No 7 (2022)

The paper deals with modern transcriptomics technologies in the study and solution of a significant obstetric problem, such as preeclampsia. Transcriptomics is currently one of the most rapidly developing areas of systems biology, bioinformatics, and medicine, which make it possible to get information about the functional activity of the genome, by analyzing all transcripts synthesized by one cell or a group of cells. The paper presents a literature review of recently published studies of placental transcriptome that is of great importance in expanding knowledge about the normal development and functioning of the placenta allows one to take into account the possible effect of fetal sex on the expression prof ile of a gene and is an indispensable tool for study ing the basic pathophysiological mechanisms of placental disorders. Genome-wide blood transcriptome analysis in pregnant women has shown multiple maternal gene expression pattern changes that are associated with preeclampsia just at the preclinical stage of its development, which will be able to identify the most accurate prognostic markers. The paper also highlights the issues of the intrauterine origin of diseases. It presents studies that have demonstrated the associations between genetic variants, changes in the placental transcriptome, and a risk for postnatal diseases. Conclusion: The paper indicates prospects for the integrated use of “omics” technologies in the study of causal mechanisms for the development of placental syndromes and in the prediction of pregnancy complications and offspring health.

Fetal macrosomia occurs in about 10% of all pregnancies, tends to increase constantly, and is often associated with an increased risk of maternal and perinatal complications. Despite the relatively high incidence of fetal macrosomia, many aspects of management and delivery in this category of pregnant women are controversial. Some authors adhere to expectant tactics, while others prefer active strategies (early pre-induction/induction of labor or planned cesarean section). Questions remain about the impact of early pre-induction/induction of labor on the risk of cesarean section and perinatal morbidity in patients with suspected fetal macrosomia. The lack of generally accepted obstetric tactics has the reason for determining the purpose of our study, namely, to assess the data available in Russian and foreign literature on the methods and terms of delivery of pregnant women with fetal macrosomia, depending on their existing carbohydrate metabolism disorders. The analysis of the data available in the literature and the results of previous studies have shown that there is a need to elaborate Russian clinical guidelines for the management of pregnant women with fetal macrosomia, the introduction of which will be able to facilitate the decision-making process when choosing obstetric tactics, as well as to reduce the rates of cesarean section and maternal and perinatal complications. Conclusion: Future investigations should aim at clarifying the optimal timing of pre-induction/induction of labor and the method of delivery for women without diabetes and fetal macrosomia, taking into account their parity and history. Increasing the accuracy of diagnosing the estimated fetal weight remains one of the priority tasks for an obstetrician/gynecologist, the solution of which will lead to a decrease in the rate of planned caesarean section and to inappropriate labor induction.

The effectiveness of assisted reproductive technologies (ART) depends not only on many gynecological factors, but also on the quality of the future father’s genetic material. One of the ways to increase the effectiveness of ART is to select the highest quality spermatozoa for their subsequent injection into an oocyte. The authors have carried out a systematic analysis of data on sperm selection methods for use in ART programs: selection of spermatozoa using Z potential analysis, Raman spectroscopy in IVF, microfluidic technologies, and other physical methods that are employed to isolate sperm during the intracytoplasmic sperm injection (ICSI) procedure in married couples with male factor infertility. The review includes data from the foreign articles that have been published over the past 10 years and found in PubMed (https://pubmed.ncbi.nlm.nih.gov). The paper describes the impact of various modern sperm selection techniques on the effectiveness of ARTprograms. Density gradient centrifugation that is able to select a fraction of motile and morphologically normal spermatozoa is most frequently applied in clinical practice. However, searching continues for more effective selection methods that exclude rough mechanical impact on male germ cells. Technologies based on different biophysical detection principles, such as magnetic-activated cell sorting (MACS), membrane zeta potential selection, and Raman spectroscopy, are being actively studied. There is also a large microfluidics-based group of fundamentally new methods for selecting male gametes. Conclusion: The above methods are promising and have a potential niche for application in reproductive medicine, but there is, unfortunately, the first evidence of clinical efficacy only for selection using the zeta potential, microfluidic plates, and MACS technology.

Objective: To investigate the clinical efficiency of graduated elastic compression stockings in pregnant women with varicose veins. Materials and methods: Sixty pregnant women were enrolled in the study, thirty of whom used compression stockings and formed a study arm; another 30 patients comprised the control group. The clinical grade of varicose disease was assessed according to the CEAP classification. The severity of varicose disease was assessed using the Venous Clinical Severity Score (VCSS). Quality of life (QOL) was calculated using the Chronic Venous Insufficiency Questionnaire (CIVIQ-20). The diameters of the great and small saphenous veins were measured using Doppler ultrasonography. The tibia circumference was measured by measuring tape in an upright position. Results: At the end of the study there was a significant reduction of VCSS index (p<0,001) in the study group, whereas in the control group varicose disease severity increased (p<0,001). The control group showed negative clinical changes according to CEAP classification: the ratio of patients with varicose disease shifted to the C3 class from 3/30 (10%) to 15/30 (50%). At the final follow-up, the overall QOL score improved in the study group (p=0.099), while the control group showed a statistically significant decrease of QOL according to CIVIQ-20 (p<0.001). The use of compression stockings was associated with a statistically significant reduction in the diameters of the great and small saphenous veins at all measurement points and a bilateral decrease in the circumference of the lower supramalleolar region (p<0,001). Conclusion: Graduated elastic compression is an effective method for the prevention and treatment of varicose vein disease during pregnancy.

Objective: To propose new approaches to the classification of the disease based on the analysis of 2352 operations of patients with endometriosis performed in the department over 10 years. Materials and methods: A total of 12125 operations were performed in the surgical department. Surgeries for endometriosis accounted for 19.4% of them (2352/12 125). In 81.9% of cases, endometriosis was the main indication for surgical treatment. The mean age of the patients was 34.1±6.03 years. There were the following forms of the disease: ovarian endometriosis in 13.9% of cases, superficial endometriosis in 49.4% of cases, deep endometriosis with the lesion of the underlying layers of the peritoneum (muscular, submucosal, subperitoneal) in 58.3% of cases, nodular adenomyosis (the size of adenomyotic nodule exceeding 2 cm) in 3.6% of cases. Results: We proposed a new approach to the classification of endometriosis based on the depth of the lesion and type of surgical technology. The patients with stage 1 (superficial endometrioid heterotopias with a lesion depth not exceeding one layer) amounted to 25.7%; the rate of patients with stage 2 (endometriosis with the lesion of two layers (peritoneum, muscle/abdominal layers of any anatomical structure)) was 43.3%; stage 3 (endometriosis with the lesion of all layers of any anatomical structure, but without organ dysfunction) was noted in 17.2% of cases; stage 4 (endometriosis with the lesion of all layers of any anatomical structure and organ dysfunction) was detected in 7.1% of patients. Different methods of surgical treatment of endometriosis were applied, depending on the depth of the lesion: coagulation was used in 95% of patients with stage 1 lesion, excision was used only in 5% of cases with peritoneal confluent lesion. The main method of surgical treatment of patients with stage 2 was excision (100%) followed by suturing or coagulation. The clinical picture of the disease was determined not by the number of foci but by the depth of the lesion since the neurovascular unit was involved. The main method of removal of foci in patients with stage 3 (endometriosis of all layers of the organ but without impairment of its function) was excision/resection, and the method of restoring the integrity of the organ/tissue was suturing/anastomosis. In case of damage to all layers and organ dysfunction (stricture, angulation, damage to neighboring organs), the extent of surgical treatment was expanded to resection in 95% and removal of the organ in 5% of cases. Conclusion: This classification of endometriosis is relevant as the severity of endometriosis is assessed not due to the extension of the lesion but according to its depth. The use of this classification may help to identify the severity of the course of the disease most accurately and to predict further treatment tactics and rehabilitation which can improve reproductive outcomes and quality of life.

Relevance: Uterine fibroids are common tumors of the female reproductive organs which affect 15-45% of women. Pathogenesis of uterine fibroids is characterized by impaired apoptosis and immune processes due to cytokine disbalance, namely interleukins. Interleukin gene polymorphism can affect their expression and as a result it plays an important role in pathophysiology of uterine fibroids. Objective: To study the correlation between interleukin gene polymorphism and uterine fibroids. Materials and methods: The study included 492patients. The main group consisted of109patients suffering from uterine fibroids. Six polymorphic loci of interleukin genes were selected for the study, namely A/C IL10 rs1800872, C/G IL6 rs1800795, T/C IL5 rs2069812, C/TIL4 rs2243250, T/C IL1β rs16944, C/T IL1α rs1800587. The analysis was performed using polymerase chain reaction (PCR) on a CFX-96 Real-Time System thermal cycler. The odds ratio (OR) and 95% confidence interval (CI) were used to calculate the associations. The association of combinations of the gene alleles and genotypes with the formation of uterine fibroids was evaluated on the basis of the APSampler software (https://sourceforge.net/projects/apsampler /). Results: Molecular genetic markers A/C IL10 rs1800872, T/C IL5 rs2069812, S/T IL4 rs2243250, T/C IL1β rs16944, S/T IL1α rs1800587play a significant role in the development of uterine fibroids. Such genotype as TT rs1800587IL1α (OR=5.70, p=0.017), as well as a combination of polymorphic variants of Trs2243250 IL4, T rs1800587 IL1a and Trs16944 IL1β (OR=2.60, pperm =0.012), T rs1800587 IL1a, C rs2069812 IL5 and T rs16944 IL1β (OR=2.60, p =0.012), T rs1800587 lL1a, C rs2069812 IL5 and T rs16944 IL1β (OR=2.71, pperm =0.009), T rs1800587 IL1a, C rs1800872 IL10 and T rs16944 IL1β (OR=2.73, pperm=0.003) should be considered risk factors for the development of uterine fibroids. Conclusion: Polymorphic gene loci A/C IL10 rs1800872, T/C IL5 rs2069812, S/T IL4rs 2243250, T/C IL1β rs16944, S/TIL1α rs1800587are associated with the development of uterine fibroids. We identified combinations of allelic variants of polymorphic loci of interleukin genes associated with an increased risk of uterine fibroids. These combinations indicate the importance of inter-locus interactions of candidate genes in the development of this pathology. In practical medicine they can be used to identify risk groups and to carry out preventive measures.

Background: Nausea and vomiting of pregnancy are the most common symptoms of progressive gestation and occur in 70-80% of pregnant women. Nausea and vomiting of pregnancy are associated with certain adverse outcomes for the mother, fetus, and offspring, whereas their level has a significant negative impact on different aspects of women's quality of life, including working capacity, family relationships, - the ability to lead a usual social life and the willingness to become pregnant again. Objective: To study the efficacy of ginger extract in nausea and vomiting of pregnancy. Materials and methods: The observational study included 94 women at 6 to 16 weeks’ gestation with mild to moderate nausea and/or vomiting of pregnancy. The patients’ quality of life and health were assessed in a questionnaire before, during, and after the end of a treatment cycle, by determining the socioeconomic status, habits, and lifestyle from the Sickness Impact Prof ile questionnaire and the severity of nausea and vomiting of pregnancy from the Pregnancy-Unique Quantification of Emesis and Nausea. The efficacy of the Preginor complex for nausea and vomiting of pregnancy was evaluated at the end of the cycle of its administration and compared with the baseline values. Results: By the end of therapy with the complex, 37.2% of patients did not complain of nausea and vomiting and they did not require further administration of Preginor. Nausea and vomiting were assigned as mild in 55.3% of pregnant women. Only 7.5% of the women who participated in the study did not report any considerable positive changes in their health when taking the complex; they continued to have moderate nausea and vomiting with a lower symptom intensity, which improved the pregnant women’s general condition and quality of life. However, the number of these patients declined 4-fold. There was a 2.2-fold decrease in the mean total index of nausea and vomiting after a treatment cycle. Conclusion: The intake of the non-pharmacological complex Preginor substantially relieves the symptoms of nausea and vomiting and improves their quality of life. In our opinion, the use of Preginor as a dietary supplement is promising and causes its wider clinical introduction.

Objective: To clarify the frequency and pattern of intrauterine pathology in a non-selective cohort of patients participating in assisted reproductive technologies (ART) programs. Materials and methods: The frequency of intrauterine pathology was explored in 973patients aged 23 to 44 years who had participated in ART programs. The diagnosis was finally verified with office or routine hysteroscopy and histomorphological examination. The incidence of endometrial hyperplastic processes (EHPs) in assessing its relationship to the use of previous treatment with ART was determined separately in groups of patients younger and older than 35 years. Results: Intrauterine pathology was found in 38% of all the patients involved in ART programs. In patients with initially suspected uterine factor infertility, its frequency increased up to 68%. The pattern of verified intrauterine pathology predominated with EHPs, accounting for 44%. Conclusion: In the non-selective population of patients participating in ART programs, the women with intrauterine pathology showed a preponderance of EHPs in its pattern, which manifested themselves as glandular hyperplasia and endometrial polyps.

Background: High-sensitivity noninvasive prenatal DNA screening (NIPS) for aneuploidies can detect the risk of fetal aneuploidies in chromosomes 13, 18, and 21, as well as in sex chromosomes from a pregnant woman’s plasma. Genome-wide NIPS makes it possible to study not only individual chromosomes, but also a complete human chromosome set and to identify both pathology in the fetus itself and mosaic aneuploidies in placental tissues. Case report: The paper describes a clinical case of a 42-year-old patient with confined placental mosaicism who has a high risk for trisomy 16, as evidenced by NIPS. A cytogenetic study after a chorionic biopsy showed the presence of a marker chromosome. A fetal amniotic fluid examination showed a normal female karyotype. A girl weighing 2340g with a normal female karyotype was born at 40 weeks 2 days of gestation. Postpartum placental examination using the FISH method revealed trisomy 16 in 100% of the examined cells. Conclusion: This case illustrates that NIPS can detect not only the presence of fetal aneuploidies, but also mosaic placental aneuploidies. In this connection, the management strategy for pregnancy should be determined using results of an additional examination. To avoid false positive results, one should perform confirmatory diagnosis after NIPS, by applying amniocentesis rather than chorionic biopsy.

Background: Abdominal pregnancy is a rare type of ectopic pregnancy with poor maternal and fetal outcomes. A unified strategy to manage patients with abdominal pregnancy has not presently been developed in relation to the timing and methods of delivery. Case report: The paper describes a clinical case of term abdominal pregnancy with a favorable outcome for the mother and fetus. It depicts the features of delivery and postoperative patient management strategy. The applied integrated approach has allowed not only delivery without risks to the mother and fetus, but also led to the elaboration of a new approach to postoperative management. Conclusion: This clinical case demonstrates the need for an individual approach to choosing the terms and methods of delivery on the basis of the data of instrumental studies. This approach contributes to the choice of the optimal strategy of pregnancy management, delivery, and newborn care.