Introduction. Approaches to treatment of infertility have been progressively updated because the field of assisted reproductive technologies (ART) is a science-based symbiosis of the latest knowledge and advances in medicine, biology, and genetics. Today, a real-world clinical practice of a reproductive specialist needs to be assessed in the Russian Federation (RF) both in terms of a retrospectively analyzed development of RF in vitro fertilization (IVF) technologies and identifying promising approaches for infertility treatment in the future.

Aim: analysis of current therapeutic tendencies and promising trends in real clinical practice of infertility in the Russian Federation.

Materials and Methods. In 2022–2023 under the auspices of the Institute for Preventive and Social Medicine and the National Alliance for Public Health Advancement, a survey of reproductive doctors practicing at commercial and government ART centers was carried out. The questionnaire contained questions regarding describing a RF female patient’s portrait with an expected ovarian reserve and response to ovarian stimulation to propose a choice of ovarian stimulation protocol as well as basic and concomitant pharmacotherapy.

Results. The opinion of 425 fertility doctors from 156 ART centers in 42 cities of the Russian Federation was assessed. A portrait of a female patient with infertility in the Russian Federation was determined in accordance with the ovarian reserve, expected response to gonadotropin-based stimulation (normal response – 40 %, hyporesponse – 40 %, hyperresponse – 20 % of patients). The basic pharmacotherapy in the stimulation protocol in the IVF program based on agonists and antagonists of gonadotropinreleasing hormone (GnRH), various gonadotropin-containing drugs in female patients with expected normal, hypo- and hyperresponse to ovarian stimulation was assessed. The dominant protocol consists of using GnRH antagonist most often observed in patients with hyper- (95 % of cases), normal (75 % of cases) and hypo-response (45.5 %). Preferences in the basic and concomitant pharmacotherapy in IVF programs were identified as well as current trends in embryo transfer in fresh and cryoprotocols (a tendency to freeze all obtained embryos - “freeze-all” strategy), preimplantation genetic testing methods (used in 30 % of protocols in normal responders, 60 % in hyporesponders and 10 % in hyperresponders) were described.

Conclusion. Our study provides the most large-scale analysis of the real-world clinical practice of RF reproductive specialists. A portrait of a RF female patient with infertility, expected ovarian reserve and response to ovarian stimulation was described. Contemporary approaches to select stimulation protocol, basic and concomitant pharmacotherapy in real-world clinical practice were identified. The data obtained represent an important significant cross-section for current practical approaches in real-world practice of RF fertility doctors and can serve as the basis for assessing developing ART methods in the Russian Federation as well as be used to create an evidence base for analyzing future clinical and economic effectiveness of IVF programs in the Russian Federation.

Introduction. The rate of infertile couples comprises 17–24 % and tends to increase, with more of them turning to assisted reproductive technologies (ART). In case a required result is achieved, future parents-to-be prepare for birth of a healthy child in the family, but each couple may face a birth of offspring with severe genetic disorders including spinal muscular atrophy (SMA).

Aim: to access a carriage rate for SMN1 gene exon 7 deletion associated with SMA and SMN2 gene copy number in married couples planning childbirth using in vitro fertilization (IVF).

Materials and Methods. There were enrolled 170 couples (340 subjects) suffering from infertility and referred for IVF in the Sverdlovsk region (SR) of Russia. The search for deletions/duplications in the SMN1 and SMN2 genes was carried out by quantitatively analyzing number of gene copies using the SALSA MLPA Probemix P460 commercial kit (MRC-Holland, the Netherlands). The Hardy–Weinberg ratio was used to calculate estimated rate of homozygous carriers with SMN1 deletions in the next generation.

Results. Among 340 patients, a deletion of exon 7 in the SMN1 gene (one copy out of two) was found in 9 individuals (3 males and 6 females) unrelated to marital relations. Thus, only 9 out of 340 examined subjects carry such gene mutation associated with SMA, with total rate of carriage comprised 2.65 % (1/38). Given the number of IVF procedures performed in SR, it may be assumed that the probability for birth of a sick child in such couple comprises at least 1:6410. A number of patients had SMN1 gene duplications – 9 (5.29 %) males and 4 (2.35 %) females baring 3 copies of the SMN1 gene. In addition, the majority of study participants (54 %) turned out to have 3 copies of the SMN2 gene.

Conclusion. The rate of SMA carriage in married couples planning a pregnancy with aid of ART corresponds to the general population reaching 1:38 level. It is believed necessary that all couples entering the IVF program should be examined for carriage of SMN1 gene mutations to assess SMA risk in offspring.

Aim: to study the contribution of maternal blood endothelial proteins to developing relapse of early preeclampsia (ePE).

Materials and Methods. A proteomic analysis of the peripheral blood of 137 pregnant women was performed. Clinically, three groups were identified at the end of pregnancy: control (n = 40), patients with favorable course of the current and previous pregnancy; comparison group (n = 59) – patients with a history of еPE episode, but favorable course of ongoing pregnancy, and main group (n = 38) – patients with еPE relapse. Biologically active substances evidencing about impaired endothelial function were subject to dynamic monitoring (11–13, 19–21 and 27–28 weeks): activity of endothelin-1 (ET-1) and metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), von Willebrand factor (vWF) level and homocysteine (HC) concentration. The ADAMTS-13/vWF ratio was evaluated separately.

Results. For patients with recurrent еPE, a significant increase in ET-1 is characteristic at all stages of gestation: 0.92; 1.07 and 1.36 pmol/ml vs. 0.29; 0.33 and 0.29 pmol/ml in the control group (p < 0.0001 at all points). Regardless of pregnancy outcome, increasing gestational age was paralleled with elevating vWF level, however, upon еPE relapse, this parameter (Me = 343 IU) is significantly higher (p < 0.0001) than in control group (Me = 260 IU). In all groups, there was a significant decrease in ADAMTS-13 activity, whereas in main group ADAMTS-13 activity at first time point was minimal – 63.4 % (p = 0.0007 relative to control group). With regard to ADAMTS-13/vWF axis in relapsed еPE, significant differences were found compared with control group both at 11–13 weeks (0.32 vs. 0.52; p < 0.0001) and at 27–28 weeks (0.15 vs. 0.22; p < 0.0001) pregnancy. The HC concentration declines with gestational age, but at first time point patients from main group had it (Me = 8.0 µmol/L) at significantly higher level than in control group (Me = 5.9 µmol/L; p < 0.00010).

Conclusion. At gestational age of 11–13 weeks, all analyzed biomarkers contribute to developing еPE relapse accounting for an overall impact of 62.3 % of developing ePE risk. During pregnancy at 19–21 weeks, an imbalance in the ADAMTS-13/vWF along with elevated ET-1 level determine the risk of disease relapse in 65.6 % of cases. It was found that at a gestational age of 27–28 weeks, the associated shift in ET-1, vWF and ADAMTS-13 magnitude accounts for 67.9 % of risk for disease relapse.

Aim: to identify specific associations between genes polymorphism associated with sex hormone-binding globulin (SHBG) level and breast cancer (BC) of various molecular biological subtypes.

Materials and Methods. The retrospective comparative study was conducted using specimens collected from 261 patients with BC of two molecular biological subtypes – luminal A/B (n = 153) and triple negative (n = 108) as well as 1140 women in control group. All study participants (n = 1401) underwent a molecular genetic study of four single nucleotide polymorphism (SNP) loci, which showed a relationship with circulating SHBG level in previously conducted genome-wide association study (GWAS): rs12150660 SHBG, rs10454142 PPP1R21, rs780093 GCKR, rs17496332 PRMT6.

Results. The analysis revealed an association between SHBG SNP candidate genes and a BC risk in patients with luminal A/B subtypes and lacked significant associations between the loci assessed and triple negative BC subtype. CC female genotype of rs10454142 PPP1R21 increased a risk of luminal A/B subtypes BC by more than 2-fold (recessive model [CC vs. TC+TT]; odds ratio = 2.07; 95 % confidence interval = 1.14–3.77; p = 0.017; pperm = 0.018). This SNP is localized in functionally "significant" regions of the genome (enhancers/active enhancers, promoters/active promoters) and affects methylation level in several hepatocyte DNA sites [cg15846641 (chr2:48541264)].

Conclusion. The genetic variant rs10454142 PPP1R21 is associated with the risk of developing ВС luminal A/B subtypes, but not with ВС triple negative subtype.

Introduction. During pregnancy, a woman becomes vulnerable to develop symptoms of depression and anxiety, which in turn are associated with increased risk of perinatal complications, postpartum depression as well as behavioral problems in children.

Aim: to assess the prevalence of symptoms related to depression and anxiety in pregnant women with threatened abortion (ТА), non-developing pregnancy (NP) as well as those with physiological course of pregnancy (РР) in the first trimester of pregnancy; to reveal major predictors of psycho-emotional disorders in pregnant women.

Materials and Methods. Three groups of pregnant women were stratified: 62 patients with TA, 60 patients with NP and 57 women with PP. Clinical history and physical examination were performed in all subjects. All pregnant women were assessed by Hamilton Anxiety Rating Scale and the Beck Depression Inventory.

Results. It was found that the mean Beck’s score was significantly higher in NP vs. TA and PP groups (p < 0.05). Moreover, significant differences were also observed while comparing TA and PP groups (p = 0.037). Clinically important depression was found in 3.3 % NP women and in 1.6 % TA women. Preclinical depression was found in 13 % and 6.5 % women with NP and TA, respectively. The mean Hamilton scale score was significantly higher in NP vs. PP group (p < 0.05), but was comparable with that in TA group (p > 0.05). The mean score on the anxiety scale was significantly higher in TA vs. PP group (p = 0.001). Clinically significant mild to moderate anxiety was found in 4.9 % and 1.6 % TA and NP women, respectively. Mild anxiety symptoms were noted in 35.5 % of women with TA, 38.3 % of women with NP, and 15.7 % of women with PP. Multiple linear regression analysis revealed that a burdened obstetric history and the duration of the patient hospital stay had the strongest association with symptoms of depression and anxiety.

Conclusion. Symptoms of prenatal anxiety and depression are widespread and should be identified in a timely manner. Psychological counseling and testing of pregnant women should be included into recommendations for pregnancy management.

The formation of neutrophil extracellular traps (NETs), described first in 2004 as a previously unknown neutrophil strategy for combating microbes, has been attracting a growing interest in research community. NETs play a key role in inflammation and infection exploiting effector functions such as degranulation, phagocytosis as well as production of reactive oxygen species (ROS). NETs play a crucial role in defense against systemic infections. Additionally NETs involved in inflammation, and in the pathogenesis of non-infectious diseases, such as autoimmune diseases and cancer.

Aim: to summarize new data regarding the effectiveness of nutritional support during pregnancy.

Materials and Methods. A search for publications was carried out in the PubMed/MEDLINE, Scopus, Web of Science, RSCI databases by retrieving queries for the following keywords: nutritional support, pregnancy, micronutrients, vitamins, macronutrients, without language restrictions. 71 sources with full text access were selected for analysis.

Results. Nutritional status during pregnancy markedly impacts on mother's and neonate’s health. During pregnancy, requirements for macro- and micronutrients increase to maintain maternal homeostasis and support fetal growth. Increasing calorie intake in general female population demonstrates modest effects on pregnancy and fetal outcomes, whereas for pregnant women in poor income countries it results in no long-term benefits for children by assessing their anthropometric parameters and neurocognitive development. Despite the lack of conclusive evidence, in many countries sensible calorie restriction during pregnancy is recommended. Some micronutrients are vital for mother and fetus, because their deficiency is accompanied by increased risk of adverse pregnancy outcomes. For instance, folic acid deficiency is associated with the risk of developing fetal neural tube defects, iodine deficiency is coupled to the risk of emerging pediatric intellectual development disorders associated with congenital hypothyroidism, and calcium deficiency is related to a high risk of maternal hypertensive disorders. Therefore, micronutrient supplementation represents a technology with good potential in fighting for maternal and child health. Nonetheless, despite some advances in understanding nutritional support in pregnant women, many studies provide controversial data substantiating a need to conduct further investigations.

Conclusion. Overall, recent year research confirms that the supplementation of micro- and macronutrients during pregnancy is an effective tool for “fetal programming” allowing to impact on maternal and fetal health. At the same time, an analysis of the literature showed a significant lack of research in the field of creating individual nutrition programs and nutritional support for pregnant women belonging to different segments of the population, living in different geographical regions, etc.

Pelvic organ prolapse (POP) is a fairly common gynecological problem. The relevance for studying this disease is accounted for by a substantial impact it has on patients' quality of life. A part from physical discomfort, a woman suffering from POP experiences profound emotional depression, a sense of shame, which may result in refusing professional medical care. In the treatment of POP, it is necessary to take into account the features of morphological disorders as well as associated changes in vaginal microbiota. Here, we analyze current insights into POP causes and risk factors. The main advantages and drawbacks for diagnostic methods used have been identified, and promising options for POP predictive assessment are described. The effectiveness of the most common methods for conservative treatment is evaluated. In addition, we also describe the types of contemporary surgical correction as well as new modifications of operations to remove POP.

In recent years, the number of risk factors for thrombosis associated with pregnancy has increased substantially due to the active introduction of new medical technologies not used 30 years ago or because their role in emerging thrombosis has not been studied, e.g., during pregnancy after assisted reproductive technologies (ART) particularly in vitro fertilization (IVF). The risk of venous thromboembolic complications (VTEС) related to ovarian hyperstimulation during ART is often overlooked. We present the case of a 37-year-old woman who developed thrombosis of the right internal jugular vein 3 weeks after embryo transfer within the IVF protocol. Ovarian hyperstimulation during hormonal IVF protocols provokes procoagulant changes in the hemostasis and fibrinolysis system able to result in venous and arterial thrombosis. The localization of VTEС typical to ART is more often located in the internal jugular vein being accompanied by neck pain and edema. Thrombosis risk factors should be assessed in all women in the IVF program, and appropriate thromboprophylaxis should be carried out to all high risk subjects.

An obstetrician-gynecologist faces in clinical practice cases requiring to weigh up not only benefits of administering preventive agents for venous thromboembolic complications (VTEC) but also risks related to concomitant coagulopathy. Here, we discuss issues related to using low molecular weight heparins (LMWHs) in pregnancy particularly nadroparin calcium for patients at high risk of VTEC and immune thrombocytopenia as a factor of coagulopathic bleedings.published VTEC prevention data in pregnancy and postpartum are presented. Moreover, literature review about VTEC prevention effect on pregnancy course and delivery in women with immune thrombocytopenia are discussed. A clinical case of a patient with immune thrombocytopenia and high thrombosis risk during pregnancy along with administered calcium nadroparin is described.