The thesis presents a new solution to the scientific problem of obstetrics and gynecology, which consists in a theoretical synthesis of the results of the study of mechanisms and factors contributing to the recurrent pregnancy loss (RPL) after artificial fertilization in the cycles of assisted reproductive technologies (ART) and on this basis – pathogenetic substantiation and development systems of treatment and prophylactic measures, improvement of diagnostics, therapy of ART for rehabilitation of reproductive function in these women.
The study consisted of 4 stages. At the first stage, based on a retrospective analysis of medical documentation, 157 couples after the ART in the main group and 30 fertile couples in the control group K, the clinical and anamnestic risk factors of RPL after artificial fertilization were determined.
At the second stage, 655 couples were prospectively examined comprehensively, of which 240 women with RPL after ART cycles and their husbands; 200 women with RPL after natural congenital cycles and their men; 115 women with infertility who became pregnant after an ART and gave birth without any abortions; 100 conditionally healthy fertile women of the control group with a history of at least one urgent labor and the absence of episodes of spontaneous abortions and their husbands.
At the third stage, a comprehensive system of treatment and prevention measures for rehabilitation of reproductive function in women with RPL after ART was substantiated and developed.
The fourth stage evaluates the effectiveness of the developed integrated system of treatment and prevention measures for the rehabilitation of reproductive function in women with RPL after ART. To evaluate the effectiveness of the developed comprehensive system of treatment-and-prophylactic measures for the rehabilitation of reproductive function in women with RPL after ART in group with RPL after ART cycles, two groups were selected: patients with RPL after cycles of ART who received the developed complex personalized system of treatment preventive measures for the rehabilitation of reproductive function, and their husbands; patients with RPL after ART I cycles who received the traditional system of therapeutic and prophylactic measures for the rehabilitation of reproductive function, and their men.
On the basis of complex research, a new concept of RPL after ART was proposed in conjunction with thyroid function disorders, hypomelatoninemia and insufficiency and deficiency of 25(OH)ergocalciferol, serum disimmunoglobulinemia, psycho-emotional disorders, urogenital microbiota disorders in women and their husbands, the presence of intrauterine membranes, immune uterine dysreactivity and changes in the transcriptional gene profile of the immune response in the endometrium on the day of the predicted implantation window, chromosomal abnormalities in pairs, cytogenetic characteristics of male sperm, chorionic chromosomal abnormalities, mononuclear cell cytotoxic activity disturbances and cytokine levels of interleukin-1 (IL-1), IL4, IL-10, IL-17, tumor necrosis factor α in connection with the presence of single-nucleotide polymorphism of their genes, the presence of anitiphospholipid syndrome.
The identified fundamental mechanisms of the emergence and development of involuntary interruption of induced pregnancy allowed to substantiate the system of therapeutic and prophylactic measures for the rehabilitation of reproductive function in women with RPL after ART, the application of which leads to a possible improvement in the state of genital microbiota, receptivity of endometrium, hormonal, immune reactivity, improvement of psychoemotional characteristics and the frequency of pregnancy in the ART cycles is 3,31 times (OR 6.84; 95% CI: 3.21-14.59) and can be recommended for widespread introduction into clinical practice.
