Clinical bottom line
Chronic endometritis (CE) is an underrecognized inflammatory condition of the endometrium implicated in infertility, recurrent pregnancy loss, and implantation failure. Advances in diagnostic modalities, including hysteroscopic evaluation combined with immunohistochemical staining for plasma cells, have improved detection rates but remain imperfect. Emerging evidence highlights the potential role of targeted antibiotic regimens and adjunctive therapies, though optimal management strategies are not yet standardized. Clinicians should consider CE in patients with unexplained reproductive failure and adopt a multidisciplinary approach to diagnosis and treatment, while recognizing current limitations in evidence quality and consensus guidelines.
What the evidence shows
Chronic endometritis is characterized histologically by the presence of plasma cells in the endometrial stroma, often accompanied by subtle hysteroscopic findings such as micropolyps or stromal edema. However, diagnosis is challenging due to variability in sampling techniques and interpretation criteria (Tadahiro et al., 2022). Bai et al. (2026) emphasized the shared pathophysiological mechanisms between CE and endometriosis, including chronic inflammation and immune dysregulation, which may contribute to infertility. This overlap suggests that CE may be a modifiable factor in reproductive outcomes when adequately identified and treated.
Recent advances focus on improving diagnostic accuracy through combined hysteroscopic and histopathological approaches, including CD138 immunostaining to enhance plasma cell detection (Tadahiro et al., 2022). Despite these improvements, no single diagnostic modality has emerged as a definitive gold standard, and false negatives remain a concern.
Therapeutically, broad-spectrum antibiotics targeting common pathogens such as Mycoplasma and Ureaplasma species have shown promise in small cohorts, with some studies reporting improved pregnancy rates post-treatment (Bai et al., 2026). However, standardized antibiotic regimens and treatment durations vary widely, and robust randomized controlled trials are lacking. Adjunctive therapies addressing immune modulation and microbiome restoration are under investigation but remain experimental.
Caveats and uncertainty
The heterogeneity in diagnostic criteria and sampling methods limits comparability across studies and complicates clinical decision-making. The prevalence of CE in infertile populations varies widely depending on diagnostic approach, raising concerns about over- or under-diagnosis. Moreover, the causal relationship between CE and adverse reproductive outcomes is associative rather than definitively proven.
Antibiotic treatment efficacy is based primarily on observational data and small interventional studies, with no consensus on optimal agents or treatment duration. The potential for antibiotic resistance and impact on the uterine microbiome are additional concerns that warrant cautious use.
Furthermore, the overlap of CE with other gynecological conditions such as endometriosis introduces confounding factors that may influence both diagnosis and treatment response (Bai et al., 2026). Larger, well-designed prospective studies are needed to clarify these relationships and establish evidence-based management protocols.
How this may change practice
Clinicians managing infertility and recurrent pregnancy loss should maintain a high index of suspicion for chronic endometritis, particularly in patients with unexplained reproductive failure. Incorporating hysteroscopy with targeted biopsy and immunohistochemical staining may enhance diagnostic yield, although local expertise and resource availability may limit widespread implementation.
Pending further evidence, empiric antibiotic therapy may be considered in selected cases with confirmed CE, balancing potential benefits against risks such as microbiome disruption. Multidisciplinary collaboration involving reproductive endocrinologists, pathologists, and microbiologists can optimize diagnostic accuracy and individualized treatment planning.
Future integration of molecular diagnostics and microbiome profiling may refine patient selection and therapeutic targeting. Until then, clinicians should interpret CE findings within the broader clinical context and counsel patients regarding the current uncertainties and evolving nature of management strategies.