Hypothesis/aims of study. The ongoing global problem of health care and medical science is an associated increase in the frequency of endocrine and metabolic diseases and cancer, including in women of childbearing age. Thus, the frequency of diabetes in the population has been growing rapidly for many years. Similar trends were observed in the dynamics of the frequency of cancer pathology, especially of breast cancer, which is one of the leading places in the structure of the cancer incidence in the female population. It is known that diabetes and related insulin resistance have a very negative effect on the female reproductive function, leading to hyperplastic processes of the mammary glands. The least studied problem so far is understanding the mechanisms of development, timely diagnosis, prevention, and treatment of fibrocystic mastopathy, the proliferative forms of which underlie malignant tumors, while its atypical variations are regarded as a precancerous condition. It is likely that the pathogenesis of hyperplastic processes in the mammary gland and the risk of neoplastic transformation in disorders of carbohydrate metabolism may have special factors. The actual problem is the development of a method for pathogenetically substantiated correction of fibrocystic breast disease. This is essential for the development of pharmacological strategies for secondary prevention of breast cancer and, in this regard, it is of great interest to study application possibilities of biguanides. The purpose of the present study was to conduct a comparative assessment of the effectiveness of metformin therapy in fibrocystic mastopathy patients with and without insulin resistance. Study design, materials, and methods. The study involved 120 women, aged 18 to 40 years inclusive, with clinical and / or ultrasound signs of fibrocystic breast disease. According to the results of calculating HOMA index, patients were divided into two groups: the first group comprised 66 patients with insulin resistance (HOMA > 2.5) and the second group consisted of 54 patients with no insulin resistance (HOMA < 2.5). Assessment of mastalgia was performed using the Visual Analogue Scale. Breast ultrasound examination was performed on days 5 to 7 of the menstrual cycle. For the purpose of quantitative image analysis of the breast parenchyma, the following parameters were evaluated: a) thickness of the parenchyma (fibroglandular zone); b) diameter of the milk ducts; c) echogenicity. All patients received metformin at a dose of 1500 mg per day. Dynamic control of the clinical picture of the disease, as well as of mammographic breast parenchymal pattern, was performed after 3 and 6 months from the start of therapy. Results and conclusion. After 6 months of therapy, there was a decrease in the frequency of mastalgia, and significant changes in breast ultrasound picture were observed. The data obtained on the positive effect of metformin on clinical mastitis and structural changes in the mammary parenchyma in patients with mastopathy allow considering such an approach as a promising therapeutic strategy in this pathological association.

Reproductive losses are quite frequent in the modern world. They include: infertility, infertility of unknown etiology, multiple losses when IVF, recurrent implantation failure, miscarriage, recurrent miscarriage, both in the natural cycle and after ART management. It is important to note that the classification of some of these categories are not established yet. The etiology of reproductive losses is extremely diverse. Successful development of pregnancy at early terms is determined by genetic and immunological factors. Among the reproductive failures of unclear etiology, immunological causes are 50-80%. Over the past 20 years there are already known many different immunological factors that play role in the processes of fertilization. In this case, the evidence base on the role of each of them in the pathogenesis of reproductive failures is only being formed. Currently, the immunological relationship between mother and fetus is considered as a two-way communication process: the presentation of fetal antigens on the one hand, and on the other – the recognition and response to these antigens of the maternal immune system. Implantation of the embryo is accompanied by an increase in the production of proinflammatory cytokines followed by a sharp change in the cellular composition in the decidualizing endometrium, and the main population is NK cells. That is why this type of cells have a significant role in the normal development of pregnancy. The properties of NK cells in the uterus and peripheral blood are significantly different. To predict the onset and prolongation of pregnancy, peripheral blood NK (activity and quantity) is used. Evaluation of endometrial NK is often performed for the diagnosis of chronic endometritis. Currently, the definition of NK cells in peripheral blood in many clinics is proposed as a useful diagnostic test to address the issue of further appointment of immunoglobulins and evaluating the effectiveness of this therapy in patients with reproductive losses.

Granulocyte colony-stimulating factor (G-CSF) promotes proliferation, survival, and differentiation of myeloid-lineage cells, as well as normal hematopoietic cells. The immunomodulating effects of G-CSF, which consist in stimulating the Th2 biased type immune response, prevent the development of graft-versus-host disease (GvHD) and, as a special case of GvHD, are responsible for the embryo implantation into the endometrium after the embryo transfer. G-CSF stimulates subpopulations of neutrophils, which display anti-inflammatory properties and are involved in tissue regeneration. The increased secretion of annexin A1 and IL-10 ensures the anti-inflammatory and immunomodulating effects of neutrophils. This review article presents data from four meta-analyzes aimed to explore the efficiency of G-CSF on infertile women undergoing in vitro fertilization. These data demonstrate an increase in the embryo implantation rate and clinical pregnancy rate, which is provided by the change in the endometrial receptivity and/or the invasive potential of the developing embryo.

Structural transformation of the endometrium during the menstrual cycle is a genetically determined process and is provided by complex molecular-biological interactions aimed at the onset and development of pregnancy. Sex steroid hormones play a key role in endometrial morphogenesis, which mediate or directly affect angiogenesis and immunogenesis.

Background. According to WHO data (2014), more than two billion people are deficient in microelements or have a “hidden hunger” due to the deficiencies of vitamins and minerals. Currently, experts estimate the vitamin D deficiency as a new type of pandemic of the XXI century. Aim. The current analysis was undertaken to evaluate the effect of vitamin D on women’s reproductive health. Materials and Methods. Based on the findings of retrospective and prospective studies, meta-analyzes, and material trials over the past 20 years, as well as in accordance with the results of 290 prospective cohort randomized trials, the level of vitamin D affects 172 basic physiological indicators associated with the risk of such complications of pregnancy as miscarriage, preeclampsia, gestational diabetes mellitus, and bacterial vaginosis. Results. Vitamin D has been shown to be able to act as an immune regulator during the implantation. The placenta produces and responds to vitamin D, which has a local anti-inflammatory response and simultaneously induces the production of decidual growth factors for successful pregnancy. Activated T- and B-lymphocytes have the vitamin D receptors and therefore 1,25(OH)2D is an effective modulator in the immune system. It is able to inhibit the proliferation of Th1 and to restrict the production of such cytokines as interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α). In addition, vitamin D is able to induce cytokines of Th2 that have the protective effect on  pregnancy. Conclusion. Adequate vitamin D intake is important for the successful conception and prolongation of pregnancy, as well as for the health of the fetus and newborn.

Background. A local inflammatory reaction in the endometrium caused by viral infection and associated with external genital endometriosis (EGE) can affect the implantation properties of endometrium and be one of the causes of infertility. The aim of the study was to investigate the expression of estrogen and progesterone receptors, pro-inflammatory markers and inhibitor of cyclin-dependent kinases p16ink4a in the endometrium of women with infertility associated with EGE. Materials and methods. The object of the study was the material taken from 133 patients aged 19-35 years. Inclusion criteria were the presence of external genital endometriosis confirmed by laparoscopy and the absence of hormone treatment for 6 months prior to this study. Endometrial biopsies were obtained on 19-24 day of the menstrual cycle. Histological and immunohistochemical studies of endometrial biopsies were performed using standard methods. The expression of estrogen (ER) and progesterone receptors (PgR), inflammatory markers (CD8+, CD20+, CD4+, CD138+) and inhibitor of cyclin-dependent kinase p16ink4a were examined by immunohistochemistry. The evaluation of the expression of studied markers was performed in the epithelium of the glands and endometrial stromal component separately, using semiquantitative method H-Score, as well as qualitative and quantitative methods in image analysis system “Morphology 5.0” (VideoTest, Russia). Statistical analysis was performed using statistical software (STATGRAPHICS v.6.0). Results. A significant decrease in the expression of ER and PgR in endometrial stromal component was noted on the background of the high incidence of chronic endometritis in patients with EGE. All patients of the main group had a positive expression of p16ink4a. Conclusions. The obtained results indicate a high incidence of disorders of eutopic endometrial secretory transformation in patients with infertility associated with external genital endometriosis. The high incidence of the virus associated with chronic endometritis and sensitivity violation of endometrial tissue to sex steroid hormones, such as progesterone, may be a major determinant of infertility of patients in this group.

Introduction. Cytochrome P450 aromatase is a key enzyme in the biosynthesis of estrogens from androgens. Some gynecological diseases are accompanied with changes in the activity of ovarian aromatase. Moreover, changes in the acti vity of ovarian aromatase are associated with the response to standard gonadotrophin stimulation in women undergoing in vitro fertilization. A new effective method determining the activity of ovarian aromatase without using ovarian tissue biopsy has been developed. The purpose of the present study was to compare the detection of ovarian aromatase activity using the ratio of estradiol to AMH on the second day of the menstrual cycle through the immunocytochemical evaluation of aromatase expression in cumulus cells. Methods. Depending on the activity of the ovarian aromatase, calculated on the second day of the menstrual cycle, 16 patients undergoing IVF protocols were categorized into three groups: eight patients with low activity, four with normal activity, and four with high activity. The patients did not differ in age and BMI. The expression of aromatase in cumulus cells obtained through transvaginal puncture was investigated by the immunocytochemical method. Results. The fluorescence intensities in the low, normal, and high activity groups were 134 (122–161), 238 (201–251), and 259 (240–299), respectively. Differences between these groups were statistically significant (p = 0.008). There was a pronounced positive correlation between the activity of ovarian aromatase, calculated on day two of the menstrual cycle, and the intensity of aromatase fluorescence in cumulus cells (Spearman, r = 0.75, p = 0.001, n = 16).

Hypothesis/aims of study. To date, one of the most important avenues of research in the field of reproductive medicine is the searching for new biochemical markers of oocyte quality and the prediction of the effectiveness of in vitro fertilization (IVF) protocols. The aim of this study was to assess the effect of relaxin levels in blood serum and follicular fluid on the efficiency of ovulation stimulation, fertilization, and characteristics of the embryos. Study design, materials and methods. This prospective randomized cohort study included 11 patients undergoing infertility treatment in a superovulation stimulation protocol using gonadotropin-releasing hormone antagonists. Age, body mass index, hormonal status, ovarian response, endometrial thickness and structure, the number and quality of oocytes and embryos, as well as fertilization efficiency were assessed. The level of relaxin in blood serum and follicular fluid samples was determined on the day of transvaginal follicle puncture using enzyme immunoassay. Results. A correlation between follicular fluid relaxin levels and body mass index, age, the number of oocytes, and their fertilization efficiency (p 0.05) was established. Changes in follicular fluid relaxin level were revealed depending on the gonadotropin preparations (p 0.05) and triggers of final maturation of oocytes (p 0.05). The tendency of the effect of gonadotropin doses on circulating relaxin levels, and of the hormone itself on endometrial thickness and the quality of oocytes was determined. Conclusion. Determination of the relaxin concentration can be considered as a promising method for predicting the result of ovarian stimulation and the efficiency of fertilization in IVF protocols.