microbiota being shown to modulate organ function throughout the body, interest is growing in assessing the vaginal microbiome as a potentially treatable marker of endometrial receptivity and predictor of treatment outcome. Study design, size, duration: this randomised, double-blinded, placebocontrolled study was conducted at a single University fertility clinic between April 2019 and February 2021. The vaginal microbiome composition of eligible patients referred for IVF treatment was determined using a validated PCR based IS-pro technique dividing samples into three overall profiles: low, medium, and high quality. Seventy-four women with an unfavourable vaginal microbiome (low or medium profile) were included and randomly assigned 1: 1 to receive either vaginal probiotic capsules or placebo. Participants/materials, setting, methods: following screening and inclusion, participants completed a 10-day treatment with vaginal probiotic capsules (containing >108 CFU of Lactobacillus gasseri and >108 CFU Lactobacillus rhamnosus) or placebo. Samples to determine the effect on the vaginal microbiome were taken following completion of treatment (primary outcome) and again in the subsequent menstrual cycle (secondary outcome). Improvement in the microbiome was defined as a shift from low to medium, low to high, or medium to high profiles. Main results and the role of chance: seventy-seven women were randomised, 74 women completed the intervention and follow-up. Randomisation yielded 38 women in the lactobacilli group and 36 women in the placebo group. The demographic and baseline characteristics were similar in the two groups. Primary outcome: the vaginal microbiome improved after intervention in 34.2% of all participants with no significant difference between the two groups (lactobacilli group 28.9%, placebo group 40.0%), RR=0.72 (95% CI 0.38-1.38), P = 0.32. Similarly, in the cycle after intervention (secondary outcome), the vaginal microbiome composition was improved relative to baseline samples in 31.9% of all participants with no significant difference between the groups (lactobacilli group 30.6%, placebo group 33.3%), RR=0.92 (95% CI 0.47-1.80), P = 0.80. Limitations, reasons for caution: the intervention did not include all strains of lactobacilli implicated in influencing fertility outcomes. The broad categorisation of the vaginal microbiome profile as either low, medium or high may mask more subtle changes. Wider implications of the findings: this study indicates that administering vaginal lactobacilli probiotics may not improve a suboptimal vaginal microbiome. However, a spontaneous improvement rate of 34.2% over a period of one to three months may provide the basis for an alternative therapeutic strategy of postponing fertility treatment until spontaneous improvement occurs. Trial registration number: ClinicalTrials.gov identifier NCT03843112. EU Clinical Trials Register (EudraCT number: 2018 002376-41).