Immunomorphological signs of chronic endometritis in patients after failed attempts of auxiliary reproductive technologies

Abstract

The objective: to analyze the morphological and immunohistochemical features of the endometrium in the patients with chronic endometritis after unsuccessful attempts of assisted reproductive technologies (ART). Materials and methods. A prospective study was conducted in women with a history of chronic endometritis on the basis of the Medical Center LLC “ISIDA-IVF” for the period from 2019 to 2021. The I group included 55 women of reproductive age with chronic endometritis and repeated unsuccessful attempts of ART, the control group (CG) – 40 women of reproductive age without fertility disorders who are preparing for the replacement motherhood programs or who are oocyte donors. The results of the endometrial biopsy performed on the 5–7th and 19th–21st days of the menstrual cycle using a pipelle aspiration curette were studied for the assessment of the immunomorphological characteristics of the endometrium in the patients with chronic endometritis. The immunoperoxidase method with primary specific monoclonal antibodies was used for the immunomorphological study of estrogen and progesterone receptors. Differences at p<0.05 were considered statistically significant. Results. Pathomorphological study of the endometrium revealed characteristic signs of chronic inflammation – the presence of a large number of plasma cells in the endometrium stroma, lymphoid infiltrates near the blood vessels and the gland orifices, unevenly expressed stroma fibrosis, sclerotic changes in the walls of spiral arteries. All examined persons had two or more morphological signs of chronic endometritis (CE). An increase number of macrophages and monocytes in the endometrium glands and stroma was found by CE – 31.3±2.9 % versus 2.3±0.1 % in CG (р<0.05). An increase proliferative activity of epithelium cells of the endometrium glands and stroma on the 5-7th day of the menstrual cycle in patients in the I group compared to similar indicators of the secretion phase in CG was determined. The proliferation of glandular and stromal cells, detected on the 19th–21st days of the menstrual cycle, had the intensification of the programmed cell death process in the covering and glandular epithelium of the endometrium. This was characterized by the structural changes in the cell nuclei – the marginal state of chromatin, the appearance of karyorrhexis and karyopyknosis. In the endometrium stroma the presence of capillary-type vessels was found, the intensity of their development had a strong correlation with the degree of severity of the inflammatory changes (r=0.74; p<0.05). During the study of progesterone receptors mainly a decrease of the level of expression in the glands both compared to the indicators of healthy women and in the secretion phase compared to the proliferation phase - H-score 145.5±7.7 was found, in the proliferation phase versus H-score 55.5±10.4 in the secretion phase (р<0.05). Conclusions. Immunomorphological study of the endometrium in patients with chronic endometritis after unsuccessful attempts of assisted reproductive technologies demonstrates that the inflammatory changes in the tissues have clear morphological criteria, which are most pronounced on the 5-7th day of the menstrual cycle – the presence of plasma cells, stroma fibrosis, sclerosis vessel walls, decrease of the estrogen and progesterone level receptors. These morphological and immunohistochemical changes persist in the secretory phase of the menstrual cycle with the most significant manifestations in the form of a decrease in the level of progesterone receptors.

The features of endometrial receptivity in women underwent in vitro fertilization procedure

“…In the various studies the role of endometrium receptivity markers was assessed [13,[18][19][20]. But despite the large number of proposed markers, there is presently no single generally accepted universal marker(s) for assessing the ability of the endometrium to ensure embryo implantation [21].…”