Persistent inflammation of the endometrial mucosa is known as chronic endometritis (CE). This condition is characterized by the microscopic identification of plasma cells in the endometrial stroma. Numerous bacteria, primarily gram-negative and intracellular (such as Enterococcus faecalis, Mycoplasma, ureaplasma Chlamydia, Escherichia coli, and Streptococcus spp.), have been associated with the development of CE, but some cases of abacterial CE are described. Although frequently asymptomatic, women with CE often complain of vaginal discharge, dyspareunia, pelvic pain, and abnormal uterine bleeding. Furthermore, multiple studies have shown women with primary infertility, recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL) to have a higher prevalence of CE compared to the general population, suggesting a potential correlation between CE and reproductive disorders. The deleterious impact of CE on fertility is often attributed to the aberrant infiltration of plasma cells with the consequent release of antibodies and cytokines, but it is still subject to debate. Notably, women with CE also display altered endometrial expression of genes encoding for proteins implicated in the inflammatory response, proliferation, and apoptosis. Hysteroscopy is the current gold standard technique for both the diagnosis and treatment of intracavitary and endocervical lesions. Hysteroscopy has already been shown to have high diagnostic accuracy in women with endometrial polyps, submucosal fibroids, hyperplasia, and endometrial cancer. As a result, hysteroscopy is considered as an effective first-line diagnostic technique for women with infertility, in whom the presence of endometrial pathology may negatively influence the endometrial receptivity for the embryo. In this respect, a comprehensive examination of the endometrial cavity, including targeted biopsies if needed, is enabled through a hysteroscopic approach. To assess the diagnostic accuracy of current hysteroscopic criteria compared with histopathological analysis (with or without additional immunohistochemistry) for the detection of chronic endometritis MEDLINE, Scopus, SciELO, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without date limit or language restrictions. Studies were selected if they were randomized, prospective, or retrospective and estimated the diagnostic accuracy of hysteroscopy for chronic endometritis by comparing hysteroscopic criteria with histopathological (with or without immunohistochemistry) diagnosis. Primary outcomes were the diagnostic odds ratio, area under the summary receiver operating characteristic curve, sensitivity, and specificity. Positive and negative likelihood ratios were secondary outcomes. Diagnostic accuracy meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses and Synthesizing Evidence from Diagnostic Accuracy Tests recommendations and Synthesizing Evidence from Diagnostic Accuracy Tests methodological guidelines. Quality assessment was conducted using the Quality Assessment Tool for Diagnostic Accuracy Studies. Publication bias was evaluated with Deeks funnel plot asymmetry test. Thirteen studies compared available hysteroscopic criteria (stromal edema, diffuse or focal hyperemia, “strawberry aspect,” micropolyposis) with subsequent histopathological analysis of endometrial sampling. After pooling all the studies, the diagnostic odds ratio was 40 (95% confidence interval, 12-133). The evaluated area under summary receiver operating characteristic curve was 0.93 (95% confidence interval, 0.90-0.95), correlating with very high diagnostic accuracy. Sensitivity and specificity were 84% (95% confidence interval, 0.68-0.93) and 89% (95% confidence interval, 0.75-0.95), respectively. In addition, the positive and negative likelihood ratios were 7.4 (95% confidence interval 3.2-17.0) and 0.19 (95% confidence interval, 0.09-0.39), respectively. This systematic review and DTA metaanalysis shows that the use of currently available hysteroscopic features for diagnosing CE has high accuracy. Data could be computed from all 13 papers that were part of the systematic review. Hysteroscopy has results comparable to the gold standard of histopathology, as seen by the area under the SROC curve, which indicates high accuracy for the index test. A high PLR (>5.0) and low NLR (<0.2) are additional requirements for a diagnostic test to be deemed effective. The PLR score of 8.3 in this meta-analysis indicates that women meeting at least one hysteroscopic criterion are nearly 9 times more likely to test positive for endometritis at histopathology. Moreover, in women without hysteroscopic suggestive findings, the NLR value of 0.20 represents a 5-fold reduction in the likelihood of having CE. CIs for the evaluated outcomes overlapped, suggesting good quality evidence. This systematic review and DTA metaanalysis on both infertile and noninfertile women show that the current hysteroscopic criteria for diagnosing CE demonstrate accuracy prior to histopathological confirmation. Accordingly, the absence of hysteroscopic findings suggestive of the presence of CE would not need histologic confirmation and would make supplemental biopsy of more limited yield. However, the limitations of this study and reviewed evidence do not allow to draw strict conclusions. In fact, when clinical suspicion is high, hysteroscopic results are unclear, or patient anxiety or history warrants additional confirmation, histopathologic confirmation is recommended. Hysteroscopic biopsy and/or second look confirmation may also be extremely important for assessing the therapeutic response to antibiotic regimens and for identifying CE instances that have resistant features and necessitate additional histopathological assessment. Moreover, integrating RTPCR could increase diagnostic precision, especially in uncertain cases. Additional studies are required to propose the integration of molecular diagnostics as a complementary standard and to clarify the role of hysteroscopic targeted endometrial biopsy, relative to blind techniques, in obtaining optimal samples for subsequent histopathological analysis in patients with suspected CE. Source: Gaetano Riemma, John Preston Parry, Pasquale De Franciscis; American Journal of Obstetrics & Gynecology JULY 2025 https://doi.org/10.1016/j.ajog.2025.03.005