Зміни гормонально-імунологічної регуляції як предиктор невиношування вагітності у жінок з гіперандрогенією

Abstract

Для нормального перебігу вагітності окрім гормонального забезпечення надзвичайно важливим є імунологічна толерантність материнського організму до антигенів плоду. Науковий і практичний інтерес представляє вивчення в динаміці окремих параметрів системного імунітету та їх вкладу в становлення гестаційного процесу, а також розробка ранніх методів прогнозування та профілактики ранніх втрат вагітності на тлі гіперандрогенії, спрямованих на безпечне завершення вагітності.

The organism of pregnant woman must maintain a state of immunological balance between full immune competency against alien microorganisms and immunologic tolerance to the developing foetus. Disorder of tolerance formation processes leads to pathological conditions characterized by activation of cellular and humoral links of the immune system with the development of clinical manifestations of ovum rejection of varying severity that is considered as the starting point of reproductive losses. Therefore, the aim of the research was to study the imbalance of sex hormones and disorders of systemic and local immunity in patients with recurrent miscarriage on the background of hyperandrogenism (HA) to predict the development of the next pregnancy. The indicators of reproductive hormones and content of populations and subpopulations of peripheral blood lymphocytes were studied in 45 patients with adrenal hyperandrogenism (AHA) and early reproductive losses in the anamnesis (the main group) and 20 women with normal reproductive function (control group); local cellular immunity in endocervical bioptates of 15 healthy non-pregnant women and 25 pregnant women of the main group was studied. A tendency of synthesis progesterone decrease toward the median of the control group was observed in women with adrenal hyperandrogenism (AHA); this phenomenon of progesterone relative deficiency should be considered as a biochemical marker of the luteal phase inferiority of the cycle in conditions of androgen excess, that leads to the secondary function inhibition of the ovaries granular cells. Estradiol level did not differ from the mean normal values for women of reproductive age. Subpopulation analysis of peripheral blood lymphocytes in patients of the main group stated that the number of T-helpers (CD4) before the pregnancy is significantly decreased, the number of natural killer cells (CD16), the activation marker interleukin-2 (CD25), the number of dendrite cells (HLA-DR) and cells that are ready to apoptosis (CD95) are increasing. The presence of luteal phase insufficiency in women leads to the unavailability of the endometrium to embryo implantation. In women of risk group with miscarriage, T-supressor immunity decreases, natural killer cells, which are capable to commit aggression against the fetus, while passing through placenta are activated upon the occurrence of pregnancy. The increase of functional activity of lymphocytes can be used to predict the development of pregnancy in the first trimester. Considering the general mechanisms of cell activity regulation, it can be assumed that the decrease in function and possible loss of cytotrophoblast are caused by the high cytotoxic activity of natural killers, which is one of the pathogenetic links of pregnancy miscarriage. The tendency towards the increase of the number CD19 lymphocytes during the pregnancy, which probably stated the activation of autosensibilization and also predetermines an unfavorable outcome of pregnancy is noteworthy. The following predictive immunological risk markers of miscarriage of the next pregnancy in women with hyperandrogenism can be proposed: reduction of immunoregulatory index (CD4/CD8); increased level of natural killer cells (CD16); the increase in the number of activated cells (CD25; CD95); high level of HLA-DR Conservative correction of hyperandrogenism dysfunction on preconception stage will facilitate normalization of the main parameters of hormonal and immunological mechanisms and restore mother’s organism ability to ensure full implantation and normal development of pregnancy on early stages