Igor Yu. Kogan’s research while affiliated with Research Institute of Obstetrics and Gynecology named after D.O. Ott and other places

Background Diastrophic dysplasia is a rare autosomal recessive disorder characterized by abnormalities in bone and cartilage development, caused by pathogenic variants in the SLC26A2 gene. Case presentation This article presents a clinical case of preimplantation genetic testing for monogenic disorders (PGT-M) conducted for a family with two previous pregnancy losses due to diastrophic dysplasia in the fetus. We report a previously uncharacterized variant c.1358C > T in the SLC26A2 gene associated with diastrophic dysplasia. We detail the approach to performing PGT-M in the absence of material from the proband and close relatives from one partner for analysis. A testing system was developed to analyze pathogenic variants in the SLC26A2 gene, alongside with indirect markers such as short tandem repeats and single nucleotide polymorphisms. This allowed us to identify linkage groups associated with the analyzed pathogenic variants during the in vitro fertilization cycle with PGT-M, enabling the selection of an embryo that did not inherit pathogenic variants from either parent. The transfer of this embryo resulted in a successful pregnancy, resulting in the birth of a healthy child. Conclusion To our knowledge, this is a first report of variant c.1358C > T in the SLC26A2 gene associated with diastrophic dysplasia. The successful application of PGT-M enabled the selection of an embryo free from inherited pathogenic variants from both parents, highlighting the importance of PGT-M in improving reproductive outcomes for affected families.

Background: Vaginal microbiota is a factor that determines a woman’s health. Infectious complications of pregnant women, women in labor and newborns are often associated with a significant change in its composition. Analysis of the species diversity of vaginal microbiota during pregnancy and the postpartum period primarily contributes to the study of physiological processes and the concept of a “healthy” vaginal environment during these significant periods of a woman’s life. Aim: The aim of this study was to evaluate the dynamic change in the species composition of vaginal microorganisms before delivery and at different times of the postpartum period in women with natural labor. Materials and methods: This study involved 24 pregnant women who delivered vaginally. Each patient was examined at three time points: 37–40 weeks of pregnancy (visit 1), 4–5 days of the postpartum period (visit 2), and 6–8 weeks after delivery (visit 3). The species composition of the vaginal microbiota was studied using a comprehensive test based on real-time quantitative polymerase chain reaction. Results: We found a decrease in the total bacterial mass in the vaginal biotope of women in labor after 4–5 days of the postpartum period and 6–8 weeks after delivery in comparison with the examination before delivery (p 0.0005). Similar changes were noted in the composition of the lactobacillary microbiota: the concentration of lactobacilli decreased in the postpartum period in comparison with that before delivery (p 0.05). Compared to the examination before delivery, 6–8 weeks after delivery in women, we observed a decrease in the frequency of Lactobacillus crispatus dominance (p 0.05), while the frequency of Lactobacillus iners dominance in the postpartum period increased (p 0.05). Among the representatives of the opportunistic vaginal microflora, the most frequently prevalent species were Gardnerella vaginalis, Prevotella bivia, Porphyromonas spp., Fannyhessea vaginae, Staphylococcus spp., Streptococcus spp., and Ureaplasma spp. In all women with severe vaginal microbiota disruption before delivery, an ascending bacterial infection was established according to the histological examination of the placenta after delivery (p 0.05). Conclusions: In most cases, the observed changes in the qualitative and quantitative composition of the vaginal microbiota in pregnant women and women in labor are physiological. At the same time, a consistent study of the vaginal microbiota during pregnancy and at different times of the postpartum period will allow for identifying possible risk factors for the development of infectious diseases in the mother and newborn and expand the possibilities for timely diagnosis and treatment of the identified disorders.

Background: Chronic hyperglycemia and abnormal glucose variability are established risk factors for perinatal complications. Abnormal fetal growth and diabetic fetopathy can be associated not only with carbohydrate metabolism disorders, but also with impaired production of cytokines, chemokines, and growth factors that regulate intercellular interactions. Aim: The aim of this study was to evaluate cytokine and growth factor levels in the blood serum of pregnant women with type 1 diabetes mellitus and in umbilical cord blood of their neonates, as well as assessing the associations of these levels with the development of fetal macrosomia and diabetic fetopathy. Materials and methods: This prospective study included 88 women with a singleton pregnancy and cesarean delivery. All the patients provided informed consent for participation. The study groups comprised individuals with type 1 diabetes mellitus (n = 32) and non-impaired glucose tolerance (n = 56). The levels of interferons alfa 2 and gamma, monokine induced by interferon-gamma, interleukin-1α, -1β, -2, -3, -4, -5, -6, -7, -8, -9, -10, -13, -15, -16, -17, -18, interleukin-1 receptor antagonist, interleukin-2 receptor alpha subunits, p40 and p70 subunits of interleukin-12, monocyte chemotactic protein-1, -3, macrophage inflammatory protein-1α, -1β, leukemia inhibitory factor, macrophage ingibitory factor, nerve growth factor beta, stem cell factor, cutaneous T-cell-attracting chemokine, growth-regulated oncogene alpha, hepatocyte growth factor, stem cell growth factor beta, stromal cell-derived factor-1 alfa, interferon gamma inducible protein 10, platelet-derived growth factor-bb, vascular endothelial growth factor, basic fibroblast growth factor, eotaxin, chemokine ligand 5, and macrophage, granulocyte, and granulocyte/macrophage colony-stimulating factors, tumor necrosis factor alfa and beta, and tumor necrosis factor-related apoptosis-inducing ligand were measured with multiplex immunoassay in the blood serum of women at 36–40 weeks of gestation and in the umbilical cord blood serum of their neonates. Results: Cytokine levels varied widely in the both study groups. Women with type 1 diabetes mellitus had higher levels of interleukin-1β, -6, -17, basic fibroblast growth factor, macrophage inflammatory protein-1α, -1β, and lower levels of interleukin-1ra compared to the control group. Their neonates had higher levels of interleukin-6, -8, granulocyte colony-stimulating factor, macrophage inflammatory protein-1α, -1β. Higher levels of interleukin-1β, -6, -17, and basic fibroblast growth factor in the blood serum of the women were associated with time in range less than 70% and the development of diabetic fetopathy. Time in range was inversely associated with the interferon gamma / interleukin-5 (ρ = −0.531; p = 0.013), interferon gamma / interleukin-10 (ρ = −0.441; p = 0.045), interleukin-2 / -10 (ρ = −0.473; p = 0.030), interleukin-1β / -10 (ρ = −0.561; p = 0.008), interleukin-1β / -1ra (ρ = −0.635; p = 0.002), and interleukin-6 / -10 (ρ = −0.540; p = 0.012) ratios. Conclusions: Cytokine profile alterations were the most pronounced in pregnant women with non-target time in range values and in those with diabetic fetopathy development. Serum cytokine levels correlate with glycemic profile parameters but are considered non-specific markers of pregnancy complications.

Background: The role of the microbial factor in the genesis of early miscarriages (up to 10 weeks of pregnancy) has not been established. However, disruption of the vaginal microbiota may be associated with the occurrence of late miscarriage. Aim: The aim of this study was to evaluate the frequency of early and late miscarriages and to determine the prognostic significance of the microbial factor in early pregnancy registration. Materials and methods: This study involved 113 pregnant women registered before 10 weeks of gestation, who were divided into two study groups. Group I consisted of 22 women whose pregnancy ended in miscarriage before 22 weeks (subgroup IA of 19 patients with early miscarriage and subgroup IB of three patients with late miscarriage). Group II comprised 91 women whose pregnancy ended in term delivery. Vaginal microflora was investigated using microscopic and molecular biological methods. Results: The frequency of miscarriages among the examined women was 20.4%. The proportion of early miscarriages was 86.4% and late miscarriages 13.6%. In Group I, the number of births in the anamnesis was higher than in Group II. The average rate of births per woman was 2.0 in Group I and 0.9 in Group II (p = 0.037); the number of previous pregnancy loss per woman was 1.2 in Group I and 0.5 in Group II (p = 0.019). Lactobacilli were detected in the vaginal biotope of all pregnant women. Lactobacillus iners and Lactobacillus crispatus were the most frequently occurring species. In subgroup IA and Group II, opportunistic pathogenic microorganisms were detected with equal frequency at first pregnancy examination and did not alter the existing vaginal microbiocenosis. In subgroup IB, Gardnerella vaginalis, Atopobium vaginae, Enterobacteriaceae, Staphylococcus spp., Streptococcus spp., Mycoplasma hominis or Ureaplasma spp. were detected simultaneously in early pregnancy, with Lactobacillus cristatus predominating. Conclusions: The proportion of early miscarriages was six times higher than that of late miscarriages. We have not found an association between the quantitative and qualitative compositions of vaginal microorganisms in the first trimester of pregnancy and early miscarriages. The microbial factor was established to be important in late miscarriages. Further studies are needed to assess the prognosis of late miscarriages at the time of pregnancy registration.

Background: Uterine fibroids are a common benign tumor that negatively affects reproductive function. The criteria for tumor evolution have not yet been determined. It is assumed that tumor growth and the number of growth points are associated with the transformation of blood circulation in the uterus and myomatous node. Recently, data have appeared on the prospects for three-dimensional ultrasound to be used with a specialized program that allows for describing the characteristics of blood supply throughout the entire tumor volume at the level of the microvasculature, which has low speed parameters, namely Virtual Organ Computer-aided Analysis (VOCAL). Aim: The aim of this study was to assess the characteristics of the blood supply to intramural and intramural-subserous myomatous nodes of various sizes using ultrasound and power Doppler in three-dimensional mode using specialized VOCAL software. Materials and methods: This study included 40 patients with uterine fibroids with a single myomatous node of intramural-subserous or intramural localization (International Federation of Gynecology and Obstetrics types 4–6). Four study groups were formed. Group I consisted of ten patients with uterine fibroids with a node diameter of up to 4.0 cm inclusive. Group II comprised ten patients with a node diameter from 4.0 to 5.0 cm inclusive. Group III included ten patients with a node diameter from 5.0 to 8.0 cm inclusive. And Group IV included ten patients with a node diameter of more than 8.0 cm. Ultrasound examination was carried out using a W10-RUS ultrasound scanner (Samsung Medison Co., Ltd., South Korea) on days 5–7 of the menstrual cycle. Results: We found that the most vascularized were myomatous nodes with a diameter of up to 4.0 cm. With an increase in the diameter of myomatous nodes, vascular resistance increased, which in turn indicates a decrease in vascularization. In addition, a decrease in resistance in the central vessels of the tumor compared to its peripheral vessels indicates the characteristic development of the vascular network of the myoma. This is characterized by the formation of new blood vessels mainly from the periphery of the tumor, which form a highly vascularized vascular capsule, while the center of the myomatous node is a hypovascular core. Conclusions: Evaluation of uterine vascularization and uterine fibroids using the specialized VOCAL program allows us to describe the features of blood supply and re-evaluate the mechanisms of tumor development. The use of power Doppler in 3D mode with the use of the specialized VOCAL program makes it possible to further study the vascularization of tumor tissue and establish “hemodynamic variants” of the intramural form of uterine myoma to search for the relationship between tumor growth and the transformation of the associated myometrium.

Purpose We aimed to determine fetal liver perfusion in PGDM and GDM pregnancies and to assess the relation of ductus venosus (DV) shunt fraction with adverse pregnancy outcomes. Methods We conducted a prospective longitudinal observational study including 188 pregnant women: group I—patients with pregestational DM (PGDM, n = 86), group II—patients with gestational DM (GDM, n = 44), group III—control (n = 58). The patients included in the study underwent ultrasound examination at 30⁺⁰–40⁺⁰ weeks of pregnancy. We evaluated volumetric blood flow adjusted to EFW (Q, ml/min/kg) for umbilical vein, DV, left and main portal vein. The relative risk was calculated for adverse pregnancy outcomes. Results In PGDM pregnancies, umbilical blood flow was redistributed to the fetal liver, increasing left portal and total liver volumetric blood flow (p < 0.001) compared with GDM and control groups. Pathological reduction in the DV shunt fraction (≤ 16.5%) was associated with an increased relative risk of preterm delivery (3.61 [95%CI 1.68; 7.71]), LGA-birth (1.64 [95% CI 1.26; 2.12]), neonatal adiposity (1.53 [95%CI 1.18; 1.98]), fetal hypoxia (3.47 [95%CI 1.34; 9.05]), emergency cesarean Sect. (1.93 [95%CI 1.26; 2.97]), and neonatal intensive care unit stay of more than 5 days (1.78 [95%CI 1.08; 2.93]). Conclusion Decreased DV shunt fraction reflects changes in fetal hemodynamics in PGDM-pregnancies and associated with an increased risk of adverse perinatal outcomes.

This article examines the endothelial protective role of the vascular glycocalyx. Macromolecules protruding above the surface of endothelial cells, consisting of proteoglycans, glycoproteins and especially glycosaminoglycans, due to their negative charge prevent the contact of protein molecules, platelets, white blood cells and adhesion molecules with the endothelium. It is the destruction of the glycocalyx that leads to the development of vascular complications and underlies many diseases. The pathogenesis of pre-eclampsia is also directly related to thinning and destruction of the glycocalyx. The glycocalyx is a target for the prevention of vascular pathology. The complex medication glycosaminoglycan sulodexide is considered by many researchers as an effective agent for the protection or restoration of the glycocalyx. There are several studies showing the efficacy of sulodexide for the prevention of obstetric complications in high-risk pregnant women. This article presents a clinical case of an effective use of sulodexide in the preconception period and in the second and third trimesters of pregnancy in a patient with a history of recurrent severe early pre-eclampsia. Key words: glycocalyx, glycosaminoglycans, sulodexide, pre-eclampsia

Aim: to study the prevalence of lysosomal acid lipase deficiency (Wolman disease and cholesteryl ester storage disease) among high-risk patients using selective biochemical screening. Material and methods. Samples from 2805 patients are collected as dried blood spots on filter paper test forms. Biochemical study of the lysosomal acid lipase (LAL) enzyme activity was carried out according to Hamilton’s protocol of, using 4-methylumbelliferyl palmitate as a substrate and LAL inhibitor Lalistat-2. Changes in fluorescence in the wells were recorded on Wallac 1420 Multilabel Counter analyzer at absorption wavelength of 355 nm and emission wavelength of 460 nm. Sequencing of the LIPA gene (NM_001127605) was carried out on an Illumina MiSeq device (Illumina, USA) from dried blood spots from patients with reduced LAL enzyme activity to define genetic variations. Results. As a result of biochemical screening for LAL deficiency among patients from high-risk groups, 20 patients with reduced values of LAL enzyme activity were found. For 17 patients, search for mutations in the LIPA gene was carried out using NGS. In 9 patients, pathogenic genetic variants were found that led to decrease in LAL activity and the manifestation of clinical symptoms. In 100 % of detected cases, genetic mutations in the LIPA gene included single nucleotide substitution c.894G>A. Along with this mutation, two previously undescribed mutations (c.35dup and c.176A>G) were discovered in a compound heterozygous state. Conclusions. The variety of clinical symptoms and wide range of ages at which symptoms may begin (in the case of cholesteryl ester storage disease) can lead to errors in diagnosis. The c.894G>A variant is the most common variant worldwide among patients with a confirmed diagnosis of LAL deficiency and was present in all confirmed cases in this study, suggesting that this variant is the predominant mutation in the LIPA gene in Russian population. Pathogenicity status of previously undescribed discovered mutations (c.35dup and c.176A>G) needs to be determined.

The article analyzes the major obstacles impeding the development of biobanks in the Russian Federation, outlining future trends in this field. Biobanks form a key component of research infrastructure, serving as repositories for unique biological samples for use by researchers and physicians when investigating disease pathogenesis and developing personalized treatment decisions. The biobanking industry in Russia faces significant challenges, including low awareness among the general population and the professional community directly involved in the interaction with biobanks and donors. In addition, the lack of a coherent legal and regulatory framework, as well as social support measures, creates uncertainty regarding protection of the rights of potential donors and hinders the work of scientific organizations. The results obtained highlight the need for a comprehensive strategy to advance biobanking in Russia. This strategy should encompass the formulation of a legal and regulatory framework to foster public support for this initiative and facilitate a dialogue between the academic community, governmental agencies, and the larger public.

Intrauterine growth restriction (IUGR) is one of the most common pregnancy complications and a leading cause of iatrogenic preterm birth. AIM: To examine the potential causes of fetal growth restriction and available treatment options, based on a comprehensive literature review from the past decade utilizing search databases such as PubMed and Elibrary. The most common etiology of intrauterine growth restriction is abnormal placentation, frequently associated with impaired placental blood flow. Fetuses with growth restriction and significant abnormalities in umbilical artery blood flow are at increased risk of adverse outcomes, including intrauterine fetal demise, neonatal death, and neonatal morbidity such as hypoglycemia, hyperbilirubinemia, hypothermia, intraventricular hemorrhage, necrotizing enterocolitis, and seizure syndrome. Additionally, epidemiological studies indicate that fetuses with IUGR are predisposed to cognitive delays during childhood and conditions such as obesity, type 2 diabetes, and ischemic heart disease in adulthood. Various pharmacological interventions are being explored as potential adjuncts to improve fetal outcomes.