Obstetrics and Gynecology

The role of iron in the development of disorders of carbohydrate metabolism has been known for a long time. The first observations were based on the increased risk of diabetes mellitus in patients suffering from hereditary disorders of iron metabolism with increased iron deposition in the liver and pancreas in haemochromatosis. Subsequently, disorders of carbohydrate metabolism during pregnancy (gestational diabetes mellitus) were associated mainly with increased insulin resistance, impaired insulin secretion in genetically predisposed individuals, with obesity and metabolic syndrome in women before gestation. However, there is increasing evidence to support the hypothesis of the role of iron overload associated with metabolic syndrome, metabolically associated fatty liver disease, induction and progression of disorders of carbohydrate metabolism. The article presents current data on the association between disorders of iron metabolism and the risk of developing gestational diabetes mellitus. It discusses the mechanisms how ferrokinetics influence glucose intolerance and considers the role of iron supplements in the development of gestational diabetes mellitus. The review refers to the current clinical recommendations and algorithms of medical care adopted in the Russian Federation and abroad, as well as to the data of some of the most recent studies on the issue.

Conclusion: The process of iron metabolism in pregnant women is complex and involves various regulatory mechanisms. It is associated with metabolic risks that are present before pregnancy or that arise during pregnancy. Iron overload may increase the risk of developing gestational diabetes mellitus, and this should be considered when developing a personalized algorithm for monitoring pregnant women.

The review presents the issue of development of gestational complications through the concept of defective decidualization. The main stages of the phylo- and ontogenetic development of decidua are discussed; the factors that directly or indirectly influence the decidualization process itself are also considered. The review provides a comprehensive analysis of the existing knowledge on the multifaceted functions of the placental decidua, its participation in the uteroplacental hemocirculation. It also explores the creation of an immunoprivileged and metabolically optimal environment at the border of the decidua-chorion system, which is critical for ensuring normal pregnancy. The article shows the possibilities of decidualization therapy, laboratory control of the functional state of decidua basalis and implementation of measures aimed at reducing the incidence of pre-eclampsia, placental insufficiency, fetal growth retardation, miscarriage and preterm labor.

Conclusion: Decidua plays a key role in establishing normal pregnancy, as it is the main factor in the development of gestational complications, both in the early and late stages of gestation. The effectiveness of preventive measures aimed at increasing the receptivity of the endometrium and its complete transformation in the process of decidualization makes this area particularly relevant for further study given the worldwide fertility crisis.

Background: Despite the efficacy of antimicrobial therapy for inflammatory diseases of the lower genital tract, the high recurrence rate and growing resistance of microorganisms make it necessary to search for and implement alternative or adjuvant approaches aimed at restoring a healthy vaginal microbiome. Lactic acid is a key metabolite of lactobacilli and it plays a vital role in maintaining the vaginal microbiota by providing an acidic environment that inhibits the growth of pathogens and modulates the local immune response.

Objective: To organize the current literature data on the role of lactic acid in the pathogenesis of bacterial and viral vaginitis and on the use of acid-containing medications to restore vaginal microbiota, maintain fertility; to analyze the data in menopausal and pregnant women.

Materials and methods: The Russian and foreign databases, namely eLibrary, PubMed, and Russian Science Citation Index (RSCI), were analyzed for the keywords, ‘lactic acid’, ‘lactobacilli’, ‘microbiota’, ‘dysbiosis’, ‘bacterial vaginosis’, ‘human papillomavirus’, ‘genital herpes’, and ‘genital infections’. Literature sources were selected for analysis according to the objective.

Results: This article summarizes the data on the physiological functions of lactic acid and its mechanisms of action, including its antimicrobial, viricidal and immunomodulatory effects. The possibilities of using lactic acid in the therapy of bacterial vaginosis, vaginitis of nonspecific and mixed etiology, viral infections in pregnant and postmenopausal women are considered. The article highlights the data on the role of lactic acid in maintaining fertility, preparing the endometrium for implantation and reducing the risk of obstetric complications. The high safety of topical application of lactic acid is emphasized, especially in the context of the limitations of antibacterial therapy in pregnant women and in the setting of recurrent bacterial vaginosis.

Conclusion: Lactic acid is not only a metabolite providing physiological acidity of the vaginal environment, but also an active component of innate immunity, capable of resisting both bacterial and viral infections. Its use in vaginal preparations represents a valid strategy for restoring vaginal microbiota and preventing recurrent vaginal infections.

It is known that reduced placental size, abnormal development of placental villi and reduced E-cadherin expression are observed in pregnancies with fetal growth restriction.

Objective: To identify the features of the E-cadherin/β-catenin signaling pathway in the placenta and peripheral blood of pregnant women by determining expression of the MMP-9, CCND1 and BIRC5 genes induced by the nuclear β-catenin translocation, as well as WNT2 gene expression, and to analyze the features of apoptosis of the placental cells.

Materials and methods: The study included 82 patients. The main group consisted of 46 women with the postnatal diagnosis of fetal growth restriction without hypertension complications. The control group consisted of 36 patients with normal pregnancy. Investigation of the features of the E-cadherin/β-catenin signaling pathway was carried out by determining expression of the MMP-9, CCND1 and BIRC5 genes induced by the nuclear β-catenin translocation, and WNT2 gene expression in the placental tissue and peripheral blood, as well as analyzing the features of apptosis of placental cells.

Results: It was found that MMP-9 and BIRC5 expression levels in the placenta were significantly higher in fetal growth restriction (p=0.03 and p=0.02, respectively). MMP-9 expression level in the peripheral blood was lower in fetal growth restriction (p=0.001). Increased apoptosis of the placental cells was observed in fetal growth restriction (p=0.03). Excessive apoptosis of trophoblast cells was in fetal growth restriction compared with normal pregnancy (p=0.017).

Conclusion: Lower level of E-cadherin expression in the placenta in fetal growth restriction can be associated with activation of the E-cadherin/β-catenin signaling pathway and development of apoptosis of placental trophoblast cells.

Relevance: The primary goal of infertility treatment using assisted reproductive technologies (ART) is to increase the rates of embryo implantation and the birth of healthy children. Scientific research has focused on enhancing culture conditions, particularly the co-culture of embryos at various developmental stages with somatic cells and extracellular vesicles (EVs). Experimental animal models have demonstrated that adding EVs derived from follicular fluid (FF) during in vitro culture can modulate embryo development and improve implantation rates. FF-derived EVs were specifically selected because of their proven roles in regulating oocyte quality and subsequent post-implantation embryo development.

Objective: To evaluate the clinical efficacy of ART for optimizing the embryological stage of infertility treatment by co-culturing FF-derived EVs with embryos in patients who have experienced multiple unsuccessful IVF attempts.

Materials and methods: This study involved married couples with a history of more than two unsuccessful IVF attempts, a normal karyotype, and mild pathozoospermia. A total of 76 women were included in this study. As part of the standard ART protocol, FF was collected on the day of transvaginal puncture from which EVs were isolated through sequential ultracentrifugation. After fertilization, oocytes were randomly divided into two groups: group 1 underwent co-culture of zygotes with FF-derived EVs for 24 h, while group 2 underwent classical culture. The addition of FF-derived EVs was performed as follows: in a well of a 4-well plate containing 0.3 ml of culture medium and post-ICSI oocytes, 2 μl of the medium with FF-derived EVs was added and incubated for 24 h. On the first day of culture, embryos at the zygote stage from group 1 were transferred to classical culture medium to continue developing to the blastocyst stage. Embryological and clinical outcomes were assessed, with the primary endpoint being pregnancy rate after transferring one embryo into the uterine cavity. The level of statistical significance was set at p<0.05.

Results: Assessment of early embryogenesis parameters revealed a statistically significant increase in fertilization rate for the co-culture group with FF-derived EVs: 88.1% compared to 77.3% in the classical culture group (p<0.001, chi-square test). Additionally, group 1 exhibited a significantly higher frequency of excellent- and good-quality blastocyst formation (55.0% vs. 42.6 %, p<0.01). When fertilized post-ICSI oocytes were co-cultured with FF-derived EVs, there were significantly more blastocysts suitable for transfer into the uterine cavity and cryopreservation, with a median of 1 [0; 1.25] in group 1 compared to 0 [0; 1] in group 2. Clinical data analysis indicated a pregnancy rate of 27.2% in group 2, while group 1 (EV FF) achieved clinical pregnancy in 14 of 45 transfers, with two biochemical pregnancies. The clinical pregnancy rate in group 1 was 31.1%. Notably, no statistically significant differences in clinical parameters were found across the overall cohort of women with a history of multiple IVF failures. However, there was a tendency for an increased pregnancy rate with co-culture of FF-derived EVs in younger women, in contrast to the near-complete absence of positive outcomes in patients of advanced reproductive age.

Conclusion: The results suggest that co-culture with FF-derived EVs may significantly enhance the embryological stage of infertility treatment programs in women with a history of multiple ART failures. Further studies are needed to establish statistically significant differences in clinical outcomes.

Objective: To study changes in placental growth factor (PlGF) levels at 11–14 weeks of gestation and before delivery (at 37–40 weeks) in relation to various pregnancy complications, including gestational diabetes mellitus, fetal macrosomia, premature birth, and abnormal placentation.

Materials and methods: The study included 3,274 pregnant women who underwent first-trimester screening at V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. Serum PlGF levels were measured at various gestational ages. The Mann–Whitney U test and χ² Pearson test were used for the analysis, with statistical significance set at p<0.05.

Results: No statistical differences were found in PlGF levels at 11-14 weeks between the groups, in contrast to the PAPP-A levels. However, there were distinct patterns of PlGF level changes associated with various pregnancy complications. Gestational diabetes was characterized by a decline in PlGF levels as pregnancy progressed, with the most pronounced reduction observed in patients receiving insulin therapy (p<0.001). In contrast, elevated PlGF levels were detected in the third trimester in cases of fetal macrosomia (p=0,004). In cases of abnormal placentation (particularly placenta previa), a significant increase in PlGF level was detected prior to delivery (p=0,01). In cases of preterm birth, the changes in PlGF levels did not reach statistical significance.

Conclusion: The findings of the study highlight the potential usefulness of evaluating PAPP-A and PlGF levels across various stages of pregnancy to assist in risk stratification for complicated pregnancies. Lower PAPP-A levels during the first trimester are linked to an increased risk of gestational diabetes mellitus (GDM) and preterm birth, while PlGF levels in the third trimester area are associated with the severity of metabolic and placental complications.

Objective: To evaluate the potential of non-invasive method for determining LOXL1 levels for the diagnosis of pelvic organ prolapse (POP) in women of reproductive age.

Materials and methods: A total of 48 women with POP and 32 women who had no vaginal prolapse were examined. LOXL1 levels in vaginal secretions were determined using enzyme-linked immunosorbent assay.

Results: LOXL1 levels were significantly higher in women with vaginal prolapse and in women with hypertension (p<0.05). LOXL1 levels were lower in women with varicose veins of the lower extremities, hemorrhoids and nephroptosis.

Conclusion: The study evaluated the potential of quantitative measurement of LOXL1 in vaginal secretions in women of reproductive age, that can become an effective prospective method to predict the diagnosis of pelvic organ prolapse.

Objective: To improve the introduction of new medical technologies in obstetrics and gynecology in medical organizations of the constituent entities of the Russian Federation within the framework of the organizational and methodological guidance of the National Medical Research Center.

Materials and methods: Between 2019 and 2024, the staff of the National Medical Research Center conducted a total of 170 events to study and analyze the organization of medical care in the field of obstetrics and gynecology in all supervised regions of the Russian Federation. During these events, the specialists of the National Medical Research Centre determined the necessity and possibility of introducing modern methods of prevention, diagnosis, treatment and medical rehabilitation (hereinafter referred to as medical technologies) used in global medical practice in the field of obstetrics and gynecology. Four medical technologies were approved by the Ministry of Health of the Russian Federation in 25 constituent entities of the Russian Federation; these technologies had to be introduced in 2024 in medical organisations of the constituent entities of the Russian Federation in the field of obstetrics and gynecology.

Results: Given the measures taken to introduce medical technologies in medical organisations, 28 certificates were received by medical organisations in the constituent entities of the Russian Federation in 2024 for the introduction of medical technologies in obstetrics and gynecology.

Conclusion: The introduction of medical technologies in obstetrics and gynecology in medical organisations in the constituent entities of the Russian Federation demonstrated the interest of regional executive authorities and medical organisations in improving the quality of medical care.

Endometrial thickness (ET) <8 mm has an unfavorable impact on perinatal outcomes. One of the areas in treatment for thin endometrium is the use of cellular technologies that influence the reparative process, such as autologous platelet-rich plasma, peripheral blood mononuclear cells (PBMCs). The use of acellular secretome is a new trend with similar therapeutic properties that has been developed in regenerative medicine.

Objective: To evaluate the effect of secretome of peripheral blood mononuclear cells (SPBMC) on ET in women with thin endometrium and infertility.

Materials and methods: The study included 252 reproductive-aged infertile patients with a previous history of two or more attempts of assisted reproduction and the presence of thin endometrium not responding to therapy using other methods. In addition to the standard therapy, the patients received SPBMC Superlymph 25 units one suppository vaginally at night for 20 days from the 5th to the 25th day of the menstrual cycle from 1 to 3 months until there were satisfactory parameters of ET (8 mm or more) confirmed by ultrasound. All patients had a single cryopreserved embryo transfer performed.

Results: The statistical analysis of the data (n=252) showed a significant increase in ET to 8 mm or more in 80.2% of patients compared to the initial values. The effectiveness of assisted reproduction was as follows: the overall rate of clinical pregnancy per transfer was 38.1% (105/247), namely 47.2% (17/36) in patients aged 18–29, 39.8% (37/93) in patients aged 30–35, 38.5% (37/96) in patients aged 36–40, and 13.6% (3/22) in patients aged 41–45. The birth rate was 35.3% (36/102), namely 36.8% (7/19) in patients aged 18-29, 42.2% (19/45) in patients aged 30-35, and 27.8% (10/36) in patients aged 36-40.

Conclusion: The use of SPBMC in combination with standard therapy increases endometrial thickness, improves pregnancy and live birth rates in patients with thin endometrium and infertility.

Objective: To assess the incidence of adverse drug reactions in women taking dienogest after surgical treatment of endometriosis and to determine the influence of baseline clinical and demographic characteristics on discontinuation of recurrence prevention therapy in the postoperative period.

Materials and methods: The study included 48 female patients who underwent surgical treatment for endometriosis and received recurrence prevention therapy with dienogest for 120 days between January and March 2024.

Results: There were 38/48 (79.2%) patients who completed the full course of dienogest therapy for 120 days and 10/48 (20.8%) patients who had to discontinue therapy due to the development of undesirable adverse reactions to dienogest. The leading causes for discontinuing dienogest therapy were abnormal uterine bleeding in 6/48 (12.5%) patients and migraine in 5/48 (10.4%). Psychiatric side effects were also experienced by 5/48 (11.6%) patients, with symptoms including depressive disorders, emotional instability and cognitive impairment.

Conclusion: Regardless of age, body mass index or clinical indicators of endometriosis, the use of dienogest may be associated with a risk of adverse drug reactions and may lead to the discontinuation of recurrence prevention therapy.

The quality of clinical laboratory tests is characterized by clinical informative value, which is one of the main parameters. Activator tests and nonactivated thromboelastometry (NATEM) are performed with the ROTEM Delta thromboelastometer. Activator tests provide rapid assessment of fibrinogen activity, coagulation factors, fibrinolysis and the effect of heparin on clot formation, which determines their high clinical information value for Point Оf Care evaluation of coagulation and targeted therapy for massive bleeding. NATEM is more commonly used in clinical practice due to its ease of implementation and low cost; however, there is a lack of convincing evidence of its clinical value in identifying the causes of bleeding, particularly in obstetrics and gynecology.

NATEM parameters were shown to have high sensitivity to hypercoagulability and low sensitivity to detect von Willebrand disease, F:VII and F:XII deficiency in patients with obstetric and gynecological coagulopathy. In the presence of lupus anticoagulant, NATEM parameters do not reflect prothrombotic risk, but are instead in the area of hypocoagulation. In hemorrhage, NATEM parameters are multidirectional and fail to differentiate the cause of the hemorrhagic syndrome.

Conclusion: NATEM has low diagnostic value for the detection of coagulopathy in obstetric and gynecological patients. NATEM parameters are highly sensitive to hypercoagulation, which may mask clotting factor deficiency. NATEM does not provide diagnostic evidence of the cause of coagulopathic bleeding; activator tests should be performed for this purpose.

Background: Abdominal pregnancy is a rare form of ectopic pregnancy characterized by an increased risk of serious obstetric complications, maternal morbidity and mortality, neonatal morbidity and perinatal loss. Despite the use of modern imaging techniques in prenatal diagnosis, detection of abdominal pregnancy remains a difficult task and in most cases the pathology is not diagnosed before surgical intervention.

Case report: The paper presents two clinical cases of abdominal pregnancy that were observed in the same period of time. In the first case, laparotomy was performed at 34 weeks gestation for abdominal pain in a multiparous patient with placenta increta (PAS Grade 2) and progressive oligohydramnios; abdominal pregnancy was detected intraoperatively. A live infant without developmental anomalies was born. Hysterectomy was performed due to the attachment of the placenta into the uterine wall (PAS Grade 2), blood loss was 3000 ml. In the second case, abdominal pregnancy was also localized on the uterus, but the pregnancy was terminated early and the diagnosis was made only during emergency laparoscopy; blood loss was about 1000 ml.

Conclusion: According to the current literature, most cases of abdominal pregnancy are diagnosed intraoperatively. Lack of a standardized diagnostic algorithm is its contributing factor. The detection of abdominal pregnancy (especially in late gestation) during surgery is associated with technical and tactical difficulties for obstetricians and gynecologists, the need for emergency involvement of doctors of different surgical specialties and transfusion medicine specialists. The classification of reported cases of abdominal pregnancy in late gestation and their systematic analysis may help to standardize approaches to diagnosis and treatment, and reduce the risk of complications for both mother and fetus.