Chronic endometritis and reproductive failure: The paradigm shift from microbial eradication to ecological...

Despite advancements in assisted reproductive technologies, such as preimplantation genetic testing, clinical success rates have plateaued, thereby increasing the clinical focus on the endometrial factor. Chronic endometritis (CE), a persistent and often asymptomatic mucosal inflammation, is an underdiagnosed condition associated with reproductive failure, particularly in cohorts with repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). This review examines the evolving understanding of CE pathophysiology, transitioning from a traditional infection model toward a framework involving endometrial dysbiosis and potential bacterial biofilm formation. These microbial alterations are hypothesized to trigger maladaptive immune activation and may induce persistent epigenetic modifications that desynchronize endometrial receptivity. We critically evaluate current diagnostic modalities, addressing controversies regarding CD138 immunohistochemistry thresholds and the interpretive limitations of molecular microbiome screening associated with relic DNA. Therapeutically, while antibiotic regimens remain the standard of care, there is conflicting evidence regarding their universal clinical efficacy. Consequently, we review the rationale for transitioning from generalized broad-spectrum microbial eradication toward antibiotic stewardship and targeted ecological restoration using biotherapeutics. Synthesis of current evidence, including data from euploid embryo transfers, suggests that resolving histopathological inflammation improves live birth rates in specific high-risk cohorts. The future management of CE necessitates the implementation of risk-stratified algorithms and therapeutic strategies that focus on functional endometrial recovery rather than isolated histological clearance.