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Vol 71, No 4 (2022)

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Reviews

Premature rupture of membranes in preterm pregnancy: prospects for prediction

Afanasyeva M.K., Bolotskikh V.M., Nikolova T., Avdeyeva E.A.

Abstract

One of the major issues in modern midwifery is premature birth, which is often the result of premature rupture of membranes. Currently known methods for predicting premature rupture of membranes do not have sufficient predictive value in preterm pregnancy. This article summarizes modern views on the biochemical, immunological and microbiological aspects of the etiology and pathogenesis of premature rupture of membranes and premature birth. Further ways of searching for predictors of these complications are outlined herein.

Journal of obstetrics and women's diseases. 2022;71(4):85-94
pages 85-94 views

Maternal circadian rhythm and its implications for offspring health

Evsyukova I.I.

Abstract

This review presents data on the circadian system hierarchy and its unique reorganization at the onset of pregnancy, which plays a fundamental role in maintaining maternal homeostasis and creating optimal conditions for the implementation of the genetic program of fetal development. A particular emphasis is made on the protective mechanisms of the circadian rhythm of maternal melatonin, which is the primary messenger of biorhythms. This paper thoroughly discusses the mechanisms and consequences of maternal chronodisruption in pregnant women exposed to adverse environmental conditions (shift work, stress, irregular nutrition, etc.), as well as in those with chronodestruction-related diseases (obesity, diabetes mellitus, etc.). Elucidating the circadian system status in the patients and, in particular, whether they have a daily rhythm of melatonin production will determine a new approach to risk assessment and timely prevention of cardiovascular, metabolic, neuroendocrine and mental disorders in the offspring in later life.

Journal of obstetrics and women's diseases. 2022;71(4):95-105
pages 95-105 views

Anatomical and pathophysiological features of fetal circulation in the umbilical-portal venous system

Shelayeva E.V., Tsybuk E.M., Kopteyeva E.V., Kapustin R.V., Kogan I.Y.

Abstract

Being facilitated in recent years by the advent of high-resolution gray-scale, color Doppler and three-dimensional ultrasound, prenatal visualization of venous vessels has improved much and well contributed to a better understanding of the value of fetal venous circulation. The fetal liver plays an important role in ensuring normal fetal blood circulation, receiving up to 70–80% of venous return from the placenta. Of particular importance is its role in the regulation of intrauterine growth. Venous inflow to the fetal liver is significantly influenced by maternal factors. Ultrasound evaluation of the fetal venous system remains to be not an easy task. This article discusses the significance and features of the anatomical and functional development of the fetal intrahepatic venous system.

Journal of obstetrics and women's diseases. 2022;71(4):107-119
pages 107-119 views

Original Research

Perinatal outcomes of pregnancy and childbirth in moderate to severe COVID-19 patients

Bezhenar V.F., Nesterov I.M., Dobrovolskaya I.A.

Abstract

BACKGROUND: The presence of COVID-19 caused by SARS-CoV-2 during pregnancy increases the incidence of adverse perinatal outcomes, which are manifested in more frequent spontaneous miscarriages, premature births, antenatal fetal deaths, and fetal growth retardation, as well as in the development of intraamniotic infection and respiratory distress syndrome of the newborn. The most likely cause of premature birth can be considered severe respiratory failure of the mother with hypoxemia, which leads to circulatory disorders in the hemodynamic system of the mother-placenta-fetus. Currently, there is no single expert opinion on pregnancy prolongation tactics, as well as the timing and methods of delivery in patients with COVID-19, which is decided individually by an interdisciplinary consultation of the experts, taking into account the severity of the patient’s condition, gestational age and fetal condition.

AIM: The aim of this study was to analyze perinatal outcomes of pregnancy and childbirth in the presence of moderate and severe COVID-19.

MATERIALS AND METHODS: We carried out a retrospective analysis of perinatal outcomes in patients with the novel coronavirus infection in a specialized level III infectious hospital in St. Petersburg, Russia in 2020–2021 (from the first to the fourth wave of COVID-19) based on the birth histories of 50 patients with moderate (n = 31) and severe (n = 19) forms of the disease.

RESULTS: Most of the patients suffered from chronic somatic diseases, with the course of pregnancy and childbirth complicated by premature rupture of amniotic fluid and progressive fetal hypoxia (fetal distress). In severe COVID-19, preterm labor prevailed and the proportion of operative abdominal delivery more than doubled that of vaginal delivery. The course of the postpartum period was determined by the COVID-19 positive dynamics. The majority of patients in the study groups showed significant changes in laboratory parameters such as anemia, an increase in the level of neutrophilic leukocytes with a subsequent decrease in their count, lymphopenia followed by lymphocytosis, and an increase in the levels of C-reactive protein and the activities of lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. The study of the relationship between the most characteristic laboratory parameters in the disease dynamics showed the presence of statistically significant correlations between inflammation markers and metabolic markers, which allowed for assessing the severity of the patient’s condition.

Antenatal diagnosis of the fetal functional status based on cardiotocography, ultrasound and Doppler sonography data revealed a predominantly compensated fetal condition in the study groups. The condition of newborns in all patients with moderate COVID-19 and in most of patients with the severe form of the disease was satisfactory. In severe COVID-19, the birth of children with moderate asphyxia was due to prematurity and antenatal hypoxia resulted from decompensation of chronic placental insufficiency. The histopathological patterns of the afterbirth in the study groups were represented by inflammatory changes and chronic placental insufficiency.

CONCLUSIONS: The data obtained suggest that the basis for favorable perinatal outcomes is an adequate assessment of the condition of the pregnant woman and the fetus with timely delivery before the onset of irreversible organ damage.

Journal of obstetrics and women's diseases. 2022;71(4):5-12
pages 5-12 views

The experience of extended in vitro human embryo cultivation in a culture medium containing endometrium cells. A pilot study

Bespalova O.N., Kogan I.Y., Komarova E.M., Lesik E.A., Tolibova G.K., Tral T.G., Zagaynova V.A., Obyedkova K.V., Gzgzyan A.M.

Abstract

BACKGROUND: At present, the knowledge on initial human embryogenesis stages is limited to the period of development from zygote to blastocyst. The creation of models based on the interaction between the embryo and endometrium in vitro, which accurately imitate the in vivo processes, represents the major way for implantation and post-implantation evaluation. Currently, no reports have been made on models reflecting the both processes simultaneously: the interaction of the embryo with the substrate, which represents many aspects of normal implantation, and the early post-implantation embryo development. The creation of a relevant model would allow investigation of implantation and early post-implantation processes as a whole.

AIM: The aim of this study was to evaluate the vitality and developmental potential of human embryos from the day 6 blastocyst stage during their extended co-incubation with the endometrium in a culture medium specifically designed for cultivation to the blastocyst stage.

MATERIALS AND METHODS: Embryos obtained in assisted reproductive technology programs were cultivated from the day 6 blastocyst stage up to 14 days of development in vitro in a culture medium designed for cultivation to the blastocyst stage, in the presence of endometrium cells. On day 14 of development, embryos and endometrial samples were first evaluated under an inverted microscope using Hoffman modulation contrast, then transferred to a special mold and impregnated with paraffin for cytoblock preparation. Obtained blocks were sliced, stained with hematoxylin and eosin and morphologically assessed.

RESULTS: The first sample visual assessment on day 14 of cultivation in a culture medium with endometrium cells revealed a viable developing embryo with no signs of degradation. During the histological examination, the endometrial sample corresponded to the secretory phase of the cycle. The morphological assessment of the conceptus detected trophoblast cells. The second sample visual assessment on the day 14 of cultivation in a culture medium with endometrium cells revealed a viable embryo with no signs of degradation, which was in direct contact with the endometrial component. A histological examination detected a secretory endometrial fragment of the surface (luminal) epithelium. During the morphological assessment of the embryo, trophoblast cells were detected.

CONCLUSIONS: The data obtained indicate the ability of the embryo to further develop from the day 6 blastocyst stage up to 14 days in a culture medium specifically designed for cultivation to the blastocyst stage, in the presence of endometrium cells. The latter can serve as an experimental model for both in vitro endometrial receptivity evaluation and intercellular interactions during implantation investigation.

Journal of obstetrics and women's diseases. 2022;71(4):13-20
pages 13-20 views

Significance of metabolomic disorders in infertility and miscarriage in patients with endometriosis

Ermolova N.V., Levkovich M.A., Petrov Y.A., Avrutskaya V.V., Krukier I.I., Savchenko A.V.

Abstract

BACKGROUND: Despite numerous studies, the causal relationships of endometriosis, associated infertility and miscarriage have not yet been clarified.

AIM: This article discusses the significance of insulin-like growth factor 1, matrix metalloproteinase 9 and activin A levels in the blood serum and peritoneal fluid of patients of reproductive age with endometriosis in the clinical aspects of infertility and miscarriage and as per stages of the disease.

MATERIALS AND METHODS: The overall group consisted of patients with endometriosis (group I: stages I–II, n = 25; group II: stages III–IV, n = 38). The control group comprised patients without the disease (group III: n = 25). The stage of endometriosis was classified during laparoscopy in accordance with revised American Society for Reproductive Medicine classification (1996).

RESULTS: In endometriosis, primary infertility predominated (up to 40.8% of cases), while secondary infertility occured in 21.2% of cases. Primary infertility accounted for 68.0% of cases in stages I–II versus 39.5% of cases in stages III–IV. Secondary infertility accounted for 28.0% versus 23.0% of cases, respectively. In minimal stages of the disease, non-developing pregnancies (12.0%) and spontaneous miscarriages (4.0%) occurred in 16.0% of cases. In severe stages, these nosologies occurred in an equal percentage of cases (5.2%).

The group of patients with endometriosis showed multidirectional changes in activin A levels in the blood serum and peritoneal fluid, a decrease in matrix metalloproteinase 9 level by 27% in the peritoneal fluid and an increase in insulin-like growth factor 1 level by 36% in the blood serum. In minimal stages of endometriosis, the tendencies of changes in the parameters remained intact as compared to the overall group, the correspondence of matrix metalloproteinase 9 levels to the control values in the blood serum and peritoneal fluid being noteworthy. Stages III–IV of the disease implied more significant changes as compared to the control or the overall group of patients. We found a decrease in insulin-like growth factor 1 level by 56% in the peritoneal fluid, a decrease in activin A level by 19% in the blood serum with an increase in the parameter by 27% in the peritoneal fluid, and a decrease in matrix metalloproteinase 9 level by 4% in the peritoneal fluid.

CONCLUSIONS: Modifications of the studied compounds activin A, MPP-9 and IPFR-1 are associated with infertility and miscarriage in patients with endometriosis.

Journal of obstetrics and women's diseases. 2022;71(4):21-31
pages 21-31 views

Evaluation of the factors influencing labor outcomes in women with a history of abdominal delivery

Mochalova M.N., Alekseyeva A.Y., Akhmetova E.S., Mudrov V.A.

Abstract

BACKGROUND: The rapid increase in the frequency of caesarean sections has led to the emergence of a special group of patients with a uterine scar who want to give birth through the natural birth canal. Repeated operative delivery is associated with high risks of both intraoperative and postoperative complications, therefore, every year the number of women with a uterine scar who prefer natural childbirth is growing.

AIM: The aim of this study was to create a model that allows, based on a comprehensive assessment of risk factors, for predicting the outcome of childbirth in women with a history of abdominal childbirth.

MATERIALS AND METHODS: We carried out a retrospective analysis of 173 birth histories of women with a uterine scar after a previous caesarean section, delivered in the Chita City Maternity Hospital in 2021–2022. Three groups of individuals were designed for the study: Group 1 included 110 women delivered by caesarean section in a planned manner; Group 2 comprised 20 women delivered by caesarean section during childbirth, while Group 3 consisted of 43 women who gave birth through the natural birth canal. The groups were comparable in terms of nationality, age, material and social conditions of the patients. On the eve of delivery, all patients underwent general clinical and obstetric ultrasound examination, with the anamnesis details clarified. The data obtained were processed statistically using the IBM SPSS Statistics version 25.0.

RESULTS: Using binary logistic regression, a model was developed to predict the outcome of childbirth through the natural birth canal in women with a uterine scar, which takes into account statistically significant indicators such as gestational age, estimated fetal weight, parity, and the presence of chronic endometritis and weakness of labor activity in history. The sensitivity of the developed prognostic model is 0.86, the specificity being 0.70. The area under the ROC curve is 0.87 (95% confidence interval 0.78–0.96; p < 0.001).

CONCLUSIONS: The comprehensive analysis of risk factors allows for predicting the outcome of natural childbirth in women with a uterine scar, which in the future will optimize the tactics of their delivery and prevent the development of complications in childbirth for the mother and fetus.

Journal of obstetrics and women's diseases. 2022;71(4):33-40
pages 33-40 views

Analysis of the pathogenic CYP21A2 gene variants in patients with clinical, biochemical and combined manifestations of hyperandrogenism

Osinovskaya N.S., Glavnova O.B., Yarmolinskaya M.I., Sultanov I.Y., Klyuchnikov D.Y., Tkachenko N.N., Nasykhova Y.A., Glotov A.S.

Abstract

BACKGROUND: The association of heterozygous carriage of pathogenic variants in the CYP21A2 gene with various manifestations of hyperandrogenism remains poorly understood to date.

AIM: The aim of this study was to analyze the relationship between the carriage of pathogenic variants in the CYP21A2 gene in women and various manifestations of hyperandrogenism.

MATERIALS AND METHODS: Clinical description, hormonal testing and molecular genetic analysis of the CYP21A2 gene were performed in 97 women with clinical, biochemical and combined manifestations of hyperandrogenism and in 46 people in the control group. The mean age of the patients was 27.3 ± 0.6 years. Levels of 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and androstenedione were measured in the blood serum of the study participants. To identify pathogenic variants in the CYP21A2 gene, we used next generation sequencing, restriction fragment length polymorphism analysis, real-time polymerase chain reaction, and multiplex ligation-dependent probe amplification analysis. A statistical analysis of the frequency of pathogenic CYP21A2 gene variants in the study groups and hormone levels in different study subgroups was carried out.

RESULTS: In patients with hirsutism, acne, menstrual irregularity, miscarriage and infertility, pathogenic variants in the CYP21A2 gene were identified in 31% (30/97) of cases in the heterozygous state and in 6% (5/97) of cases in the homozygous state. The frequency of these variants (in the heterozygous state only) was significantly higher — 6.5% (3/46) of cases, when compared to the control group (p < 0.0001). The identified pathogenic variants included both single nucleotide substitutions such as P31L (n = 1), I2splice (n = 1), V282L (n = 15), I173N (n = 3), Q319X (n = 8), R357W (n = 1), P454S (n = 1), and P483S (n = 1) and deletions of various lengths (n = 10). We found no significant difference in the levels of dehydroepiandrosterone sulfate and androstenedione between heterozygous carriers and the control group and between heterozygous carriers and patients with the wild type CYP21A2 gene (p > 0.05), while 17-hydroxyprogesterone level in the group of patients with heterozygous changes was higher, when compared to the control group (p < 0.001).

CONCLUSIONS: Heterozygous carriage of pathogenic variants in the CYP21A2 gene is associated with manifestations of hyperandrogenism. However, further study of the mechanisms underlying this association is required.

Journal of obstetrics and women's diseases. 2022;71(4):41-52
pages 41-52 views

Analysis of cell immune regulation features in recurrent ovarian endometriosis

Petrovskaia N.N., Pechenikova V.A.

Abstract

BACKGROUND: The prevalence of endometriosis among women of reproductive age and the complexity of choosing the methods for its effective treatment necessitate the study of the clinical and morphological features of ovarian endometriosis in its recurrent course, as well as the search for available informative diagnostic and prognostic markers which allow identifying risk groups for relapse and form prevention methods. Endometriomas have a recurrence rate of 50–55 % after treatment.

AIM: The aim of this study was to conduct a comparative analysis of cell immune regulation features in recurrent ovarian endometriosis.

MATERIALS AND METHODS: We studied clinical data, the value of peripheral immunocompetent blood cells, as well as morphological and immunohistochemical data of 196 patients operated on for endometrioid ovarian cysts, including 45 patients with a recurrent course of the disease and 151 women without relapse. Monoclonal mouse antibodies to T helpers (CD4), T killers (CD8), B lymphocytes (CD20), and macrophages (CD68) were used for immunohistochemical examination of the surgical material. Immunological examination of peripheral blood was performed by flow cytometry with the assessment of helper T lymphocyte, killer T lymphocyte and B lymphocyte subpopulations and their ratios.

RESULTS: The recurrence rate of endometrioid ovarian cysts was 22.96%. Most patients (48.87%) relapsed 3–4 years after the first operation. In patients with recurrent endometrioma, we more often detected complaints of dyspareunia, dysmenorrhea, primary infertility and a history of operations on the uterine appendages unrelated to endometriosis in anamnesis, as well as the third degree of the pathological process. During morphological examination, the glandular-cystic variant and morphologically active lesions were detected more often in recurrent endometriosis compared to the relapse-free course. Cytotoxic T killers (CD8) and macrophages (CD68) were shown to be the predominant subpopulation of cells found in the inflammatory infiltrate of cytogenic stroma and endometrioid cyst capsule. More of them were detected in recurrent endometrioid cysts in the surgical material of both the first and second operations compared to the relapse-free course. B lymphocyte count was significantly higher in the cyst capsule with recurrent endometriosis than in cases of the relapse-free course. T helpers (CD4) were found only in the surgical material of an already diagnosed recurrence. Immunological examination of peripheral blood of patients with recurrent endometrioma revealed an increase in the total population of T lymphocytes due to a subpopulation of T helpers, the number of which per microliter exceeded the reference values.

CONCLUSIONS: An increase in the number of free stromal cells in the foci of endometriosis with its recurrent course indicates the importance of hyperreactivity and the autoimmune mechanism in the chronization and progression of the disease.

Journal of obstetrics and women's diseases. 2022;71(4):53-63
pages 53-63 views

Evaluation of the effectiveness of modified CRD tests in the diagnosis of preeclampsia

Fedotov S.A., Gerasimova E.M., Vashukova E.S., Pakin V.S., Kapustin R.V., Pachuliya O.V., Glotov A.S., Kulichikhin K.Y., Chernoff Y.O., Rubel A.A.

Abstract

BACKGROUND: Preeclampsia is a multisystem complication of pregnancy associated with an increased risk of maternal / perinatal morbidity and mortality. In this regard, the development and following improvement of low-cost and convenient methods for diagnosis of preeclampsia is essential for accurate prediction, quick confirmation of the diagnosis and convenient monitoring of the pathology.

AIM: The aim of this study was to optimize a preeclampsia diagnosis test system based on the binding of proteins to the Congo red dye (CRD test).

MATERIALS AND METHODS: The study used 70 urine samples obtained from patients diagnosed with preeclampsia (n = 25) and from non-preeclampsia pregnant women (n = 45). The samples were stained with Congo red and the dye retention in the sample on the membrane after washing was calculated. Before staining, protein concentrations in the urine samples were equalized using centrifugal concentrators or the samples were used with the original protein concentrations. To wash the samples from the unbound dye, either methanol or ethanol was used. To compare the effectiveness of four CRD test variants differing in sample preparation, staining, and washing, ROC analysis was performed (IBM SPSS Statistics 20 software).

RESULTS: The express CRD test was designed as an optimization of the conventional CRD test. The effectiveness of the express test (the area under the ROC curve being 0.9) was higher than that of the other three test options (the area under the ROC curve ranges from 0.67 to 0.82). The developed express CRD test can provide 95% specificity and 73% sensitivity, which indicates the promise of using this method in clinical diagnostics for the specific detection of preeclampsia patients.

CONCLUSIONS: Optimization of the CRD test has provided more effective protocols for diagnosis of preeclampsia from urine samples using Congo red (express CRD test) and has simplified the routine application of this test in clinical practice.

Journal of obstetrics and women's diseases. 2022;71(4):65-74
pages 65-74 views

Microbiological features and perinatal outcomes in patients with preterm premature rupture of membranes and oligohydramnios

Chistyakova O.M., Chervinets V.M., Chervinets Y.V., Grebenshchikova L.Y., Radkov O.V.

Abstract

BACKGROUND: Oligohydramnios in preterm premature rupture of membranes is the cause of increased perinatal morbidity and mortality among preterm newborns. Microbiological features in women with preterm premature rupture of membranes and oligohydramnios are probably some of the determining factors affecting the implementation of an unfavorable outcome of gestation.

AIM: The aim of this study was to determine microbiological features and perinatal outcomes in patients with preterm premature rupture of membranes and oligohydramnios.

MATERIALS AND METHODS: This retrospective study conducted from 2018 to 2021 included 161 pregnant women with PPROM at 24 to 33 weeks and 6 days of gestation. Of these, the main group consisted of 83 patients with signs of oligohydramnios, while the control group comprised 78 patients without oligohydramnios. Patient examination upon admission to the hospital included analysis of the amniotic fluid index, the white blood cell differential, plasma ferritin and C-reactive protein levels, and bacteriological tests of vaginal secretions by isolating and growing microbes on optimal culture media.

RESULTS: The patients with oligohydramnios had shorter latent period (р = 0.004), but the noted distinctions were a higher frequency of clinical chorioamnionitis (р = 0.025), fetal distress (р = 0.030), and earlier parturition (р = 0.040) with more frequent caesarean sections (р = 0.016) compared to the control group. Vaginal microbiota in the main group showed a higher prevalence of Staphylococcus aureus (р = 0.008), Bacteroides spp. (р = 0.030), Streptococcus spp. (р = 0.002), Micrococcus spp. (p < 0.001), Bacillus subtilis (p < 0.001), Bacillus megaterium (p = 0.009), Bacillus buchneri (р = 0.008), Klebsiella pneumoniae (р = 0.002), Haemophilus spp. (р = 0.005) and no Candida albicans compared to the control group. In the main group, newborns more often had a lower body weight at birth (р = 0.002) and a lower Apgar score at the fifth minute (р = 0.011). They also showed higher incidences of respiratory distress syndrome (р = 0.006), bronchopulmonary dysplasia (р = 0.036), congenital pneumonia (р = 0.011) and necrotizing enterocolitis (р = 0.022) and more often needed treatment in an intensive care unit (р = 0.034), including surfactant supplementation (р = 0.007), cardiotonic support (р = 0.004) and artificial lung ventilation (р = 0.006) compared to the control group.

CONCLUSIONS: Oligohydramnios in preterm premature rupture of membranes is associated with pronounced dysbiotic changes in the vaginal microbiota including the prevalence of Micrococcus spp., Streptococcus spp., Staphylococcus aureus and absence of Candida spp. from the isolates, as well as increased incidence of adverse perinatal outcomes.

Journal of obstetrics and women's diseases. 2022;71(4):75-84
pages 75-84 views


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