Orlova V. Optimization of pre-gravid pre preparation and ovulation stimulation schemes in women with tubal-peritoneal infertility in assisted reproductive technology

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0420U000036

Applicant for

Specialization

  • 14.01.01 - Акушерство та гінекологія

05-03-2020

Specialized Academic Board

Д 26.613.02

Essay

Dissertation is devoted to one of the most important medical, social, economic nationwide problems - infertility. In our country, every fifth family is infertile. Tubal-peritoneal factor is a major cause of female infertility, covering between 20 and 72 % of all forms of impaired reproductive function and does not tend to decrease. The most effective way to achieve pregnancy with tubal-peritoneal infertility is to use assisted reproductive technologies (ART). But the question of efficiency is quite relevant, which a lot of researches is devoted in domestic and foreign literature: the influence of hormonal and immunological status, which is becoming more popular with gene expression studies, and development of oxidative stress (OS) and apoptosis in the reproductive tract are considered as potential predictors of ART failure. Some forms of infertility are characterized by accumulation of free radicals (FR) in the reproductive tract: tubal-peritoneal, uterine, endometriosis, and infertility of obscure genesis. Investigation of protein and lipid oxidation products, DNA fragmentation, and endometrial antioxidant enzymes has revealed an imbalance in the pro/antioxidant system and impaired apoptosis in women with tubal-peritoneal infertility. To date, the negative impact of OS and impaired regulation of apoptosis on reproductive function has been confirmed. Under certain conditions, it is known that even the physiological level of reactive oxygen species (ROS) in cells can contribute not only to their survival, proliferation and differentiation, but also to cause death by induction of apoptosis or necrosis. Tubal-peritoneal microenvironments affect fertilization and early embryonic development, and the increased concentration of ROS in these environments can adversely affect sperm, oocytes, and embryos in both the fallopian tube and abdominal cavity. There is an opinion that ART is also accompanied by the occurrence of induced OS, so an adequate correction of this condition is advisable. The epiphysis hormone, melatonin, acts as a powerful antioxidant, anti-inflammatory and anti-apoptotic properties, serving as a direct FR neutralizer and activator of superoxiddismutase and catalase enzymes. Therefore, we suggested that women with tubal-peritoneal infertility be treated with exogenous melatonin during pre-gravid preparation and controlled ovarian stimulation. The effectiveness of the proposed correction scheme was evaluated by measuring pro- and antioxidants in the reproductive tract, as well as evaluating the results of ART: quality of oocytes, embryos, frequency of pregnancy and birth. The results showed that exogenous melatonin therapy for 3.5 months is sufficient to restore the balance in pro/antioxidant system and to regulate the processes of apoptotic death of endometrial cells and follicles, which positively affected oocyte maturation, fertilization, embryonic development, and implantation. According to the literature, an increase in antioxidant protection is associated with an improvement of oocytes quality, embryos and pregnancy. We received a higher percentage of pregnancy rates - in 1,3 times, low rates of miscarriage (in 4 times), and increased birth rates on 9% in the group of women who treated by melatonin. Therefore, the identification of apoptosis and oxidative stress markers make it possible to identify abnormalities in pro / antioxidant system of the reproductive organs that adversely affect the quality of oocyte maturing, division of the growing embryo, implantation, and endometrial sensitivity which is responsible for pregnancy. Our study has shown that timely adequate antioxidant therapy with exogenous melatonin successfully corrects the effects of OS and apoptosis disorders, thereby increasing the efficacy of ART.

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