No 9 (2024)

An analysis of modern literature data on the study of extracellular vesicles in the context of biomarker molecules is presented. The article focuses on their key role in communication between mother and fetus. The possibility of obtaining extracellular vesicles from various types of nerve cells, their role in regulating nervous system plasticity, neurotransmission, brain development, as well as the pathogenesis of neurological disorders are discussed. This paper reviews the function of neuronal exosomes as important mediators of placenta-associated mechanisms of perinatal inflammation and fetal brain damage. New data on the study of the level of signaling molecules that are part of exosomes of neuronal origin are presented. These data support the possibility of using the molecules as biomarkers for liquid biopsy of the brain. This paper describes the successful use of technology for obtaining neuronal fetal exosomes from maternal blood, which can be used to assess adverse outcomes of fetal nervous system development resulting from ethanol exposure in the first trimester of pregnancy.

Conclusion: The technology of obtaining neuronal fetal exosomes from maternal blood presents a unique opportunity for non-invasive dynamic assessment of the brain and the degree of dysfunction of the fetal nervous system during pregnancy. This assessment is based on the study of biomarker molecules that compose neuronal exosomes. The improvement of the algorithm for pregnancy management using this technology can reduce the risk of neonatal brain damage and avoid the long-term consequences of neurological disorders in adulthood.

Currently, operative abdominal delivery remains highly frequent, and this determines the relevance of the issue of uterine scar and associated complications. Uterine scar defect (USD) is associated with a large number of complications, including uterine rupture and placenta increta, infertility, and ineffectiveness of assisted reproductive technologies. The article presents a review of modern methods of scar diagnosis after cesarean section (ultrasound, MRI, sonohysterography, hysteroscopy), including techniques that can assess the qualitative characteristics of tissues (elastography, functional MRI). Despite the numerous proposed techniques, there is no gold standard for assessing the quality of the scar after cesarean section. It should be noted that the correlation between the mathematical parameters of the scar defect and adverse pregnancy outcomes explains the considerable diversity of the data obtained and cannot be considered unambiguous. The assessment of qualitative scar characteristics is of particular importance.

Conclusion: Despite the variety of techniques, to date there is no gold standard for diagnosing USD. In this regard, the development and implementation of methods that not only increase the accuracy of USD diagnosis, but can also assess the qualitative properties of the scar and adjacent myometrium are of particular importance. Therefore, the introduction of functional diagnostic methods seems to be the most promising and needs further study.

As the trend towards increasing life expectancy in developed and developing countries continues, and the speed and scale of demographic change in the world increase, there is a need to formulate and implement effective measures to preserve the quality of life in view of the general aging of the population. Age-related hormonal changes in the body that occur during the menopausal transition and postmenopause have a negative impact on the overall health and quality of life of women. Menopausal hormone therapy (MHT) prescribed for perimenopausal and postmenopausal women helps to correct the deficiency of sex hormones and contributes to the alleviation of menopausal symptoms, improvement of general condition and prevention of age-related metabolic disorders.

Today there are various forms of MHT in the world and in the Russian Federation. The choice of therapy should certainly be based on a personalized approach and in accordance with the available regulatory documents.

This review considers the basic principles of the use of different forms of systemic MHT from the perspective of international communities and large studies. It compares the efficacy and safety of different forms of estrogens and the progestogen component, as well as the characteristics of a personalized approach in patients with comorbid conditions and cardiometabolic risks. This paper presents tactics for selecting the optimal approach for the correction of menopausal disorders, taking into account the relevant regulatory documents.

Conclusion: The combination of the transdermal route of estradiol administration with micronized progestogen has been found to be the optimal choice in terms of the balance of benefit and risk, as it not only leads to reduced risks of total and cardiovascular mortality, fracture prevention, and improved quality of life, but it does not increase the risk of thromboembolic complications, ischemic stroke, cholelithiasis, and possibly breast cancer.

Menopause is the final stage of a woman’s reproductive life characterized by the cessation of monthly menstrual periods due to a decline in ovarian activity. The average life expectancy of women today is estimated to be about three to four decades after menopause. The hormonal changes related to menopause can affect physical, emotional, mental and social well-being. This period is associated with an increased risk of metabolic disorders, such as insulin resistance and abdominal obesity, which in turn can lead to cardiovascular diseases. The gut microbiome changes with the onset of menopause and may impact women’s health indirectly. Estrogen deficiency leads to a decrease in the species diversity of the intestinal microbiome and loss of its sexual dimorphism. The gut microbiome of postmenopausal women becomes identical to the gut microbiome of men of the same age. The results of experimental studies have demonstrated that the use of hormone replacement therapy can positively affect the homeostasis of the gut microbiome and balance the processes associated with estrogen deficiency.

Conclusion: Hormone therapy prescribed to correct menopausal symptoms has been shown to have the potential to positively affect the homeostasis of the gut microbiota. However, the findings are mostly based on experimental work with a relatively small sample size. Therefore, it is necessary to conduct more large-scale studies aimed at examining the gut microbiome of peri- and postmenopausal women and its changes during hormone therapy.

Objective: To examine the characteristics of systemic and placental hemodynamics in women with preeclampsia.

Materials and methods: This case-control study was based on a prospective cohort study that included 95 pregnant women. The women were divided into three groups: group 1 (n=29) consisted of women without preeclampsia, group 2 (n=32) consisted of pregnant women with moderate preeclampsia, and group 3 (n=34) consisted of pregnant women with severe preeclampsia. This study examined the results of assessing uteroplacental-fetal hemodynamics and fetal biometric parameters, brachial artery endothelium-dependent vasodilation during pregnancy, arterial stiffness indices (CAVI), and vascular age at 6–8 weeks postpartum.

Results: Women with preeclampsia had primary hemodynamic disorders associated with chronic arterial hypertension and a history of preeclampsia. Severe preeclampsia in the second trimester was linked to changes in uterine and fetal blood flow, as well as fetal growth restriction. After brachial artery compression, the percentage increase in brachial artery diameter in patients with severe preeclampsia was pathologically low (4.8%). In severe preeclampsia, the brachial artery diameter after decompression was negatively correlated with uterine and umbilical cord blood flow and severe asphyxia of the newborn, and positively correlated with gestational age at delivery and the newborn Apgar score. At 6–8 weeks postpartum, women with preeclampsia still had significantly higher blood pressure, CAVI, and vascular age than normotensive women. There were negative correlations between CAVI and Apgar score, while positive correlations were found with biological age, body mass index, baseline (first trimester of pregnancy), and current (6–8 weeks postpartum) blood pressure levels.

Conclusion: Characteristics of endothelial dysfunction have been proposed as potential early diagnostic markers for preeclampsia and its consequences. Identification of these markers may allow timely initiation of preventive and therapeutic measures.

In this article, we discuss the experience and effectiveness of endoscopic hysterectomy using a vaginal natural orifice transluminal endoscopic surgery (vNOTES) in obese patients with post-cesarean peritoneal adhesions. Performing surgery through the vagina combines the advantages of transvaginal and laparoscopic surgery, making it a potentially preferred option for patients with somatic comorbidities and a complicated obstetric and gynecological history.

Objective: To describe and illustrate the experience of performing vNOTES in obese patients undergoing hysterectomy for post-caesarean peritoneal adhesions.

Materials and methods: The authors present their experience with vNOTES for hysterectomy in 19 patients aged 42–57 years with recurrent endometrial hyperplasia, concomitant obesity, and post-cesarean pelvic adhesions. This study was conducted at the clinical facilities of the Department of Obstetrics and Gynecology No. 2 of the Bashkir SMU, Ministry of Health of Russia.

Results: The advantages of vNOTES for hysterectomy in obese patients with post-cesarean peritoneal adhesions compared with traditional laparoscopic surgery include reduced risk of trocar-related complications (which increase with obesity and the presence of peritoneal adhesions), reduced risk of postoperative complications associated with an anterior abdominal wall incision, less blood loss, better cosmetic effect due to the absence of additional abdominal wall incisions, less pain, early activation, rapid recovery, and quicker return to daily activities.

Conclusion: The vNOTES technology for hysterectomy in obese patients with post-cesarean peritoneal adhesions proves to be a minimally invasive, effective, and practical approach to surgical management in this patient population. It combines the advantages of both vaginal and laparoscopic procedures, with low blood loss and minimal intra- and post-operative complications. The benefits associated with improved visualization, increased maneuverability during manipulation, and low conversion rate make it a compelling alternative to other minimally invasive surgical approaches. However, further large-scale, multicenter, prospective, randomized controlled trials are necessary to establish clear indications and contraindications and to evaluate the efficacy, safety, and long-term outcomes of this method.

Minimally invasive laparoscopic surgery and Fast Track Surgery (FTS) program for patients have had a significant impact on perioperative management and have practically replaced the practice of traditional management. This raises the question of whether long-term inpatient treatment is required.

Objective: To evaluate the protective effect of FTS technology in laparoscopic non-hysterectomy interventions in elective patients.

Materials and methods: This prospective cohort study included gynecological patients who underwent elective laparoscopic organ-preserving surgery for benign neoplasms (uterine fibroids, benign ovarian neoplasms, endometriosis, and chronic salpingitis). The study included 312 operated patients: 247 – in the Fast Track Surgery program (FTS, main group) and 65 – in traditional care (TC, control group). Data for the study were obtained from the electronic databases of the full-cycle medical information systems "Ariadna" and "Medialog" for the years 2021–2023. The primary criteria for evaluating the effectiveness of FTS technology were complications in the early postoperative period and time of patient discharge. Additionally, the dynamics of some laboratory parameters in the study groups were analyzed.

Results: The use of FTS technology led to a decrease in the length of hospital stay (RR=0.06, 95% CI: 0.03–0.11), frequency of nausea and vomiting in the postoperative period (RR=0.04, 95% CI: 0.002–0.69), and surgical site infections (RR=0.05, 95% CI: 0.002–1.00).

Conclusion: The use of FTS program in combination with minimally invasive laparoscopic gynecologic surgery for elective patients who underwent surgery for benign neoplasms of the uterus and appendages significantly reduced the incidence of postoperative complications and the duration of inpatient treatment, without increasing the frequency of rehospitalization.

Background: In recent decades, intrauterine transfusion (IUT) of donor red blood cells has become a key medical technology to prevent HDFN's adverse outcomes. However, the factors affecting neonatal outcomes in HDFN patients need further research.

Objective: To explore neonatal outcomes amongst patients with Rh(D)-mediated HDFN treated with IUTs and evaluate the effect of perinatal factors on neonatal morbidity and mortality.

Materials and methods: A single-center 16‐year cohort study included all neonates (n=132) treated with IUTs for Rh(D)-mediated HDFN at the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology from January 2008 to December 2023. Most mothers were transferred from remote country regions with low anti-D Rh immunization coverage. Primary neonatal outcomes were death and potentially disabling brain injury (PVL/IVH grade III/perinatal stroke). The main perinatal factors were the presence and severity of hydrops fetalis, number of IUTs, gestational age (GA) at 1st IUT, and dynamics of pre-IUT fetal hemoglobin (Hb).

Results: Median GA at birth was 34 weeks (IQR 32–34.4). The median number of IUTs was 2 (IQR 1–3). Hydrops fetalis reversed in 30 out of 53 patients. Lethal outcomes were observed in 8/132 neonates (6%). The need for exchange transfusion was 62/132 (47%). No cases of bilirubin encephalopathy were registered. Hydrops fetalis was associated with higher risk of death (RR=10.2; 95% CI: 1.3–82.4) and brain injury (RR=8.9; 95% CI: 2.1–38.4). Most cases (12/14) of severe brain injury developed antenatally. Among neonates with ≥2 IUTs (n=95), the absence of increment in pre-IUT fetal Hb was associated with postnatal signs of hydrops (OR=111; 95% CI: 3.6–1268), lethal outcome (OR=67.7; 95% CI: 3.6–1268), and severe brain injury (OR=19.6; 95% CI: 4.6–84).

Conclusion: Hydrops fetalis continues to be a leading perinatal factor negatively influencing neonatal survival and neurologic outcomes. The absence of positive dynamics of pre-IUT fetal Hb reflects a significantly higher risk of hydrops, severe perinatal brain injury, and lethal outcomes.

Objective: To analyze the characteristics of the management of patients with endometriosis who underwent surgery in the gynecological department over two years in order to develop personalized therapy for endometriosis; to analyze the preferable duration of use of dydrogesterone as effective anti-relapse therapy for endometriosis.

Materials and methods: The retrospective study included 292 patients of reproductive age (16-49 years old) diagnosed with endometriosis. The patients underwent laparoscopic treatment for endometriosis at the Clinic of Obstetrics and Gynecology of Pavlov First Saint Petersburg State Medical University, Russia from 2021 to 2023. The preferable duration of treatment was discussed on the basis of retrospective analysis and clinical case series.

Results: Endometriomas were found in 176/292 (60.3%) patients and were significantly more frequent in groups with stage III and IV endometriosis (p<0.0001). Peritoneal endometriosis was detected more often intraoperatively in patients with stage I and II endometriosis (p=0.000002). All patients received long-term hormone-modulating therapy when there were indications and no contraindications. Recurrence of endometriosis was noted in women who received combined oral contraceptives and dienogest as they had poor tolerance to therapy.

Conclusion: Surgical treatment for endometriosis should be performed only when indicated and during intraoperative staging of the disease. Taking into account the risks of complications and decreased quality of life in case of repeated surgical intervention for recurrent endometriosis and possible reproductive plans of the patient, further treatment in the form of personalized drug therapy is advisable. Effective and safe therapy of endometriosis with dydrogesterone can be recommended to the patient for a long time, more than 48 months, which allows to minimize the risk of recurrence of the disease.

Objective: To determine the incidence of human papillomavirus (HPV) infection of the endometrium in women with reproductive failure and to evaluate immune changes and expression of p16^ink4a protein accompanying viral invasion of the endometrium.

Materials and methods: Thirty women with chronic endometritis and reproductive failures who met the criteria were included in a prospective study. The main methods were quantitative analysis of HPV DNA, immunohistochemical examination of endometrial biopsy specimens to identify viral antigens, inflammatory markers and expression of p16^ink4a protein.

Results: Viral infection of the endometrium was detected in 100% of women. HPV was found in 70% of patients and it was often combined with type I and type II herpes virus. Proinflammatory markers, mainly cytotoxic T-lymphocytes (CD8⁺) and B-lymphocytes (CD20⁺), were elevated in most patients; their increase indicated a chronic course of the inflammatory process. The expression of p16^ink4a protein which is involved in cell cycle regulation was observed in all endometrial samples, suggesting its possible role in impaired implantation and embryogenesis.

Conclusion: Impaired reproductive function in women with chronic endometritis may be associated with viral infection of the endometrium. The expression of p16^ink4a protein may be involved in the development of reproductive failure as it affects cellular processes in the endometrium and embryo.

Cesarean scar ectopic pregnancy (CSEP) is a rare type of ectopic pregnancy when the fetal egg attaches to the scar tissue of the uterus after a previous cesarean section (CS).

This review presents the data on the etiology, pathogenesis and incidence of CSEP. The present study analyzed the risk factors associated with CS surgery and invasive procedures within the uterine cavity following CS. The morphologic forms of CSEP are described. Current methods for diagnosing and treating CSEP with their advantages and disadvantages are presented. The most frequent diagnoses observed in CSEP are vaginal bleeding, large masses on the anterior surface of the uterus, cervico-isthmic pregnancy, missed miscarriage with low location of the fetal egg, incomplete abortion, etc. These findings were obtained from a review of medical literature. This paper describes the complications of this pathology, the most common of which is profuse bleeding. It also studies preventive measures and methods of rehabilitation for this type of ectopic pregnancy.

Conclusion: CSEP is a rare but potentially life-threatening complication following CS. Understanding the etiology and pathogenesis of this condition should be relevant today for a practicing obstetrician-gynecologist and doctors of other specialties. Therefore, it is essential to ensure the accuracy of pregnancy diagnosis, minimize performing unreasonable CS, provide reliable treatment, and be sure to carry out rehabilitation after CSEP.

Frozen pelvis is an informal medical term used in medical practice to describe a condition where the pelvic organs are extensively bound together by adhesions, resulting in significant disruption of their function and anatomy. Surgical treatment of this condition is challenging, even for experienced surgeons, because of the complexity of the adhesion process and resulting anatomical changes. The most common cause of frozen pelvis in gynecology is deep infiltrating endometriosis, which involves a complex interaction between inflammatory processes, tissue damage, impaired healing mechanisms, and neovascularization. The primary goal of surgical intervention is to remove adhesions, restore the pelvic anatomy, and alleviate symptoms. Successful treatment typically requires a multidisciplinary approach involving gynecologists, colorectal surgeons, urologists, and reproductive physicians to ensure optimal patient management and outcomes.

After reviewing the available literature, we found that there is a lack of domestic scientific publications on this pathology. Therefore, we conducted an analysis of the current scientific literature to provide up-to-date information on the pathogenesis, diagnosis, and management strategies of frozen pelvis. Additionally, we present two case studies from our own practice to illustrate the surgical treatment options for patients with a frozen pelvis.

Conclusion: Our analysis of the literature and clinical observations highlights the complexity of diagnosing and surgically treating frozen pelvis in gynecological practice. An interdisciplinary approach, individualized treatment strategies, preventive measures, and long-term monitoring are crucial for optimizing treatment outcomes and improving patient quality of life. Gynecologists who encounter this challenging condition should continually expand their knowledge and skills, exchange experience, and collaborate with other specialists to enhance diagnostics and patient management.

Background: Ultrasound assessment of the pelvic organs, along with the serum levels of human chorionic gonadotropin (hCG) is a key step in the diagnosis of malignant trophoblastic tumors. However, despite the great experience and achieved success in ultrasound diagnosis of trophoblastic tumors, rare types of the disease are associated with an unusual picture; thus, it is necessary to perform additional magnetic resonance imaging with a comprehensive evaluation of the obtained data by a group of experts in the field of diagnosis and treatment of trophoblastic disease.

Case report: This case study presents an observation of an atypical clinical picture of placental site trophoblastic tumor in a 37-year-old patient. During the diagnostic phase, an ambiguous ultrasound image of trophoblastic tumor was obtained. The diagnosis was made by a group of experts in the field of trophoblast pathology on the basis of obstetric history and examination findings: slightly elevated hCG with a tendency to slow increase with a massive locally advanced tumor process in the pelvis according to ultrasound examination and MRI, and high placental lactogen levels. EMA-ER chemotherapy was prescribed. The patient underwent a total of 5 courses of chemotherapy according to the recommended scheme; the 6th course was terminated due to complications. Taking into account the resistance of placental site trophoblastic tumor to standard high-dose chemotherapy which is accompanied by severe complications, immunotherapy was administered to the patient according to the following scheme: pembrolizumab 200 mg intravenously 1 h every 3 weeks in a day hospital. During treatment, hCG and echography indicators were monitored every 3 months; positive dynamics was noted. There were 24 cycles of pembrolizumab, the last 4 were consolidation ones. Complete clinical remission was confirmed. Menstrual function gradually restored.

Conclusion: In this clinical observation, the treatment was successfully achieved through the combination of standard high-dose chemotherapy and immunotherapy, which represents a novel approach. The result was not only a cure, but also the preservation of the young patient’s ability to have children in the future. Thus, consolidation of knowledge and clinical experience of experts in the field of diagnosis and treatment of trophoblast pathology should always be the standard of specialized medical care for patients with this disease.