No 2 (2023)

The paper provides an overview of modern concepts of different forms of twin-to-twin transfusion in monochorionic multiple pregnancy. It deals with diagnostic criteria for acute twin-to-twin transfusion during monochorionic twin delivery. The pathogenetic mechanisms of risk factors for acute twin-to-twin transfusion are considered. The differential diagnosis in chronic (twin-to-twin transfusion syndrome, twin anemia polycythemia sequence) and acute (single fetal death in twin pregnancy, placentofetal and acute twin-to-twin transfusions) forms of twin-to-twin transfusion is discussed in detail.

The possibility of predicting and preventing the development of acute twin-to-twin transfusion during childbirth has not been now defined; however, it is assumed that in some cases the changes in the cardiotocographic heart rate patterns may suspect specific disorders and make a timely delivery decision to minimize both antenatal losses and neonatal morbidity and mortality rates. The review gives possible approaches to postnatal correction for neonatal hematological disorders due to acute bypass surgery during monochorionic twin delivery.

Conclusion: Further investigations are needed to clarify diagnostic criteria and risk factors for acute twin-to-twin transfusion and optimal delivery tactics and to study long-term consequences for the health of children with this complication of monochorionic multiple pregnancy.

Fetal growth restriction (FGR) remains one of the important obstetric problems, being a risk factor for antenatal and neonatal mortality and morbidity. The timely prediction of FGR is one of the most important measures in reducing adverse pregnancy outcomes. However, despite numerous studies, practical obstetrics still lacks highly sensitive and specific prognostic biomarkers for this disease.

This paper analyzes open-access modern scientific literature data in the PubMed, Cochrane, and eLibrary databases, which characterize the role of biomarkers in predicting the risk of FGR. Meta-analyses demonstrate that beta-human chorionic gonadotropin, alpha-fetoprotein, free estriol, human chorionic somatomammotropin hormone 1, pappalysin 1, inhibin α-subunit, and placental growth factor are considered the most promising predictive biomarkers for FGR. However, the data obtained by most authors suggest that the use of individual biomarkers has insufficient sensitivity and specificity in stratifying the risk of FGR. The most promising direction in this area is the creation of models for complex multiparametric screening based on the study of maternal risk factors, the levels of biomarkers (both proteomic and molecular genetic ones) in conjunction with ultrasound data.

Conclusion: Thus, studies focused on the search for new biomarkers in order to develop a comprehensive screening program that is of high prognostic value in identifying the risk of FGR are highly relevant and determine personalized patient management tactics in the future.

Endometriosis is regarded as one of the most urgent problems of modern gynecology, whereas its prevalence is about 10% (190 million females) of all reproductive-aged women worldwide. Despite the benign nature of this disease, this process has the features similar to those of malignant diseases, such as loss of cell proliferation control, a tendency for invasive growth, an elevated blood level of cancer-specific markers, and a propensity to relapse.The paper reviews the literature data by Russian and foreign authors, which have been published in the Cochrane Library, Pubmed, and eLibrary databases on the role of the following biomarkers: acetylcholine receptors, matrix metalloproteinases, paraoxonases, bradykinin receptors, and estradiol receptors, in the context of evaluating the course of endometriosis. The increasing role of this disease in the pattern of gynecological diseases, the social significance of the problem, long diagnostic periods, and treatment start since the first symptoms appear generate a need for the medical community to conduct a comprehensive study of this pathology.

Conclusion: Further in-depth study and clarification of the etiopathogenetic mechanisms of endometriosis, as well as the creation of new diagnostic models, will be able to more successfully apply and/or to combine various procedures and methods for treating this disease, developing a modern concept of epigenetic rehabilitation, and improving quality of life in these patients.

Fetal macrosomia is important to study given the high incidence of obstetric and neonatal complications. The induction of labor can reduce the incidence of adverse outcomes in complicated pregnancies. However, the effectiveness of labor induction in reducing the incidence of obstetric and neonatal complications in fetal macrosomia remains controversial.

Objective: To investigate obstetric and neonatal outcomes of different management strategies for fetal macrosomia (expectant management versus labor induction).

Materials and methods: This retrospective cohort study analyzed birth outcomes in 626 healthy primiparous women with fetal macrosomia. The patients were divided into a study group (n=334) with labor induction and a control group (n=295) with expectant management. Each group was divided into gestational age subgroups 1, 2, 3, and 4 of 37–38, 39, 40, and 41 weeks, respectively.

Results: The caesarean section rate for induction of labor at 37-39 weeks was not different from that in the expectant management group, whereas it was significantly higher at 40 weeks (p=0.02). However, at 41 weeks, the situation changed, and the rate of caesarean sections was significantly higher in the expectant management group (p=0.04). There were no differences in the rates of vaginal delivery, fetal shoulder dystocia, or perinatal outcomes.

Conclusion: With the development of fetal macrosomia, it is too late to count on the effectiveness of labor induction, which is the traditional approach to preventing complications. Preventing macrosomia and developing other approaches to prevent its adverse consequences are important.

Objective: To evaluate anamnestic data, quality of life, psycho-emotional state, eating behavior, obstetric and perinatal outcomes in women with early and late gestational diabetes mellitus (GDM).

Materials and methods: We conducted a study that included 144 women with GDM. 86 out of these women were included in group 1 with early GDM that was detected before 24 weeks of pregnancy, and group 2 comprised 68 women with late GDM detected after 24 weeks. The questionnaires Short Form 36 (SF-36), Well-being-Activity-Mood (WAM), Hospital Anxiety and Depression Scale (HADS) and the Dutch eating behavior questionnaire (DEBQ) were used. The course of pregnancy and perinatal outcomes were evaluated.

Results: Women with GDM that was detected in early pregnancy were characterized by decreased indicators of vital activity, social functioning, mental and psychological health, well-being and mood, high indicators of subclinical anxiety and subclinical depression. Women with GDM that was detected in early pregnancy were characterized by frequent mental distress (RR 3.36; 95% CI 1.67–6.78; p<0.001), miscarriages inherited from their mothers (RR 9.49; 95% CI 1.26–71.18; p=0.03), arterial hypertension during previous pregnancy (RR 5.14; 95% CI 1.20–22.01; p=0.03), recurrent miscarriage in medical history (RR 8.69; 95% CI 1.15–65.72; p=0.04), intake of methylprednisolone (RR 9.49; 95% CI 1.26–71.18; p=0.03), tranexamic acid (RR 9.49; 95% CI 2.32–38.75; p=0.002), sodium ethamsylate (RR 5.53; 95% 1.30–23.53; p=0.02), threatened early miscarriage (RR 13.84; 95% CI 3.45–55.50; p<0.001), threatened late miscarriage (RR 4.47; 95% CI 1.02–15.70; p=0.04), placental insufficiency (RR 4.47; 95% CI 1.61–12.44; p=0.004), premature birth (RR 3.89; 95% CI 1.37–11.03; p=0.01). The patients with GDM that was detected in later terms of pregnancy were characterized by more frequent presence of type 1 diabetes mellitus in first-degree relatives (RR 0.05; 95% CI 0.003–0.79; p=0.03), and in second-degree relatives (RR 0.13; 95% CI 0.03–0.56; p=0.01), late menarche (12.6 (1.3) and 13.4 (1.3); p=0.01), frequent dysmenorrhea (RR 0.47; 95% CI 0.36–0.62; p<0.001).

Conclusion: Women with early GDM were characterized by frequent mental distress, miscarriages inherited from their mothers, arterial hypertension during previous pregnancy, recurrent miscarriage in medical history, intake of methylprednisolone, tranexamic acid and ethamsylate, threatened early and late miscarriages, placental insufficiency, premature birth. Women with late GDM were characterized by the frequent presence of type 1 diabetes mellitus in first-degree and second-degree relatives, late menarche, dysmenorrhea in anamnesis.

Adenomyosis is a variety of the benign pathological process, in which tissue in endometriosis affects the muscular layer of the uterus. The main principle of surgical intervention is the removal of myometrial tissue with invasion of endometriosis. The prevalence of adenomyosis ranges from 5 to 70%. The disease affects 2 in 10 women under the age of 40 years, while the incidence rises to 8 in 10 women between the ages of 40 and 50 years. However, the incidence of adenomyosis is difficult to determine due to the lack of a unified definition and diagnostic criteria based on noninvasive diagnostic methods. Its detection rate in the population varies from 10 to 61% according to different authors.

This paper presents surgical procedures for adenomyosis excision in the patient to perform her further reproductive function. Since 2012, by using the procedure described by H. Osada, the researchers (Prof. V.B. Tskhay and T.A. Makarenko, MD) of the Department of Obstetrics, Krasnoyarsk State Medical University, have been performing surgical interventions for excision of adenomyosis in patients with its diffuse forms and uterine sizes at 10 to 22 weeks’ gestation. The authors have also shown an original approach to suturing the uterus during surgery. The researchers (Prof. N.N. Rukhlyada and K.Yu. Krylov, PhD) of the Department of Obstetrics and Gynecology, Saint Petersburg State Pediatric Medical University, did 242 operations, of which 172 were performed to restore fertility; moreover, the total number of pregnancies that had occurred was 74 (43.1% or 30.5% of all the interventions).

Conclusion: Considering our experience of surgical interventions by laparotomy, we can conclude that there is no unified technique for the surgical treatment of adenomyosis – the choice of incisions and the way of suturing the myometrium depend both on the size of the uterus and on the location of the affected myometrium, its symmetry and uniformity, as well as on the volume of remaining intact tissue and the form of the defect.

Objective: To investigate changes in cardiometabolic risk factors in women during menopausal transition and the feasibility of correcting the identified abnormalities using cyclic hormone therapy with drospirenone-containing COC.

Materials and methods: The study enrolled 178 women who underwent a menopausal transition with manifestations of the menopausal syndrome. The study group included 87 women who received COC consisting of drospirenone 3 mg/ethinyl estradiol 20 μg. The control group included 91 women who had not received COC. Kupperman–Uvarova MMI was used to assess the severity of menopausal symptoms. Clinical evaluation included measurements of lipid metabolism, fasting blood glucose, IRI, HOMA-IR, WC, and WC/HC ratio.

Results: More than half of the women had excessive body weight and signs of abdominal obesity, one-third had lipid metabolism disorders, and 41 (23%) were diagnosed with metabolic syndrome. At the end of the study, women in the study group showed a significant reduction in body weight and abdominal obesity. By the end of the study, women in the control group had higher HOMA-IR values, concurrent with higher postprandial blood glucose levels. Women in the study group did not show significant changes in these parameters, and the levels of total and LDL cholesterol were reduced.

Conclusion: The study findings showed a high incidence of metabolic risk factors in women during the menopausal transition. Administration of COC to menopausal women prevents an increase in body weight and visceral obesity, contributes to a decrease in IR and impaired carbohydrate metabolism, and favorably affects lipid metabolism.

Objective: To evaluate the effect of ferrous fumarate/folic acid (FF/FA) on the clinical and laboratory signs of anemia in pregnant women in the second trimester.

Materials and methods: The investigation enrolled 160 women at 14 to 20 weeks’ gestation who were diagnosed with anemia and were prescribed FF/FA.

Results: The use of FF/FA caused a significant improvement in clinical and biochemical blood test results reflecting the severity of anemia: an increase in Hb, Ht, RBC, MCV, MCH, MCHC, serum iron, and ferritin, a decrease in the frequency of microcytosis and serum latent iron-binding capacity. After 3 months of therapy, the total study population displayed an increase in mean values of HgB from 102.0 to 117.0 g/l, ferritin from 46.2 to 55.9 µg/l, serum iron from 12.02 to 20.49 µmol/l. The proportion of patients without anemia was 77% (118/153); that with mild and moderate anemia were 20% (31/153), and 2% (3/153), respectively, which shows a significant improvement compared to that at the start of therapy. In the group with iron deficiency anemia (IDA), (Hb<110 g/l, ferritin<30 µg/l), Hb increased from an average of 103.3 to 109.8 g/l, ferritin from 14.4 to 24.3 µg/l, serum iron from 11.87 to 20.53 µmol/l. After 3 months, mild and moderate IDA was present in 30% (28/93) and 3% (3/93) patients, respectively.

Conclusion. The findings are comparable with international and Russian data and can conclude that FF/FA is an effective and safe way to correct IDA in pregnant women and is suitable for long-term use.

Objective: To compare the levels of urinary estradiol metabolites in women with COMT rs4680 gene polymorphisms and different types of estrogen support in a cryo-protocol using gonadotropin-releasing hormone (GnRH) agonists and hormone replacement therapy (HRT).

Materials and methods: Thirty-nine ART cryo-cycles were analyzed; the level of estrone and estradiol metabolites was measured. The urinary levels of hydroxyestrone, methoxyestrone, and estradiol were estimated in women on the day of progesterone start. The indicators were comparatively analyzed according to the estrogen type used: 0.1% transdermal estradiol gel in Group 1 and estradiol valerate pills 2 mg in Group 2 after the preliminary use of GnRH agonists.

Results: The use of oral estrogens is associated with the higher urinary level (by 10 times or more) of hydroxylated forms of metabolites than that of the transdermal gel for any of the COMT gene polymorphism variants. The COMT AA and GA gene polymorphisms are related to the higher level of hydroxylated estrogen metabolic products regardless of the estrogen type used in the protocol. Thus, in women with AA polymorphism who used transdermal estradiol, the level of hydroxyl forms was 1.5 times higher than that in those with GG polymorphism (p=0.014). In women with GA polymorphism, the urinary level of these metabolites was 1.6 times higher than that in those with the GG genotype (p=0.010).

Conclusion: The cryo-protocol that uses GnRH agonists in combination with 0.1% transdermal estradiol gel is characterized by the higher level of methoxy forms of estrogen metabolites than hat of estradiol valerate pills. In patients with COMT AG and GG polymorphisms in the long protocol, it is advisable to apply transdermal estrogen as a drug that does not increase the accumulation of hydroxylated forms of estrogen metabolites.

Timely treatment for benign breast dysplasia (BBD) should be considered as a cancer prevention measure.

Objective: To evaluate the efficiency of BBD treatment with the non-hormonal herbal remedy indole carbinol (Indinol Forto).

Materials and methods: A total of 150 women aged 30–49 years were comprehensively examined using breast examination and sonography and mammography. The patients were divided into 2 groups. A study group consisted of 75 women with BBD: with benign changes (according to Breast Imaging-Reporting and Data System 2 (BI-RADS 2), manifested as small cysts (up to 10 mm), as well as duct ectasias concurrent with cyclical mastalgias. All the patients were prescribed combination treatment, including concomitant measures. The study group women took indole carbinol-based drugs to treat BBD. A comparison group included 75 women with benign changes (BI-RADS 2), who refused drug treatment for various reasons.

Results: Minor mammographic density was noted in 69.3% of the study group patients and in 34.7% of the comparison group (p<0.001); moderate one was seen in 26.6 and 42.7%, respectively (p=0.040). Severe mammographic density was determined in 2.7% of cases in the study group and in 13.3% of those in the comparison group (p=0.017); pronounced one was observed in 1.3% and 9.3% in these groups, respectively (p=0.030).

Conclusion: Indinol Forto is shown to be highly effective in treating BBD. Combined with concomitant measures, 6-month therapy with this drug substantially reduces mammographic density. The drug is well tolerated and has no adverse side effects. It can be recommended for widespread use as a first-line drug in women with increased breast density.

Over 100 years ago, endometriosis was described as endometrial-like tissue outside the uterus. There are many theories to explain endometriosis. Understanding the pathogenesis of any disease helps find the key to treatment. The evidence-based approach to endometriosis requires special consideration. Endometriosis is often ruled out because of the negative results of studies, including imaging, which results in a well-known diagnostic delay in the disease. Drug therapy is offered to relieve pain, to prevent new lesions or recurrences, and is prescribed as a self-treatment or as a second stage after surgery. In Russia, hormone therapy for endometriosis is used by only 24% of the women, for whom this is indicated. Informing women about their disease, the duration of treatment, possible side effects of hormone therapy, and ways to solve these problems will be able to reduce the risk of self-discontinuation of drugs and subsequent recurrences of endometriosis. Gestagen monotherapy to minimize the risk of progression of endometrioid lesions seems to be a more reasonable solution in the treatment of patients. The possible growth of lesions during therapy should be monitored and, if pain relief is inadequate, other options should be considered. Dydrogesterone is highly effective and safe in endometriosis; this allows you to take into account all the wishes of patients, which makes it possible to continue treatment for endometriosis for a long time before and after implementing reproductive plans, as well as before menopause.

Conclusion: Understanding the etiology and pathogenesis of endometriosis, timely diagnosis, and prescription of effective therapy with a high safety profile and with the ability to individually approach each patient will be able to alleviate symptoms, to improve quality of life, and to reduce the risk of recurrences in women suffering from this pathology.

Background: The steady increase in the number of patients with a history of even one caesarean section leads to a rise in the frequency of such form of ectopic pregnancy, as pregnancy in the scar. The choice of the optimal organ-sparing treatment option for this category of patients depends on timely diagnosis. The formation of retrochorial hematoma that accompanies non-developing pregnancy in the scar in the early stages significantly complicates the diagnosis.

Case report: The paper describes a clinical case of a reproductive-aged patient, in whom a long episode of menometrorrhagia ended with the formation of a round mass up to 8 cm in diameter in the area of the scar after cesarean section at the uterine isthmus. Erroneously diagnosed incomplete abortion during uterine pregnancy and uterine fibroids served as a reason for uterine curettage complicated by massive blood loss. The final diagnosis was established after pathological mass excision and metroplasty.

Conclusion: A pathological uterine mass localized in the scar area after cesarean section, which is suddenly detected during abnormal uterine bleeding, requires the exclusion of pregnancy in this area. Correct diagnosis of non-developing pregnancy in the scar is the key to successful organ-sparing surgery.