Obstetrics and Gynecology

This review presents the issue of fetal metabolic programming within the concept of epigenetic regulation of the genome. The paper discusses the main mechanisms of metabolic programming of the fetus in case of placental insufficiency, impaired energy supply, changes in the formation of the microbiome, somatic pathology and the influence of other factors in terms of epigenetics. The review provides a systematization of the existing knowledge about the role of epigenetic modifications of the genome in the metabolic programming of the fetus and the analysis of their significance in increasing the risk of cardiovascular diseases in the postnatal period. The analysis of the literature revealed that epigenetic mechanisms, such as DNA methylation/demethylation, histone modifications, microRNAs are able to program fetal metabolism due the changes in chromatin organization and DNA availability; fetal metabolism can be programmed under unfavorable intrauterine conditions under the influence of external and internal stimuli. The review shows the possibilities of epigenetic therapy and preventive measures aimed at reducing the burden of non-communicable diseases which are the leading causes of mortality.

Conclusion: When the number of diseases associated with metabolic syndrome steadily increases, epigenetics should be considered as a key factor reflecting the indicators of individual health. It is the fetal period that is fundamental in terms of the possibilities of epigenetic prevention and therapy, making this area promising for further study.

Currently, there is an increase in the frequency of cesarean sections, and the number of young fertile women with a scar on the uterus rises as well. The presence of any scar on the uterus is always a risk for reproductive complications. If there is a severe myometrial defect, it can lead to thinning of the myometrium of less than 3 mm and formation of a defect on the part of the uterine cavity (niche). This article discusses the issues of terminology, the causes of formation and the clinical consequences of the defects in the scar area. Uterine rupture along the scar during pregnancy and childbirth is a life-threatening complication that can occur in the absence of timely diagnosis and treatment of this pathology in women planning a pregnancy. Modern algorithms for diagnosis and choice of treatment tactics depending on the clinical and instrumental results of the examination are presented in the article. Ultrasound examination, sonography, MRI, hysteroscopy are the main methods for diagnosing pathology in the area of the uterine scar after cesarean section. Depending on the clinical symptoms, the patient’s reproductive plans and the location of the defect, both dynamic observation and surgical correction of the uterine scar are possible. Hysteroscopic niche resection and metroplasty are the main methods of surgical treatment of patients with uterine scar defects.

Conclusion: The comprehensive examination of women with a uterine scar after cesarean section, the combination of at least two examination methods (ultrasound and MRI) can significantly increase the accuracy and quality of diagnosing the condition of the postoperative uterine scar. The choice of treatment for defects in the area of the uterine scar after cesarean section depends on the severity of clinical symptoms, the woman’s reproductive plans, the characteristics and localization of the myometrial defect in the area of the scar. Reconstructive surgery on the uterus (metroplasty) makes it possible not only to improve the quality of a woman’s life and restore fertility, but most importantly it can reduce the risks of life – threatening complications during pregnancy.

There are currently more than 30 million women aged over 45 in the Russian Federation. More than one million women reach menopause every year. Therefore, it is necessary for obstetricians and gynecologists to provide competent counseling and rationally assess the potential risks caused by estrogen deficiency. The change in the hormonal balance of androgens, estrogens and progesterone during peri- and postmenopause causes pathological changes in the cardiovascular, musculoskeletal and nervous systems. Peri- and postmenopausal women are at a higher risk of developing obesity which can also affect the unfavorable outcome of the clinical picture. It is important to pay special attention to patients with signs of hypoestrogenism in order to provide timely counseling and take therapeutic and preventive measures. The paper presents practical aspects that a clinician should take into account.

Conclusion: The key aspect for obstetricians and gynecologists about a menopausal woman is to improve the quality of her life and increase its duration. Menopausal hormone therapy (MHT) and its timely prescription reduces the risk of overall mortality by 31%, the risk of developing type 2 diabetes by 30%, and the risk of fractures by 30%. When choosing MHT, it is necessary to consider the safety profile of estrogens and progestogens included in the medication. When menopausal transition begins, the production of endogenous estradiol decreases, and a state of relative hyperandrogenism develops. It is important to find a balance between all hormones by selecting an adequate dosage of estrogen and a selective progestogen in MHT. It is worth noting that the progestogenic component should not decrease, but rather enhance, the beneficial effects of estrogen. Due to the completion of estrogen levels and the high selectivity of the progestogen, MHT with dydrogesterone helps to ensure a balance of activity of all three sex hormones, namely estrogens, progestogens and endogenous androgens in the female body.

Background: Fetal growth restriction (FGR) is a common complication of pregnancy and, in severe cases, leads to increased perinatal mortality, neonatal morbidity, and poor prognosis for life expectancy in patients with congenital malformations of the central nervous system and hypoxic-ischemic changes in the brain. Early detection of brain injury in IUGR enables to predict short-term and long-term outcomes for the development of the central nervous system, that currently remains a serious issue.

Objective: The aim of the study was to assess the role of ultrasound and MRI in diagnosis of FGR in combination with pathological changes in fetal brain.

Materials and methods: The retrospective study included 24 patients with suspected FGR. The mean age of patients (Me; Q1–Q3) was 33 (25–41) years, the average pregnancy length was 27.5 (20–35) weeks. The patients underwent simultaneous diagnostic US and MRI of the fetuses in the second and third trimester of pregnancy to assess fetal head circumference using percentile values of nomograms, and identify comorbidity, including the changes in fetal brain.

Results: No false positive results were found. MRI data and US imaging data were absolutely similar in nomograms for measurement of fetal brain volume using percentile method in 24 fetuses (100%) with FGR. Among them, FGR in combination with congenital diaphragmatic hernia was diagnosed in 3 fetuses (12.5%), and spina bifida in 1 fetus (4.2%). Comparison of two imaging techniques showed that false-negative results of ultrasound detection of malformation of the cortical plate and assessment of sulcation of the fetal brain were found in 3 fetuses (12.5%) versus 7 fetuses (29.2%) using MRI. Also, ultrasound imaging in diagnosing isolated unilateral cerebellar hypoplasia, showed false negative results in 2 fetuses (8.3%) versus false negative MRIs in 5 fetuses (20.9%).

Conclusion: The study showed that diagnostic ultrasound and MRI are comparable techniques in assessing biometry of the fetal brain using centile nomograms. However, MRI helps to perform more careful assessment of the concomitant pathology of the fetal brain.

Relevance: Adenomyosis is a common disease of the female reproductive system that affects 15–45% of women. One important aspect of the pathogenesis of adenomyosis is the disruption of apoptosis and immune processes, which are caused by an imbalance of growth factors (VEGF, EGF, TGFβ1, IGF1, and FGFR2). Polymorphisms in growth factor genes may influence their expression and therefore play a role in the pathophysiology of adenomyosis.

Objective: To evaluate the involvement of polymorphic loci in growth factor genes in the development of adenomyosis.

Materials and methods: This study included 102 patients with adenomyosis and 778 control women. Five polymorphic growth factor gene loci were selected for the study: rs4444903 EGF c.-382A>G and rs6214 IGF1 c.*2716G>A, rs2981582 FGFR2 c.109+906T>C, rs833061 VEGF c.-958C>T, rs1800469 TGFb1 c .-1347 T>S. The analysis was performed by real-time PCR. The APSampler program was used to assess inter-locus interactions (https://sourceforge.net/projects/apsampler/).

Results: The study results showed that the genotype GG IGF1 rs6214 (OR=2.64, p=0.01) should be considered a risk factor for the development of adenomyosis, as well as the combination of polymorphic variants G rs6214 IGF1, C rs1800469 TGFb1, A rs4444903 EGF, and T rs833061 VEGF (OR=1.88, pperm=0.0021), and the alleles G rs6214 IGF1, C rs1800469 TGFb1, T rs833061 VEGF, and C rs2981582 FGFR2 (OR=1.71, pperm=0.003).

Conclusion: The gene combinations rs4444903 EGF, rs6214 IGF1, rs2981582 FGFR2, rs833061 VEGF, and rs1800469 TGFb1 are associated with the development of adenomyosis. These results indicate the importance of interlocus interactions between growth factor genes in the development of adenomyosis. In the future, the obtained data could be used in practical medicine.

Objective: This study aimed to examine changes in the hemostatic system and determine the presence or absence of a tendency for thrombus formation with the prophylactic use of tranexamic acid during conservative laparoscopic myomectomy.

Materials and methods: This study included 33 patients with multiple uterine fibroids, anemic syndrome, and a low risk of venous thromboembolism (VTE) who underwent surgery, including laparoscopic myomectomy. Two days before surgery, all patients received iron carboxymaltose infusion, and intraoperatively, they received tranexamic acid at a dose of 20 mg/kg. We conducted dynamic monitoring of coagulation and thromboelastography parameters, as well as ultrasound screening of veins in the lower extremities on the 6th day after surgery.

Results: The use of tranexamic acid resulted in hypercoagulable changes within the first 24 h after surgery, but these changes remained within the compensatory-adaptive limits. On the 6th day after surgery, patients still showed a tendency towards hypercoagulation, with elevated levels of fibrinogen, D-dimer, and SFMCs exceeding the reference values. This tendency was associated with the extent of surgery and initial anemia, indicating an ongoing risk of VTE, including hidden thrombosis.

Conclusion: The identified tendency towards hypercoagulation in patients with multiple uterine fibroids after laparoscopic conservative myomectomy necessitates constant monitoring of the hemostatic system and the development of effective measures to prevent VTE, including the use of low-molecular-weight heparins.

When assisted reproductive technologies are used, recurrent implantation failures are observed in 7.7–67.5% of patients with chronic endometritis (CE).

Objective: To develop a predictive model of the probability of clinical pregnancy and live birth in women with uterine infertility due to CE using neural network technology at the stage of selection for in vitro fertilization (IVF) programs with cryotransfer and evaluate the effectiveness of this model.

Materials and methods: The secondary analysis of the results of the TULIP-2 randomized controlled trial was carried out. A total of 188 patients who met the objectives of this analysis were selected from the electronic database. The patients were divided into two comparison groups: group I (n=102) included patients who became pregnant, group II (n=86) included those who did not become pregnant.

Results: The model of predicting the success of IVF was created on the basis of 11 most significant parameters, which were identified after obtaining the results of the logistic analysis. The model was made using neural network technology. In order to predict the outcome of IVF, the following indicators were included in the structure of the multilayer perceptron: treatment, which included a complex of antimicrobial peptides and cytokines, CD-138, pulsation index in radial arteries according to Dopplerometry, oxygenation indices, proliferative activity, structuring according to laser conversion testing, interleukins such as -4, -10, -1ß, tumor necrosis factor-α according to enzyme immunoassay. The accuracy of the prediction was 97.9% (sensitivity is 100.0%, specificity is 96.4%). The information value of the model was confirmed by ROC analysis, the area under the curve (ROC-AUC) was 0.9, p<0.001. An online calculator was developed for the practical use of the model of individual prediction of IVF success.

Conclusion: The model of predicting clinical pregnancy and live birth as a result of IVF in patients with infertility caused by chronic endometritis, using neural network technology, has a high predictive accuracy and makes it possible to determine the need for administering another course (courses) of treatment for chronic endometritis or making a decision on the IVF procedure.

In the Russian Federation, reproductive losses mainly refer to abortive outcomes of pregnancy. Since the demographic situation in the country is difficult, it is necessary to analyze the situation and find the solutions to increase the birth rate.

Objective: To determine the dynamics of the main reproductive losses (abortions) in the Russian Federation, in the Far Eastern Federal District and its regions from 2003 to 2022.

Materials and methods: This is the analysis of the data of Form No. 13 of the Federal Statistical Observation in the Russian Federation, Federal Districts and regions of the Far Eastern Federal District for 2003–2022. The research method is a continuous statistical observation; dynamic series indicators were calculated; direct ranking method and descriptive statistics were used.

Results: From 2003 to 2022, there was a decrease in the absolute number of all types of abortions in the Far Eastern Federal District, as well as in the Russian Federation, in general, by 71.32% and 76.4%, respectively. The abortion rate per 1,000 women of reproductive age decreased by 73.0% (from 42.3 to 11.41) in the Russian Federation and it decreased by 72.37% (from 58.3 to 16.1) in the Far Eastern Federal District. The rate of various types of abortions also decreased: the rate of medical (legal) abortions reduced by 84.2% in the Russian Federation and by 79.5% in the Far Eastern Federal District; the rate of spontaneous abortions decreased by 46.8% in the Russian Federation and by 41.0% in the Far Eastern Federal District; the rate of medically indicated abortions reduced by 10.4% in the Russian Federation and by 66.0% in the Far Eastern Federal District, and the rate of socially indicated abortions decreased from 0.7731 to 0.0005 in the Russian Federation and from 1.2234 to 0.0021 in the Far Eastern Federal District.

Conclusion: The absolute number and rate of all types of abortions decreased in the Far Eastern Federal District, as well as in the Russian Federation as a whole, in 2003–2022, but their level remains high. The prevention and successful treatment of miscarriage with the preservation of each desired pregnancy is a real reserve for increasing the birth rate.

Natural orifice transluminal endoscopic surgery (NOTES) is a new approach used in various surgical disciplines. In this article we describe our experience of performing transvaginal surgeries vNOTES.

Objective: To describe and illustrate a standardized approach to vNOTES hysterectomy.

Materials and methods: A total of 31 patients aged 48 to 59 years old underwent vNOTES surgery. The study was carried out on the basis of the Department of Obstetrics and Gynecology.

Results: Hysterectomy with tubal removal was performed in 21 cases, hysterectomy with unilateral salpingoophorectomy was done in 7 cases, hysterectomy and bilateral salpingoophorectomy were performed in 3 cases. All the patients had less severe pain syndrome in the postoperative period: the average value of pain intensity according to the VAS scale after 24 hours was 2.4; the average duration of vNOTES surgery was 96 minutes (ranging from 70 to 130 minutes). The advantages of vNOTES compared to traditional laparoscopic approaches are reduction of postoperative pain, early activation, faster recovery of patients after surgery, shorter hospital stay, improved cosmetic effect and reduced risk of intraoperative injuries to internal organs.

Conclusion: Transluminal endoscopic surgery vNOTES combines good access and visualization provided by endoscopy, maximum cosmetic effect, and can be considered as an alternative to other minimally invasive procedures. This method is preferable for obese patients, as well as for patients who refuse traditional laparoscopy wishing to obtain aesthetic and cosmetic results.

Objective: To improve the outcomes of correction of genital prolapse by modifying the colporrhaphy technique and prescribing Epigen Intim spray as an anti-inflammatory and regenerating agent in the postoperative period.

Materials and methods: The study included 60 perimenopausal patients with signs of POP-Q stage 2 or higher cystocele/rectocele. The traditional colporrhaphy technique was used in group 1, and subfascial dissection of tissues was performed in group 2. After discharge from the hospital, the postoperative stage of patients in group 2 was modified: they used Epigen Intim spray for a prolonged period of time, twice a day for 45 days.

Results: In 45 days after the treatment, the signs of complications in the form of hematoma, compaction and edema in the area of postoperative sutures were noted in 10% of cases among the patients of group 1; there were complaints of pelvic pain in three cases in group 1, and only in one case in group 2 (3.3%). The analysis of the vaginal microbiome using PCR showed that the ratio of normoflora/opportunistic microorganisms had a more favorable profile in group 2 (Lactobacillus spp. – 10^6.5 (68.6%) in group 1, 10^7.2 (78.3%) in group 2). Moreover, various dynamics of Veillonella spp. and Gardnerella vaginalis concentrations was revealed (10^2.6 in patients with complications versus 10^0.7 in uncomplicated patients; 10^5.1 versus 10^2.7 in group 1 and 10^2.4 in group 2).

Conclusion: The surgical correction of genital prolapse requires an efficient approach; therefore, it is necessary to apply the optimal technique of colporrhaphy due to subfascial dissection of tissues and choose the proper postoperative tactics. The use of special medications, such as Epigen Intim spray with anti-inflammatory and regenerating effects after subfascial colporrhaphy allows patients to adapt the state of the vaginal microbiome and accelerate tissue regeneration, which can reduce the risk of complications.

Chlamydia infection is one of the most common sexually transmitted infections which is caused by the intracellular microorganism Chlamydia trachomatis. Chlamydia has a tropism to the cylindrical epithelium and is capable of affecting the mucous membrane of the urethra, cervical canal, rectum, oropharynx and conjunctiva of the eyes. In women, chlamydial infection can cause cervicitis, urethritis, pelvic inflammatory diseases, tubal factor infertility. During pregnancy, this infection is a provocative factor for preterm birth, premature rupture of membranes, intrauterine infection of the fetus and low birth weight. The analysis of the studies presented in this review substantiates the need for timely detection and treatment of chlamydia infection, especially during pregnancy. In this regard, the choice of an effective and safe drug during gestation is an important issue. The review examines the principles of diagnosis and treatment regimens for urogenital chlamydia infection in pregnant women. Data from clinical studies on the effectiveness and safety of azithromycin in the treatment of cervicitis of chlamydial etiology in this category of patients are presented.

The article presents a description of clinical cases on the use of Azithromycin EXPRESS in pregnant women with diagnosed C. trachomatis infection.

Conclusion: Treatment with Azithromycin EXPRESS was accompanied by clinical and microbiological recovery, with no adverse reactions during therapy or complications in the ante- and postnatal period.

Relevance: The frequency of congenital uterine malformations ranges from 4 to 10%. These malformations are characterized by morphological and functional inferiority of the organ, which contributes to the difficulty in the processes of implantation and placentation, causing infertility, miscarriage, abnormal variants of placentation.

Case report: The article presents an obstetric history of the course of three pregnancies of a patient with a bicornuate uterus: the first two pregnancies resulted in premature termination due to premature placental separation and premature rupture of the membranes complicated by chorioamnionitis and placenta increta; besides, the patient had cervical incompetence. The effectiveness of using a two-balloon Zhukovsky catheter in combination with a hemostatic suture in the patient at risk for obstetric bleeding during delivery was shown.

Conclusion: Repeated reconstructive plastic surgery on the uterus with the restoration of the normal anatomy of the uterine cavity, timely treatment of cervical incompetence made it possible to carry the third pregnancy. Successful delivery using a two-balloon Zhukovsky catheter in combination with a hemostatic suture gave a chance to complete the pregnancy and perform an organ-sparing operation.