No 3 (2018)

Objective. To analyze the modern literature data characterizing the prevalence, etiology, clinical presentation, diagnosis, complications, outcomes, and treatment of infective endocarditis (IE) in pregnancy. Material and methods. The paper includes data from foreign and Russian sources published in the past 10 years and found in PubMed on this topic. Results. The paper gives current ideas on the prevalence, causes, and clinical features (premorbid experience, localization of valve injury, nature of visceral lesions), complications, prognosis, and outcomes of IE during pregnancy. It analyzes current approaches to IE diagnosis, its difficulties in pregnancy, and the reasons for their emergence, including those caused by changes in the cardiovascular system in pregnant women. It also discusses the aspects of management tactics for patients with IE during pregnancy: the features of drug therapy and the possibilities of cardiac surgery and prevention in the presence of risk factors. Conclusion. Further investigations of various aspects of the problem of IE during pregnancy are needed to optimize patient management and to improve maternal and fetal prognosis. Achievements in modern medicine, as well as interdisciplinary interaction between specialists make it possible to preserve pregnancy and to save the life of both mother and baby even in the presence of a serious disease, such as infective endocarditis.

Objective. To carry out a systematic analysis of the data available in the current literature on the effects of some anthropogenic chemicals on human fertility, including on the effectiveness of assisted reproductive technology programs. Material and methods. The review includes the articles by foreign and Russian authors on this topic, which have been published in the Pubmed journals in the past 10 years. Results. The authors analyze the literature data on the effects of heavy metals, phthalates, and bisphenol A on various aspects of human reproductive function. They present data on the possible pathogenetic mechanisms of action of anthropogenic chemicals on the quality of gametes and the efficiency of treatment for infertility. Conclusion. It is necessary to further study the molecular mechanisms of negative action of toxicants on human fertility in order to determine management tactics in infertility patients.

Objective. To carry out a systematic analysis of the data available in the literature on rational therapy for vaginal microbiocenotic disorders during combined antibacterial therapy to optimize the use of probiotics. Material and methods. The review includes the data of foreign and Russian articles found in the international system Pubmed. Results. The polymicrobial etiology of the inflammatory process requires combined antibacterial therapy using 2-3 antibiotics, which predisposes to dysbiotic states and the growth of opportunistic pathogens, including Candida fungi. It is advisable to prophylactically take probiotics simultaneously with the initiation of antibiotic therapy, which is more effective than the use of probiotics immediately after completion of an antibiotic therapy cycle. The vagina can be colonized by probiotic bacteria following oral administration if acid-resistant strains of lactobacilli are used. Conclusion. It is expedient to simultaneously take acid-resistant probiotic strains per os during antibiotic therapy in order to restore a normal protective flora and to suppress the opportunistic intestinal microorganisms that are able to colonize the urogenital area.

Objective. To determine the plasma concentrations of total extracellular DNA (tDNA) and its fractions during pregnancy, by taking into account the possible impact of the body mass index (BMI) of women, anemia in pregnant women, fetal and placenta weight. Material and methods. The blood concentrations of tDNA, fetal DNA (fDNA) and maternal DNA (mDNA) were determined in women at 11-14, 24-26, and 30-32 weeks. The level of tDNA was estimated by quantitative PCR through determination of the concentration of the RASSF1A gene and that of fDNA was calculated through determination of the hypermethylated RASSF1A gene. Results. The concentration of extracellular tDNA and mDNA did not change substantially during pregnancy. Until mid-gestation, there was a relatively stable fDNA level (averaged 1265.11+577.51 GE/ml at 11-14 weeks and 1309.09+561.01 GE/ml at 24-26 weeks) and its considerable increase in the second half of pregnancy. The level of extracellular DNA and its fractions did not change in relation to the women’s BMI and fetal and placental weight. In anemia, the concentration of mDNA averaged 12362.33+5533.22 GE/ml and was significantly lower than in healthy pregnant women (an average of 15268.49+5973.43) (p < 0.05). Conclusion. The f indings conf irm the change in the concentration of total extracellular DNA during pregnancy, which must be taken into account when predicting its complications. To eliminate the effects of other maternal and fetal factors, it is necessary to continue investigations.

Objective. To assess the provision of vitamin D in newborn infants and parturients in the mother-child dyad in the city of Arkhangelsk in the winter season. Subjects and methods. A total of 55 mother-child pairs from the city of Arkhangelsk were examined during the cross-sectional study. The level of 25(OH)D was determined in umbilical cord blood and parturients. Results. Vitamin D def iciency was found in the mothers: only 19 (35%) of the examined women had vitamin D levels above the recommended values (30 ng/ml). The newborns were provided with vitamin D much worse than their mothers: only 4 (7%) children had a normal level of vitamin D; 20 (36%) had the level that corresponded to its deficiency; severe deficiency and insufficiency were noted in 17(31%) and 14 (26%) newborn infants, respectively. The level of 25(OH)D in a baby was shown to be clearly related to its provision in his/her mother. Severe vitamin D deficiency was recorded in all children born to mothers with severe deficiency (25(OH)D levels below 10 ng/ml); the children born to mothers with deficiency (25(OH)D levels of 10-19 ng/ml) were observed to have severe in vitamin D deficiency in 43% of cases and insufficiency in 57%; those born to mothers with vitamin D def iciency (25(OH)D levels of 20-30 ng/ml) were found to have severe vitamin deficiency in 40% of cases, deficiency in 47%, and insufficiency in 13%. Conclusion. The critically low levels of vitamin D in umbilical cord blood (96% of the children have 25(OH) D levels below 30 ng/ml) indicate that it is necessary to introduce a system of urgent remedial measures using adequate correction schemes for both pregnant women and newborns who should be given vitamin D supplements from birth if their mothers have been found to have vitamin D deficiency. It is advisable to determine the baseline level of 25(OH)D in all pregnant women for the prescription of an appropriate dose of vitamin D.

Background. Hatching from the zona pellucida is one of the most important stages of human preimplantation embryo development and spontaneous hatching inability is one of the causes of implantation failure in assisted reproductive technology (ART) cycles. The use of mechanical integrity disorders or complete destruction of the zona pellucida (assisted hatching) can be an effective way to enhance the effectiveness of infertility treatment programs using ART techniques. Objective. To assess the results of ART programs depending on the performance and type of assisted hatching. Material and methods. The prospective cohort investigation enrolled 309 patients treated for infertility with in vitro fertilization (IVF). According to the type and performance of assisted blastocyst hatching, the patients were divided into 3 groups: 1) 106 patients undergoing laser hatching with partial removal of the zona pellucida; 2) 103 patients having pronase hatching with complete removal of the zona pellucida; 3) 100 patients with no assisted blastocyst hatching. The degree of maturity and the quality of oocytes and embryos were assessed; hatching was monitored using light microscopy. Results. The pregnancy rates were noted to be statistically higher in Group 1 than in Groups 2 and 3; the multiple pregnancy rates were significantly lower in Group 1. Conclusion. Complete zona pellucida removal is a new approach to assisted hatching, in which, firstly, there is no mechanical separation of the cells forming the embryo, and, secondly, there is a rapid contact with endometrial cells during implantation. This contributes to the reduction of the risk of monozygotic pregnancies during the transfer of one morphologically normal blastocyst, by enhancing the effectiveness of ART programs.

Objective. To investigate the expression of proliferation and apoptosis markers (Ki-67, Bcl-2), inf lammatory factors (NF-kß p65, COX-2), adhesion factors (ß-catenin), estrogen receptor-a (ER-a) and progesterone receptor-a (PR-a) in the eutopic endometrium and ovarian endometrioid cyst (OEC) sac in patients with recurrent OEC, by using an immunohistochemical assay. Subjects and methods. The investigation enrolled 60 reproductive-aged patients with OEC treated in the Department of Operative Gynecology, V.I. Kulakov Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, in 2015-2016. According to the course of the disease during a 1.5-year follow-up after surgical treatment, the patients were divided into two groups: 1) 41 patients without recurrent OEC (a comparison group); 2) 19 patients with recurrent OEC (a study group). The investigation used histological and immunohistochemical examinations. The histological examination of the endometrium and OEC sacs was performed using a standard procedure. The immunohistochemical examination of the eutopic endometrium and OEC sac was done using the Tissue-Tek Quick-Ray kit that allows one to make paraffin blocks containing a large number of tissue samples (tissue matrices). The investigation used antibodies against Ki-67 (clone 30-9, VENTANA), Bcl-2 (clone 124, VENTANA), NF-kß p65 (clone p65, Spring Bioscience Corp.), COX-2 (clone СХ-294, Agilent), ß-catenin (clone 14, VENTANA), ER-a (clone SP1, VENTAN), and PR-a (clone 1E2, VENTANA). The specimens were prepared according to the standard protocol using a Ventana Ultra immunohistostainer. Positive and negative controls were used to correctly make immunohistochemical assays. Statistical analysis was carried out using the applied statistical analysis software (Statistica 10.0, Microsoft Excel). Results. The immunohistochemical examination showed that the ectopic endometrium (OEC sac) was characterized by a change in the expression of ER-a, PR-a, Ki-67, Bcl-2, NF-kß p65, COX-2, and ß-catenin, which are the factors involved in the pathogenesis of endometriosis. The patients with recurrent OEC had an increased PR-a expression in the epithelial component of the OEC sac (p = 0.0277), a reduced Ki-67 expression in it (p = 0.044), a reduced NF-kß p65 and COX-2 expression in the stromal component of the OEC sac (p = 0.0082; p = 0.00245, respectively) and an increased ß-catenin expression in it (p = 0.017). The immunohistochemical examination revealed that the patients with recurrent OEC showed increases in the expression of PR-a in the epithelial component of the eutopic endometrium in the secretory phase (p = 0.0253) and in that of NF-kß p65 in the stromal component of the eutopic endometrium in the proliferative phase (p = 0.0278). Conclusion. The immunohistochemical examination of the expression of PR-a, Ki-67, NF-kß p65, COX-2, and ß-catenin in the OEC sac and that of PR-a and NF-kß p65 in the eutopic endometrium can assist in identifying patients at high risk for recurrent OEC immediately after surgical treatment. Further investigations of these factors will be able to study the molecular mechanisms underlying the pathogenesis of recurrent OEC, which will affect these mechanisms to eliminate the fundamental causes of recurrent endometriosis.

Objective. To assess the epidemiological situation of cervical cancer (CC) among the female population in the Omsk Region in 2002-2016. Subjects and methods. Intensive and extensive indicators and their standard errors were calculated in the descriptive observational retrospective epidemiological study. The dynamic series of indicators were analyzed with alignment using the least squares method and with calculation of growth (decrease) rates (Rinc/dec in %), that character ized the long-term epidemic trend. The official statistical data of the Russian Federal State Statistics Service on population size by sex and age were used for calculations. Results. In the period 2002-2016, the incidence of CC in the Omsk Region was stable and averaged 19.63±0.360/0000 (Rinc = +0.05; p > 0.05); that in the Russian Federation (RF) did 18.46±0.040/0000and was considerably lower (p < 0.01); moreover, there was a moderate, statistically significant tendency to increase this indicator (Rinc = +1.72; p < 0.001). The analysis of the CC neglect index in the RF showed the stability of the situation; this indicator in the Omsk Region had a moderate positive tendency to decrease from 52.7% in 2001 to 40.6% in 2016; p < 0.001). The average annual rate for the region was 46.7±0.88%, which was 1.2 times higher than thefederal rate (38.1±0.11%; p < 0.001). In 2013-2016, the cytologic screening coverage of public health care facilities in the Omsk Region was 31.9 to 36.7%. The maximum incidence of CC was observed in the age group of 55-59 years (37.41±1.46), its moderate growth rate was traced in the age groups of 20-24 years (Rlnc = +3.3%) and 70-74 years (Rinc = +4.1%). The study of the age structure in patients with CC established that 50-54-year-old women constituted the largest proportion in both the Omsk Region (13.0%) and the RF (12.8%). Conclusion. The incidence of CC in the female population of the Omsk Region was stable over 15 years (2002- 2016), while the RF showed a moderate significant trend towards increasing this rate. The Region displayed a tendency to reduce the CC neglect index during the period of analysis from 52.7 to 40.6% (p < 0.001); however, but the average annual rate exceeded the similar federal rate by 1.2 times. Women aged 50-54 years were prevalent cases of CC. Rejuvenation of the latter is confirmed by the disease growth rates in the age group of 20-24 years in the Omsk Region and the RF. The insufficient effectiveness of opportunistic cytological screening in the public healthcare system, which negatively affects CC morbidity rates and neglect index in the Omsk Region.

Objective. To evaluate the colposcopic, cytological, and immunocytochemical features of the cervix uteri in adolescent girls who have had no sexual intercourses, have primary estrogen def iciency, and have therapeutically taken a drug containing 17-ß-estradiol and dydrogesterone in the time-sequential mode. Subjects and methods. A comprehensive survey was conducted among 48 sexually inactive adolescent girls aged 15-18 years. Among them, 24 adolescents had primary estrogen deficiency, who were therapeutically given a two-phase estrogen-gestagen drug for developing and maintaining hormone therapy (DMHT) and 24 more healthy girls who formed a control group for colposcopy and cytology. Before and within 9 months of treatment, the cervix uteri was evaluated by the results of extended colposcopy, cytological and immunocytochemical examinations of impression smears from the exo- and endocervix. The expression of estrogen receptor-a (ER-a), progesterone receptor A and B, epidermal growth factor, Ki-67, TNF-a, and Cas (LabVision, R&D Systems, and Novocastra Lab Ltd.) was targetedly analyzed. Results. The use of 17ß-estradiol as part of 9-month DMHT contributes to a three-fold increase in the expression of ER-a and in the moderate activation of proliferation processes with unchanged apoptosis, which manifests itself as restoration of maturity of the cervical and vaginal epithelium and as normalization of vaginal microbiocenosis. Conclusion. The found changes suggest that the combination drug containing 17ß-estradiol and dydrogesterone has a positive effect on the vaginal epithelium and cervix uteri in adolescent girls with primary estrogen deficiency

Urinary tract infections (UTIs) are a common infectious disease during pregnancy, while the range of effective and safe medications for the mother and fetus is limited. Objective. To assess current concepts on the etiology, pathogenesis, clinical presentations, diagnosis, and treatment of UTIs in pregnant women. Material and methods. Publications by Russian and foreign authors were reviewed and analyzed. Results. Particular attention is paid to the classification of UTIs, to their predisposing factors, etiology, pathogenesis, and diagnosis during pregnancyy, to the impact of UTIs on the development of pregnancy complications and fetal diseases, and to antimicrobial therapy policy. Emphasis is laid on the need for the prevention and combination treatment of asymptomatic bacteriuria in pregnant women and there is evidence that the large cranberry (Vaccinium macrocarpon) drug phytolysin prenatal should be used to prevent recurrent UTIs during pregnancy. Conclusion. The timely diagnosis and rational therapy of UTIs in pregnant women can reduce the risk of recurrences and pregnancy complications.

Objective. To carry out a systematic analysis of the data presented in world literature on the current possibilities of colposcopy in the diagnosis of cervical squamous intraepithelial lesions. Material and methods. The paper includes the data of 21 articles from the PubMed and Medscape resources published in the past 10 years on this topic. Results. The paper describes the main current methods to diagnose cervical pathology, including a dynamic spectral imaging system (DySIS), for the timely detection of human papillomavirus (HPV)-associated cervical pathology. Conclusion. The use of DySIS will be able to increase the frequency of early diagnosis of cervical squamous intraepithelial lesions, to reduce the frequency of diagnostic errors, and to avoid unfounded invasive interventions.

Objective. To review published scientific papers in order to analyze an evidence base for a strategy for choosing therapy in women with abnormal uterine bleeding (AMC), obesity, and smoking. Material and methods. Foreign and Russian articles published in the past 7 years and selected in Pubmed were used. Results. The types of AMC were analyzed in relation to its etiological factors. Different methods for treating patients with uterine bleeding varying in severity were comparatively analyzed. Conclusion. It is appropriate to concomitantly use dydrogesterone and tranexamic acid in phase 2 of the menstrual cycle during 3-4 menstrual cycles in women who smoke and/or in those with obesity and AMC.