ОRIGINAL ARTICLES
Introduction. Hyperhomocysteinemia (HHC) is one of the arms in the pathogenesis of thrombotic complications in female cancer patients.
Aim: to assess an HHC-related impact to developing thrombotic complications in patients with malignant neoplasms of the female genital organs and breast cancer.
Materials and Methods. There were retrospectively evaluated the data collected from 236 patients: with ovarian tumors (n = 63), cervical cancer (n = 51), breast tumors (n = 64), malignant neoplasms of the uterine body (n = 58). The control group consisted of 50 women without malignant neoplasms. The analysis of homocysteine (HC) concentration, the frequency of polymorphisms of the genes encoding folate cycle enzymes MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G as well as the rate of thrombotic complications was carried out. A risk of blood HC level-related thrombotic complications was assessed.
Results. Plasma HC concentration comprised ≥ 22 μmol/l in 30.5 % of patients. Thrombotic complications within one year after discharge from the hospital were developed in 15.3 % cases. The risk of thrombotic complications turned out to be higher in patients with elevated plasma HC level (≥ 22 μmol/l) (odds ratio = 2.99; 95 % confidence interval = 1.11–8.08). No significantly increased prevalence of polymorphisms in the genes encoding folate cycle enzymes among female cancer patients was detected.
Conclusion. Monitoring HC level in female cancer patients contributes separately to predict a likelihood of thrombotic complications. Prescribing drugs that reduce HC level (folic acid) and monitoring its concentration in female cancer patients during therapy, including chemotherapy, can potentially lower an incidence of thrombotic complications.
Aim: to assess the effects of a dual trigger by gonadotrophin-releasing hormone (GnRH) agonist and low-dose human chorionic gonadotropin (hCG) on in vitro fertilization (IVF) outcomes in women with normal ovarian response.
Materials and Methods. This case-control analysis comprised 118 patients who responded normally to ovarian stimulation with a GnRH antagonist protocol at Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between January 2018 and October 2019. Recruitment was achieved through case-control matching: a case (with Dual trigger – group A) was paired with control (with hCG trigger – group B) in a 1:1 ratio. The primary markers of success were the retrieval of oocytes and embryological data, the pregnancy rate, and the incidence of ovarian hyperstimulation syndrome (OHSS).
Results. 59 patients in group A and 59 women in group B were recruited. Two groups had comparable patient characteristics and ovarian reserve. The initial dose, total dose, duration of gonadotropin administration, and peak of estradiol level were not statistically different across groups. The number of recovered oocytes (10.3 ± 4.2 vs. 10.0 ± 3.3; p = 0.663), mature oocytes (8.6 ± 3.7 vs.
8.1 ± 2.8; p = 0.346), and high-quality embryos (56.2 ± 28.9 vs. 59.8 ± 35.9; p = 0.555) was equivalent. Fertilization, clinical pregnancy, and live birth rates were comparable between the dual trigger and hCG groups. In neither group were any occurrences of OHSS seen.
Conclusion. Dual trigger may substitute hCG for final oocyte maturation and fresh embryo transfer in patients with normal responses to GnRH antagonist protocol-induced ovarian stimulation without compromising IVF outcomes.
Aim: to identify inherited and acquired thrombophilia as well as features of pregnancy course in women with abnormal placenta location.
Materials and Methods. Within the framework of a prospective controlled cohort non-randomized, interventional study there was analyzed pregnancy course in 135 women with abnormal placenta location: group I – 42 patients with abnormal placenta location in history; group II – 61 women with placenta previa detected during ongoing pregnancy; group III – 32 patients with placenta previa detected both in ongoing and previous pregnancy. The control group consisted of 120 pregnant women with normal placenta location without a previous complicated obstetric history. All patients underwent clinical examination of pregnancy course assessing fetus intrauterine growth retardation (IUGR) and fetal biophysical profile; inherited and acquired thrombophilia were identified – analyzing circulating antiphospholipid antibodies (APAs) by ELISA, inherited thrombophilia by polymerase chain reaction to identify mutations in genes encoding 5,10methylenetetrahydrofolate reductase (MTHFR), G20210A mutations in prothrombin gene, V Leiden mutation, polymorphismin fibrinogen and plasminogen activator inhibitor 1 (PAI-1) genes.
Results. Inherited thrombophilia was detected in 101 (74.81 %) pregnant woman with abnormal placenta location: group I – in 31 (73.8 %) patients, group II and group III – in 44 (72.1 %) and 26 (81.3 %) patients, respectively. Inherited forms of thrombophilia were detected in 29 (24.2 %) women from control group. Multigenic forms of thrombophilia peaked in group III (14/43.8 %), followed by group I (16/38.1 %) and group II (23/37.7 %). In the control group, multigenic thrombophilia was detected in 16 (13.3 %) women. Selective inherited thrombophilia and АРАs circulation were detected in 30 (22.22 %) women with abnormal placenta location: group I – in 8 (19.0 %) patients, group II – in 13 (21.3 %), and group III – in 9 (28.1 %) cases. In the control group, there were only 8 (6.7 %) such patients. Patients with IUGR signs were identified in all study groups: 4 (9.52 %) in group I, 6 (9.84 %) in group II, 6 (18.75 %) in group III as well as in control group in 6 (6.67 %) women.
Conclusion. Pregnancy management in patients with thrombophilia and placental abnormalities should be accompanied by an proper fetal assessment (biophysical profile) and, in some cases, anticoagulant or antiplatelet therapy. However, insufficient number of cases requires to conduct further investigations to assess a relation between thrombophilia, placenta previa and a risk of obstetric complications particularly IUGR.
Introduction. Studies evidence about a relation between increased circulating free DNA (cfDNA) concentrations and chemotherapy, the majority of which have been focused on considering a tumor as a source of cfDNA. It has been suggested that neutrophils also contribute to this process, as cancer-related cfDNA characteristics resemble those of neutrophil extracellular traps (NETs). Therefore, the elevated concentration of cfDNA observed in chemotherapy patients may be associated with NETosis.
Aim: assessment of NETosis markers in surgical treatment and adjuvant chemotherapy of patients with malignant neoplasms of the female reproductive system.
Materials and Methods. A prospective non-randomized interventional controlled study was carried out by enrolling 111 patients with malignant breast diseases and female genital organs of various localizations and stages hospitalized for elective surgical treatment or chemotherapy course. The control group included 33 healthy women. 69 patients underwent surgical treatment. Adjuvant chemotherapy with paclitaxel and carboplatin was performed in 25 patients with ovarian cancer and 17 patients with breast cancer. In cancer patients, citrullinated histone H3 (citH3) and myeloperoxidase (MPO) were chosen as NETosis biomarkers allowing to distinguish NETs from other tumor-derived cfDNA thereby improving quality of research study. The concentration of NETosis markers was assessed before surgery or onset of chemotherapy upon admission to hospital and 14 days after surgery or 14 days after the second course of chemotherapy.
Results. In all patients, the concentrations of NETosis markers before the start of therapy were significantly increased compared to the control group as well as 14 days after surgical treatment and 14 days after the second course of chemotherapy. However, in surgical patients, no significantly increased concentration of NETosis markers postvs. pre-surgery magnitude was observed. Upon that, patients underwent 2 courses of chemotherapy vs. baseline level were found to have significantly elevated magnitude of NETosis markers.
Conclusion. The study revealed the relationship between administration of paclitaxel-containing chemotherapy in patients with ovarian cancer and breast cancer and a rise in NETs level. Chemotherapy is an essential component for management of patients with malignant neoplasms of the female reproductive system, therefore, development of new strategies to lower a risk of thrombosis and resistance to it is of crucial importance.
Aim: to assess the blood level of biological endothelial damage markers in women with previous early-onset preeclampsia (еPE) during both the preconception (PC) stage and the first trimester of pregnancy.
Materials and Methods. A prospective single-center cohort study was conducted. The control group comprised 40 women with uncomplicated pregnancies. The observation group consisted of 97 patients with a history of ePE, stratified based on pregnancy outcome into the comparison group (n = 59) characterized by a favorable gestational course, and the main group (n = 38) with relapsed еPE (30 patients were excluded from the study). Markers of systemic endotheliosis were determined in women at the PC stage and at 11–13 weeks of gestation: endothelin-1 (ET-1) and endothelial extracellular vesicles (EVs; CD-144).
Results. At the PC stage, women in the control group and patients from the comparison group had comparable median (Me) ET-1 levels – 0.39 and 0.40 pmol/ml (p = 0.5935), respectively; at the same time, patients with relapsed еPE vs. control group had it significantly elevated (Me = 0.55 pmol/ml; p = 0.0382). At gestational age of 11–13 weeks, ET-1 level was significantly higher in the group with relapsed еPE (Me = 0.93 pmol/ml) than in control group (Me = 0.29 pmol/ml; p < 0.0001) and comparison group (Me = 0.42 pmol/ml; p = 0.0003). No significant changes in E-EVs (CD-144) level at various PС stages were observed, whereas in the study groups such parameters remained differed.
Conclusion. Biological markers evidencing about systemic endothelial dysfunction/destruction – ET-1 and E-EVs (CD-144) in patients with previous ePE can be considered as predictive tests of disease relapse with an accuracy of 63.5 % and 83.0 % at the PС stage and 85.7 % and 94.2 % at gestational age of 11–13 weeks, respectively.
REVIEW ARTICLES
Here, we analyze the data on genetic factors involved in developing endometriosis available in current publications. To date, the genome-wide associative studies (GWAS) have revealed more than 190 loci associated with endometriosis development, however, only few polymorphisms were associated with this disease identified in two GWAS (rs1537377 CDKN2B-AS1, rs71575922 SYNE1, rs11674184 GREB1, rs1903068 KDR, rs2235529 WNT4, rs7412010 CDC42), and only one rs12700667 TSEN15P3/MIR148A polymorphic locus in four studies. Several polymorphisms located in the region of two genes GREB1 (rs11674184, rs13394619, rs35417544) and WNT4 (rs2235529, rs12037376, rs7521902) are associated with endometriosis in several GWAS. The association of 5 polymorphic loci with endometriosis was confirmed in two or more replication studies: rs13394619 GREB1, rs7521902 MIR4418/WNT4, rs1250248 FN1 and rs6542095 CKAP2L/IL1A – in two studies, rs12700667 TSEN15P3/MIR148A – in four studies. At the same time, the relationship between the vast majority of GWAS-significant polymorphic loci (more than 95 %) and endometriosis has not been confirmed in other independent studies, necessitating a need to continue endometriosis-related genetic studies, including those aimed at confirming previously identified associations.
Prediction of a risk group and early diagnostics of preeclampsia (PE) are crucial for a comprehensive follow-up of women to improve maternal and fetal outcomes. This review presents current data regarding PE prognosis. We have substantially progressed in understanding PE pathogenesis and in the field of angiogenic markers, but not a single test meets the criteria to serve as an optimal biomarker. It has been increasingly emphasized that the role of maternal hemodynamics may be important in predicting PE risk. The cerebral and ophthalmic arteries, blood volume, potential echocardiographic markers to predict PE as well as a marker of heart failure, brain natriuretic peptide (BNP), are actively investigated. The analysis summarizes the data on contemporary markers for PE prognosis by focusing on impaired pregnancy-related maternal cardiovascular adaptation. Assessing hemodynamics represents a potential prognostic marker for impaired maternal cardiovascular adaptation.
The literature review is dedicated to the topical subject in current endocrinology and gynecology – clitoromegaly. At present, clitoromegaly is considered as a symptom of an endocrinological disease associated with impaired testosterone or androgen production. However, in most cases, the cause of the disease cannot be determined. A condition described in the clitoromegaly classification as an "idiopathic clitoromegaly" holds a leading place. Despite an opportunity to perform a successful clitoroplasty in childhood, adult patients with clitoromegaly quite often seek specialists` help. Such girls and women often suffer from anxietydepressive disorders related to social maladjustment associated due to sexological and psychological problems, which requires a sexologist or psychotherapist` supervision and treatment. Here, we provide the data on genetic syndromes accompanied by clitoromegaly. Differential diagnostics algorithms for neonates, young and adult women are proposed.
Introduction. Uterine artery embolization (UAE) is an effective minimally invasive manipulation that has been widely applied in obstetric and gynecological practice. The expediency of using this method of surgical treatment in patients with reproductive plans is still controversial. The main clinicians' concerns are the risk of developing local endometrial ischemia able to lead to habitual miscarriage, premature birth and pathological placentation as well as decreased ovarian reserve due to impaired adequate ovarian blood supply.
Aim: to analyze the literature data regarding UAE effect on reproductive function.
Materials and Methods. The search for literature was carried out in databases Web of Science, eLibrary, Scopus, PubMed/MEDLINE. We selected articles for the years 1995–2023 devoted to assessing UAE influence on reproductive function. The articles were searched by the keywords "embolization", "uterine arteries", "reproductive function", "prognosis", "assessment". No methodological filter was used to exclude the omission of suitable articles. The study included full-text sources and literary reviews on the subject under study. Articles that are not directly related to the subject UAE were excluded from the review. In order to avoid the inclusion of duplicate publications if two same author studies were found, the study period of each author was assessed, and if publication dates coincided, the most recent publication was selected.
Results. Based on the review of domestic and foreign literature sources over recent years, it can be concluded that there are restrictions on the frequency and outcomes of pregnancy in such cohort of patients who underwent UAE. Many patients included in existing studies and case reports have variable factors complicating direct analysis or comparison such as age of patients, previous spontaneous abortions, previous uterine surgery, different techniques and professional training of X-ray endovascular surgeons, uncertainty of a woman regarding further reproductive plans and other forms of infertility, which can also distort research results. In addition, the most well-controlled studies often have small patients sample sizes not allowing to obtain meaningful clinical information from thereof.
Conclusion. Pregnancy is possible in women after UAE, and many of these pregnancies proceed without complications and lead to successful childbirth. The actual fertility rate after UAE remains uncertain, but is approaching 38.3 % based on the available published results.
Antibiotics are most often used to combat urinary tract infections (UTIs). Taking into account the side effects related to antibiotic therapy, existing antibiotic-resistant strains of uropathogens, as well as the low effectiveness of the vast majority of antibiotics against bacterial agglomerations (biofilms), a search for alternative approaches to treat UTIs is highly relevant. One of the important in such search is presented by use of nutraceuticals – D-mannose (prevents interaction between pathogenic E. coli strains and the urothelium, destroys bacterial biofilms), Lactobacilli (prevents formation of bacterial pathogen biofilms, normalizes human microbiome, alleviates inflammation) and standardized cranberry extracts (inhibits uropathogen adhesion, exerts anti-inflammatory action). The results from basic and clinical studies suggest not only about high safety of such pharmaconutraceutical support of UTIs therapy, but also the effectiveness of separate and combined use of such nutraceuticals comparable to that of antibiotics, especially in treatment of uncomplicated UTIs forms
Introduction. Due to the dynamic development of modern imaging technologies in recent years, much attention has been paid to radiomics particularly texture analysis. The complexity of clinically evaluated tumor procession in cervical cancer (CC) accounts for a need to expand knowledge on applying medical imaging technologies in oncologic diagnostics spanning from predominantly qualitative analysis to a multiparametric approach, including a quantitative assessment of study parameters.
Aim: to analyze the literature data on the use of radiomics and image texture analysis in diagnostics and prediction of aggressiveness of oncogynecological diseases including СС.
Materials and Methods. A 2016–2023 systematic literature search was carried out in the PubМed/MEDLINE, eLibrary, Scopus databases, NCCN, ESUR, ACR resources. All publications on radiomics and image texture analysis used in CC diagnostics and prediction were investigated, with queries for key words and phrases in Russian and English: «cervical cancer», «radiomics»,
«texture analysis», «oncology». The study included full-text sources and literature reviews on the study subject. Duplicate publications were excluded.
Results. The features and advantages of using radiomics and image texture analysis in CC diagnostics were summarized. The introduction of the radiomic approach has expanded the views on interpretation of medical imaging data. The radiomics-based parameters extracted from digital images revealed high informativeness in some studies that contribute to improving diagnostic accuracy as well as expanding opportunities for predicting therapeutic effectiveness in CC patients.
Conclusion. Radiomics used in diagnostics of oncogynecologic diseases including СС is one of the promising actively developing areas of analysis in radiology that requires to be further investigated.
Introduction. In the last decade, a high-throughput 16S ribosomal RNA (rRNA) sequencing allowed to markedly extend insights into female reproductive tract microbiome. However, evidence about its role on in vitro fertilization (IVF) outcomes remains scarce and controversial.
Aim: to analyze literature data for assessing an impact of the vaginal, uterine, and ovarian microbiome on IVF outcomes.
Materials and Methods. The review was carried out based on publications from available in PubMed/MEDLINE, EBSCO, ResearchGate, Google Academy and еLibrary databases released over the last 20 years. For this, there was search for keywords and their combinations in Russian- and English-written publications: «vaginal microbiome», «cervical microbiome», «uterine microbiome», «ovarian microbiome», «microbiome of ovarian follicles», «IVF», «miscarriage», «early pregnancy loss», «implantation failure», «ovarian failure», «inflammasome». Only full-text original articles and reviews published in peer-reviewed journals were included in the review. Exclusion criteria were as follows: studies containing less than 10 observations per group, abstracts of conferences, studies on the male reproductive tract microbiome. Duplicate publicationswere excluded. The publications were selected independently by two co-authors, and in case of discrepancy two other co-authors were involved.
Results. Vaginal, uterine, and ovarian microbiomes were characterized by providing relevant classifications and the features related to implantation failures and pregnancy loss after IVF. It was found that a decline in total Lactobacillus level and elevated proportion of L. jensenii, G. vaginalis, and Proteobacteria in the vaginal microbiome were predictors of implantation failure. In addition, IVF failure was also associated with the presence of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Streptococcus, Haemophilus, Staphylococcus, Brevundimonas, and Ralstonia in the uterine cavity as well as Bifidobacterium, Gardnerella, and Klebsiella in the endometrial tissue. On the other hand, Lactobacillus dominance in the uterine microbiome has a favorable effect. The colonization of the follicle by any microorganisms as well as the presence of follicular fluid anaerobic bacteria-derived metabolite trimethylamine-N-oxide (TMAO) associated with bacterial vaginosis additionally alters IVF outcomes. Moreover, the role of infectious cues in lowered ovarian reserve has also been established. Activation of the NLRP3 (NLR Family Pyrin Domain Containing 3) inflammasome by microbe-derived ligands stimulates production of pro-inflammatory cytokines and contributes to reduced follicle number. Blocking NLRP3 in mouse experiments can delay depletion of the follicle pool and result in elevated fertility.
Conclusion. Favorable IVF outcomes are associated with Lactobacillus predominance in the vaginal and endometrial microbiome as well as lack of follicular fluid microorganisms. TMAO detected in the follicular fluid as well as activated NLRP3 inflammasome serve as negative predictors of IVF outcomes.
CLINICAL CASE
The course of the pandemic revealed that despite the general populational risks for developing novel coronavirus infection (NCI) COVID-19, pregnant women are more susceptible to its severe course and unfavorable perinatal outcomes. Currently, NCI is associated with a high risk of spontaneous miscarriages, premature rupture of fetal membranes, preterm delivery, development of fetoplacental insufficiency, fetal growth retardation, fetal distress, exacerbation of chronic somatic pathology, and postpartum bleeding. A brief literature review and the described clinical case demonstrate a need to thoroughly examine puerperal women with preterm delivery.
EVENTS
An issue of venous thromboembolic events (VTEs) in pregnant women and puerperas in Russia as well as throughout the world remains relevant. Specialized events with expert’s participation could not be better to promote active discussion and constructive solution of complex problems, which refer to issues of VTEs prevention. Indeed, not disputable issues can be solved, but critical look and reasoned opinion leader presentations in the field undoubtedly improve our understanding and approaches to prevention of threatening complications in pregnant women and puerperas such as VTEs. In addition, actively discussed new data for dosing of low molecular weight heparins (LMWH) in pregnant women will allow to update current clinical guidelines, which would probably improve clinical outcomes of therapy.

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