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Obstetrics, Gynecology and Reproduction

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Vol 16, No 3 (2022)

ОRIGINAL ARTICLES 

228-243 210
Abstract

Introduction. Currently, endothelial dysfunction caused by inflammation and immunothrombosisis considered as one of the crucial mechanisms in developing the SARS-CoV-2 virus-mediated coronavirus disease 2019 (COVID-19). A mass endothelial damage followed by release of untypical large quantity of von Willebrand factor (vWF) multimers and subsequent consumption of metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is described during severe COVID-19. The activation of innate immune cells including neutrophils results in formation of neutrophil extracellular traps (NETs) and myeloperoxidase (MPO) release that, in turn, contributes to spread of inflammation and microvascular thrombosis.

Aim: to evaluate a pathogenetic role and predictive significance for serum markers of inflammation, endothelial dysfunction and hemostatis activation such as vWF, ADAMTS-13 and MPO for in-hospital mortality in severe COVID-19 patients requiring mechanical lung ventilation.

Materials and Methods. There was performed a single-center observational study with 129 severe COVID-19 patients on mechanical lung ventilation at the intensive care unit, by assessing serum in all subjects vWF, ADAMTS-13 as well as in 79 patients MPO level along with other potential predictors for in-hospital mortality.

Results. A multivariate analysis revealed that increased serum level for vWF antigen (vWF:Ag) and MPO antigen (MPO:Ag) were significantly and independently related to high mortality probability: vWF:Ag (IU/ml) – adjusted odds ratio (OR) = 3.360; 95 % confidence interval (95 % Cl) = 1.562–7,228 (р = 0,0019); MPO:Ag (ng/ml) – adjusted OR = 1.062; 95 % = 1.024–1.101 (p = 0.0011). Such data allowed to obtained a simplified mortality score for categorizing patients as those having a higher or lower score compared with the median score level: a high score was associated with lower cumulative survival rate (p < 0.0001), with 50 % of the cases linked to lethal outcome on day 13 post-hospital admission.

Conclusion. Severe COVID-19 patients requiring mechanical lung ventilation were found to have elevated level of serum MPO activity and vWF correlating with poor survival.

244-254 236
Abstract

Introduction. The frequency of side effects when taking combined oral contraceptives (COCs) is still high, which is the reason for refusal to take COCs by women worldwide with a frequency of 30 to 81 %. Management of side effects will help increase the user's adherence to the chosen method of contraception.

Aim: to identify approaches to prevent users from refusing to take COCs due to side effects and increase adherence to their use.

Materials and Мethods. The search for foreign literary sources in English was carried out in the international bases PubMed/MEDLINE, Google Scholar, Cochrane Library, in Russian in еLibrary database, by keywords: «hormonal contraception», «combined oral contraceptives», «side effects», «adherence». Search depth was 30 years (1992–2022). 437 and 74 articles were identified, respectively, of which the review included 44 manuscripts that satisfied the criteria for inclusion on the topic studied: full-text manuscripts with the results of original studies, systematic reviews and meta-analyses.

Results. In the literature, there is a lower incidence of side effects of COCs containing 30–35 µg of ethinylestradiol (tri- and monophasic) compared with 20 micrograms of ethinylestradiol. It was found that the risk of intermenstrual bleeding is 30 % lower when using COCs containing thirdgeneration progestogens compared with second-generation progestogens (relative risk (RR) = 0.71; 95 % confidence interval (CI) = 0.55–0.91) using monophasic combinations as an example. The use of a three-phase COC containing desogestrel (DSG) was characterized by a low incidence of irregular bleeding (3.3 % in the first cycle and a decrease to 2.3 % by the 12th cycle), no effect on physiological parameters, a decrease in blood androgens content and a positive effect on seborrhea and acne, excellent tolerance (2.6% failures due to adverse events). Three-phase COCs are characterized by a lower frequency of intermenstrual bleeding (by 2 times) and amenorrhea (by 3 times) compared with other COCs. A positive effect on reducing the frequency of irregular spotting and breakthrough bleeding was shown when switching from a COC of another composition to a three-phase one containing DSG, and continuing to use it.

Conclusion. A three-phase COC containing DSG continues to be a topical hormonal contraceptive for women both for the first time and when switching from another COC due to side effects, including those associated with menstrual irregularities.

255-265 290
Abstract

Introduction. The issues of rise in incidence and malignant transformation of endometrial pathology along with elevating proportion of postmenopausal women in global population remain relevant.

Aim: to evaluate clinical and laboratory data of postmenopausal patients with endometrial polyp.

Materials and Methods. There were enrolled 156 cases of morphologically verified endometrial polyp; the age of the study patients averaged 61.39 ± 7.78 years. Clinical and laboratory data of the obstetric and gynecological history were analyzed; the somatic history was assessed (cardiovascular diseases, arterial hypertension, coronary heart disease). Analysis of laboratory data was performed: complete blood count (CBC), general urinalysis, biochemical parameters – level of cholesterol (Cholesterol), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, alanine aminotransferase (ALAT), asparagine aminotransferase (ASAT), tumor marker CA-125. Statistical processing of the results was carried out.

Results. Endometrial polyps were found by 17% more frequently in patients with late postmenopausal age, which were more (95.5%) prevalent in subjects without history of impaired fertility. Moreover, they also had a high rate (84.6%) of medical abortions and use of intrauterine contraceptives (every second patient). In the vast majority of cases (1/3), the patients had a history of inflammatory diseases of the uterus and uterine appendages, whereas before surgery they had in 37.2% vaginal inflammation requiring sanitation. According to the clinical course, the endometrial polyp manifested equally in early and late post-menopause, with a predominance of spotting (27.5%) and complaints of pain (24.4%). A high frequency of relapses after polypectomy was revealed so that every third patient had already undergone relevant surgery. A high incidence of arterial hypertension (71.6%), fat metabolism disorders (82.1%) were revealed in both early and late postmenopausal patients, while fat metabolism disorders were associated with the symptomatic course of endometrial polyps.

Conclusion. The study results showed a statistically significant relationship between the endometrial polyp formation in postmenopausal patients and detected inflammatory pathology of the pelvic organs, diseases of the cardiovascular system and fat metabolism disorders. Further studies are necessary to verify importance of the identified factors as clinical prognostic factors.

266-276 215
Abstract

Introduction. Normal ovarian reserve (OR) determining the ovarian response to follicle development containing fully-featured oocytes is an important factor in pregnancy, including assisted reproductive technology (ART) programs. The causes of premature OR decrease are multifactorial. The study of gene polymorphism as a cause of the premature OR decrease deserves attention.

Aim: to determine genetic predisposition to premature OR decrease and create a prognostic model based on study results.

Materials and Methods. A retrospective comparative cohort study was conducted. A total of 200 reproductively active patients with infertility underwent ART were examined. The patients were divided into 2 groups: Group 1 included 100 patients with a premature OR decrease; Group 2 consisted of 100 patients with a normal OR. All patients underwent molecular genetic study. Genetic polymorphisms of the genes ESR1, ESR2, FSHR, CYP19A were studied.

Results. The final clinical phenotype is shaped by multiple factors – genetic and environmental. Several genetic variants contribute to the formation of premature decrease in ovarian reserve. Gene combination of CYP19A1 and FSHR displayed the greatest synergistic effect, potentiating each other and predisposing to a poor ovarian response as part of stimulated superovulation.

Conclusion. Identifying genetic markers is a promising method for individual OR evaluation, including its premature decline. Multilocus analysis and a prognostic model based on combining several polymorphic gene variants will allow to assess risks of premature OR decrease and individualize ART programs.

277-286 133
Abstract

Introduction. Currently, various hormonal preparations are used in assisted reproductive technology (ART) programs which allow to profoundly improve protocols for stimulating superovulation.

Aim: to comparatively analyze effectiveness of recombinant follicle-stimulating hormone preparations in in vitro fertilization (IVF) and embryo transfer (ET) programs.

Materials and Methods. In order to evaluate the effectiveness of gonadotropic drugs, a retrospective analysis of 75 outpatient medical records after routine infertility treatment with IVF and ET programs using follitropin alfa (Gonal-F®), follitropin beta (Puregon®), biosimilar follitropin alfa (Primapur®) for ovarian stimulation was performed. Women examined were divided evenly into groups of 25 patients receiving each drug. The main efficiency indicators of IVF and PE cycles were as follows: the number of aspirated oocytes, the number of embryos obtained, the percentage of clinical pregnancy, as well as «Take Home Baby» parameter.

Results. The patients were comparable in age, hormonal status, major parameters of somatic and gynecological history, parity, and infertility factors. The maximum and minimum number of embryos on day 5, including “high quality” embryos was observed in the Primapur® group (4.24 ± 0.52), and the Puregon® group (2.76 ± 0.37), respectively. In the group of patients using Primapur®, the incidence of clinical pregnancy was 44.0 %, in the group using Gonal-f® – 48.0 %, and in the group using Puregon® – 44.0 %, that did not significant differed between groups (p > 0.05). While assessing the frequency of live births, no significant inter-group differences were found. «Take Home Baby» parameter was 52.0 % in the Gonal-f® group, 60.0 % in the Puregon® group (p > 0.05) that was insignificantly higher in the group of patients treated with biosimilar follitropin alfa (64.0 % ).

Conclusion. The new drug being a biosimilar follitropin alfa does not differ in clinical efficiency from other gonadotropins and can be used for controlled superovulation induction in ART programs.

287-295 157
Abstract

Introduction. One of the actual problems of modern obstetrics is hypertensive disorders during pregnancy. Pregnant women living in highlands are exposed to adverse factors, the most important of which is decreased oxygen in the air. Hypertension of pregnant women in high altitude conditions is conjoin with exogenous hypobaric hypoxia, and as a total organ pathology leads to functional and morphological changes in all organs and systems.

Aim: to study the features of hemostasis system in pregnant women with hypertensive disorders in highlands.

Materials and Мethods. A prospective comparative study included 114 pregnant women with hypertensive disorders, which were divided into 2 groups: group 1 – 63 pregnant women living in highlands, and group 2 – 51 pregnant women living in lowlands. In group 1, 42 pregnant women (67 %) and in group 2, 24 (47 %) pregnant women were diagnosed with severe preeclampsia. Hemostasis parameters were studied: blood clotting time, prothrombin index, content of fibrinogen and soluble fibrin-monomer complexes (SFMC), international normalized ratio (INR), activated partial thromboplastin time (APTT) index, thrombin time, platelet count.

Results. In pregnant mountaineers, compared with pregnant women in lowlands, a higher content of such hemostasis parameters as APTT index (1.654 ± 0.426 vs. 0.892 ± 0.1145; p < 0.001) and SFMC level (4.921 ± 0.753 mg% vs. 3.590 ± 0.5676 mg%; p < 0.001), thrombin time values (103.206 ± 3.734 seconds vs. 93.920 ± 7.8268 seconds; p < 0.001) were revealed, as well as lower fibrinogen concentration (3.762 ± 0.809 g/l vs. 4.160 ± 1,3015 g/l; p = 0.048).

Conclusion. In pregnant women living in highlands compared with pregnant women in lowlands with the addition of severe forms of preeclampsia (67 % vs. 47 %) hypercoagulation characteristic of normal pregnancy disappears, but, on the contrary, iso- and hypocoagulation appears.

REVIEW ARTICLES 

296-305 177
Abstract

Aim: to analyze the causes and level of global maternal mortality (MM) according to the data published within the last 7 years.

Materials and Methods. Search for publications in the PubMed/MEDLINE database was conducted according to the criteria: metaanalysis, free full-text, English, 2015–2021 period. The PICO principle (Patient/Problem, Intervention, Comparison, Outcome) and the keywords "maternal mortality causes", "maternal death causes", "maternal outcomes" were used. The search was finished on October 13, 2021 after retrieving 137 results.

Results. The rate of MM and cause pattern has been changing during COVID-19 pandemic. The first weeks of the COVID-19 lockdown showed that in-hospital mortality among pregnant women increased from 0.13 up to 0.20 % (p = 0.01) and in MM the proportion of respiratory diseases elevated up to 32 % versus 5.6%. Certain geographic regions of the world showed that MM due to COVID-19 reached extremely high values extending 3399 per 100,000 live births as well as increased general MM rate. Heart and vascular diseases (pericarditis, myocardial infarction, thromboembolism) have a significant position among the causes of MM. The rate of MM due to cardiovascular disease was inversely related to the population income level. Cardiomyopathy is the cause of death in 4 % (95 % confidence interval (95 % CI) = 2–7) of mothers in developed countries and 14 % (95 % CI = 10–18) in developing countries. The mortality rate 6 weeks after delivery among women with pregnancy-related myocardial infarction was 5.03 % (95 % Cl = 3,78–6,27), whereas it associated with thromboembolism among women with a mechanical heart valve was related to the agent used to prevent thrombosis, ranging from 0.9 (95 % CI = 0.1–1.6) for vitamin K antagonists up to 3.4 (95 % CI = 0–7.7) for unfractionated heparin per 100 pregnancies with a mechanical heart valve. After 2000, the proportion of anesthesia among immediate MМ causes decreased from 3.5 % (95 % CI = 2.9–4.3) down to 2.4 % (95 % CI = 1.9–2.9) in low- and middleincome countries. High MM odds due to maladjusted pregnancy are still observed: OR (odds ratio) = 17 (95 % CI = 9.6–28.8) for hypertension, OR = 3.70 (95 % CI = 1.72–7.99) for HELLP syndrome with acute kidney injury. Severe obstetric complications cause MM in sub-Saharan Africa and South Asia: bleeding (OR = 28.8; 95 % CI = 20.3–40.7), preeclampsia or eclampsia (OR = 9.13; 95 % CI = 6.10–13.7), maternal infections in antenatal period (OR = 2.80; 95 % CI = 1.63–4.80). About 67 % of pregnant women in such countries obtain no antenatal care (OR = 2.80; 95% CI = 1.63–4.80), predominantly giving birth at home in sub-Saharan Africa. In Ethiopia, ММ results from obstructed home delivery resulting in maternal death in 17.27 %, where uterine rupture is cause of death in 7.75 % of women.

Conclusion. The COVID-19 pandemic contributed a lot to MM. Diseases of the cardiovascular system markedly elevate the MM risk and long-term mortality after delivery. For countries with traditionally home births in the absence of medical care, a high MM remains due to complicated and protracted labor complicated by uterine rupture.

306-316 220
Abstract

Preeclampsia (PE) is a multisystemic disease that has been recorded as a complication in up to 15 % of pregnancies being lead cause of maternal mortality worldwide. Despite that PE pathophysiology has not been fully elucidated, it is currently believed that the endothelial dysfunction and pro-inflammatory status play a key role in its development, which account for impaired implantation processes as well as trophoblast invasion during placentation. Altogether, it results in developing generally accepted clinical symptoms “triad”: arterial hypertension, proteinuria, and edema. PE is also characterized by clotting disorders that cause an increased risk of maternal venous thromboembolism. It should be remembered that the related risk may be markedly elevated in the postpartum period. The mechanisms underlying the development of thrombosis high risk remain to be fully investigated, albeit upregulated expression of procoagulant factors, endothelial dysfunction, compromised endogenous anticoagulant activity, and increased platelet activity result in prothrombotic predisposition.

CASE REPORTS 

317-323 180
Abstract

Here, a clinical case of generalized actinomycosis of the pelvic organs occuring very rarely usually observed in immunocompromised patients is presented. Patient T. referred to the women's clinic with complaints of prolonged genital discharge, itching, burning, and occasional sub-fever. The patient had a history of prolonged hormonal immunosuppressive therapy. After a thorough examination, the patient was consulted by two oncologists. Preliminary diagnosis: suspicio cancer coli; suspicio cancer vaginae. In order to clarify the diagnosis, an in-hospital multifocal scalpel biopsy was performed. The biological material obtained was sent out for intravital pathological and anatomical examination; no signs of malignancy were found. To prevent complications during surgery, the patient underwent separate diagnostic scraping of the uterine cavity and cervical canal after repeated sanitation of the vagina and additional patient examination; hysteroscopy; vulval biopsy; colpocentesis. The final diagnosis was made after obtaining the results of in-surgery microbial culture on nutrient media. Active growth of actinomycetes was detected in the material obtained. The final clinical diagnosis was pelvic actinomycosis, generalized form. Patient T was discharged in satisfactory condition after antibacterial treatment according to the diagnosis for further under gynecologist observation at the women's clinic.

HISTORIC CASES 

324-327 86
Abstract

The article highlights historic aspects of medical and research work of the most prominent scientists and physicians – Giuseppe Sanarelli and Gregory Schwartzman.

328-331 119
Abstract

Here, the history оf Maternity Hospital at the City Clinical Hospital № 67 as well as the history of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health of Sechenov University are discussed.

LETTER TO THE EDITORS 

332-341 152
Abstract

Open letter by Galina N. Sukhodolova, MD, Toxicologist, Dr Sci Med, Professor, Senior Researcher, Department of Acute Poisoning and Somatopsychiatric Disorders, Clinical and Research Institute for Emergency Medicine, Moscow, Russia; Professor, Department of Pediatric Anesthesiology and Intensive Care, Pirogov Russian National Research Medical University, Moscow, Russia; Chairman of the Association of Clinical Toxicologists of Russia. The open letter dedicated to the ongoing resonant case of Elina Sushkevich.

EVENTS 

 
342-344 124
Abstract

On June 02, 2022, the results of the elections to the Russian Academy of Sciences (RAS) were announced. The two members of the Editorial Board of our Journal were elected as Foreign Members of the RAS: Professor Jean-Christophe Gris (France) specialized in hematology-hemostaseology and Professor Sam Schulman (Canada) specialized in hemostaseology. The most prominent foreign scientists who have received recognition from the world scientific community are elected as Foreign Members of the RAS. In total, according to the results of the 2022 elections, 48 scientists from 24 countries became new Foreign Members of RAS. The Editors of the Journal congratulate Professor Jean-Christophe Gris and Professor Sam Schulman with election as Foreign Members of the Russian Academy of Sciences.



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