No 8 (2020)

Studying of the expression of CaV1.2 calcium channels is relevant in the practice of an obstetrician/gynecologist, as well as in therapy, psychiatry, neonatology, and gynecologic oncology. The clinical effects of calcium channel disorders depend on the level of expression of the CACNA1C gene, its penetrance and can determine a number of clinical conditions with the formation of a sarcopenic phenotype: asthenic hypotrophic body type (30%), muscle asthenia, childhood-onset refractive errors (22.2%), arterial hypotension (60%), functional isthmico-cervical insufficiency during pregnancy (23%), oxytocia and accelerated labor (37.6%), a tendency towards constipation (55%), varicosity (39.5%), pelvic floor protrusion and relaxation (50%), apical genital prolapse (60%), joint hypermobility (48.8%), grade 2 scoliosis (33 %), grade 3 platypodia (73.8%), hypotonic bowel dysfunction (50- 60%) A relationship was shown between the lower expression level of CaV1.2 calcium channels in the round ligament of the uterus in patients with genital prolapse and the incidence of incomplete right bundle branch block (33%), ST segment elevations (15%), cardiac structural abnormalities (88%), and apical genital prolapse (60%) in young patients. Conclusion. Studying the expression level of the a-1 subunit of the CaV1.2 voltage-dependent calcium channel and the level of protein expression in smooth muscle tissue will help not only to explain the etiopathogenetic mechanisms of a number of pathological conditions in obstetrics, gynecology, and neonatology (miscarriage, hypertension during pregnancy, childbirth and postpartum; a sarcopenic phenotype in pregnant women, congenital heart rhythm disturbances, cardiomyopathy, Brugada syndrome in newborns, etc.), as well as in operative gynecology and general surgery, but also to apply a personalized approach to choosing a method for treatment, prevention, and rehabilitation.

Uterine myoma is a benign tumor, which in 10-30% of cases grows rapidly during gestation and can cause serious complications in both the mother and the fetus. Myomectomy during pregnancy raises many controversial issues. For a better understanding of this surgical problem, a systematic analysis of the data available in modern Russian and foreign literature has been carried out using the databases: eLibrary, Scopus, PubMed, MEDLINE, ScienceDirect, and Cochrane Library from the moment of their creation to December 2019, which shows that abdominal myomectomy in pregnant women is not a common practice with successful rates in the hands of specialists with extensive surgical experience. In recent years, most authors have been inclined to believe that myomectomy during cesarean section does not increase the risk of perioperative bleeding and pyoseptic complications if necessary surgical technique is used. Conclusion. The problem of myomectomy during pregnancy and cesarean section requires further large-scale randomized trials to assess the risks and benefits of these operations for both the mother and the fetus.

Antiphospholipid antibodies (aPL), a heterogeneous group of autoantibodies, have a pathogenetic and diagnostic value for obstetric APS. Aim.0h RSM were 3.4-8.5 times more likely to be positive for antibodies against β2-glycoprotein-I (β2-GP-I), cardiolipin (CL), annexin A5 (An A5), phosphatidylserine/prothrombin complex (PS/PT), and phosphatidylethanolamine (PE) than healthy women. Serum level of IgG antibodies to β2-GP-L >17.6 U/ml was associated with a high probability of the presence of antibodies to domain I. IgG2 subclass of aPL with moderate and high levels of avidity were predominant. The panel of antibodies to β2-GP-I, An A5, PS/PT, and PE showed a high diagnostic value for RSM. Conclusion. In patients with early RSM, the aPL profile testing including antibodies to CL, β2-GP-I, domain I, antibodies to An A5, PE, and PS/PT improves the accuracy of diagnosis in APS.

Relevance. Fetoscopic laser coagulation (FLC) of placental anastomoses is the only pathogenetically oriented treatment of twin-to-twin transfusion syndrome (TTTS). Aim. To investigate the effect of the learning curve for TTTS on treatment outcomes and the incidence of postoperative complications. Material and methods. This retrospective study included 126 patients with monochorionic diamniotic twins who underwent fetoscopic laser coagulation of placental anastomoses for TTTS at the V.I. Kulakov NMRC for OG&P in 2014-2019. The patients were divided into three equal groups of 42 women each. Groups 1, 2, and 3 included pregnant women who underwent FLC in 2014-2016, 2017-2018, and 2018-2019, respectively. The study investigated the effect of the learning curve on fetal survival and complication rates. Statistical analysis was performed using the D’Agostino-Pearson test, the Mann-Whitney U-test, and the Kruskal-Wallis test. Differences were considered statistically significant atp <0.05. Results. Increasing surgeon caseload for FLC was associated with higher overall (from 61.9% to 88.1%) and both twins’ survival rates (from 38.1% to 59.5%). Postoperative complication rates reduced from 64.3% to 52.4%. The incidence of neonatal morbidity and mortality decreased along with an increasing number of FLCs performed. We achieved satisfactory FLC results for overall survival (at least 73%) after performing 34 procedures, and 80 procedures for the survival of both twins (at least 55%). Conclusion. The accumulation of experience and concentration of fetal surgery at a high-volume provider contributes to better overall and both twins’ survival with a concomitant reduction in the incidence of postoperative complications. FLC and other in utero surgical procedures should be concentrated at highly specialized high-volume centers with high patients’ flow.

Relevance. Monochorionic multiple pregnancies complicated by twin-to-twin transfusion syndrome carry a high risk of perinatal morbidity and mortality. Aim. To investigate perinatal outcomes of monochorionic multiple pregnancies complicated by TTTS. Material and methods. This prospective study comprised 253 monochorionic pregnancies, including 153 pregnancies complicated by TTTS (study group) and 100 uncomplicated pregnancies (control group). The study group was divided into subgroups categorized as treated with laser coagulation of placenta anastomoses (n = 126), amnioreduction (n = 11), and having no in utero treatment of TTTS (n = 16). The groups and subgroups were compared regarding the course of the antenatal period and the neonatal outcomes. Differences were considered significant atp <0.05. Results. The antenatal death rates in patients with TTTS and control groups were 51.6% and 1%, respectively. The term of delivery in patients with and without TTTS was 31.8 and 36.0 weeks, respectively. The earliest term of delivery was observed among patients undergoing amnioreduction (29.6 weeks) and having no in utero treatment (27.1 weeks). Birthweight of newborns from pregnancies affected by TTTS was significantly lower than that from uncomplicated pregnancies. Neurological morbidity was higher among TTTS infants (26.2%) and was highest in the subgroups of amnioreduction and uncomplicated pregnancy (47.1% and 46.7%). Respiratory disorders were detected only in the study group and had the highest rates in subgroups II and III. Early neonatal mortality was noted only among newborns from pregnancies affected by TTTS (10.8%). Conclusion. Monochorionic twin pregnancies complicated by TTTS are associated with a high risk of antenatal fetal death and neonatal morbidity and mortality. Laser coagulation of placental vascular anastomoses improves perinatal outcomes in TTTS.

Objective. To evaluate the effectiveness of mechanical (osmotic) dilators Dilapan-S and laminaria tents in preparing the cervix for term programmed labor in patients with extragenital pathologies. Materials and methods. Fifty-seven pregnant women at 380-6 to 390-4 weeks of gestation were divided into two groups: group 1 (main) included 32 patients who underwent Dilapan-S induction and group 2 (control) enrolled 25 women using laminaria tents. The condition of the cervix was assessed with the Bishop score before placing and after extracting the dilators. The condition of the fetus during cervical preparation was monitored using cardiotocography. Results. According to the Bishop score, when the action of Dilapan-S finished the degree of cervical ripening increased from Me 3 (Q1 2; Q3 4) to Me 8.5 (Q1 8; Q3 9) points (+5.5; p=0.001) and it was higher than in group 2, Me 8 (Q1 7; Q3 8) points (+5; p=0.01). The women had vaginal delivery in 75% (24/32) of cases in group 1 versus 68% (17/25) in group 2 (р=0.77). Spontaneous onset of labor was observed in 46.9% (15/32) versus 20% (5/25) of cases, (RR = 2.3; 95% CI: 0.99-5.57; p=0.07), respectively. Side effects of both Dilapan-S and laminaria tents were noted rarely and were insignificant. Conclusion. Dilapan-S facilitates cervical ripening more effectively than laminaria tents. There is no statistically significant difference in labor induction rate and its outcomes. Dilapan-S has a good safety profile.

Objective. To determine the efficacy of intrauterine use of granulocyte colony-stimulating factor (G-CSF) for the increase of endometrial thickness and pregnancy rates in patients with thin endometrium in frozen embryo transfer programs. Materials and methods. The main group included 15 patients with thin endometrium, which was refractory to standard methods of treatment; embryo transfer cycles were cancelled several times due to insufficient endometrial thickness in these patients. In addition to hormone replacement therapy (HRT), the patients were given an intrauterine injection of G-CSF on the 5-6th and 12-13th days of the menstrual cycle. The control group included 17 patients with thin endometrium, they received only HRT. The endometrial thickness was measured by ultrasound on the 14-15th and 20-21st (the day of embryo transfer) days of the menstrual cycle. The primary outcome was an increase in endometrial thickness greater than 7 mm on the day of embryo transfer, the secondary outcome was pregnancy rate. Results. Endometrial thickness greater than 7mm was observed in 7 patients (46.67%) in G-CSF group, and in 8 (47.06%) patients in the control group; the difference was not statistically significant (p=0.983). The average increase in endometrial thickness compared to the previous cycle was 0.6 mm. The average thickness of the endometrium was 7.32 mm in the main group. Embryo transfer was performed in 8 (53.33%) patients in G-CSF group, pregnancy occurred in 4 (50%) patients, clinical pregnancy in 3 (37.5%) patients, one patient had a biochemical pregnancy. At the time of the article’s publication there were two (25%) livebirths and one ongoing pregnancy. In the control group, the average thickness of the endometrium was 6.9 mm. Embryo transfer was performed in 4 patients (23.53%). But no pregnancy was achieved in any of the patients, the difference was not statistically significant (p=0.84). Conclusion. Despite the results that were not statistically significant, patients in G-CSF group showed a tendency for the increase in endometrial thickness and pregnancy rates, as well as the decrease in embryo transfer cycle cancellations. It is worth conducting studies with a larger sample of patients to obtain more reliable results.

Aim. To assess the state of the vaginal microbiota in patients with tuberculosis (TB) of the respiratory tract during the monitoring of chemotherapy (CTH). Materials and methods. The study “case-control” was conducted in compliance with STROBErecommendations, where the «case» meant the presence of TB of the respiratory tract and CTH; “control” - the absence of TB of the respiratory tract and CTH. 108 women of reproductive age were examined. They were stratified into 2 groups: group 1 - 54 patients with TB of the respiratory tract treated with CTH; group 2 - 54 women without TB of the respiratory tract and CTH. The standard obstetrical-gynecological and phthisiological researches were used; special study of vaginal microbiota was conducted with the use of “Femoflor” test system with a realtime polymerase chain reaction and quantitative characteristics of 28 conditionally pathogenic microorganisms. Statistical data analysis was performed using scripts in the R programming language version 3.5 in the R Studio environment. Results. With prolongation of therapy (for 60 and 150 days after CTH), a statistically significant decrease in Lactobacillus spp. - 6 [5,7; 6,6], 0 [0; 4] и 0 [0; 3] (р40,0001), a gradual increase in the majority of associates of conditionally pathogenic microflora (the most indicative were Gardnerella vaginalis and Candida spp.) were noted in microbiota. The m icroscopic characteristic of the vaginal biotope was the presence of normocenosis prior to CXT in the vast majority in group 1 - 47 (87%). 60 and 150 days after CXT, there was absence of normocenosis - 0 (0%), and statistically significant increase in the incidence of dysbiosis and an inflammatory bowel disease was 29 (54%) (р<0,0001) and 12 (22%) (р=0,02); 25 (46%) (р<0,0001) and 29 (54%). Conclusion. The presence of 2 aggressive factors - TB of the respiratory tract and CXT damage the vaginal biotope resulting in formation of aerobic-anaerobic dysbiosis. No statistically significant relationship was observed between the development of vaginal dysbiosis and the clinical form of TB of the respiratory tract, the severity of the specific process and the selected chemotherapy regimen. Further studies in this direction should be continued.

Aim. To assess the possibility of diagnosis of lymph node metastasis of breast cancer by lipid profile in normal and malignant breast tissue. Materials and methods. Semiquantitative evaluation of the lipids in tissue was performed using HPLC-MS/MS of tissue organic extracts. The lipids were identified by accurate molecular masses and tandem mass-spectra (MS/ MS). To create the logistic regression based on the Akaike information criteria, the lipids with significantly lipid level difference were used (p<0.05by Mann-Witney U-test). Results. The obtained diagnostic models based on normal tissue had sensitivity 81% and specificity 79%, the diagnostic model based on malignant tissue had sensitivity 78% and specif icity 81 % respectively. The lipids, which were selected as markers of lymph node metastases, belonged to sphingomyelins, ether lipids, phosphatidylcholines and phosphotidylethanoamines. Conclusion. The study confirmed that ether lipids and sphingomyelins may be the indicators of metastasis and demonstrated the possibility to use them for metastasis diagnosis.

Objective. To optimize surgical treatment for uterine aplasia. Subjects and methods. Sixty-three patients with uterovaginal aplasia were examined and operated on at the Department of Operative Gynecology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, in 2016 to 2020. Results. Multiple uterine myoma was detected in 8 patients, which was 12.7%, of whom 3 patients had giant uterine myoma. The authors had not found similar cases in the literature. Uterine rudiments in complete uterovaginal aplasia had a certain proliferative potential, which was conf irmed by clinical cases of an increase and manifestations of functional activity, new formation of leiomyoma, including giant myoma of uterine rudiments. Conclusion. To optimize surgical treatment, it is advisable to verify clinical and anatomical options, to assess the likelihood of potential growth of pluripotent cells, and to expand indications for the preventive removal of uterine rudiments.

Objective. To investigate the eff iciency and safety of monotherapy with the transdermal micronized progesterone Progestogel for diffuse fibrocystic mastopathy. Materials and methods. The observational study enrolled 722 patients aged 37.1±0.3 years with preserved menstrual function and diagnosed diffuse fibrocystic mastopathy. The observation period consisted of a continuous medication usage period about 3 months (3 cycles), or, if necessary, a second course of as many as 6 months (6 cycles). The main criterion for the efficiency of the therapy was to estimate the number of masses, as evidenced by ultrasonography. During the study, the investigators made breast ultrasound and radiographic examinations, Breast Imaging-Reporting and Data System (BI-RADS) assessment, recorded pain intensity with a visual analogue scale (VAS), and assessed a patient’s health status according to the Clinical Global Impression Scale (CGI). Results. The clinical breast assessment throughout the investigation, by using the main efficiency criterion showed a decrease in the average number of masses in one patient during the treatment: 5.09±0.15 (before treatment), 2.97±0.13 (after 3-month therapy), and 2.29±0.16 (after 6-month therapy), (p < 0.001). There was a significant reduction in the signs of the disease, as assessed by ultrasonography of mass sizes (p <0.001). The changes in the breast detected by its clinical examination and mammography showed statistically significantly better BI-RADS scores (p < 0.001). Pain syndrome intensity assessment using the VAS demonstrated a significant decrease: 47.5±0.8 (before treatment), 13.5±0.6 (following 3 months), and 7.7 ± 0.8 (following 6 months) (p <0.001). Conclusion. The investigation provided evidence for the sufficient efficacy and safety profile of Progestogel monotherapy for fibrocystic mastopathy.

The article presents the guidelines for organizing microbiological monitoring in neonatal departments of perinatal centers of the Russian Federation; the guidelines have been developed for neonatologists, pediatric surgeons, and intensive care specialists. Establishing and applying a single principle for monitoring healthcare-associated infections in newborns make it possible to assess and compare the prevalence of opportunistic microorganisms in the departments of one medical organization and in perinatal centers, including those located in different regions of the country.

Epidermolytic ichthyosis is a rare congenital keratinopathic ichthyosis characterized by a blistering phenotype at birth, which progressively becomes hyperkeratotic. The disease has an estimated prevalence of 1:200,000- 300,000 newborns. It is caused by mutations in the genes encoding epidermal suprabasal keratins 1 (KRT1; 12q13.13) and 10 (KRT10; 17q21-q23), which damage intermediate keratin filaments in the suprabasal keratinocytes. Bullous (epidermolytic) ichthyoses are manifested by symptoms, such as erythroderma at birth, skin erosions and blisters, hyperkeratosis, and increased susceptibility to infections. Case report. The paper describes a clinical case of epidermolytic ichthyosis and congenital lung malformation in an infant. It presents the clinical manifestations of epidermolytic ichthyosis, its current diagnostic methods, and specific features of therapy. Conclusion. The described clinical case is unique due to the concurrence of two congenital diseases in one infant, affecting different body systems, and these associations require further investigation.