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Obstetrics, Gynecology and Reproduction

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Vol 16, No 6 (2022)

ОRIGINAL ARTICLES

648-663 1083
Abstract

Introduction. Neutrophil extracellular traps (NETs) and von Willebrand factor (vWF) are integral players in thrombosis and inflammation in cancer patients. It has been increasingly evident that an active interplay exists between NETs and vWF. Some studies suggest that NETs cause decrease in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity, being an arm in the pathogenesis of both thrombotic microangiopathies (TMA) and other thrombotic complications during oncological process.

Aim: to assess a crosstalk between NETs, vWF, and ADAMTS-13 in uterine, ovarian, breast malignant neoplasms as well as cervical canal adenocarcinoma.

Materials and Methods. From September 2019 to July 2022, a prospective controlled interventional non-randomized study was carried out with 106 patients hospitalized for planned surgical treatment aged 30 to 72 years. The main group included 73 patients with malignant neoplasms of the female genital organs and mammary glands, stage I–III: uterine cancer (subgroup 1; n = 18), ovarian cancer (subgroup 2; n = 21), cervical cancer – adenocarcinoma of cervical canal (subgroup 3; n = 9) and breast cancer (subgroup 4; n = 25). The control group consisted of 33 women with female genital tract and breast benign neoplasms. In all patients, serum levels of vWF, citrullinated histone H3 (citH3), MPO (myeloperoxidase) antigen, ADAMTS-13 activity, ADAMTS-13 antigen, and D-dimer were evaluated.

Results. The study revealed significant differences in the concentration of NETosis markers between the main and control groups. Patients with uterine cancer and adenocarcinoma of the cervical canal peaked at NETosis markers. At the same time, there were significant differences in citH3 concentration among patients with «early» (stage I) and «not early» (stage II–III) disease forms. While assessing level of von Willebrand factor (vWF:Ag), antigen (ADAMTS-13:Ag), and ADAMTS-13 activity (ADAMTS-13:Ac), significant differences were found between the main and control groups (p < 0.0001). The vWF in the main groups was sharply increasedwhereas ADAMTS-13 antigen concentration and activity were decreased. A сorrelation analysis among oncological patients in main group showed that while citH3 level increased, it was also paralleled with rise in vWF:Ag (ρ = 0.80; p < 0.01) and MPO:Ag (ρ = 0.87; p < 0.01); increase in MPO:Ag level was coupled to rise in vWF:Ag (ρ = 0.70; p< 0.01), but increase in vWF:Ag occurred along with decline in ADAMTS-13:Ac (ρ = –0.43; p < 0.01) and ADAMTS-13:Ag (ρ= –0.42; p < 0.01).

Conclusion. The interplay between NET, vWF, and ADAMTS-13 leads to a vicious circle, reduces ADAMTS-13 activity by increasing serum vWF concentration, which positively correlates with severity and mortality in TMA, acute ischemic infarction, and COVID-19. Targeting the NETs-vWF axis may pave the way for therapeutic strategies for immunothrombosis in various diseases, including cancer.

664-675 2288
Abstract

Introduction. Annually, more than 13 million neonates are born with fetal growth retardation (FGR) worldwide. FGR increases prenatal mortality and morbidity. Due to no effective treatments for FGR are available, its prevention and prognosis are of extreme relevance.

Aim: development of prognostic clinical and anamnestic mathematical model for assessing a risk of developing FGR during pregnancy.

Materials and Methods. A prospective, controlled, open, continuous study was performed. The main group (1) included 75 patients who had FGR during pregnancy; the control group (2) consisted of 414 women with favorable pregnancy outcome. All subjects underwent examination, including collecting medical history, a complex of prenatal diagnostics in the first trimester of pregnancy – ultrasound, Doppler uterine arteries, serum level of pregnancy-associated plasma protein-A (PAPP-A), free beta-subunit of human chorionic gonadotropin (β-hCG), placental growth factor (PlGF), and non-invasive prenatal test (NIPT).

Results. To determine the relative contribution of each individual trait to the formation of FGR risk and develop a prognostic index, a discriminant analysis was carried out, on the basis of which a prognostic F-index was developed. The formula for calculating the F-index includes the age of pregnant woman, obstetric history data, method of conception, recorded nicotine addiction in pregnancy, detected uterine fibroids, body mass index, biochemical parameters (PAPP-A, β-hCG, PlGF), nuchal translucency of the fetus, the pulsation index of the uterine artery, the level of the fetal fraction and fetal gender (determined during NIPT). The parameters of sensitivity and specificity of the FGR prognosis were 90.1 and 82.18 % respectively, the method effectiveness was 83.97 %.

Conclusion. The method developed for predicting FGR can be used in clinical practice to form risk groups for FGR development and choose tactics for pregnancy management.

676-691 1303
Abstract

Introduction. It is believed to be relevant to assess a profile in patients not using menopausal hormone therapy (non-MHT) with climacteric syndrome (CS) and surgical menopause, because this cohort includes patients with malignant neoplasms of the reproductive system at the stage of rehabilitation after radical surgery, for whom few study data in real-world data are available.

Aim: to describe a profile of non-MHT women with CS and surgical menopause included in the MAGYN study.

Materials and Methods. A non-interventional epidemiological study screened for magnesium deficiency in 1528 non-MHT women with CS and surgical menopause; 29 patients were at recovery period after radical surgical treatment of reproductive system cancer (vulvar, cervical, endometrial, ovarian, and breast cancer). The number and proportion of women with magnesium deficiency was assessed using the Magnesium Deficiency Questionnaire (MDQ), and a biochemical blood test was performed to measure serum magnesium concentration. Quality of life (QoL) was assessed using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). There were analyzed general somatic pathology, complaints, symptoms of magnesium deficiency by using visual analog scale, as well as the data of drug therapy, including a combination of magnesium citrate + vitamin B6 (pyridoxine) applied for 4 weeks.

Results. According to the MDQ, the prevalence of magnesium deficiency was 72.3 % (55.1 % with moderate and 15.2 % with severe deficiency). Of 469 women, serum magnesium concentration ≤ 0.80 mmol/L was found in 377 (80.38 %), ≤ 0.70 mmol/L – in 278 (59.28 %). Surgical menopause was significantly more common in patients with magnesium deficiency (13.0 %). Among the symptoms of CS in patients with magnesium deficiency, neuropsychiatric symptoms were significantly more common: 47.3 % vs. 43.2 % (p = 0.035). After 4 weeks of therapy, the MDQ score decreased from 46.0 ± 12.7 to 29.2 ± 15.1 points (p < 0.001), serum magnesium level increased to 0.79 ± 0.23 mmol/L. The WHOQOL-BREF demonstrated a significantly improved QoL compared to pre-therapy, including physical and psychological well-being (21.1 ± 4.5 vs. 26.2 ± 3.5 score; p < 0.001), selfperception (18,2 ± 3.7 vs. 22.2 ± 3.6 score; p < 0.001), social well-being (24.8 ± 4.9 vs. 28.1 ± 4.4 score; p < 0.001) and satisfaction with microsocial support (9.3 ± 2.7 vs. 11.0 ± 2.8 score; p < 0.001).

Conclusion. The high prevalence of magnesium deficiency and its close relationship with symptoms decreasing QoL (neuropsychic symptoms, hot flashes, irritability, sleep disturbances, fatigue, chronic stress, frequent headaches, etc.) have been confirmed. Further research is needed to assess an effect of magnesium deficiency correction as part of complex medical rehabilitation on the QoL of women with malignant neoplasms of the reproductive system after radical surgery.

REVIEW ARTICLES

692-705 4212
Abstract

More than two year-experience in monitoring patients with severe novel coronavirus disease revealed an increased risk of macroand microcirculatory thrombosis, clinically manifested by heart attack, stroke, thromboses of rare localizations (thrombosis of the hepatic veins, mesenteric veins, cerebral sinuses, portal vein), being the main cause of adverse outcomes. Thromboembolic complications, expressed as sepsis-induced coagulopathy, disseminated intravascular coagulation, venous and arterial thromboembolism, pulmonary embolism, microthrombosis, and thrombotic microangiopathy were noted to affect various organs such as the lungs, heart, kidneys, and brain. Earlier, we showed that hypercoagulability is closely related to inflammatory diseases and hemostasis dysregulation. Endothelial injury and dysfunction have been identified as critical pathways to thrombosis, and other mechanisms occurring in the microvasculature were described such as endothelial activation, cytokine storm, and formation of neutrophil extracellular traps (NETs). However, a role of platelets in severe COVID-19 has not been examined. Platelets are small non-nucleated cells most known as the central mediators of hemostasis. However, upon activation, platelets release a variety of immunomodulatory cytokines and chemokines involved in regulating immune response. Because platelets are involved in both immunity and coagulation, they play a central role in immunothrombosis, a physiological process wherein immune cells induce microthrombogenesis both to prevent spread of pathogens and facilitate their clearance. Moreover, platelets can directly interact with viral receptors including those related to SARS-CoV-2. Platelet dysfunction includes both thrombocytopenia and platelet hyperactivation. It should be noted that persistent thrombocytopenia is usually correlated with mortality being associated with thrombosis of the cerebral sinuses, splanchnic system, autoimmune reactions, as well as with administered heparin and vaccines. Therefore, here we review a role of platelets in the pathogenesis of COVID-19.

706-716 2109
Abstract

Here, we discuss an importance and necessity of genetic research in work of an obstetrician-gynecologist of primary health care upon providing medical care. Infertility, habitual miscarriage, the birth of children with congenital malformations greatly affects psycho-emotional state of both women and men, which is why every practicing doctor needs to have at least minimal knowledge about genetic research to prevent/warn negative consequences of certain conditions. We believe that an issue on genetic testing should arise at the stage of preconceptional preparation/in the first trimester of pregnancy, because it is the most favorable period for prevention of multiple conditions.

718-731 1087
Abstract

Recently, there have been published the data of large randomized trials on the use of antithrombotic agents for reducing a risk of thromboembolic complications, multiple organ failure and mortality in COVID-19 patients. However, principles of selecting optimal therapy remain open. Strategies for the use of antithrombotic drugs in outpatient and inpatient settings, thromboprophylaxis in specific patient populations, and treatment of acute thrombosis in hospitalized COVID-19 patients are being developed. In October 2021, the International Society on Thrombosis and Hemostasis (ISTH) formed an interdisciplinary international panel of experts to develop recommendations for use of anticoagulants and antiplatelet agents in COVID-19 patients. Expert opinions are published. Here, we summarize all the publications available globally at the present time on this issue, obtained by using the principles of evidence-based medicine.

732-743 3543
Abstract

Introduction. During the COVID-19 pandemic, the question regarding an effect of related infection on the body of pregnant women and the fetoplacental complex has emerged, with many aspects of this issue still being unknown. At the moment, it has been proven that in some cases the course of COVID-19 can be accompanied by severe systemic inflammatory reaction leading to hypercoagulable state.

Aim: to search for evidence of a direct and/or indirect effect of SARS-CoV-2 infection on human placenta structure.

Materials and Methods. Taking into account the goal, this review was compiled according to the type of a narrative review of publications on a topic of interest. A search for English-language publications dated of 01.12.2019 till 01.12.2021 in PubMed/MEDLINE, Cochrane, Web of Science databases was made. The search queries included the following keywords: combinations of «coronavirus» and «infection during pregnancy», «placental structure» and «2019-nCoV», «COVID-19 and pregnancy», «SARSCoV-2 and pregnancy». In the process of writing the article, in order to improve the reader's understanding of the essence of debated issue, there was a need to discuss some of the results with literary sources published earlier 2019 that were not directly related to the topic of the new coronavirus infection (there are 6 such sources). We analyzed full-text publications, both reports on original research and meta-analyses on relevant topics. In total, 351 full-text publications met the query criteria, of which 54 were selected as meeting the objectives of the study. The select reports were discussed by the co-authors, duplicates were excluded and 34 of them were included in this review. In those that were excluded from the review, information about the clinical course of pregnancy and its outcome during novel coronavirus infection prevailed, or isolated cases of studying insignificant placental structural changes were discussed. Studies with a small number of observations were selected only in the case of the uniqueness of the published data, the absence of scientific papers where similar studies would have been conducted in larger sample.

Results. Pregnancy complicated by COVID-19 may be accompanied by placental structural changes, which represent both a manifestation of compensatory-adaptive reactions and a consequence of the damaging effect to the placenta due to infectious process. In case of late (in the III trimester) disease in pregnant woman with mild COVID-19, placental disorders are predominantly of compensatory-adaptive nature, specific cytological signs of viral cell damage are uncharacteristic. During COVID-19 infection, chronic histiocytic intervillositis and syncytiotrophoblast necrosis occur more often than in average population, and adverse fetal outcomes are characterized by additional marked increase in intervillous fibrinoid deposition. Before COVID-19 pandemic, chronic histiocytic intervillositis was described in about 6 out of 10,000 placentas (0.6 %) in II and III trimesters.

Conclusion. The high frequency of chronic histiocytic intervillositis, both in the placenta of paired women with live-born infants infected prenatally due to maternal virus transmission, and in the placentas of stillborn infected infants, allows us to cautiously assume that such placental structural changes are more characteristic for damage by SARS-CoV-2 rather than other infectious agents. It is necessary to study a relationship between placental structural changes occurred at different gestation ages, as well as clinical course and outcome of pregnancy during COVID-19.

FROM HISTORY

744-746 586
Abstract

Here, we describe the historical aspects of the life and scientific work of Joseph Skoda as well as his contribution to medicine.

ANNIVERSARIES

EVENTS

 
749-755 1478
Abstract

On November 19, 2022, the production facility manufacturing of biotechnological substances for women's reproductive health was opened at the Zavod Medsintez LLC in Novouralsk. In 2018, Zavod Medsintez LLC, together with IVFarma LLC, has launched industrial-scale operation of the first Russian follicle-stimulating hormone (FSH) drug Primapur® for infertility treatment within the framework of in vitro fertilization (IVF) protocol. Primapur® shows high efficiency, safety and quality not inferior to international analogues. The launch of the new department will substantially increase the capacity and production scale not only of Primapur®, but also other Russian medicines for reproductive health. Moreover, it is also able to provide a decent import substitution and access to world markets.

OBITUARY



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