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Obstetrics, Gynecology and Reproduction

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Vol 17, No 2 (2023)

ОRIGINAL ARTICLES

176-187 2089
Abstract

Introduction. Antiphospholipid antibodies (APAs) exert multifaceted effects on the course of pregnancy by disrupting microcirculation, affecting the hemostasis, as well as damaging the endothelial membranes, leading to early reproductive loss and development of placenta-associated complications depending on the affected gestation stage. Planning and management of pregnancy in women in the absence of criteria for complete antiphospholipid syndrome (APS) currently remains unresolved issue. The absence of generally accepted treatment standards for this category of patients and inability to substantiate the diagnosis according to the APS classification criteria complicate selection of therapeutic tactics.

Aim: to conduct a comparative analysis of therapy-based complications and outcomes of pregnancy in APA carriers.

Materials and Methods. During the period 2019–2021 a prospective study of 150 patients who entered pregnancy with aggravated obstetric and gynecological history, serum APA level was examined. Considering the risks of developing obstetric and thrombotic complications, all patients were prescribed prophylactic doses of low molecular weight heparins (LMWHs) and low doses of acetylsalicylic acid (ASA). The patients were divided into 3 groups using a random number generator. Group 1 (n = 50), in addition to the prescribed LMWH (enoxaparin sodium 40 mg 1 time per day) and ASA (150 mg 1 time per day), also underwent plasmapheresis (PF) 4 sessions per 1 course in 6–8, 12–14 and 22–24 weeks of pregnancy; group 2 (n = 50) received courses of intravenous immunoglobulins (IVIG) at a course dose of 300 ml (15 g) simultaneously; group 3 (n = 50) received no additional therapies. Rate of pregnancy complications was comparatively assessed – development of fetal growth retardation (FGR), low birth weight fetus, gestational arterial hypertension (AH), moderate and severe preeclampsia (PE), anemia and delivery outcomes.

Results. It was found that in group 3 there was a higher incidence of gestational hypertension (p2,3 < 0.0001), moderate PE (p 1,3 =0.071; p 2,3 = 0.0019), low weight fetus for gestational age (p2,3 = 0.0002) and FGR (p2,3 = 0.003). In group 1, compared with group 2, there were more often observed small weight for gestational age fetus (p1,2 = 0.018) and FGR (p1,2 = 0.024), gestational hypertension (p1,2 = 0.0008), anemia (p1,2 < 0.0001) and latent iron deficiency (p1,2 < 0.0001). Also, groups 2 and 3 vs. group 1 were more likely to have intrahepatic cholestasis during pregnancy (p1,2 = 0.013; p1,3 = 0.003).

Conclusion. In the group of patients receiving complex therapy consisting of LMWHs prophylactic doses, low ASA doses and IVIG courses, the risks of developing placenta-associated complications and iron deficiency were reduced compared to other groups indicating about a higher efficiency of this therapy regimen. However, the development of intrahepatic cholestasis during pregnancy was less common in the group of patients receiving PF courses, in contrast to using IVIG courses, which can be accounted for by additional effect of efferent therapeutic methods and should be taken into account in a differentiated approach for management of patients with liver and gallbladder pathology.

188-201 1053
Abstract

Introduction. During pregnancy COVID-19 poses a serious threat to both maternal health and health of paired unborn child. Pregnant women have a high probability of complications due to respiratory viral infections followed by developing critical conditions caused by physiologically altered immune and cardiopulmonary systems. However, asymptomatic COVID-19 in pregnant women may be accompanied by fetal inflammatory response syndrome (FIRS) that results in unfavorable sequelae for neonatal life and health.

Aim: to assess a fetal inflammatory response resulting from maternal COVID-19 in pregnancy.

Materials and Мethods. A prospective randomized comparative study involving 92 pregnant women was carried out. The main group included 62 pregnant COVID-19 convalescent women: subgroup 1 consisted of 30 pregnant women found to be positive for SARS-CoV-2 by using polymerase chain reaction (PCR) 4–6 weeks before delivery; subgroup 2 – 32 pregnant women with SARS-CoV-2 detected by PCR earlier during pregnancy. The control group enrolled 30 healthy pregnant women. The level of circulating cytokines – interleukins (IL) IL-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), macrophage inflammatory protein-1β (MIP-1β), C-X-C motif chemokine ligand 10 (CXCL-10) and cell markers (CD86, CD80, CD4, CD25, CD25, CCR7) were analyzed. In addition, all neonates underwent thymus gland ultrasound screening.

Results. Cord blood dendritic cells from neonates born to mothers in subgroup 1 vs. control group showed a significantly upregulated expression of CD80 and CD86 (p = 0.023). Moreover, such cord blood samples in subgroup 1 were found to have increased percentage of CD4+, CCR7+ T cells paralleled with decreased proportion of naive CD4+ T cells as compared with control group (p = 0.016). It was found that count of maternal regulatory CD4+CD25+Foxp3+ T cells (Treg) did not differ significantly, whereas Treg cell functional activity in mothers with severe COVID-19 (subgroup 2) was significantly suppressed. Significantly higher level of neonatal proinflammatory cytokines and chemokines was detected in subgroup 1 vs. control group (p < 0.05). However, the cytokines level in maternal peripheral blood samples in main and control groups upon delivery was changed insignificantly. SARS-CoV-2-positive pregnant women showed a strong antigen-specific T cell response. A reduced thymus size was found in neonates born to paired COVID-19 mothers.

Conclusion. Fetal inflammatory response syndrome occurs upon COVID-19, which is characterized by activated fetal immune system and increased production of pro-inflammatory cytokines. The disease severity in pregnant women has no correlation with FIRS intensity during neonatal period and can vary from minimally altered laboratory parameters to developing sequelae at organ and body system levels.

202-209 3970
Abstract

Introduction. Iron deficiency (ID) of varying severity is the most common and rather serious extra-gynecological complication of adenomyosis resulting from meno/metrorrhagia of varying intensity, up to abnormal uterine bleeding requiring surgical hemostasis. Taking into account the chronic course of the disease, the complexity of radical therapy as well as a systemic effect ID also particularly affecting reproductive system, an issue of sufficient and timely ID correction in patients with adenomyosis of varying severity remains relevant.

Aim: to study an efficacy of ID therapy with drug containing ferrous fumarate and folic acid in patients with adenomyosis.

Materials and Methods. An observational study was conducted, which included 90 patients with isolated adenomyosis of varying severity: 30 patients with degree 1 adenomyosis (group 1), 30 patients with degree 2 adenomyosis (group 2), 30 women with degree 3–4 (group 3). All patients received ferrous fumarate plus folic acid for 30 days. To identify an ID variant, the level of serum ferritin, iron, transferrin, total iron-binding capacity of blood serum (TIBC), clinical blood test parameters such as hemoglobin level, erythrocyte count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) were measured.

Results. A significant increase in ferrokinetic parameters was found in all patient groups. The most significant and clinically important dynamics was noted for serum iron level and TIBC. For instance, after the therapy, the level of serum iron increased in group 1 from 11.0 ± 0.6 μmol/l up to 15.0 ± 1.1 μmol/l, in group 2 – from 9.0 ± 1.6 μmol/l up to 14 .0 ± 0.8 μmol/l, in group 3 from 7.0 ± 1.3 μmol/l up to 12.0 ± 1.3 μmol/l (p < 0.05). In addition, a decreased TIBC was found in group 3: from 68.0 ± 1.8 μmol/l down to 58.0 ± 1.7 μmol/l (p < 0.05); in groups 2 and 3 TIBC level tended to insignificantly decrease.

Conclusion. The use of a preparation containing ferrous fumarate along with folic acid can effectively correct background ID of varying severity in patients with adenomyosis of varying intensity. An earlier and longer administration of iron preparations in patients with adenomyosis along with clinical and laboratory parameter monitoring is recommended to achieve more pronounced clinical effect.

211-220 1217
Abstract

Aim: to improve the efficiency of predicting a clinically narrow pelvis (СNP) using neural network data analysis and to evaluate its prognostic characteristics.

Materials and Мethods. The study was designed as a retrospective non-randomized clinical trial. An analysis of 184 born neonates was carried out: group 1 included 135 female patients whose delivery occurred through the natural birth canal, group 2 – 49 patients whose delivery was complicated by СNP development and ended up with emergency caesarean section. Examination of patients was carried out on the eve of childbirth (1–2 days) and included anamnesis, general and special obstetric examination, including pelvimetry, a clinical assessment of cephalopelvic disproportion was carried out during childbirth. The condition of newborns was assessed using the Apgar scale, height and body weight were measured. Neural network analysis was performed using the built-in Neural Networks module of SPSS Statistics Version 25.0 (IBM, USA).

Results. Despite hypothetically important role of anatomically narrowed pelvis in development of cephalopelvic disproportion, no significant inter-group differences were found. Significant parameters (abdominal circumference, uterine fundus height and woman’s weight, fetal head circumference, as well as data on the presence or absence of oligohydramnios and fetal macrosomia) were determined, which were included in the test database to create the basis for training the multilayer perceptron. Out of 135 patients of group 1, the prognosis was negative in 131 (97.0 %), positive in 4 (3.0 %); out of 49 patients in group 2, negative in 0 (0.0 %), positive in 49 (100.0 %). The forecast accuracy of the developed model was 98 % (sensitivity – 100 %, specificity –97 %). The information content of neural network data analysis in СNP predicting is presented in ROC analysis: area under the curve (AUC) = 0.99 (95 % confidence interval = 0.97–1.00). Neonatal anthropometric parameters were significantly higher in group 2 vs. group 1, and the Apgar score at 1 minute was correspondingly lower.

Conclusion. The use of neural network analysis of clinical data obtained on the eve of childbirth allows to predict СNP development at sufficient degree of accuracy (98.0 %), which, in the future, after being introduced into clinical practice, will optimize a choice of delivery method in patients at risk (anatomically narrow pelvis, large fetus), reduce emergency caesarean sections and improve birth outcomes.

221-230 1329
Abstract

Introduction. The pandemic of a novel coronavirus infection has demonstrated the importance of assessing the ADAMTS-13/vWF axis in patients with COVID-19, because a decline in this ratio mirrors disease severity. However very few data in the global literature on crosstalk and ADAMTS-13/vWF levels in pregnant women remaining very contradictory are available. Taking into consideration an impact of the ADAMTS-13/vWF axis on prevalence of thrombosis and disorders in the hemostasis system, investigation of this issue is highly demanded.

Aim: to assess the functioning of the ADAMTS-13/vWF axis during physiological pregnancy.

Materials and Methods. A controlled non-randomized study was conducted: main group included 44 women with physiologically occurring pregnancies at I, II and III trimesters; the control group consisted of 45 healthy non-pregnant women. The plasma level of ADAMTS-13 inhibitor (ADAMTS-13:i), ADAMTS-13 antigen (ADAMTS-13:Ag), vWF antigen (vWF:Ag), and ADAMTS-13 activity (ADAMTS-13:Ac) as well as relevant ratio (ADAMTS-13:Ac/vWF:Ag) were measured.

Results. It was shown that in parallel with increasing gestational age, significant changes occurred in the ADAMTS-13:Ac/vWF:Ag ratio. In main group, patients at II trimester were found to have level of ADAMTS-13:Ac/vWF:Ag 0.359 ± 0.121, in III trimester –0.253 ± 0.741, which significantly differed (p < 0.01) compared to control group with non-pregnant women (1,134 ± 0,308).

Conclusion. Our study provides new insights into the functioning of the ADAMTS-13:/vWF axis in women with physiologically occurring pregnancy at I, II and III trimesters. Decline in ADAMTS-13:Ac was demonstrated along with increasing vWF:Ag level observed in parallel with increasing gestational age. Apparently, the progressive decrease of ADAMTS-13 concentration during pregnancy is associated with its increased consumption due to high vWF level. However, due to the small single-center patient cohort, further studies with larger-scale studies are needed.

231-243 855
Abstract

Aim: comparative analysis of the expression profile of plasma microRNAs and target genes in patients with complicated pregnancy.

Materials and Methods. A prospective observational comparative study in parallel groups was carried out. The study included 73 women divided into three groups: the main group – 42 patients with preeclampsia (PE), the comparison group – 12 pregnant women with fetal growth retardation (FGR), the control group – 19 clinically healthy women with uncomplicated pregnancy. An examination was performed, which included the analysis of clinical characteristics and the study of microRNA expression in blood plasma using the real-time polymerase chain reaction.

Results. MicroRNA hsa-miR-210-5p and hsa-miR-1972 were not identified in any plasma sample. Analyzing plasma microRNAs in group of women with PE showed significant changes in the expression levels of hsa-miR-517a-3p (p = 0.025), hsa-miR-517c-3p (p = 0.036), hsa-miR-574-5p (p = 0.015), hsa-miR-517a-3p (p < 0.001) and an increase in miR-20a-5p (p = 0.046) compared to control group. No significant differences were found in the miRNA expression profile in group of women with FGR compared to control group. Assessing an influence of the studied microRNAs on regulatory signaling pathways allowed to establish that hsa-miR-miR-146a-5p, -181a-5p, -210-3p, -517a-3p, -517c-3p, -574-3p, -574-5p, -1304-5p are potential regulators of the reaction cascades involved in the PE pathogenesis.

Conclusion. The changes revealed in the circulating blood plasma miRNA level indicate the presence of specific transcriptomic alterations during complicated course of pregnancy.

244-251 846
Abstract

Introduction. The problem of artificial pregnancy termination is of global importance. Any woman faced with the problem of reproductive choice is vulnerable, needs both to be advised by an obstetrician-gynecologist and high-quality psychological support. At the stage of pre-abortion counseling, it seems possible to influence a decision to keep pregnancy by identifying risk factors for premature ovarian failure (РОF), laboratory and ultrasound criteria for reducing ovarian reserve (OR).

Aim: optimization of the pre-abortion counseling algorithm by introducing an assessment of OR. 

Materials and Methods. A retrospective study was conducted, which included 58 women under 40 living in the Volgograd region and planning to terminate own first pregnancy. In order to identify factors of early decrease in OR, anamnestic data of patients were evaluated. A comprehensive assessment of the main OR parameters was performed by assessing blood serum level of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH) and inhibin B, ultrasound counting the number of antral follicles.

Results. In the main group of patients, 8 (13.8 %) of the examined patients had a birth weight of about 2800 g, 6 (10.3 %) – with a history of ovarian surgery and ovarian cysts were found after menarche. A relationship was also found between OR laboratory parameters in primigravida and the age of menopause in paired mothers: 2 (3.4 %) – 45 years, 8 (13.8 %) – 48–50 years. According to the diagnostic results, 10 (17.2%) patients showed a decrease in ОR and 48 (82.8%) patients had a normal OR. Taking into account the data obtained, a modified project of pre-abortion counseling was developed for the first time devoted to РОF.

Conclusion. The modified section of pre-abortion counseling takes into account the specifics of maternal OR and can improve quality of medical care for women planning to terminate own pregnancy due to more comprehensive information as well as affect the awareness of reproductive plans in the future.

252-256 532
Abstract

Aim: to examine an efficacy of various stimulation methods in a group of successful pregnancies.

Materials and Methods. In a single center retrospective study 47 pregnancy cases were examined after performing embryo transfers at our institution from the years 2017 to 2021. Patients were divided into four groups: i) clomiphene hyperstimulation (CH), ii) stimulation with gonadotropin-releasing hormone (GnRH) agonist, iii) with GnRH antagonist, and iv) progestin-primed ovarian stimulation (PPOS). Age, anti-Mullerian hormone, presence of chronic disease, number of in-vitro fertilizations prior to conception, dosage of follicle stimulating hormone (FSH), presence of premature luteinizing hormone surge, number of egg retrievals, fertilization rate, and live birth rate were assessed.

Results. The number of pregnancies obtained by CH, agonist, antagonist, and PPOS methods comprised 25, 12, 2, and 8 cases, respectively. No significant difference in parameters between CH group and non-CH groups, excepting FSH was observed. The FSH was used in CH group and non-CH group at dose of 1108 ± 468 IU and 1756 ± 394 IU, respectively (p < 0.0001).

Conclusion. CH is not commonly used due to potential luteal phase defects, but it is thought to be cost-effective, requiring lower FSH doses, requiring no ovulation suppression antagonists, and exerting no effect on frozen embryos or fetuses. Hence, CH could be a suitable protocol for egg retrieval in Japan.

REVIEW ARTICLES

257-268 3556
Abstract

Hypercoagulation is a typical condition for cancer patients. In addition, various arms of the hemostasis system become involved in tumor growth, invasion, metastasis, neoangiogenesis as well as immunoevasion. The magnitude of activated hemostasis is driven by tumor phenotype. Parameters characterizing coagulation, intensity of fibrinolysis processes, platelet aggregation and activation as well as endothelial activation mirror magnitude of hemostasis activation in oncological process, but may also be considered as candidate markers of tumor progression and predictors of oncological diseases outcome. This review summarizes the study data assessing a value of predictive hemostasis biomarkers for overall survival and response to therapy in oncogynecology and mammology. The most promising biomarkers have been identified and used in the future for risk stratification as well as personalized patient management.

FROM HISTORY

269-273 759
Abstract

Here, we highlight aspects of visualizing twins in the fine arts. The works of artists Leonardo da Vinci, Jacopo Pontormo, Ker-Xavier Roussel, Jean-Bruno Gassies, Peter Paul Rubens, Sebastiano Ricci and others are presented.

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