The association between endometrial and vaginal microbiota with recurrent pregnancy loss: a case-control study. TOIVE

Objective: To study the associations of endometrial and vaginal microbiota with recurrent pregnancy loss (RPL). Design: 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). Endometrial biopsies and vaginal samples were collected 6-8 days after a positive ovulation test. Methods: The endometrial and vaginal microbiota compositions, analysed with 16S rRNA gene amplicon sequencing, were compared between RPL women and controls, and between individual vaginal and endometrial samples. The mycobiota composition was analysed with internal transcribed spacer 1 amplicon sequencing for a descriptive summary. The results were adjusted by BMI and age, and q-values (False Discovery Rate -adjusted P-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 17.3% in RPL vs. 47.3% in controls, q = 0.01). Gardnerella vaginalis was more abundant in RPL women than in controls in both endometrial (mean relative abundance 13.8% in RPL vs. 8.9% in controls, q < 0.0001) and vaginal samples (9.4% vs. 8.7%, q < 0.001). The vaginal microbial composition correlated strongly with the endometrial microbiota (R = 0.85, P < 0.0001). Fungi were detected in 19% of the endometrial and 27% of vaginal samples. Conclusions: Unfavourable endometrial and vaginal microbiota was associated with RPL. It may be a novel risk factor for pregnancy losses.