Study on the Effects of Doxycycline Treatment on Endometrial Microbiota and Pregnancy Outcomes in Chronic Endometritis.

BACKGROUND

This study aimed to characterize the endometrial microbiota in patients with chronic endometritis (CE) after doxycycline treatment and to compare microbial profiles and pregnancy outcomes between treated CE patients and those without CE.

METHODS

Fifty-two women undergoing frozen-thawed embryo transfer were enrolled. Based on histopathological findings before oocyte retrieval, patients were categorized into the CE treatment group or the non-CE group. CE patients received doxycycline (100 mg twice daily for 14 days). Endometrial tissue was collected 1 day before endometrial transformation and analyzed by 16S rRNA gene sequencing of the V3-V4 region using QIIME2. Clinical and microbiological outcomes were compared between the groups.

RESULTS

The two groups showed no significant differences in age, body mass index, endometrial thickness, number of embryos transferred, or transfer protocol (p > 0.05). Infertility duration was significantly longer in the CE group (p < 0.05). Alpha-diversity analysis revealed lower microbial richness and diversity in the CE group (p < 0.05). Firmicutes abundance was significantly reduced (p = 0.0214), whereas Bacteroidetes and Planctomycetes were increased (p < 0.05). At the genus level, Lactobacillus remained dominant but was markedly decreased in the CE group (p = 0.0157), while Ralstonia and Methylobacterium were enriched (p < 0.05). The clinical pregnancy rate and biochemical pregnancy rate showed no significant differences between the groups (p > 0.05), but the live birth rate was significantly lower in the CE group (p = 0.036).

CONCLUSION

Despite histological resolution following doxycycline therapy, CE patients exhibited persistent dysbiosis characterized by decreased Lactobacillus and increased opportunistic taxa, which may impair endometrial receptivity and pregnancy outcomes. These findings suggest that antibiotic therapy alone may not fully restore microbial balance in CE, warranting further investigation into microbiota-targeted interventions to improve reproductive success.