The incidence rate of intrahepatic cholestasis of pregnancy (ICP) ranges from 1 % to 27 % depending on the region and ethnicity. Besides itching, the disease, from a light to a severe form, is associated with obstetric and perinatal pathology. There are no clear and uniform guidelines for the management of such pregnancies and treatment is not always effective. The use of assisted reproductive technologies is a significant risk factor for ICP (OR 2.79, 95 % CІ 2.15-3.64). The dissertation is dedicated to the improvement of the effectiveness of prognostication and prevention of obstetric and perinatal complications in women with intrahepatic cholestasis who got pregnant owing to assisted reproductive technologies, on the basis of updated risk factors. We have carried out a examination of 80 pregnant women treated with ART: 40 women presenting manifestations of ICP (basic group) and 40 women without such manifestations (comparison group). The reference group included 50 women with spontaneous pregnancy of normal physiological course. The majority (62.5 %) of patients were diagnosed with ICP after 30 weeks of pregnancy, the rest of them (37.5 %) in the period from 24 to 30 weeks. Some patients (27.5 %) noted short episodes of ICP manifestations before the 24th week of pregnancy. In 7 women (17.5 %), ICP was characterized by a severe course. A third of women from the basic group had a recurrence of ICP whereas in the comparison group, there were only isolated cases of ICP in anamnesis. 42.5 % of patients from the basic group presented an ICP-positive family history. Almost a third of women (27.5 % vs. 12.5 % in the comparison group, p<0.05) had the polycystic ovary syndrome in their anamnesis record. The basic group was divided into two subgroups: Subgroup 1 – 22 (55.0 %) women with ICP who had got pregnant owing to ART and presented significant obstetric and perinatal complications and Subgroup 2 – 18 (45.0 %) pregnant women without such complications. We have established a higher incidence rate of mutation variants of C3435T polymorphism in the MDR1 gene in pregnant women affected by ICP as well as an increased occurrence of the T-allele in cases of obstetric and perinatal complications. Women with ICP also presented increased characteristic biochemical values: total bilirubin level, concentrations of bile acids, hepatic enzymes, GGT, AP and cholesterol in terms of low and very-low-density lipoproteins and the concentration of triglycerides. Patients with obstetric and perinatal complications presented increased levels of total bilirubin and bile acids in their blood. In pregnant women affected by ICP, we found a suboptimal level of vitamin D and in part of them a vitamin D deficit. Patients with obstetric and perinatal complications presented a vitamin D deficit. Women with ICP presented an increased cortisol level in the 1st trimester of pregnancy, and in the 3rd trimester, with ICP manifestations, the increase was even more apparent. An increased level of the hormone was associated with the development of obstetric and perinatal complications. The levels of sexual hormones (progesterone, estradiol) were increased in the 1st trimester in women affected by ICP. In the 3rd trimester, we also recorded an increased level of progesterone. The tendency to hypocoagulation found in pregnant women affected by ICP (relatively decreased prothrombin ratio and increased APTT). In cases of obstetric and perinatal complications, one could observe decreased prothrombin ratios. Our mathematical analysis has enabled singling out the most informative risk factors for obstetric and perinatal complications in pregnant women treated with ART and with a high risk of ICP. On the basis of these factors, we have developed an algorithm of prognostication of obstetric and perinatal complications. The prognosis accuracy has made up 90.0 %. We have suggested a pathogenetically substantiated complex of treatment and prevention measures for women involved in ART programs and presenting a high risk of ICP, which consists of the preconceptive stage and 2 stages of pregnancy management (in the 1st trimester and in case of ICP manifestation). The recommended complex of therapeutic and organizational measures has made it possible to improve of the general homeostasis of pregnant women, to decrease the incidence rate (from 52.5 to 36.3 %) and a severe course of ICP, to decrease the frequency of obstetric and perinatal complications. Key words: intrahepatic cholestasis of pregnancy, assisted reproductive technologies, obstetric and perinatal complications, prognosis, prevention. Branch-Medicine.
