The association between female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study
Abstract Objective To study the associations of endometrial and vaginal microbiota with recurrent pregnancy loss (RPL). Design A nested case-control study. Setting Helsinki University Hospital, Finland. Population Women with two or more consecutive pregnancy losses (n=47) and healthy control women without a history of pregnancy loss (n=39). Methods The endometrial and vaginal microbiota compositions, analysed using 16S rRNA gene amplicon sequencing, were compared between RPL women and controls, and between individual vaginal and endometrial samples. The mycobiota composition was analysed using internal transcribed spacer 1 amplicon sequencing for a descriptive summary. The models were adjusted for confounding variables BMI, age, and parity, and FDR-corrected P-values (q-values) were used to define nominal statistical significance at q < 0.05. Main outcome measures Mean relative microbial abundances. Results Lactobacillus crispatus was less abundant in the RPL endometrial samples compared to controls (mean relative abundance 17.2% vs. 45.6%, q = 0.04). Gardnerella vaginalis was more abundant in RPL women than in controls in both endometrial (12.4% vs. 5.8%, q < 0.001) and vaginal samples (8.7% vs. 5.7%, q < 0.01). The individual vaginal and endometrial microbial composition correlated strongly (R = 0.85, P < 0.001). Fungi were detected in 22% of the endometrial and 36% of the vaginal samples. Conclusions Unfavourable reproductive tract microbiota was associated with RPL and may represent a novel risk factor for pregnancy losses.