ENDOMETRITE CRONICA: UNA PATOLOGIA SUBDOLA CHE SOTTENDE A DIFETTI DI RECETTIVITA’ E LESIONI PROLIFERATIVE DELL’ ENDOMETRIO. UN PROGETTO DI RICERCA MULTISFACCETTATO.

Chronic endometritis (CE) is a chronic inflammatory disorder of the endometrium characterized by the infiltration of plasma cells within endometrial stromal compartment. The diagnosis of CE is challenging. Clinical examination and transvaginal ultrasound are nonspecific for CE. Immunohistochemistry for the plasmacyte marker CD-138 is currently the most reliable and time-saving diagnostic method for CE. However, this technique is not exempt from limitations. Endometrial epithelial cells constitutively express CD-138 on the basolateral sides of their plasma membrane, potentially leading to misdiagnosis. Therefore, further staining techniques for CE would be useful. In a recent study, we found a dysregulation of several genes involved in cell cycle regulation in the endometrium of women with CE, with a dominance of proliferative and anti-apoptotic activity. CE may therefore represent a substrate for the development of endometrial proliferative lesions, including endometrial polyps (EPs). Different studies have investigated the correlations between CE and EPs, with controversial results. A summary of evidence on this topic is still missing. Moreover, CE may impair the endometrial receptivity towards the embryo, resulting in infertility and recurrent pregnancy loss. Unfortunately, the exact mechanisms underlying CE-related infertility are still unknown. An electron microscopy study investigating any alterations in the morphological markers of endometrial receptivity in CE is still missing. Over that backround, our multifaceted research program had the following objectives: i) to evaluate the accuracy and reliability of a novel immunohistochemical marker (Multiple Myeloma Antigen-1) for the diagnosis of CE; ii) to summarize current evidence on the correlation between CE and EPs; iii) to evaluate whether CE induces morphological changes in the mid-secretory endometrium (as assessed by transmission electron microscopy [TEM]) that may account for defective receptivity. i) We found that immunohistochemistry for MUM-1 and CD-138 had similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Therefore, MUM-1 immunohistochemistry may represents a novel, promising add-on technique for improving the diagnostic process in women with CE. ii) Our systematic literature review found high prevalence of CE in pre-menopausal women suffering from EPs. The risk of CE was higher in women with EPs compared to women with a non-polypoid endometrium, as well as in those with three or more EPs compared to those with a single EP. Available evidence in pre-menopausal women suggests that CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process. iii) TEM analysis revealed lower expression of pinopodes and higher expression of microvilli and cilia in the mid-secretory endometrium of women with CE compared to controls. These endometrial features in CE may account for defective endometrial receptivity. As our study is still ongoing, full results will be required to draw firm conclusions regarding the expression of endometrial organoids in the mid-secretory endometrium of women with CE.