Аbstract. Relevance. The number of women of older reproductive age is steadily increasing, and repeated failures of Assisted Reproductive Technologies programs during the transfer of high-quality embryos indicate the possibility of disruption of embryo implantation processes associated with impaired receptivity and functionality of the endometrium. Morphological, immunological and immunohistochemical changes in the endometrium associated with age factor may be decisive for the formation of the «implantation window» and correction of these changes and may improve the outcomes of Assisted Reproductive Technologies for a cohort of patients of older reproductive age. The aim of the study - to expand the pathogenetic understanding of the violation of the implantation ability of the endometrium in healthy patients of older reproductive age. Materials and Methods. A prospective sample study of 46 patients (group 1), aged 38 to 45 years with an officially registered diagnosis of infertility lasting no more than 4 years, with a successful gynecological and obstetric history, who were about to have their first IVF attempt, was conducted. The patients were examined according to Order № 803n of the Ministry of Health of the Russian Federation. Additionally, the level of peripheral blood melatonin, the determination of progesterone, estrogen, HLA-DR (MHC II), CD56 (NK cells), CD138, leukemia inhibiting factor receptors in the endometrium were studied. Concentrations of IL-6, IL-10, TGFß, and VGEF were determined in the cervical secretion, with the calculation of the pro-inflammatory index, as the ratio of IL-6/IL-10 cu and the ratio of TGFß1/VEGF. Statistical data processing was performed using the Statistica 10.0 application software package (StatSoft, Inc., USA). Results and Discussion. In the group of healthy patients of older reproductive age, there is an imbalance of steroid receptors and secretory transformation of the endometrium against the background of relative hyperestrogenism, with a decrease in the reception of own hormones in the endometrium. A decrease in melatonin signals a disorder of pineal and pituitary control over ovarian cycling. There is a decrease in the expression of leukemia inhibiting factor. Signs of inactive chronic endometritis with an autoimmune component are monitored, confirmed by a pro-inflammatory cytokine balance. The predominance of fibrosis processes over angiogenesis processes is confirmed by an increase in the ratio of TGFß1/VEGF and highly resistant blood flow in the uterine arteries. Conclusion. Standard pre-gravidar preparation cannot compensate for all factors that violate the implantation potential of the endometrium in this cohort of patients and requires the development of new complex techniques that directly affect the diversity of all factors that ensure the natural extinction of reproductive potential in order to increase the effectiveness of Assisted Reproductive Technologies programs.

Purpose: comparative study of the structure of infertility and outcomes of ART programs among patients of different age groups. Materials and methods: the case histories of 180 patients with infertility were studied: Group I ≥ 35 years old; Group II <35 years old. Laboratory and immunohistochemical studies were carried out, and the outcomes of ART were assessed. Results: in group I, a shortened menstrual cycle was determined in comparison with group II (27,15 ± 3,39 days vs 29,57 ± 2,38 days, p = 0,001). Also, in group I, the following were more often found: inflammatory diseases (p = 0,05); history of unilateral tubectomy (p = 0,019); increased FSH levels (9,73 ± 2,43 vs 8,74 ± 2,50); decrease in the concentration of LH, progesterone, AMH (p <0,05). In the cells of the aspirate of the uterine cavity in patients of group I, there was an increased content of progesterone receptors and a decreased concentration of estrogen receptors (p <0,05). Patients of group I received a smaller number of oocytes (8,34 ± 3,51 vs 10,78 ± 4,37) and quality embryos by the 5th day of cultivation (82,7% vs 87,97%; p <0,05). The number of pregnancies in groups I and II was 22,22% and 36,67%, respectively, and live births – 14,44% and 27,78% (p <0,05). Patients who gave birth had increased progesterone levels, greater endometrial thickness, more oocytes with transvaginal puncture, and high-quality embryos. Conclusion: the factors that reduce fertility were: genital pathology, inhibition of ovarian function, depletion of the follicular reserve. Fewer live births are associated with defects in embryonic and implantation factors.

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