No 8 (2022)

Current literature data on the role of fetal programming in fetal growth retardation are analyzed. The paper considers the mechanisms and scientific hypotheses of fetal programming, which lead to the formation of a predisposition in children to metabolic, endocrine, and cardiovascular diseases just in adulthood. It discusses the role of the growth hormone-insulin-like growth factor axis in fetal programming and its relationship between fetal growth retardation and obesity, diabetes mellitus, and hypertension. The paper describes a pregnant woman’s exposure to various adverse environmental factors and their influence on the expression of the genes responsible for the synthesis of the hormones that regulate energy metabolism. A special role is assigned to epigenetic mechanisms. The latter manifest themselves as responses to certain negative prenatal factors, form the basis for fetal programming, determine not only the final weight and growth rates for the newborn, but also form the latter’s predisposition to various diseases. Conclusion: Emerging information about the role of fetal programming in the development of certain diseases in adult life may become an important driving force in an attempt to stop the incidence rate of this pathology.

Endometriosis is a hormone-dependent disease associated with the development of chronic inflammation. The prevalence of this disease does not tend to decrease. The absence of a unif ied generally accepted theory on the origin of endometriosis is the basis for continuing investigations aimed at searching for possible mechanisms for the development of the disease in order to improve the principles of diagnosis and therapy of this pathological process. One of the theories of endometriosis is the hypothesis of bacterial infection, in which the bacterial endotoxin lipopolysaccharide is supposed to be a triggering factor for the onset and progression of endometriosis. Current data indicate that changes in the composition of gut microbiota and/or different stages of the female reproductive tract can be used prognostically as a tool for diagnosing the disease, whereas a number of microorganisms can be marker for assessing its form and prevalence. This review considers the present-day ideas on the relationship between the gut and genital microbiotas and endometriosis, on possible mechanisms and diagnostic approaches to this pathological condition. Conclusion: To study the composition of the microbiota seems to be a fairly new and very promising area from both scientific and practical point of view.

The paper presents the European Society for Urogenital Radiology (ESUR) guidelines for the radiodiagnosis of cervical cancer (CC) and current concepts in its primary staging, by taking into account the main characteristics of the tumor and the possibilities of treating CC. Objective of this review - to systematize relevant scientific data on the possibilities and prospects for developing medical imaging techniques in CC. The ESUR guidelines standardize and promote the higher efficiency of using radiodiagnostic techniques for CC. The updated ESUR guidelines consider into account all the changes given in the FIGO classification in accordance of the 2009/2018 revisions and the 8th edition of the Timor-Node-Metastasis (TNM) staging system. In accordance with the updated FIGO system, the paper shows a significant role and place of MRI in CC before, during, and after antitumor treatment. Clinical assessment of the neoplasm is the basis of the FIGO classification as before. Modern instrumental diagnosis makes it possible to increase the objectivity of estimating the prevalence of the tumor process in the preoperative stage. This enables radiodiagnostic techniques to be used as an additional tool in clinical staging. The ESUR clarifies the criteria for primary staging and for planning anticancer therapy. The paper considers clinical cases with an emphasis on MRI staging criteria, evaluation of the efficiency of treatment and prognosis, diagnosis of recurrent CC. The review highlights the possibilities for the development of medical imaging, which are aimed at using hybrid methods for imaging and radiomics in the staging of advanced CC. Conclusion: The current scientific data on urogenital radiology are of particular interest for radiation diagnosis and gynecologic oncology and serve as the basis for clinical application.

Objective: To investigate the clinical value of a phenotypic approach for the analysis of perinatal outcomes in fetal growth restriction (FGR). Materials and methods: This retrospective analysis included 230 pregnancy cards and delivery notes. The patients were divided into Group I including 200/230 (87%) pregnant women with adverse FGR outcome; Group II consisted of30/230 (13%) pregnant women with uncomplicated pregnancy and normal fetal growth trajectory. The phenotypic approach consisted of classifying FGR cases according to maternal, placental, and fetal risk factors for this pathology and then analyzing the contribution of each phenotype to the probability of an adverse fetal outcome. Results: In step 1, all analyzed observations were divided into 7 clinical FGR phenotypes. In step 2, the FGR clinical phenotypes were divided into three risk groups according to adverse perinatal outcomes: high, intermediate and low risk of perinatal loss. High-risk according to the study results corresponds to the FGR clinical phenotypes "preterm delivery" (59.6%), "infections" (45.1%), "hypertensive disorders during pregnancy" (37.3%), and "bleeding in the second and third trimesters" (24.8%). The intermediate risk was "chronic maternal disease" (9.9%), "no baseline risk factors" (11.4%), and the lowest risk model included the remaining clinical phenotypes. Among stillborns with FGR (n=64), the following FGR phenotypes were observed: "infections" (34.4%), "preterm delivery" (20.3%), "hypertensive disorders during pregnancy" (14.1%), and "bleeding in the second and third trimesters" (14.1%). Early neonatal mortality was highest in the clinical phenotypes "preterm delivery" (39.3%) and "hypertensive disorders during pregnancy" (23.2%). Conclusion: Seven clinical phenotypes of FGR associated with different risk of adverse perinatal outcomes were analyzed. The highest risk of stillbirth was noted in FGR concurrent with severe prematurity (the "premature delivery" phenotype), infectious affection of the fetal placental unit (the "infection" phenotype), and in II- III trimester hemorrhages caused by placental abruption, recurrent retrochorial hematomas, and placental abnormalities.

Objective: To develop a new method for predicting spontaneous miscarriage in women with threatened miscarriage in early pregnancy by detection of alternatively activated monocytes expressing the scavenger receptor CD163 in peripheral venous blood. Materials and methods: The study included 71 women between 5 and 12 weeks of gestation. Of these, 54 women gave birth at full term (Group 1) and 17 women had early and late spontaneous miscarriages (Group 2). The relative abundance of CD14+CD16++ monocytes expressing the scavenger receptor CD163 was determined using a FACScanto II flow cytometer (Becton Dickinson, USA). Peripheral venous blood served as the material for the study. Results: There was no significant difference between the two groups in the content of classically activated and intermediately activated monocytes expressing the scavenger receptor CD163. However, the content of alternatively activated monocytes expressing the CD163 scavenger receptor in women with spontaneous miscarriage was statistically different from that of women who gave birth at full-term. Conclusion: The content of alternatively activated monocytes expressing the CD163 scavenger receptor in peripheral blood can be used as a predictor of spontaneous miscarriage in women with threatened miscarriage in early pregnancy.

Objective: To evaluate the effect of systemic ozone therapy (OT) on the concentration of pro-inflammatory and anti-inflammatory cytokines in the blood in the complex treatment of COVID-19 patients. Materials and methods: The study included 65 patients with a confirmed diagnosis COVID-19 characterized by a moderate and severe course of the disease. The patients were admitted to the Infectious Disease Hospital of the V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. The patients’ age ranged from 29 to 78 years. All patients were treated in accordance with the Temporary Guidelines of the Ministry of Health of Russia “Prevention, Diagnosis and Treatment of Coronavirus Infection (COVID-19)”. Two groups of patients were randomly formed. The first group included 35 patients whose complex therapy included OT: intravenous administration of 400 ml of ozonated saline solution with an ozone concentration of 4 mg/L; a total course consisting of 6procedures performed every other day. The second group included 30patients who did not have OT. Clinical and laboratory parameters were evaluated on admission to the Infectious Disease Hospital and after two weeks of complex treatment; clinical, laboratory, special, statistical research methods were used. The content of cytokines GM-CSF, IFN-y, TNF-a, IL-2, IL-4, IL-6, IL-8, IL-10 and their ratios were determined with a multiplex method on the Bioplex 200 analyzer (Bio-Rad, USA) using Bio-Plex Pro Human Cytokine 8-plex Panel (Bio-Rad, USA). Results: On admission to the Infectious Disease Hospital 47/65 (72,3%) patients had a moderate course of the disease and 18/65 (27.7%) patients had a severe one. The length of hospital stay in the group of patients with OT averaged 12.2 (2.7) (8-17) days, and it was 17.9 (4.2) (12-26) days in the group of patients who did not have OT. On admission, all patients had an increase in the level of C-reactive protein in their blood serum; the cytokine content in patients of the groups differed from the initial cytokine level and it was different between groups after two weeks of therapy. The medians of the pro-inflammatory cytokines IL-2, IL-6, IL-8 were particularly different. The content of these cytokines remained elevated in the second group of patients who did not have OT, compared with the baseline data and compared with the first group. The study of anti-inflammatory cytokines showed that the patients of the first group who had OT demonstrated a significantly higher IL-10 content compared to IL-10 content in the patients of the second group. Ratios of pro- and anti-inflammatory cytokines IL-2/IL-10, IL-2/ IL-4, IL-6/IL-10, IL-6/IL-4, IL-8/IL-10, IL-8/IL-4, TNF-a/IL-4 in the first group of patients with OT significantly decreased compared to the baseline indicator, which can be suggestive of a marked decrease in the activity of the inflammatory process. Conclusion: The positive effect of systemic OT on the clinical course of the disease has been revealed. Laboratory indicators in COVID-19 patients have shown a decrease in the severity of the inflammatory response. Besides having anti-inflammatory and immunomodulatory effect, OT helps to stop the process, improve the condition of patients and reduce the length of hospital stay. Systemic OT should be considered as an additional adjuvant method in the complex treatment of patients with SARS-CoV-2 infection.

Background: Early-onset neonatal sepsis and pneumonia remain one of the leading causes of neonatal loss. The role of microbiological examination of body surface cultures on the first day of life (DOL) in preterm neonates with high risk for early-onset infections currently remains insufficiently studied. Objective: To estimate the clinical value of microbiological examination of body surface cultures in preterm neonates on the first day of life. Materials and methods: The study included 173 preterm neonates at 24-36 weeks’ gestation admitted directly from the delivery room to the Neonatal Intensive Care Unit (NICU) from January 2020 to April 2021. Microbiological examination was carried out using classical (microscopic, cultural) and innovative methods (proteometric MALDI-TOF-MS analysis). Biological material was taken from three loci (blood culture and two surface cultures, namely oral and rectal swabs). All neonates were divided into two main groups: group I included 43 neonates with positive body surface cultures, group II included 130 neonates with a negative surface culture result. According to their gestational age (GA), the patients were compared in the following subgroups: a) GA<33 weeks (Ia n=10 vs IIa n=47); b) GA=33-36 weeks (Ib n=33 vs IIb n=83). The relationship between surface culture results and the incidence of early neonatal infections (pneumonia, sepsis), complications, as well as severity scores (nSOFA, NEOMOD), inflammation markers, and complications was studied. Results: The subgroups did not differ in anthropometric data, antenatal steroids rates, Apgar, NEOMOD and nSOFA scores. There were no differences in the incidence of early-onset neonatal infections (sepsis and/or pneumonia) (8/10 vs 36/47, in subgroups Ia and IIa, respectively, p>0.05; 11/33 vs 27/83 in subgroups Ib vs IIb, p>0.05). However, additional analysis without regard to commensal bacteria revealed statistically signif icant increase in early-onset neonatal clinical sepsis (EONS) in the neonates <33 weeks GA with positive surface cultures (E. coli and/or Candida sp., and/or Klebsiella sp. and/or Acinetobacter sp. and/or Enterococcus sp.): 4/7 vs 7/47 in Ia and IIa, respectively (p=0.02); this subgroup also had a higher level of C-reactive protein on DOL3 (Me=2.7mg/L, Q1-Q3 1.6-23.4 vs Me=0.95 mg/L, Q1-Q3 0.33-5.0 in subgroups Ia vs IIa, respectively, p=0.08). This pattern was absent in neonates of GA 33-36weeks. Necrotizing enterocolitis (NEC) incidence was found to be higher in all preterm neonates colonized with E. coli and Candida sp. on DOL1 (E. сoli: RR=4.8 (95% CI 1.6-14.7); Candida sp.: RR=9.6 (95% CI3.5-26.7)). Conclusion: Microbiological examination of body surface cultures on DOL1 may be considered as a valuable clinical tool for EONS in preterm neonates born before 33 weeks GA. It can also be regarded as a prognostic method in all premature babies: the absence of E. coli and/or Candida colonization significantly decreases the risk of subsequent development of NEC.

Objective: To demonstrate the feasibility of preoperative preventive use of vaginal Elgin tablets with an applicator (VERTEX, Russia) to prevent contamination of the uterine cavity with vaginal microflora during hysteroscopy and separate diagnostic curettage. Materials and methods: A prospective observational clinical study was conducted in parallel groups involving 50 patients. The investigators formed a study group (n=30) and a control group (n=20), which included patients with vaginal normocenosis and indications for hysteroscopy. The vagina was preoperatively cleansed with Elgin for 6 days in the study group. No preventive treatment was performed in the control group. The study methods included general clinical examinations and real-time polymerase chain reaction (Femoflor-16, DNA-Technology, Moscow). Resuls: The indications for hysteroscopy and separate diagnostic curettage in the study and control groups were infertility of unknown origin (16.7% and 20%), endometrial polyp (46.7% and 50%), and suspected endometrial disease (36.7% and 30%). After a cycle of preventive therapy with Elgin, the vaginal concentration of lactobacilli vagina did not change, but there was a substantial decrease in opportunistic pathogens (Enterobacteriaceae by 5.7 times, Gardnerella vaginalis by 1.5 times, and Mobiluncus by 1.86 times) (p40.001). Staphylococci, streptococci, mycoplasmas, Candida fungi, veillonella, and fusobacteria were completely absent. The intrauterine microbiota in the study group patients was represented only by lactobacilli. The total bacterial mass in the uterine cavity was 1.48 times lower than that in the vagina, while the concentration of lactobacilli was almost 1.5 times lower. A variety of bacteria was identified in the uterine cavity of the control group patients. All the bacteria were characterized by a quantitative decrease as compared to vaginal biocenosis. The titer of streptococci and staphylococci in the uterine cavity was 1.2 times lower than that in the vagina, there were reductions in the titers of gardnerella by 1.7 times, eubacteria by 1.9 times, veillonella by 1.5 times, mobiluncus by 1.4 times, and Candida fungi and ureaplasma by 1.3 times. In the control group, the uterine cavity displayed the representatives of the intestinal microflora and eubacteria in significantly higher titers (the titer was 1.8 times higher), streptococci and staphylococci (that was 2.1 times higher), veillonella and ureaplasma (1.3 times higher), and mobiluncus (1.9 times higher). Conclusion: A preventive vaginal cleansing cycle before intrauterine manipulations can reduce overall vaginal bacterial contamination and the risk of intrauterine ascending infection from indigenous microflora.

The incidence of extragenital endometriosis (EE) is 6-8% of all forms of endometriosis; however, there has been an increase in the prevalence of the disease in recent years. EE is characterized by the growth of tissue similar in morphological structure and function to the endometrium in the organs and tissues that are not related to the reproductive system. A wide range of non-specific clinical manifestations and the ensuing difficulties in diagnosing EE at various sites lead to its delayed diagnosis and to the absence of pathogenetically based therapy. The authors reviewed literature on the diagnosis and treatment of EE and analyzed their own experience on this topic. They described clinical cases, by providing the features of female patients’ medical histories, diagnosis, surgical and medical treatments for endometriosis of the intestine, catamenial pneumothorax, urinary system, and umbilicus. Conclusion: The diagnosis and treatment of extragenital forms of endometriosis requires an interdisciplinary approach, by attracting gynecologists, general and thoracic surgeons, urologists, and gastroenterologists, to decide on the personalized strategies for patient management and on the mandatory prescription of long-term pathogenetically based anti-relapse therapy.

Background: Isolated torsion of the fallopian tube (IFTT) is extremely rare - in 1 out of 1500,000patients. Its possible causes include anomalies of the structure of the fallopian tubes, paraovarial cysts, hydrosalpinx, long mesosalpinx, hydatids of Morgagni. The main clinical manifestations are nonspecific: sudden pain in the lower abdomen, accompanied by nausea, vomiting and frequent urination. Visualization during instrumental research is difficult. The preferred method of treatment that allows to preserve the organ, and hence the fertility of the patient, is the detorsion of the fallopian tube, with the ineffectiveness of which tubectomy is indicated. Case report: A first-pregnant patient at 35-36 weeks gestation went to an obstetric hospital with complaints for pain in the ilio-lumbar region on the right. Palpation revealed soreness in the right iliac region and a weakly positive symptom of pounding on the lower back on the right. Ultrasound examination of the kidneys revealed right-sided pyelokalikoectasia, the patient was diagnosed with gestational pyelonephritis and underwent infusion, antispasmodic and antimicrobial therapy, as well as drainage of the right calyx-pelvic system. Taking into account the persistent pain syndrome, the appearance of symptoms of peritoneal irritation and the detection of free fluid in the abdominal cavity, the pregnant woman underwent a diagnostic laparotomy, which revealed necrotic changes in the right fallopian tube against the background of its isolated torsion. Tubectomy was performed. Conclusion: The expansion of the calyx-pelvic system in patients in the second half of pregnancy is due to a violation of the passage of urine due to compression of the ureters by the growing uterus. Stagnation of urine in the cup-pelvic system is a favorable environment for the reproduction of opportunistic microorganisms with the development of gestational pyelonephritis, which is a risk factor for severe maternal and perinatal complications. In this clinical observation, the most probable diagnosis for pregnant women was established - gestational pyelonephritis - with appropriate treatment, which turned out to be ineffective. Diagnostic laparotomy was delayed, and therefore organ-preserving treatment in the amount of detorsion was inappropriate and the necrotically altered fallopian tube was removed.