No 2 (2020)

The paper considers the impact of cancer on pregnancy and fetal health. It describes the impact of chemotherapy on the course of pregnancy, the fetus and the state of the immune system in the pregnant woman and fetus, the risks of central nervous system and cardiovascular system diseases, and the general health and physical development of newborn infants. What is the immune status in a newborn of mothers who received chemotherapy during pregnancy, vaccination in the first day of life for children whose mothers have received chemotherapy during pregnancy. The paper shows pregnancy management tactics, optimal terms for prescribing and discontinuing chemotherapy; pregnancy outcomes after early and delayed initiation of therapy. There are the latest results of studies to optimize delivery terms for both the mother and fetus.

Hypertension in pregnancy is an urgent problem of modern medicine due to its high prevalence (it occurs in 5-30% of pregnant women in the Russian Federation) and to the risk of maternal and fetal complications. Considering the complex and incompletely studied pathogenesis of hypertension during pregnancy, the selection of antihypertensive therapy (AHT) remains open and is now being actively studied. In recent years, prescription of AHT for pregnant women has come under consideration in the context of personalized medicine. The genetic characteristics of a patient, which affect a pharmacological response, are point mutations and the so-called single nucleotide polymorphisms. The existence of single nucleotide polymorphisms in one gene or another can define the genetically determined contribution to an individual’s pharmacological response. Endothelial dysfunction that is manifested inter alia by decreased nitric oxide (NO) synthesis is an important pathogenetic element in the development of hypertension in pregnant women. There is a relationship between endothelial NO synthase (eNOS) (NOS3) gene polymorphism and AHT responses in preeclampsia (PE). The ‘C- Glu-a’ and ‘T-Asp-a’ haplotypes were found to be associated with the presence and absence of the response, respectively. There was no association of vascular endothelial growth factor gene polymorphismbi (C-2578A rs699947) and (G-634C rs2010963) with AHT responses in PE. Taking into account the role of systemic inflammation in the development of hypertension in pregnant women, it seems important to study the level of proinflammatory cytokines, visfatin in particular, in these patients. The association between AHT responses and visfatin/NAMPTgene polymorphism is now being actively studied. The C, A haplotype was associated with AHT responses in patients with PE. Further investigation of genetic polymorphism and gene-drug interactions may contribute to the elaboration of new therapeutic approaches to prescribing AHT in pregnancy.

The paper reviews publications on the microbiota state in endometriosis, various endometrial abnormalities (endometrial polyps, endometrial hyperplasia, chronic endometritis), and endometrial cancer, as well as in infertility. The investigators identified certain microorganisms that can be potentially considered as predictors for the effectiveness of assisted reproductive technology (ART) programs. An analysis of the literature proves the relationship of microbiome disorders to the development of benign and malignant diseases. The investigation results raise questions regarding the molecular mechanisms of tissue and cellular homeostatic disorders between the microbiota and the human body in various pathological processes. These support the expediency of conducting investigations in this area.

To analyze the data available in the literature on the efficiency of using a self-sampling technique as part of cervical cancer (CC) screening. It is noted that an increase the number of women to be examined and optimization of techniques for high-risk human papillomavirus (hr-HPV) typing are currently considered as main areas for improvement of CC screening programs. Self-sampling shows a high concordance with physician-taken sampling for HPV detection. The possibilities of delivering self-sampling devices directly to women’s homes as part of CC screening programs are considered.There is an urgent need for new approaches to screening with self-sampling devices that are economically affordable, can be easily mailed to the women to be examined, acceptable and convenient to use, technically reliable and compatible with the techniques used to detect hr-HPV.

Using the overview of Russian and foreign literature, the authors present their standpoint on the management of menopausal women with endometriosis from the point of view of evidence-based medicine. The paper shows the main regimens and routes of menopausal hormone therapy and their advantages. It highlights the expert position on the management of patients with a history of endometriosis during surgical and natural menopause. There is information on the prevalence of postmenopausal endometriosis and its treatments.

Objective. To comparatively analyze the Russian nomogram developed at the Ulyanovsk State University (the UlSUnomogram) and the foreign nomogram developed at the Memorial Sloan-Kettering Cancer Center (the MSKCC nomogram) for accurately predicting metastatic regional lymph node involvement in the same population of patients with breast cancer (BC). Subjects and methods. The study enrolled 420patients with morphologically verified invasive BC who had been treated at the Ulyanovsk Regional Clinical Oncology Dispensary or the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology. At least one metastatic axillary lymph node was diagnosed in 137/420(32.6%) patients. The probability of axillary lymph node metastasis was calculated using the MSKCC nomogram available on the Memorial Sloan-Kettering Cancer Center website (USA) and using the UlSU nomogram. For each nomogram, receiver operating characteristic (ROC) curves were constructed; the integrated assessment of the diagnostic potential of the nomograms was determined by the area under the ROC curve (AUC). Results. Univariate analysis revealed that primary node tumor size (p = 0.001), lymphovascular invasion (p < 0.001), total malignancy score (p <0.001), estrogen receptor status (p = 0.025), and HER2 status (p = 0.032) were statistically significantly associated with metastatic regional lymph node involvement in BC patients. Both nomograms showed moderate prediction abilities: the AUC (95% CI) for the UlSU nomogram was 0.669 (0.6141-0.7239); that for the MSKCC nomogram was 0.694 (0.6405-0.7479); the differences were not statistically significant. Conclusion. The comparative analysis using the MSKCC nomogram has demonstrated that the UlSU nomogram has equal prognostic value and is more convenient to use.

Growth restriction of one or both fetuses during a multiple pregnancy is one of the main causes of perinatal losses. The development of specialized normative scales for estimated fetal weight for monochorionic and dichorionic twins will be able to diagnose more accurately this pregnancy complication. Objective. To assess the features of fetal growth during a multiple pregnancy according to the type of chorionicity and to develop normative scales for estimated fetal weight. Material and methods. A total of 578 uncomplicated multiple pregnancies (128 with monochorionic and 450 with dichorionic twins delivered after 34 weeks’ gestation, who underwent echographic studies and calculation of estimated fetal weight. Results. A total of 1,156 fetuses underwent 5,286fetometric studies. Regardless of chorionicity, the twin fetal growth trend is not linear - there is weight gain acceleration, starting in the second trimester, which lasts until the end of pregnancy. The mean fetal weight in dichorionic twins was higher than that for monochorionic twins, beginning at 30 weeks’ gestation. Conclusion. The developed normative scales and percentiles charts of estimated weight for different types of placentation will contribute to the improved prenatal assessment of fetal growth in a multiple pregnancy. The revealed difference in fetal growth in uncomplicated mono- and dichorionic twins will be able to reduce the false-positive rate for the diagnosis of selective growth retardation syndrome.

Aim. The evaluation of the laparoscopic surgery for cesarean scar insufficiency after a previous cesarean section. Material and methods. Between 2018 and 2019, 15 patients with uterine scar dehiscence were managed at the department of operative gynecology, Federal State National Medical Research Center of Obstetrics, Gynecology and Perinatology named after. V.I. Kulakov, Russian Ministry of Helthcare. Results. A new method was developed for laparoscopic metroplasty of uterine scar insufficiency using a new intrauterine manipulator with a groove. The use of the new method resulted in the optimization of the insufficient scar excision, which is evaluated such surgical stages, as: scar incision; conjoin to connecting margins and myometrial suturing of all layers, for repair the complete myometrial segment, that allows for effective restoration of the lower uterine segment with the formation of a mature scar. Conclusion. The new intrauterine manipulator with a groove can be recommended for routine clinical application to optimize the management of uterine scar insufficiency after previous surgery.

Objective. To identify the immunohistochemical (IHC) phenotypes on the basis of the representation of molecular markers in the endometrioid ovarian cyst (EOC) capsule (EOCC) in order to justify a differentiated approach to therapy and to reduce relapse rates. Subjects and methods. To identify the features of the IHC profile of EOCC (the expression of estrogen and progesterone receptors, Ki-67, p53) and to estimate the impact of personalized anti-relapse therapy after surgical treatment, the investigators examined 170 women with EOC, who formed three comparison groups: 1) 50 women who received anti-relapse treatment with regard to the IHC profile of EOCC; 2) 80 women who had hormone therapy after the surgical stage of treatment without regard to the IHC phenotype; 3) 40 women who refused subsequent hormone therapy after surgical treatment. Control endometrial samples were taken from 25 healthy women. Results. Four IHC phenotypes of EOCC were identified. A differentiated approach to treatment with regard to the type of the IHC prof ile showed the higher eff iciency than hormone therapy without regard to the IHC phenotype: the number needed to treat (NNT) was 2 to prevent an unfavorable outcome in one patient [95% CI, 1-2; p < 0.001] versus NNT of 3 [95% CI, 2-6; p <0.001], OR, 0.06 [95% CI, 0.02-0.25; p <0.001] versus OR, 0.42 [95% CI, 0.27-0.65;p <0.001]. Conclusion. EOCs are characterized by molecular structural and functional heterogeneity, which objectifies IHC analysis of EOCC for the selection of a pathogenetically sound medical therapy regimen.

Objective. To design and carry out clinical testing a Russian transcriptional gene signature for the diagnosis of molecular breast cancer subtypes. Subjects and methods. The investigation enrolled 168 women aged 29 to 82 years with breast cancer (BC) who had been treated at the Department of Breast Pathology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology. The investigators performed a pathomorphological study of surgical materials and immunohistochemical (IHC) tests for Ki-67, ER, PR, HER2/neu and determined the expression profile of 45 genes of proliferation, apoptosis, invasion, hormone receptors, and growth factor receptors, DNA replication and repair, immunity, transcription factors, and cell differentiation markers by a real-time quantitative polymerase chain reaction assay. Results. The investigators established the main patterns of mRNA expression of the test genes for various BC subtypes and their correlations, devised and tested methods for the molecular genetic classification of breast tumors as compared with the traditional IHC study. Conclusion. The developed transcriptional gene signature reflects the heterogeneity of breast tumors and can be used for their molecular genetic classification.

Objective. To study the level of expression of paraoxonases (PONs) in the cervical epithelium of healthy women and that of female patients with cervical dysplastic processes. To comparatively analyze the expression level of PON1, PON2, and PON3 between the groups. To identify the relationship of changes in the level of expression of PONs to the development of cervical dysplastic processes. Subjects and methods. The investigation covered 47patients who were divided into 3 groups: 1) 16patients with CIN I-II; 2) 17 patients with CINII-III; 3) 14 healthy women. The expression of paraoxonases was analyzed by real-time PCR using primers specific to these genes. Results. The authors found a significant increase in the expression level of the PON3 gene in the cervical epithelium of women with cervical dysplastic processes compared to the control group. There were no significant differences in the level of PON2 expression between the two groups. PON1 gene expression was unidentified in all the samples. Conclusion. During the investigation, the authors found a clear relationship between the higher expression of PON3 and the presence of CIN. The findings suggest that the enzyme PON3 may play a role in the development of dysplastic processes; therefore, determination of the level of PON3 expression may possess certain clinical potential in the diagnosis of precancerous cervical diseases. Thus, further researches in this area are required to develop new prognostic markers for the diagnosis of cervical dysplasia and diagnostic markers for the transition of CIN to cancer, wh ich will be able to improve the quality of early diagnosis of precancerous diseases of the cervix and to optimize differentiated treatment policy.

Objective. To evaluate the eff iciency of empirical therapy with tergynan in reproductive-aged women in routine clinical practice. Subjects and methods. The TERRA multicenter post-registration observational study enrolled 430 reproductive-aged patients diagnosed with acute vulvovaginitis. Based on their complaints, clinical symptoms, and objective examination, the patients received empirical therapy with the combination antimicrobial drug Tergynan as a single vaginal tablet once daily for 10 days. Gynecological examination, pH-metry, and bacterioscopic and bacteriological examinations of discharge (Femoflor-16) were performed, and the time course of changes in clinical symptoms evaluated. Results. There was less vaginal discharge, a complete disappearance of unpleasant odor, and a feeling of vaginal itching and burning (74.5 and 67.1%, respectively). There were increases in the detection rate of Lactobacillus spp. by 2 times with a dissemination level of 106-107 CFU/ml, in the suppression of obligate anaerobic representatives (associations of Gardnerella vaginalis + Prevotella bivia + Porphyromonas spp., as well as Eubacterium spp.) by 5 times, facultative anaerobic bacteria (Enterobacteriaceae and Streptococcus spp.) by 3 times, and yeast-like fungi of the genus Candida by 2 times. Conclusion. This investigation demonstrated the high clinical (96.5%) and microbiological (97.3%) efficiency of empirical therapy with tergynan in 430 reproductive-aged women with acute nonspecific vulvovaginitis

As bacterial vaginosis (BV) develops, opportunistic pathogens begin to prevail in the vaginal biocenosis, and it is important that BV-associated microbes are able to form hard biofilms that represent microbial communities. In this case, the bacteria are less susceptible to drugs, antiseptics, and immune defense factors, as they show quorum sensing-mediated signaling that can withstand aggressive agents and develop resistance to antibiotics. Moreover, the development of disease relapses is often associated with the presence of biofilms. This presents certain difficulties in treating BV. Objective. Presentation of data on the use of the drug "Tergynan" in the treatment of BV. Subjects and methods. The study covered 45 women aged 18 to 45 years with a confirmed diagnosis of BV. The diagnosis was based on complaints, the data of objective examination, laboratory tests using Amsel’s criteria, and those from investigations of the vaginal microbiocenosis by a real-time polymerase chain reaction assay (Inbioflor. Bacterial vaginosis). The patients received a cycle of treatment with a vaginal Tergynan tablet overnight for 9 days. Results. Immediately after the performed therapy cycle, the quantity of Gardnerella vaginalis in the vaginal contents of the examined patients decreased sharply from 91.1% to 2.2%. There was also a change in the quantity of Atopobium vaginae (the detection rate decreased from 93.3% to 11.1%), since this microorganism is one of the key etiological causes of BV. In addition, before treatment, the allowable Mobiluncus spp. titer was found to exceed in most (95.6%) patients. After the treatment received, there was a steady-state positive effect (the detection rate decreased to 13.4% of cases). Furthermore, it is important that the concentration of Lactobacilli reached normal values in 97.7% of the cured patients. Conclusion.This multicomponent drug contributes to the improved composition of the vaginal microflora, by eradicating the opportunistic pathogenic microflora. All the above allows Tergynan to be recommended for the widespread use in the treatment of BV.

Background. Placenta increta is one of the most serious pregnancy complications, which leads to massive blood loss and hysterectomy. Case report. This paper demonstrates a clinical case of successful delivery in a patient with placenta previa partialis and placenta increta into the uterine scar region. During an operation, a technique for temporary extravasal occlusion of the common iliac artery using silicone tourniquets was applied, followed by excision of the ingrowth site and by metroplasty. Conclusion. The approach could achieve minimal blood loss, the optimal time for surgical intervention, a reduction in the length of hospital stay, and favorable obstetric and perinatal pregnancy outcomes, as well as preserve a patient’s menstrual and reproductive functions.