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 aim: To carry out a statistical analysis of physical and reproductive health characteristics in women after ineffective reattempts of using assisted reproductive technologies and identify significant medical and social factors contributing to the development of chronic endometritis. Materials and methods: We carried out a statistical analysis involving 177 outpatient medical records: group 1 includes 127 women aged under 45 with two or more ineffective attempts of in vitro fertilization; group 2 comprised 50 healthy women without reproductive disorders. The complete physical exam included past history, clinical and gynecologic examination, lab techniques and medical imaging according to outpatient medical records obtained during the follow-up care in Isida-IVF Medical Center LLC. Chronic endometritis was recognized by means of histologic examination of endometrium, with the samples obtained by an endometrial pipelle biopsy on day 4-9 of the menstrual cycle. Results: The prevalence of pelvic inflammatory disease in patients of group 1 comprised 47.2%, endometritis – 41.7%; p1.2 <0.01. The prevalence of acute endometritis among patients of group 1 comprised 6.3%; p1.2 >0.05 and was associated with an infection after abortion. In group 1, sexually transmitted infections were reported in 67.7% of patients, p1.2> 0.05, bacterial vaginosis was registered 1.5 times more often – 28.4%; p1.2 <0.05. In group 1, single induced abortion was reported in 15.0%, while 2 times it took place in 15.7% (p1.2 <0.05). Laparoscopies were previously performed in 59.8% of women, laparotomies – in 62.2%, while in 25.4% of women these interventions were reperformed. Unilateral salpingectomy, due to ectopic pregnancy, was performed in 25.4% of women, bilateral – in 12.7%. Fallopian tube removal, due to sactosalpinx, was performed in 25.4% of women, unilateral salpingectomy took place in 3.9% of cases. The most significant risk factors of chronic endometritis in groups studied are acute postabortal endometritis, RR (relative risk) = 1.439, p = 0.029 and postoperative peritonitis provoked by the complications of appendectomy, RR = 1.430, p = 0.084. We detected none of significant effects of pelvic inflammatory disease on the development of chronic endometritis (RR = 45.132, Confidence interval (CI) (6.151-331.167), p = 0.001). The analysis of reproductive failures, as a risk factor of chronic endometritis in women of group 1, showed a significant relative risk: with the past history of premature birth, RR = 1.44, p = 0.039, in case of reattempts of induced abortions, RR = 1.5, p<0.001, Spontaneous miscarriage RR = 1.572, p = 0.001. A higher relative risk of developing chronic endometritis was observed during pregnancy – RR = 1.597, p = 0.001. Conclusions: Statistical analysis of women’s reproductive health after ineffective reattempts of using ART revealed that the high rate of fetal interventions, low rate of alternative and safe abortion methods are registered in these women, as well as the nonavailability of any system of health measures after reproductive failures. A significant increase in miscarriage at early stages takes place, as well as the absence of a tendency for preterm labor to decrease in the rate. Maintaining women’s reproductive health is a considerable medical and social issue, whose resolving depends on joint efforts of governmental and public entities, healthcare agencies and the population responsibility for own health. Designing and adopting the program of preconception care and planning for pregnancy in women after ineffective reattempts of using ART, with chronic endometritis as a primary disease, should be the top priority area of a health care system.

Chronic inflammatory process in endometrium is an obvious factor of infertility and recurrent pregnancy loss. But uncertainty of its etiology in most of the clinical cases results in complications of diagnostic process of the disease despite the broad spectrum of diagnostic techniques. Shift of the focus from specific infectious agents towards opportunistic pathogens also leads to several complications in interpretation of bacteriological examination results. Moreover, the role of viruses as ethiological factor of chronic endometritis is still not well established. At the same time the capability of invasive diagnostic techniques is always discussed by the clinicians because of additional risks from intervention into uterine cavity. From this point of view treatment of chronic endometritis (CE) and pregravid preparation of women involved in in vitro fertilization algorithm with such pathology requires comprehensive analysis. Routine antibiotic administration, principles of choice of these medications and effectiveness of other therapeutical approaches, for example, physiotherapy techniques, are still controversial. This article highlights modern ideas about chronic endometritis: ethiological factors of the disorder, coincidence with infertility and reproductive failure, diagnostic methods, treatment and pregravid preparation of women with the disease and ways of optimization of patient management for preserving their reproductive potential. Key words: chronic endometritis, infertility, in vitro fertilization, antibiotic therapy.

The objective: to conduct a clinical and statistical analysis of the characteristics of the somatic and reproductive history in women with repeated unsuccessful attempts of assisted reproductive technologies and to determine significant medical and social factors in the formation of chronic endometritis. Materials and methods. A clinical and statistical analysis of 177 outpatient cards was carried out: Group I – 127 women under the age of 45 with a history of two or more ineffective attempts at in vitro fertilization; Group II – there were 50 healthy women without reproductive disorders. The comprehensive examination included data from anamnesis, general clinical and gynecological examination, laboratory and instrumental methods according to the data of outpatient observation cards at the MC LLC «Isida – IVF». The diagnosis of chronic endometritis was verified by the data of the histological examination of the endometrium obtained by the pipel biopsy method on days 4 –9 of the menstrual cycle. Results. The incidence of inflammatory diseases of the uterine appendages in patients of group I was 47.2%, inflammatory diseases of the endometrium – 41.7%; р1.2<0.01. The incidence of acute endometritis among patients of group I was 6.3%; р1.2>0.05 and was due to the implementation of the infectious process after abortion. In the first group, sexually transmitted infections were noted in 67.7% of patients, р1.2>0.05; bacterial vaginosis was recorded 1.5 times more often – 28.4%; р1.2<0.05. In the first group, one-time artificial termination of pregnancy appeared in 15.0%, twice – in 15.7% (р1.2<0.05). Laparoscopies were previously performed in 59.8% of women, laparotomies – in 62.2%, while operations were repeated in 25.4% of women. Unilateral tubectomy for ectopic pregnancy was performed in 25.4% of women, bilateral in 12.7%. Removal of fallopian tubes due to sactosalpinxes in 25.4% of women, unilateral removal of appendages appeared in patients in 3.9% of cases. The most significant risk factors for the development of chronic endometritis in the studied groups are acute post-abortion endometritis VR (relative risk) = 1.439, p=0.029 and postoperative peritonitis, which was caused by complications of appendectomy – RR=1.430, p=0.084. We did not reveal a significant effect of inflammatory diseases of the uterine appendages on the implementation of chronic endometritis (RR=45.132, CI (6.151-31.167), p=0.001. Analysis of reproductive failures as a risk factor for the development of chronic endometritis in women of group I showed a significant relative risk: with a history of PR RR=1.44, p=0.039, with repeated artifactual abortions RR=1.5, p<0.001, SV RR=1.572, p=0.001. A higher relative risk of developing XE was observed during pregnancy – RR=1.597, p=0.001. Conclusions. Clinical and statistical analysis of the reproductive health of women with repeated unsuccessful attempts at ART has shown that these women have a high frequency of intrauterine interventions, a low frequency of using alternative and safe methods of abortion, and there is no system of health measures after reproductive failures. There is a significant increase in spontaneous abortion in the early stages and the absence of a decrease in premature birth. Preserving the reproductive health of women is an important medical and social problem, the solution of which depends on the joint efforts of state and public organizations and health authorities, as well as on the responsibility of the population for their health. The development and implementation of pregravid health improvement and pregnancy planning programs for women with repeated unsuccessful attempts at ART against the background of chronic endometritis should be a priority in the health care system. Keywords: assisted reproductive technologies, chronic endometritis, ineffective attempts at fertilization, reproductive health, pregnancy.