No 11 (2019)

The review analyzes data on the use of noninvasive techniques to treat rhesus sensitization in pregnancy. The high efficiency of efferent treatment methods, such as plasmapheresis and plasma exchange, in combination with intravenous immunoglobulin can decline the number of anti-Rh antibodies and, thereby, prevent the development of hemolytic disease of the fetus and newborn, as well as reduce the percentage of use and timing of invasive treatments, such as intrauterine fetal blood transfusion in women with high antibody titers and a family obstetric history. The efficiency of treatment results from the removal of Rh antibodies from the bloodstream during efferent treatment methods, and, the administration of intravenous immunoglobulins ensures the temporary prevention of Rh antibody production.

The paper discusses the genital functional state in women of late fertile age. It presents the age-related ovarian and uterine changes that cause a decline in an ability to conceive in women of late fertile age. The main feature of the activity decayed period of the female reproductive system is considered to be a change in the function of the gonads. The paper describes the gynecological and somatic diseases that complicate the course of pregnancy in women of late fertile age. Extragenital pathology has been established to be most commonly detected with increasing age in women.

Modern medicine has great potential for searching for new rapid methods for the early diagnosis of precancerous diseases of the cervix andfor identifying a group at risk for recurrent processes after surgical treatment for cervical intraepithelial neoplasias. New and intensively developing science areas, such as metabolomics, lipidomics, and proteomics, are now being widely discussed. The review is dedicated to the analysis of lipidome in breast cancer, endometriosis, and neoplastic changes in cervical tissues by mass spectrometry as a highly informative method to search for biomarkers of human papillomavirus (HPV)-associated cervical diseases.

The authors have conducted a systematic analysis of the data available in modern literature on the role of genetic testing for mutations in the genes responsible for a predisposition to hereditary reproductive organ cancers in women. They consider data on the importance of using genetic testing in clinical practice to predict the disease development, a need for the follow-up monitoring in the presence of mutation carriage, the volume of surgical treatment and to determine combination chemotherapy policy for malignant neoplasm. The role of mutations for chemotherapy, prophylactic surgery, and preimplantation genetic diagnosis as primary prevention of hereditary cancer syndromes is described.

The authors carried out a systematic analysis of data on the role of ADAMTS-13 metalloproteinase in the pathogenesis of different pathological conditions in the neonatal period. The review includes data from foreign and Russian articles published in the past 10 years and found in e-Library and PubMed on this topic. It presents data on diagnostic criteria, the possibilities of determining ADAMTS-13 and its inhibitors, the value of ADAMTS-13 in the development of thrombotic thrombocytopenic purpura and neonatal thrombosis. Current ideas on the possibilities of treatment and correction of the above conditions are presented.

Vitamin D receptors are known to be found in 36 human tissues, including in the ovarian tissue, endometrium, fallopian tubes, decidua, and placenta of women. In the early stages, trophoblast simultaneously produces and responds to vitamin D that has a local anti-inflammatory effect and induces decidual tissue growth for a successful pregnancy. Objective. To investigate the expression of vitamin D and its receptor in the villous chorion in non-developing and physiological pregnancy. Materials and methods. Sixty-four villous chorion samples divided into 2 groups: 1) 32 from women with missed miscarriage; 2) 32 from those who had undergone medical abortion, were examined. The inclusion criteria were abortion material from women at 6-12 weeks’ gestation, singleton pregnancy, and normal fetal karyotype. Results. The trophoblast and stroma of the chorionic villi showed the uniform distribution of the expression of vitamin D and its receptors. In missed miscarriage, the relative area of the expression of vitamin D and its receptor was statistically smaller than that in Group 2 (10.3%, 15.4% (p < 0.01) and 35.9+1.8; 56.1+2.4 (p < 0.01), respectively). Conclusion. In missed miscarriage, the expression of vitamin D and its receptor is lower.

Objective. To study the diagnostic significance of transforming growth factor (TGF)-β1, TGF-β2, and TGF-β3 isoforms in fetal growth restriction (FGR). Subjects and methods. Plasma samples from 48 women were examined during this investigation. The pregnant women were divided into 2 groups: 1) 28 pregnant women with FGR; 2) 20 women with physiological pregnancy. All the patients underwent multiplex measurement of the concentrations of TGF-P1, TGF-P2, and TGF-P3 isoforms by using the standard 3-plex Bio-Plex Pro assay system on a Bio-Plex 200 System flow-through laser immunoassay device (Bio-Rad, USA), followed by the processing of the results obtained in the Bio-Plex Manager Software version 6.0 Properties (Bio-Rad, USA). Results. The level of TGF-β3 was ascertained to ne significantly lower in pregnant women with FGR (41.42pg/ml) than in apparently healthy pregnant women (48.42pg/ml) (p = 0.01). The levels of TGF-β1 and TGF-β2 did not statistically differ in the study groups. Conclusion. The findings indicate that studying the plasma levels of TGF-β3 is promising in predicting fetal growth restriction.

Aim. To optimize the diagnosis of biochemical hyperandrogenism (HA) and investigate its association with metabolic dysfunction in polycystic ovary syndrome (PCOS). Materials and methods. The study comprised 437 women with PCOS and 160 healthy women. Clinical and laboratory evaluation consisted of pelvic ultrasonography (USG), analysis of androgen profile including serum levels of total testosterone, free testosterone, and androstenedione (TT, FT, A4), a two-hour glucose tolerance test (GTT) with monitoring of glucose and insulin levels, and the blood lipid prof ile. Results. Measuring a complete serum androgen prof ile increases the detection rate of biochemical HA from 37.4 to 66.4%. The greatest contribution to the diagnosis of HA is made by determining serum A4 concentrations, which are elevated in every second patient with PCOS. HA with co-elevated serum TT and A4 is associated with a 1.5-2 fold increase in the rate of impaired glucose tolerance (IGT), hyperinsulinemia (HI), insulin resistance (IR), and dyslipidemia. Conclusion. Patients with suspected PCOS should be tested for serum TT, FT, and A4; the measurement of A4 is most important. Co-elevated serum TT and A4 may be a useful predictor of developing IR, HI, IGT, and dyslipidemia.

Objective. To predict recurrent uterine fibroids (UFs) by direct mass spectrometry. Subjects and methods. A plasma lipidomic analysis was carried out in 81 patients treated at the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, including 35 patients with newly diagnosed UFs, 31 patients diagnosed with recurrent UFs (RUFs), and 15 comparison group patients who underwent surgical treatment for infertility, intrauterine septum. Semi-quantitation of blood lipid levels was performed by high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Mass spectrometric data were processed using the orthogonal projection to latent structure discriminant analysis (OPLS-DA) to build a statistical model for classifying samples and identifying potential biomarkers. The lipids were identified by their exact mass and characteristic tandem mass spectra (MS/MS). Results. The presented patient groups differed in the lipid composition of blood plasma by the presence and level of phospholipids, sphingomyelins, cholesterol esters, and triglycerides. The created statistical models made it possible to identify lipids, potential biomarkers of both the disease itself and its recurrences. Conclusion. This investigation confirms the implication of phospholipids and sphingolipids in the pathogenesis of UFs and opens up new possibilities for predicting RUFs.

Objective. To carry out a systematic analysis of the serum level of neurokinin B (NKB) in women of different age periods and in those with and without vasomotor symptoms and sleep disturbances. To assess the time course of changes in the level of NKB during menopausal hormone therapy (MHT). Subjects and methods. The investigation enrolled 50 postmenopausal women and 30 reproductive-aged women having a regular menstrual cycle. The patients were divided into 3 groups: 1) 25 postmenopausal patients with vasomotor symptoms and sleep disturbances; 2) 25 postmenopausal patients without vasomotor symptoms and sleep disturbances. A control group (Group 3) included 30 reproductive-aged women having a regular menstrual cycle. Group 1 received MHT. The dynamics of menopausal symptoms (Greene Climacteric Scale), a subjective sleep rating scale, and NKB levels were assessed after 12 weeks of therapy. Results. There was a significant increase in serum NKB levels in postmenopausal women compared with the controls. In postmenopausal women with sleep disturbances and vasomotor symptoms, NKB levels were statistically significantly higher than in women without the above symptoms. A strong relationship was established between the level of NKB and the severity of menopausal syndrome. There was a signif icant decrease in the severity of menopausal symptoms after 12 weeks of MHT, which was accompanied by a 3.2-fold decrease in NKB levels. Conclusion. The findings suggest that the activation of KNDy neurons and the increased secretion of NKB play a possible role in the pathogenesis of sleep disturbances and vasomotor symptoms in postmenopausal women.

Ministry of Health of Russia, Moscow, Russia Objective. To investigate the features of the genetic polymorphisms that determine the implementation and characteristics of the course of congenital infections in newborn infants, by taking into account their gestational age. Subjects and methods. The investigation enrolled 379 newborn infants with respiratory disorders of different origin, which required respiratory therapy. All the babies were born in the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, and treated at the Center’s Intensive Care Unit in January 2013 to December 2015. According to the infectious or non-infectious genesis of respiratory disorders, the infants enrolled in the investigation were divided into 2 study groups: 1) 161 babies with transient tachypnea of the newborn or respiratory distress syndrome; 2) 218 infants with intrauterine infection (congenital pneumonia or early neonatal sepsis). Based on their gestational age, the babies of the two study groups were divided into four subgroups: 1) 24-28 weeks; 2) 29-32 weeks; 3) 33-36 weeks; and 4) 37 or more weeks. Results. The investigators revealed statistically significant differences between the genetic polymorphisms in the neonates born at different gestation ages who had an infectious or non-infectious cause of respiratory disorders, according to the distribution of the following genotypes and alleles: NOS3-786, NO S3-894, and IL1b at 29-32 weeks’ gestation, AGTR2, IL4R1902, IL8, GNB825, and HTR2A at 33-36 weeks, and IL8, ADD1, and ADRB3 at 37 or more weeks. Conclusion. This investigation has shown that different genetic polymorphisms are associated with the development of infectious and inflammatory diseases in newborns at different gestational ages, which appears to reflect the process of maturation of the immune system. Not only the genes of innate immunity, but also the regulators of energy metabolism and vascular tone have been found to be involved in the development of infectious complications, which suggests that there is a complex mechanism for the development of neonatal septic conditions.

Objective. To present 3-month own experience with external cephalic version at Saint Petersburg Maternity Hospital Nine. Materials and methods. A total of 58 attempts at external cephalic version in cases pelvic or transverse lie were performed at Maternity Hospital Nine in December 2017 to February 2019. All women’s gestational age was 36 to 40 weeks and 4 days. In all cases, the fetal status was evaluated by ultrasonography, cardiotocography, and Doppler study. Results. Successful attempts were achieved in 69% of the total number of pregnant women. In the successful version group, most (60%) women gave birth via vaginal delivery. Caesarean section could be avoided due to the incorrect fetal position for delivery in 24 women (41.3% of the total number of version attempts). A complication as placental abruption during the procedure occurred in one (1.7%) case. Conclusion. External cephalic version is a safe and effective procedure to reduce the number of caesarean sections. The optimal time for this procedure is 36-37 weeks of pregnancy.

Objective. To establish the specific features of the course acute vulvovaginal candidiasis (VVC) and therapy with fenticonazole in reproductive-aged women with different phenotypes of polycystic ovary syndrome (PCOS). Subjects and methods. The investigation enrolled 65 women of reproductive age (mean age, 27.4+3.6 years) with severe acute VVC. A study group included 35 women with PCOS (Group 1); a comparison group consisted of 30 women without PCOS (Group 2). To treat acute VVC, all the women received an intravaginal 600-mg fenticonazole capsule once overnight on days 1 and 4 of treatment. In both groups, the efficiency of treatment for acute VVC was evaluated at 10-14 days, 1 and 3 months after therapy. Results. At 10-14 days and 1 month after fenticonazole treatment, its efficiency was high in both groups and amounted to 94.3 and 96.7% (at 10-14 days after treatment) and 91.4% and 93.3% (at 1 month after treatment), respectively. At 3 months after treatment, its efficiency remained high in the comparison (non-PCOS) group and amounted to 90%, whereas that in the study (PCOS) group significantly decreased to 71.4% (p <0.05). In the women with PCOS, the recurrence rate of VVC depended directly proportionally (r = 0.60; p <0.001) on the presence of carbohydrate metabolic disturbances as glucose intolerance and insulin resistance (r = 0.50; p <0.01) and overweight or obesity (r = 0.77 p <0.001). Almost all women with an exacerbation of VVC were diagnosed with glucose intolerance or insulin resistance (Homeostasis model assessment of insulin resistance (HOMA-IR) was more than 2.5 scores). In women with hyperandrogenism (phenotypes A, B, C), an exacerbation of VVC occurred significantly more frequently (r = 0.40 p <0.01), Conclusion. Recurrent VVC in women with PCOS may be prevented by correcting main metabolic changes, overcoming insulin resistance, and restoring the ovulatory cycle. In case of an exacerbation of VVC in this patient group, it is recommended to use fenticonazole at a dose of600 mg twice with an interval of 3 days. Thus, fenticonazole may be recommended as the first-choice drug in treating acute VVC in reproductive-aged women.

The paper presents current data on the etiology and epidemiology of herpesvirus infection. It describes the possible clinical types of the disease, including its atypical manifestations and sites. The author sets forth the impact of herpesvirus infection on pregnancy. She discusses methods for the laboratory diagnosis of genital herpes and current approaches to its therapy in accordance with international and Russian clinical guidelines. The results of studying the efficacy of valaciclovir in treating various types of anogenital herpetic infection are presented.

Background. Each case of pregnancy in patients with multiple endocrine neoplasia type 1 (MEN-1) should be followed up by an interdisciplinary team of physicians, which is a prerequisite for the effective control of outcomes for both the mother and the fetus. Publications on this topic are quite limited in foreign literature, and Russian articles have not yet been submitted. Description. The paper gives two cases of successful pregnancy management in patients with the classical phenotype of MENP-1, which was verified before conception with a favorable outcome for the mother and the baby. One of the patients was recorded during pregnancy to have progressive pancreatic tumor growth, which required subtotal resection after delivery. Conclusion. The main therapeutic goal in the planning and managing of pregnancy in patients with MEN-1 is to correctly and consistently control its associated diseases, by analyzing the risk/benefit ratio for the chosen tactics.