Between evidence and expectation: a retrospective cohort study on chronic endometritis in repeated implantation failure and recurrent pregnancy loss

BACKGROUND: Chronic endometritis (CE) is frequently diagnosed in women with repeated implantation failure (RIF) and recurrent pregnancy loss (RPL), yet the lack of standardized diagnostic criteria and uncertainty about the timing of assessment and optimal treatment lead to open questions regarding its clinical relevance. This study aims to identify clinical risk factors that may guide targeted CE testing and to evaluate an ideal time point in the diagnostic pathway to offer CE assessment in women with RIF and RPL.

METHODS: In this retrospective cohort study, 392 women with RIF (no pregnancy after two or more transfers of good quality blastocysts) and 119 women with RPL (two or more subsequent miscarriages) who underwent endometrial biopsy with CD138 immunohistochemistry between 2016 and 2024 were analyzed. Odds ratios for presumed CE risk factors were calculated and CE prevalence and reproductive outcomes were assessed.

RESULTS: Women in the RPL group had a higher prevalence of CE compared to the RIF group (39.5 vs. 25.0%, p = 0.004). A history of cesarean delivery was associated with increased CE risk in the RPL group (OR 2.5, 95% CI 1.14-7.84). CE prevalence did not increase with the number of failed embryo transfers in RIF (32.2% after two, 21.3% after three, 24.7% after ≥ 4 transfers; p = 0.349) or miscarriages in RPL (44.2% after two, 51.4% after three, 57.1% after ≥ 4 miscarriages; p = 0.518). When RIF patients treated for CE were compared with those with normal biopsy after both two and three previous embryo transfers, we found no differences in pregnancy outcomes.

CONCLUSIONS: Our data did not confirm a significant increase in CE prevalence with an increasing number of failed embryo transfers or miscarriages. No relevant differences in the reproductive outcomes of RIF patients with normal biopsies compared with treated CE were found. While prior cesarean delivery may identify a subgroup of RPL patients who could benefit from targeted screening, the overall utility of routine CE testing and treatment remains limited. Standardized diagnostic criteria and further prospective studies are needed to clarify the role of CE in reproductive outcomes, with cautious consideration of uncritical antibiotic treatment.