Risk markers of reproductive loss in women with hyperandrogenism

Introduction: The frequency of the pathological course of pregnancy with hyperandrogenism ranges from 21 to 48%. With the predominance of androgens against the background of lowering the normal products of steroidogenesis, a pro-inflammatory immune imbalance is formed, which causes a premature termination of the development of pregnancy. Many studies indicate that hyperandrogenism is a factor in the development of obstetric pathology, including placental dysfunction. The severity of obstetric complications of pregnancy in women with hyperandrogenism depends on the duration of the disease and the quality of preparation for pregnancy. Establishing early markers of endocrine hyperandrogenic imbalance in the body of a future mother and conducting timely therapy is the key to the successful completion of pregnancy. The aim: the establishment of hormonal-immunological changes and morphological and receptive structure peculiarities of the endometrium correlations in women with PCOS at the pregnancy planning stage.

Materials and methods: 139 women with PCOS were screened at the stage of pregnancy planning. Diagnosis of PCI was conducted in accordance with the International Recommendations of Endocrine Society 2013 and the Rotterdam criteria of 2003. Endometrial aspiration was studied for the study of T and B lymphocyte populations, cytokine levels and endometrial receptors. Hormonal parameters were determined using the radioimmunological method using Immunotech (Czech Republic) and Siena Ire Sorin (France) kits. Normal values of the studied hormones in accordance with the recommendations of the manufacturer. In order to study the populations of T and B lymphocytes and endometrial receptors the aspirate, obtained by endometrial biopsies, was used taken on the 5-7 and 21-24 days of the menstrual cycle. The cytokines levels (INF-y, TNF-a, Il-4, Il-6, Il-8, Il-10) were estimated in the endometrium with the help of the test system "Protein contour" on immunoenzymatic analyzer "Multyskan EX" (Germany). The assessment of estrogens receptors at stroma and glands and progesterone receptors at stroma and glands was performed by H -Score system, lymphocytes count was carried out by the light microscope at 400 x 3 fields-of-view expansion. Statistical material analysis was carried out on the personal computer using the standard software package with applied statistical analysis (Excel 2003 and Statistica v. 6.0). The assessment of variables connection was carried out by Pirson's coefficient correlations. The statistical significance of differences was performed by the use of nonparametric Mann -Whitney criteria, χ2 and Fisher criterium. The significance threshold of statistical value was considered p = 0.05.

Results: In women with hyperandrogenism, there was a significant increase (p <0.05) in the level of DHEA-S, a decrease in the level of E2 and progesterone in the early follicular phase compared with the control group and an increase in body weight by 37.5%. At histological examination of the endometrium on the 5-7th day of the menstrual cycle there was a lag proliferative changes of the endometrium, and in one third of women hyperplastic process against the background of reduced proliferative activity. At GA there was a marked violation of expression of receptors as estrogens and progesterone stroma in all stages of the menstrual cycle. In women with hyperandrogenism, changes in the immunological profile of endometriosis with the prevalence of Th-1 orientation of immunity have been detected.

Conclusions: In women with hyperandrogenism there is a close correlation between the biochemical form of the domination of androgens, ovulatory dysfunction, immunohistochemical and morphological structure of the endometrium. Revealed features of pro-inflammatory direction of cytokine immunity.