Obstetrics, Gynecology and Reproduction

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Vol 15, No 3 (2021)


225-227 466

We have accumulated my own experience of management pregnant women with COVID-19 after assisted reproductive technologies (ART) receiving low molecular weight heparins (LMWH). All women suffered COVID-19 in mild form without respiratory failure and gave birth to healthy children. Our observations correspond to the data of world literature. Therefore, we want to draw the attention of the editors and the readers to the positive role of LMWH in the control of COVID-19.


228-235 333

Aim: to assess a rate and range of genetic and acquired thrombophilia in onco-gynecologic patients with ovarian cancer, uterine corpus cancer and cervical cancer.

Materials and Мethods. A prospective controlled cohort non-randomized interventional study was conducted: within the years 2014 to 2020, there were examined 546 women with genital malignancies, divided into 2 groups: group I – 155 cancer patients with former thrombosis, group II – 391 women with female genital cancer without former thrombotic complications. Control group consisted of 137 patients with benign female genital tumors. The spectrum of circulating APA was studied: antibodies to â2-glycoprotein I (â2-GPI), annexin V and prothrombin as well as genetic thrombophilia due to mutations genes encoding factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) including polymorphism in genes for prothrombin, platelet glycoproteins and plasminogen activator inhibitor-1 (PAI-1).

Results. It was found that frequency of circulating APA as well as incidence rate of genetic thrombophilia between cancer patients from group I vs. group II significantly differed: APA in group I vs. group II was 86 (55.5 %; p < 0.01) vs. 92 (23.5 %) compared to 7 (5.1 %) in control group. Genetic thrombophilia was dominated in group I by mutated MTHFR (92.9 %), polymorphismin PAI-1 (28.4 %) and platelet glycoprotein (44.5 %) that were significantly higher (p < 0.05) compared to group II and control group. Hence, it allows to suggest that such identified thrombophilia markers are largely associated with a risk of developing thrombotic complications.

Conclusion. Detected high percentage of patients with circulating APA and genetic thrombophilia among cancer patients with former thromboembolic complications corroborate a role for genetic and acquired thrombophilia in developing pre-thrombotic condition. Detecting a range of circulating APA and genetic thrombophilia allows to identify patients who might be referred to a high risk of thrombogenesis and require to preventive application of anticoagulant therapy.

236-244 333

Aim: to evaluate a relationship between newborn weight and single-nucleotide polymorphisms rs5918 ITGB3, rs1126643 ITGA2, rs5985 F13A1 in pregnant women with preeclampsia (PE) and fetal growth retardation (FGR).

Materials and Мethods. In this prospective comparative study, molecular genetic testing for the three polymorphic loci of hereditary thrombophilia candidate genes – rs1126643 ITGA2, rs5918 ITGB3, and rs5985 F13A1 was performed in 70 pregnant women with PE and FGR. Newborn somatometry was performed using standard methods. To assess functional effects of the rs5985 polymorphism of the F13A1 gene associated with newborn weight, we applied online bioinformatic programs GTEx Portal and HaploReg (assessing a relationship between polymorphism and level of gene transcription and related epigenetic effects).

Results. The rs5985 polymorphism of the maternal F13A1 gene is associated with newborn weight according to allelic (â = 156.60; pperm = 0.05) and additive (â = 155.20; pperm = 0.05) genetic models. The polymorphic locus rs5985 of the F13A1 gene is characterized by pronounced pleiotropic regulatory effects in vivo: it determines the amino acid substitution in the A1 subunit of coagulation factor XIII (Val35Leu), associated with the activity of blood clotting factor XIII, localized in the DNase 1 hypersensitivity region, determines DNA affinity to 11 transcription factors (AP-2, CACD, EBF, ERalpha-a, ESR2, Hic1, Klf4, Klf7, SP1, ESR1 and TFAP2C), located in the region of modified histones, marking enhancers and promoters in the culture of ectoderm, endoderm and mesoderm cells, placenta, fetal brain and adrenal glands, progenitor cells and myoblasts in skeletal muscle, adipocytes, brain etc.

Conclusion. The rs5985 polymorphism of the F13A1 gene in pregnant women with PE and FGR is associated with newborn weight.

245-257 427

Aim: to increase the effectiveness of combination therapy and reduce frequency of recurrences of inflammatory diseases in the lower genital tract of combined etiology.

Materials and Мethods. There was conducted a prospective, randomized, blind, comparative clinical study. 80 women with vaginal microbiota disorders were examined randomized into 2 groups: group I (n = 40) – antibiotic therapy was carried out in combination with the preparation Superlimph, group II (n = 40) – a standalone antibacterial therapy; group III consisted of 20 patients lacking gynecological diseases considered to provide with control laboratory parameters. Clinical and laboratory methods were used: microscopy of vaginal smears, detection of viruses and sexually transmitted infections, measurement of serum cytokine levels – interleukins (IL-1â, IL-2, IL-4, IL-6, IL-8, IL-10), tumor necrosis factor alpha, (TNF-á), interferon gamma (IFN-ã).

Results. It was found that clinical recovery occurred in 90.0 and 70.0 % of patients in group I and group II (р = 0.02), respectively. Microbiological recovery was observed in 100.0 and 67.5 % of patients, respectively (р = 0.003). In group I, the isolation of herpes simplex virus type 2 was found in 80.0 and 45.2 % of patients before and after treatment (p < 0.001), respectively, whereas in group II – in 82.5 and 77.5 %, respectively (p = 0.58), between groups – p < 0.001. Before treatment the level of all cytokines, excepting IFN-ã, was higher than the reference values in both groups: in group I, their magnitude decreased after treatment (p < 0.001) and corresponded to the reference values; in group II no changes occurred. Three months after treatment, no relapses were observed in group I, whereas frequency of relapses in group II was 22.5 %, within 1 year – 0 and 35.1 %, respectively. Predictors of recurrent dysbiosis (IL-2, IL-6 and TNF-á in increased concentrations after a course of treatment) were identified.

Conclusion. Treatment with a combined broad-spectrum antimicrobial drug along with topical immunomodulatory agent containing exogenous cytokines is an effective strategy for treating concomitant dysbiosis and preventing relapse.

258-269 621

Aim: to identify the risk factors for gestational diabetes mellitus (GDМ) and predictors of perinatal lesions of central nervous system (CNS) combined with GDМ and maternal obesity.

Materials and Methods. А retrospective observational case-control non-combined study was conducted to determine GDМ risk factors and their effect on perinatal pathology in 250 women divided into 2 groups. The main group included 150 pregnant women diagnosed with GDМ, the control group – 100 pregnant women without carbohydrate metabolism disorders. An assessment of hereditary, obstetric and gynecological history, as well as somatic health was carried out. Patients from the main group were subdivided into smaller groups: 1А (n = 77) – mothers whose newborns postnatally exerted adverse perinatal outcomes associated with impacting maternal hyperglycemia, and 1В (n = 73) – mothers whose newborns were born healthy. CHAID method (Chi Squared Automatic Interaction Detection) was used to create an algorithm for predicting adverse perinatal outcomes in GDМ. Аt the second stage, a single-center prospective observational non-combined cohort study was conducted to assess an effect of maternal hyperglycemia on formation of perinatal CNS lesions. Pre-labor concentration of neuron-specific enolase (NSE) was measured in the amniotic fluid of full-term fetuses in the group of pregnant women with GDM (n = 33) and in the group of pregnant women lacking carbohydrate metabolism disorders (n = 42).

Results. Obesity, late reproductive age, family history of type 2 diabetes mellitus, abortions, early reproductive losses, macrosomic delivery in history are the main risk factors for GDM development. An algorithm was developed that allowed to predict a risk of newborn perinatal pathology in mother with GDM with an overall percentage of correct predictions of 68.7 ± 3.8 %. Pre-labor concentration of NSE in the amniotic fluid of full-term fetuses was elevated by 1.68 times (p = 0.006) in women with combined GDM and obesity (5.56 [3.37–6.24] ng/ml) compared to pregnant women with normal weight lacking carbohydrate metabolism disorders (3.29 [1.49–4.89] ng/ml).

Conclusion. Pregnant women with obesity and type 2 diabetes mellitus familial history were featured with most prominent potential of developing perinatal complications. Rise in amniotic fluid NSE level in patients with GDМ corroborates damage of fetal CNS during antenatal period. The maximum NSE level was found in women comorbid with GDM and obesity.

270-275 374

Aim: to assess the compliance of legal norms regulating surrogate motherhood and moral concepts about motherhood and childhood in society.

Materials and Methods. The Articles 55 (clause 9) of the Federal Law "On the Fundamentals of Health Protection of Citizens in the Russian Federation", the principles of the Constitution of the Russian Federation, and traditional moral concepts common in society of the Russian Federation underwent a comparative analysis.

Results. Discrepancies between moral and legal norms were revealed in 3 issues. Issue 1 is related to the rights for surrogacy of unmarried persons and the rights of single citizens. In an ethical context, the statement of their rights does not correspond to the rights of children to a dignified upbringing in a family composed of a mother and father. Issue 2 refers to the ethical incorrectness of compensated surrogacy contracts. Commercial surrogacy cannot be separated from transformed forms of child trafficking. Issue 3 is related to the moral degradation of motherhood upon using technologies of surrogate and genetic motherhood.

Conclusion. It is necessary to conduct additional studies on using surrogate motherhood in order to prevent abuse and violations upon its application in Russia as well as open up a public discussion on this matter.

276-286 333

Aim: to study the activity of the HIF-1á (hypoxia-inducible factor-1á) hypoxia marker in pregnant women with phlebopathy and its relationship with placenta morphological changes and perinatal complications.

Materials and Methods. 70 women with phlebopathy were dynamically examined during pregnancy. The main group consisted of 30 patients with newborns showing signs of hypoxia; the control group consisted of 40 women with healthy children. All women underwent ultrasound examinations of the lower extremity veins and pelvis by assessing vascular patency, state of venous valves, and intensity of platelet sludge. Expression of the HIF-1á transcription factor at gestational age of 18–20 and 36 weeks was performed by using real-time polymerase chain reaction.

Results. Altered functional state of the veins was found in all pregnant women from the main group, which was accompanied by formation of varying degree platelet sludge in the area of the venous valves in the majority of women, as well as signs of endothelial dysfunction and venous hypoxia highlighted with HIF1-á gene expression upregulated by 2.18-fold. No changes in such parameters were observed in control group.

Conclusion. The transcription factor HIF1-á can be considered as a marker of unfavorable perinatal outcomes in pregnant women with signs of phlebopathy.


287-294 404

Aim: to analyze current literature sources on endometriosis-associated cancer (ЕАС) in gynecology.

Materials and Methods. We searched for publications in the international scientific databases: eLibrary, Google Scholar, ScienceDirect, Cochrane Library, PubMed/MEDLINE and clinical research registries. For this systematic analysis, only full-text publications were used. We evaluated the reliability of evidence and the methodological quality of the studies. The data on the modern approach to the therapy and rehabilitation of women with external genital endometriosis (EGE) are presented. Search terms for publications in Russian and English were used: «endometriosis», «endometriosis-associated ovarian neoplasia», «oncology», «rehabilitation».

Results. Despite the fact that EGE is considered a benign disease, there is a risk for its malignant transformation. However, the pathogenesis and pathomorphological mechanisms of ЕАС are not yet fully understood.

Conclusion. Active management of the rehabilitation period for women with EGE provides an opportunity for early diagnosing recurrences that will provide early diagnostics ovarian ЕАС and improve the main indicators of the quality of life for such patients.

295-312 483

Our knowledge regarding chemical structure and properties of heparin and its derivatives, including biological properties in blood plasma, on the cell surface and while interacting with receptors, has been progressively growing. New insights are followed by the expansion of therapeutic opportunities and indications for the use of heparins. There are prerequisites for the creation of new generation drugs with modified properties that reduce a bleeding risk while applied for a non-anticoagulant goal. The non-anticoagulant heparin properties allow to consider it as a candidate for pathogenetic treatment of patients with COVID-19. This review focuses on the anticoagulant and non-anticoagulant heparin properties as well as the underlying molecular mechanisms.

313-320 920

The novel coronavirus epidemic is characterized by high rates of morbidity and relatively high mortality. Laboratory test results in patients include leukopenia, an increase in liver function tests and ferritin levels reaching hundreds, and sometimes thousands of units. These data remind us about the macrophage activation syndrome (MAC). Secondary hemophagocytic lymphohistiocytosis syndrome, MAC, which pathogenesis is based on a defect in the mechanisms of T-cell cytotoxicity and decreased level of natural killer cells associated with the defect in the perforin-encoding gene as well as hyperproduction of a number of cytokines – interleukin (IL)-1â, tumor necrosis factor-á, etc. by T-lymphocytes and histiocytes, indirectly leading to the activation of macrophages and production of proinflammatory cytokines, in particular IL-6 hyperproduction. MAC is one of "hyperferritinemic syndromes". These disorders have similar clinical and laboratory manifestations, and they also respond to similar treatments, suggesting that hyperferritinemia may be involved in the overall pathogenesis and is characterized by elevated ferritin level and cytokine storm. Despite the fact that data on the immune and inflammatory status in patients with COVID-19 have only started to appear, it is already clear that hyperinflammation and coagulopathy affect the disease severity and increase the risk of death in patients infected with SARS-CoV-2. Hence, understanding the pathogenesis of the novel coronavirus infection can help in its early diagnostics and treatment.


321-329 424

The article presents a clinical case of a severe course of a novel coronavirus infection (COVID-19) that complicated the postpartum period in a patient who underwent cesarean section and resulted in lethal outcome on day 43 after delivery. This observation demonstrates the variety of clinical manifestations of a novel coronavirus infection, masking a severe systemic intravascular catastrophe in a puerperal woman.

ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)