Chronic endometritis and recurrent implantation failure: a narrative review of clinical relevance and diagnostic challenges.

Abstract: Chronic endometritis (CE) is a localized inflammatory disorder of the endometrium characterized by plasma cell infiltration, most often identified by CD138 immunostaining. Its diagnosis remains problematic due to the absence of standardized thresholds, variability in biopsy timing, and inconsistent histologic interpretation, which results in heterogeneous prevalence reports. CE has been proposed as a potential contributor to recurrent implantation failure (RIF); however, the available evidence remains limited. True RIF, defined as repeated implantation failure despite transfer of euploid embryos, affects only 2-5% of patients. Some recent comparative studies suggest that the prevalence of CE in women with RIF is not higher than in control populations. These findings indicate that the contribution of CE to implantation failure may be less prominent than previously assumed. Interpretation of existing data is further complicated by variability in diagnostic criteria, thresholds for plasma cell detection, biopsy timing, and study design. In this context of diagnostic uncertainty, management remains empirical, with antibiotics frequently prescribed without confirmed causative pathogens. This practice raises concern given the limited and inconsistent evidence of therapeutic benefit, the risk of overdiagnosis and overtreatment, and concerns regarding unnecessary antibiotic exposure and antimicrobial resistance. This narrative review synthesizes current evidence on the diagnosis, clinical relevance, and management of CE in the context of RIF and provides a clinical algorithm to guide selective screening and clinical decision-making. Overall, available data support a cautious, individualized, and selective approach. Further prospective studies are required to establish standardized diagnostic criteria and clarify whether treatment of CE improves reproductive outcomes. Lay summary: Chronic endometritis is a persistent inflammation of the inner lining of the uterus that has been suspected as a cause of repeated failure of embryo implantation during fertility treatment. However, diagnosis is challenging because there are no clear medical standards, and results vary between studies. Recent research shows that true repeated implantation failure affects only about 2-5% of patients, and chronic endometritis does not appear to be more common in these cases than in others. Despite this uncertainty, antibiotics are often prescribed without clear evidence of benefit. This may expose patients to unnecessary side effects and contributes to growing antibiotic resistance. This review summarizes current evidence and presents a clinical algorithm to guide careful and selective testing. A more cautious and individualized approach may help avoid unnecessary treatment and support safer, more effective fertility care.