No 9 (2021)

The paper reviews publications devoted to cross-sectional studies of the composition of vaginal and gut microbiotas in order to assess the relationship between impaired intestinal microbiocenosis and dysbiotic processes in vaginal microbiocenosis. An analysis of the literature has shown that the change in the number of certain types of microorganisms in a particular biotope or the identification of species that are not peculiar to this habitat serves as a signal for adaptive or irreversible changes in the appropriate component of the microecosystem. These changes are known to be interrelated and occur simultaneously in several biotopes. Vaginal dysbiosis can result in a cascade of processes that disrupt balance in the female reproductive tract, causing various infectious and inflammatory processes. In this connection, gut and vaginal microbiotas as indicators of female reproductive health deserve the special attention of obstetricians and gynecologists today. A number of recent studies have identified a correlation between microbial communities in pregnant women and women whose pregnancy was complicated. Both the vaginal and gut microbiotas contribute to mother-to-infant Bifidobacterium transmission, and establishing the fact that the vaginal and gut bacteria represent the same population is an important step for future studies of maternal and neonatal health. Conclusion: Data on the intestinal microflora serve as informative indicators of a woman's health, and the substantial changes in the composition of the intestinal microbiocenosis require adequate correction. The expediency of conducting studies in this area is confirmed.

The endometrium, the function of which depends on sex steroids synthesized in the ovaries, is one of the selfrenewal systems with high regeneration in the human body. Numerous studies are devoted to the local study of the intracrinology of sex hormones in endometrial tissue. The activation and inactivation of sex steroids by the expression of hormones and enzymes play a key role in the functional activity of the endometrium, which is a guarantee of its competence for implantation and regeneration. The increased expression of aromatases is known to be necessary to create the optimal conditions for implantation, gestation, and prolonged pregnancy. Measurement of endometrial tissue concentrations of steroids using liquid chromatography and tissue mass spectrometry could answer only a few questions about the role of synthesis of sex steroids, including endometrial androgens that act as active ligands for their receptors and as substrates for the biosynthesis of estrogens. A vivid model of the impaired expression of aromatase, the key enzyme for steroidogenesis, can be observed in the pathogenesis of endometriosis and endometrial cancer, which has led to the design of targeted drugs. Conclusion: The active design of targeted drugs of selective androgen and estrogen receptor modulators arouses interest in their clinical eff icacy in various endometrial diseases. Realizing the role of the effects of sex steroids on different organs and tissues in the female body, including cognitive, sexual functions and the realization of reproductive potential, it is necessary to individualize therapy, taking into account the peculiarities of their intracellular influence and the possibility of using them in each clinical case.

The perimenopausal and postmenopausal period is characterized by the development of many diseases of great sociomedical significance, as well as metabolic disorders, including those of purine metabolism. Despite the fact that gout is traditionally considered to be a disease that predominantly affects males, the prevalence of hyperuricemia (HU) and gout significantly increases in females when menopause occurs. The available data on the association of gout with the postmenopausal period, as well as its frequent combination with other metabolic syndrome components actualize the possible additional positive effects of menopausal hormone therapy (MHT) for GU and gout in females during perimenopause and postmenopause. The review considers the results of prospective versus large retrospective studies of the impact of MHT on changes in uric acid (UA) levels and on the risk of gout. The biological mechanism underlying the relationship between menopause, estrogen action, MHT, and serum UA levels is assumed to be an inhibitory effect of estrogens on UA reabsorption in the renal tubules. In addition, estrogen deficiency favors the development of metabolic disorders, such as abdominal obesity, insulin resistance, and dyslipidemia. The anti-inflammatory effect of estrogens may be the basis for reducing the risk of gout when using MHT. Conclusion: MHT can lead to a decrease in the level of UA and in the risk of gout. However, the decrease in the production of estrogens and progestogens only partially explains the higher risk of HU and gout. The protective effect against gout is probably due not only to the estrogenic, but also progestogenic component of MHT. It may be promising to study the impact of MHT not only on the risk, but also on the course of gout.

Aim: The study was aimed to identify association between SERPINA1/a1-antitrypsin (A1AT) and the severity of preeclampsia and perinatal/neonatal outcomes. Materials and methods: The analysis of medical histories, specific features of the course of pregnancy in 79 women, childbirth, postpartum period, and the state of health of their newborns was performed. Urine samples for testing were collected before 34 weeks of gestation, when pregnant women were admitted to hospital. All patients were divided into 3 groups: group 1 (the main group) included 41 pregnant women with preeclampsia; group 2 (the comparison group) - 17 women with chronic arterial hypertension; group 3 (the comparison group) - 18 women with normal pregnancy. Depending on the detected level of urinary SERPINA1 in pregnant women, group 1 was divided into 2 subgroups: 1a (n=23) - preeclampsia, SERPINA1 positive (PE SER+) and 1b (n=21) - preeclampsia, SERPINA1 negative (PE SER-). Results: The study confirmed the adverse effect of preeclampsia on the condition of the fetus and newborn. It was demonstrated, that determination of peptides of SERPINA1 (α1-antitrypsin) in the urine of pregnant women predicts a severe course of preeclampsia and was associated with a high incidence of growth retardation and fetal hypoxia. In infants born to women preeclampsia, SERPINA1 positive, there was a negative correlation with the body weight, Apgar score and necessity for resuscitation, as well as the duration of the newborn's stay in hospital. Conclusion: The study of the urine peptide profile - determination of SERPINA1 peptides contributes to the differential diagnosis of the severity of preeclampsia and other hypertension disorders during pregnancy helping to determine obstetric tactics and prognostically significant risk factors for the newborns.

Background: The proportion of women who undergo labor induction steadily increases due to the increasing number of indications. Most inductions of labor are carried out in inpatient settings. However, outpatient induction may be more convenient to women and cheaper for health service providers. Mifepristone as a cervical ripening agent is rapidly gaining popularity. However, the current literature is lacking regarding the outcomes of its use in outpatient settings. It is also essential to compare clinical outcomes from outpatient with inpatient mifepristone for induction of labor. The present study aimed to evaluate the efficacy and safety of outpatient versus inpatient mifepristone for labor induction. Materials and methods: This is a protocol for a randomized, prospective, open-label clinical trial. Primiparous and multiparous women (n=300) with a singleton pregnancy with fetus in the cephalic presentation at the gestational age between 39 and 41+6 weeks, cervical Bishop’s score 6 or less, indications for labor induction, who meet all inclusion criteria, none of the exclusion criteria, and sign an informed consent form will be randomly allocated to one of two groups (outpatient and inpatient). The two groups will receive a standard protocolized cervical ripening with mifepristone (one or two doses). Discussion: We expect outpatient management with mifepristone to be as effective and safe as an inpatient while increasing economic benefit and patients’ compliance during cervical ripening. Trial registration: isrctn.com. ISRCTN26164110. Registered on February 21th, 2020.

Aim: The aim of the research was to study the pathomorphological and immunohistochemical features of brain damage in cases of the most severe forms of preeclampsia and eclampsia that ended with death. Materials and methods: Tissue samples taken from 10 women during autopsy, who died from from preeclampsia and eclampsia, were examined, as well as tissue samples for comparison from 3 women, who died from other reasons. The markers of mature neurons (y-NSE) and endotheliocytes (CD-34) were used for immunohistochemistry of postmortem brain tissue. Results: The study of autopsy material from patients, who died from severe preeclamsy and eclampsy detected some features of the pathogenesis of cerebrovascular complications associated with preeclampsia: 1) pronounced vasogenic and cytotoxic cerebral edema with multiple foci of ischemia, subarachnoid and intracerebral hemorrhages; 2) the signs of severe ischemic encephalopathy, death of cortical neurons and glial cells; 3) Brain capillary endothelium destructive damage with impaired blood-brain barrier (BBB) integrity and the release of neurospecific proteins from the brain tissue into the peripheral blood flow. Conclusion: The major pathophysiological mechanisms of cerebrovascular complications of preeclampsia and eclampsia are disruption of cerebral blood flow autoregulation, destructive damage of brain capillary endothelium, impaired BBB integrity, and possibly neuroinflammation.

Objective: To determine the prevalence and types of complications after surgical treatment of patients with colorectal endometriosis using the data of the Department of Surgery, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia. Materials and methods: The results of the examination of 692 reproductive-aged women with colorectal endometriosis were analyzed. All patients attended the Department of General Surgery of the above-mentioned Centre for planned surgical treatment in the period from 2010 to 2020. The patients included in the study were operated on by experienced surgeons when there were standard indications for the operation. Various surgical approaches were performed according to clinical recommendations. Depending on the presence or absence of complications in the postoperative period, the patients were divided into two groups: the study group included the patients with complications (n=78) and the control group included the patients without complications (n=614). Results: The median age was 33.1 years (Q1-Q3: 27.0-47.0 years). Anastomosis failure after low and ultra-low resections of the rectum developed in 29/692 (4.1%) cases and manifested as pelvic abscess, diffuse peritonitis, or symptoms of endogenous intoxication. The complication always required repeated surgical intervention, suturing of the site of anastomosis failure or dissociation of anastomosis and the formation of a protective colostomy, drainage of the abdominal cavity, intensive therapy, and combined antibacterial treatment. Enteroanastomosis bleeding developed in 17/692 (2.4%) patients and was intensive with a total volume of 500 to 1500 ml. In all cases, endoscopic method with the use of argon plasma coagulation and clipping of the artery (vein) was used to stop the bleeding. Anastomosis stricture was diagnosed in 32/692 (4.6%) women. The endoscopic method for treating cicatricial strictures of colonic anastomoses is preferable. Conclusion: The treatment of complications which occur after surgery for colorectal endometriosis proves to be challenging and requires the involvement of experts from surgical centers and a multidisciplinary approach.

Objective: To investigate expression levels of long noncoding RNAs linc-ROR and MALAT1 in the normal cervical epithelium and cervical intraepithelial neoplasia and evaluate the change in their expression depending on the severity of cervical dysplasia. Materials and methods: The study included 89 reproductive age patients with histologically confirmed LSIL and HSIL and high-risk type of HPV. The comparison group included 40 patients with cytologically excluded cervical disease and test negative for HPV. The expression levels of long noncoding RNAs linc-ROR and MALAT1were analyzed by Real-Time PCR using primers specific for these genes. Results: The expression level of MALAT1 in cervical dysplasia was statistically significantly higher than in the control group, with 62.5% of patients having LSIL of 2.6±0.42 and 79.8% having HSIL of 4.9 ± 2.65 (p<0.001, Kruskal-Wallis test). No statistically significant differences between the groups were found in linc-ROR expression (LSIL 2.07±0.34, HSIL 1.91±0.86 in the study group, and 1.0±0.4 in the comparison group (p = 0.368) (Kruskal - Wallis test), which indicates no predictive value of linc-ROR for the diagnosis of precancerous lesions of the cervix. Conclusion: The search for early diagnostic markers of malignant transformation of the cervical epithelium is a priority research area aimed to reduce the incidence of cervical cancer. This study demonstrated an increase in the level of MALAT1 expression in LSIL in 62.5% and HSIL in 79.8% of patients compared with normal cervical epithelium, which indicates a high proliferative activity of cells, degradation of the gene p53 suppressing tumor growth, and blockage of apoptosis. Therefore, MALAT1 may become a promising biomarker for the progression of cervical dysplasia.

Objective: To estimate changes in the frequency and severity of menopausal syndrome (MS) symptoms and psychoemotional disorders and the frequency of adverse events 12 weeks after the end of taking the natural non-hormonal drug (NHD) Serelis. Materials and methods: The investigation enrolled 90 surgical menopausal patients with MS (45 in the Serelis group and 45 in the placebo group). The investigation lasted 36 weeks. Changes were estimated in the frequency and severity of MS symptoms, in particular psychoemotional disorders, quality of life, and the frequency of adverse events. Results: After 12 weeks of treatment, there was a decrease in the severity of MS in 40/45 (88.9%) patients in the Serelis group versus 9/45(20%) in the placebo group (OR 1.12; 95% CI 0.90-4.02, p=0.048). The Serelis group showed a statistically significant decrease in the severity of neurosplanchnic and psychoemotional symptoms on the MMI scale (p=0.018 and p=0.017, respectively), the changes in the placebo group were statistically insignificant. The median total MMI score was 33.2 in the Serelis group (p=0.034) and 50.1 in the placebo group (p=0.046). There were no statistically significant differences in the total HADS scores between the groups (p=0.048). According to the WHQ questionnaire, the decrease in the mean total score amounted to as much as 33.3% in the Serelis group and 5.3% in the placebo group (p<0.001). Serelis use in the follow-up period had a long-lasting positive impact. Conclusion: The results of our study have shown that the use of the NHD Serelis allows one to achieve a signif icant reduction in the severity of neurosplanchnic and psychoemotional symptoms, to level off anxiety-depressive spectrum disorders, and to significantly improve quality of life.

Objective: To improve the results of feminization plastic surgeries in girls with a disorder of sexual development. Materials and methods: A procedure was proposed for dissociative feminization plastic surgery, which was used in 2018 to 2019 to operate on four girls in the chronological and clinico-hormonal therapy-induced puberty period with virilization of the external genitalia, a high urethrovaginal confluence (UVC), and a long genitourinary common channel (GUCC). Results: Based on the partial urogenital mobilization described by R.C. Rink in 2006, the authors developed a new procedure of feminization plastic surgery for puberty patients with a high UVC and a long GUCC. The procedure is characterized by the preparation of a mucosal flap of the GUCC, by laying it in a W-shaped way to create the anterior and lateral walls of the artificial vaginal orifice (AVO) and preparing the posterior wall of the vagina to create the posterior wall of the AVO. The calculation of the minimum GUCC length, which is required for successful surgery, is presented. Good results were obtained in all the patients. Conclusion: The proposed procedure makes it possible to form the female external genitalia with the separately opening urethra and vagina, with the moist mucous orifice, with the possibility of adequate sexual life in the future, without the risk of vaginal stenosis and urinary disorders.

Gestational diabetes mellitus (GDM) is the most common disease complicating pregnancy. GDM is associated with the development of a number of short- and long-term complications for both the mother and the fetus; therefore it is a general medical problem. Nevertheless, there is currently no consensus on the glycemic thresholds required for diagnosis and subsequent treatment. Effective treatment in women with GDM significantly reduces the risk of perinatal complications. Maintenance of normoglycemia is mainly achieved by changing the diet, increasing physical activity, and controlling weight gain during pregnancy, but some women will also need drug treatment. One of the factors determining the efficiency of non-drug therapy and the need to initiate drug treatment in women with GDM may be directly related to the pathophysiological aspects of hyperglycemia that occurs during pregnancy, namely, to which component in the pathogenesis of GDM prevails in a given woman: insulin resistance, β-cell dysfunction, or both factors are equally expressed. The heterogeneity of the pathogenetic mechanisms underlying different GDM subtypes, which is reflected in the phenotypic signs and outcomes of pregnancy, has been demonstrated in a number of studies. The results of these studies are presented in the review and are of great importance for understanding the physiology of hyperglycemia in pregnant women, suggesting that heterogeneity in the pathogenesis of GDM affects perinatal outcomes and complications associated with hyperglycemia in pregnant women, and other characteristics of pregnant women and newborns. There are presently insufficient data to revise the approach to pregnant patients with GDM, by taking into account the predominant pathogenetic component. Conclusion: Further study of the heterogeneity of GDM and its pathogenetic subtypes certainly deserves attention, since it is the predominance of a particular pathogenetic mechanism that can be a determining factor in choosing a diagnostic, therapeutic, and preventive approach.

Background: Magnetic resonance imaging (MRI) pelvimetry is a modern, objective diagnostic technique that is used to estimate the size of the pelvic cavity when deciding on a delivery method. At the same time, there are many discrepancies in both the technique of the procedure itself and the reference values of the pelvic dimensions determined in this study. Objective: To present our MRI pelvimetry procedure and to compare the reference values with those given by other authors. Materials and methods: This paper describes the indications, contraindications, and procedure of MRI pelvimetry, which has been regularly used at the Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, since 1998. Results: Over the past period, more than 2500 MRI pelvimetry studies have been conducted. The used reference values of the indicators were compared with the data obtained by other researchers. Conclusion: The presented MRI pelvimetry procedure and the reference values of the indicators are comparable with the results obtained by other researchers and can be used in the radiology units as prescribed by an obstetrician/ gynecologist. The use of this technique will promote a reduction in the frequency of labor complications and its further improvement based on the continuation of researches.

In recent years, interest has been expressed by different physician specialties in diseases and syndromes associated with impaired prolactin (PRL) secretion. According to the Russian clinical practice guidelines, the hyperprolactinemic syndrome is a symptom complex that occurs in the presence of hyperprolactinemia, the most characteristic manifestation of which is dysfunction of the reproductive tract. The prevalence of pathological hyperprolactinemia in reproductive-aged women is 5%. At their visit to an obstetrician/gynecologist, one third of women complain about various menstrual cycle abnormalities, which may be associated, among other things, with higher prolactin levels. According to statistics, hyperprolactinemia occurs in 9% of reproductive-aged women with amenorrhea and in 17% of those with polycystic ovary syndrome. Hyperprolactinemia may be of physiological origin. Hyperprolactinemia can be a combined clinical manifestation of a number of different pathological conditions of the reproductive tract in young women. In reproductive-aged women, about 70% of menstrual irregularities can be concurrent with hyperprolactinemia due to stress and distress, surgical treatment for gynecological and non-gynecological diseases, oral hormonal contraception, and use of psychotropic drugs from a group of neuroleptics and antidepressants. This paper considers the common reasons for higher prolactin, the basics and errors of diagnosis, and the basic principles of treatment and follow-up in reproductive-aged patients with hyperprolactinemia. There is much evidence that it is necessary to work within the framework of personalized medicine, and this is not only the efficiency of a chosen treatment regimen, but also primarily safety, especially if the same holds true for reproductive-aged women who can potentially get pregnant. Conclusion: Cabergoline is recommended as a f irst-line drug, being most effective, to normalize prolactin levels and to reduce tumor size. The 2021 study has shown that cabergoline is not only an effective, but also the safest drug to relieve hyperprolactinemia.

Background: Pulmonary embolism (PE) is the most serious venous thromboembolic event (VTE) and the leading cause of death in pregnant women and puerperas. The change in the hemostasiogram parameters (except for D-dimers) in VTE practically does not differ from that in physiological pregnancy. The first-line therapy for PE is drug treatment with thrombolytics and anticoagulants, the use of which in pregnant women is associated with a high risk for obstetric bleeding and adverse perinatal outcomes. Case report: The paper presents the results of examination and treatment in a 34-year-old female patient with PE that occurred at 24 weeks’ gestation and was diagnosed using chest computed tomography and pulmonary angiography. A systemic thrombolytic session was performed, followed by the placement of an inferior vena cava filter and by the administration of low-molecular-weight heparins at therapeutic doses, which allowed the patient to prolong pregnancy to full term and to give birth to a healthy baby. Conclusion: The appearance of clinical symptoms (in this case, exertional dyspnea) is of paramount importance in predicting life-threatening pathological conditions and requires a detailed follow-up within the framework of timely diagnosis and specialized medical care.

Background: Women are most at risk for Clostridium difficile infection in the early postpartum period. Clostridium difficile-associated colitis may be mistaken for the intestinal form of COVID-19 during the ongoing novel coronavirus infection pandemic. Case report: The paper describes a clinical case of a female patient diagnosed with the novel coronavirus infection and Clostridium difficile-associated pseudomembranous colitis in the early postpartum period. It depicts the diagnosis and treatment of the identified concurrent pathology. It demonstrates data from of an endoscopic examination of the colon and spiral computed tomography of the chest and provides laboratory confirmation of the infectious etiology of comorbidity. There are data available in the literature on the high rate and recurrent course of pseudomembranous colitis in the early postpartum period. It is noted that timely C. difficile eradication and pathogenetic treatment for the novel coronavirus infection allow relief of clinical symptoms. Conclusion: The case of the novel coronavirus infection concurrent with Clostridium difficile-associated pseudomembranous colitis in the early postpartum period is of interest in connection with the need for differential diagnosis of the etiology of diarrheal syndrome, the precise identification of which determines the further tactics of patient management and the nature of anti-epidemic measures.