Recurrent pregnancy loss is associated with unfavorable composition of endometrial and vaginal microbiota

Research Question Does endometrial or vaginal microbiota composition associate with recurrent pregnancy loss (RPL)?Design Endometrial and vaginal samples were collected from 47 women with two or more consecutive pregnancy losses and 39 healthy control women without a history of pregnancy loss between March 2018 and December 2020 in Helsinki University Hospital, Helsinki, Finland. The endometrial and vaginal microbiota compositions, analysed using 16S rRNA gene amplicon sequencing, were compared between RPL and control women, 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 BMI, age, and parity. False discovery rate -corrected P-values (q-values) were used to define nominal statistical significance at q < 0.05. Results Lactobacillus crispatus was less abundant in the RPL women’s 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 compositions 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 is associated with RPL and may represent a novel risk factor for pregnancy losses.