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No 10 (2022)

Articles

New technologies in solving the problems of preeclampsia

Nikitina N.A., Sidorova F.S., Ageev M.B., Timofeev S.A., Kiryanova M.A., Morozova E.A.

Abstract

This review deals with the current state of the problem of preeclampsia in obstetrics. It is emphasized that hypertensive disorders and preeclampsia still retain their positions among the leading causes of maternal death in Russia in the presence of a progressive increase in the incidence of severe preeclampsia. The high percentage of preventable and potential preventable cases of maternal death due to preeclampsia (72.5% in 2020) suggests that there is a need for further improvement of the management strategy for these patients, as well as a deeper study of the pathophysiological mechanisms responsible for the development of this pregnancy complication. The paper emphasizes that the concept of failure of cytotrophoblast invasion as a cause of preeclampsia is currently in doubt. Taking into account the modern principles of personalized medicine, there is a need for innovative large-scale, high-throughput, unbiased researches. These requirements are met by the latest methods in systems biology, in particular, the so-called omics technologies (genomics, epigenetics, transcriptomics, proteomics, and metabolomics). The paper presents studies published in the largest databases on the use of omics technologies in the study of preeclampsia. Conclusion: A comprehensive study of the structure of a genome, as well as many ways of implementing genetic information (a systematic multi-omic design) will be able to gain a complete idea of the physiological and pathological processes, including preeclampsia.
Obstetrics and Gynecology. 2022;(10):5-13
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The role of lipidomic studies in human reproduction and in the outcomes of infertility treatment programs using assisted reproductive technologies

Fortygina L.A., Makarova N.P., Nepsha O.S., Lobanova N.N., Kalinina E.A.

Abstract

Lipids and lipophilic trace elements are of increasing interest as potential non-invasive predictive molecules for in vitro fertilization outcomes. Their antioxidant and/or pro-inflammatory activities have an impact on female and male reproductive functions. Since the causes of fertility disorders may be related to metabolic imbalance, metabolomics can be applied to reproductive medicine to identify and quantify low-molecular-weight metabolites in follicular fluid and in the germ cells of couples undergoing assisted reproductive technologies. Studying the effect of lipids on the outcomes of assisted reproductive technologies in order to correct lipid metabolism disorders will help to improve live birth rates. Data from the Russian and foreign articles found in PubMed (http://pubmed. ncbi.nim.nih.gov) and published over the past 5 years were systematically analyzed. The paper presents data from studies investigating the lipidome of follicular fluid, spermatozoa and seminal plasma, blood plasma from couples and the possible prospects for studies in assisted reproductive technology programs. Conclusion: Despite the extent of current investigations, the question of the combined mutual influence of the lipid profile of female and male gametes and blood of patients on the parameters of oogenesis, spermatogenesis, and embryogenesis, and, accordingly, on the outcomes of assisted reproductive technology programs, remains open. Further investigations are needed to study lipidome in order to predict the outcomes of treatment with assisted reproductive technologies and to develop possible interventions to correct the lipidome composition.
Obstetrics and Gynecology. 2022;(10):14-20
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Main criteria and risk factors for the development of recurrent endometriosis

Senina D.N., Chuprynin V.D., Buralkina N.A., Chursin V.V., Smolnova T.Y., Davidyan L.Y., Abosov A.S.

Abstract

Objective: To analyze the data available in the current literature on the recurrence of different forms of endometriosis and to identify the main criteria and risk factors for the development of a relapse of the disease. The review article includes the data published by foreign and Russian authors in the Pubmed, UpToDate, and eLibrary databases on the keywords "endometriosis", " deep infiltrating endometriosis", and "recurrent endometriosis". Endometriosis is observed in 10% of reproductive-aged women and ranks third among gynecological diseases. The literature review focuses on risk factors for recurrent endometriosis. The term “recurrent endometriosis” is non-uniform and ambiguous; different studies describe various parameters of recurrent disease. This concept is used in different sources of literature in different ways: as recurrent pain, as the detection of new lesions by pelvic ultrasound or MRI, as a repeated increase in CA-125 levels, or as a surgical finding of new endometrioid implants during surgery unassociated with endometriosis. Conclusion: At the moment, there are no unified clinical and molecular criteria for recurrent endometriosis. The lack of understanding of risk factors for recurrent endometriosis cannot build a unified strategy for early diagnosis, timely therapy and surgical treatment
Obstetrics and Gynecology. 2022;(10):22-26
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Colorectal endometriosis: morphofunctional and pathogenetic aspects

Krishtal Z.O., Magnaeva A.S., Asaturova A.V., Tregubova A.V., Kometova V.V., Dumanovskaya M.R., Tabeeva G.I., Buralkina N.A., Chuprynin V.D., Matronitsky R.B., Pavlovich S.V.

Abstract

Despite more than a century of studying the etiology, pathogenesis, and clinical course of endometriosis, advances in its treatment remain very modest from both therapeutic and surgical viewpoints. Colorectal endometriosis is one of the types of deep infiltrating endometriosis. Occurring mainly in reproductive-aged women, the above disease dramatically reduces quality of life in patients, while taking into account the complexity of clinical, pathophysiological, and cellular manifestations, the study of the etiopathogenesis and morphological manifestations of colorectal endometriosis seems relevant. The paper presents the modern concepts of development of deep infiltrating endometriosis, including colorectal endometriosis, in conjunction with its morphological manifestations. Based on data from the modern literature, it can be concluded that the formation of ectopic endometrial foci may be due to discoordination of immune processes and to infiltration of the lesion with various inflammatory cells that affect the expression of matrix metalloproteinases, cytokines, angiogenic factors, neurotrophins, etc. This stimulates angiogenesis and neurogenesis, epithelial-mesenchymal transition, transdifferentiation of fibroblasts into myofibroblasts, as well as stromal cells into smooth muscle cells, which ensures the survival of endometrioid heterotopias. Conclusion: Further study of the profile of various biological substances in ectopic endometrial lesions may contribute to the development of targeted treatments for endometrioid disease.
Obstetrics and Gynecology. 2022;(10):28-36
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Experience of using high-throughput sequencing (NGS) for noninvasive prenatal screening of fetal aneuploidy at the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Tarasenko O.A., Vashukova E.S., Kozyulina P.Y., Morshneva A.V., Maltseva A.R., Pachulia O.V., Talantova O.E., Koroteev A.L., Ivashchenko T.E., Bespalova O.N., Kogan I.Y., Baranov V.S., Glotov A.S.

Abstract

Objective: To evaluate the clinical efficiency of noninvasiveprenatal screening of fetal aneuploidies in the mother’s blood conducted at the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction from December 2019 to April 2022 in comparison with f irst trimester combined screening. Material and methods: A total of4272 blood samples obtained from pregnant women were analyzed. Noninvasive prenatal screening of fetal aneuploidies was performed by means of the analysis of extracellular DNA (eDNA) of the fetus in the mother’s blood by high-throughput sequencing (NGS). Results: A high risk of fetal aneuploidy was noted in 173/4272 cases (4.05% of all studies). The results were confirmed by invasive diagnostic methods in 138 cases. Among them, the most common disorders are trisomy 21 (Down syndrome) - 74.63% of cases, trisomy 18 (Edwards syndrome) - 7.97%, trisomy 13 (Patau syndrome) - 6.52%; these results are consistent with the findings obtained in the Russian and foreign practice. The prognostic value of detecting trisomy 21, 18, and 13 is significantly higher in comparison with first trimester combined screening. There is a high percentage of fetuses with abnormalities (2.41%) in women of the so-called fetal concern group; their percentage is equal to that (2.46%) in pregnant women of “intermediate risk” according to the results of early prenatal screening. Conclusion: The results of the study show the high clinical efficacy of noninvasive prenatal screening of fetal aneuploidy by NGS method. In case of detecting a high risk of fetal chromosomal pathology, it is necessary to refer the patient to a geneticist for consultation and for solving the issue of invasive prenatal diagnosis as well.
Obstetrics and Gynecology. 2022;(10):37-49
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The role of immunological markers in predicting the course and outcome of pregnancy in patients with isthmic cervical insufficiency

Timokhina E.V., Strizhakov A.N., Pesegova S.V.

Abstract

Objective: To investigate the clinical value of cervical canal IL-6, IL-8, and MMP-8 in predicting gestational age at delivery in pregnant women with isthmic cervical insufficiency (ICI). Materials and methods: A prospective cohort study enrolled 60 pregnant women with ICI. Women were divided into 2 groups categorized by gestational age at delivery. Pregnant women in Group 1 (n=23, 38.3%) and Group 2 (n=37, 61.7%) gave birth before and after 32 weeks of gestation, respectively. During vaginal speculum examination, all patients underwent cervical mucus sampling from the cervical canal to determine IL-6, IL-8, and MMP-8 concentrations. Results: In Group 1, the concentration of IL-6, IL-8, and MMP-8 was 12.2 pg/ml, 283.2 pg/ml, and 28.1 ng/ml. In Group 2, the concentration IL-6, IL-8, and MMP-8 was 7.2 pg/ml, 142.4 pg/ml, and 14.6 ng/ml. Correlation analysis between cervical marker levels and gestational age at delivery revealed a strong negative statistically significant correlation for all markers (p<0.001). Linear regression showed association between gestational age at delivery and the concentrations of immunological markers at the time of initial diagnosis of ICI: the higher the level of cervical markers, the higher the risk of spontaneous preterm birth (PB). ROC curve analysis determined the optimal threshold values for each of the markers including IL-6 concentration of 9.6 pg/ml, IL-8 of 195.6 pg/ml, and MMP-8 -of 21.5 ng/ml. Conclusion: Threshold values for IL-6≥9.6 pg/mL, IL-8≥195.6 pg/mL, and MMP-8≥21.5 ng/mL concentrations in the cervical canal can be recommended as predictive of very early and early PB, and are highly likely to be predictors of intraamniotic inflammation/infection regardless of the results of the cervical content culture.
Obstetrics and Gynecology. 2022;(10):50-57
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Efficacy of the tourniquet hemostasis combined with vaginal balloon tamponade using a Zhukovsky vaginal catheter during delivery in placenta accreta spectrum

Kulikov I.A., Shmakov R.G., Belousova T.N., Plakhotina E.N., Nizyaeva N.V., Geilis I.A., Iskakov D.D., Milyutina E.R., Vdovichenko E.A., Prochakovsky D.V.

Abstract

Objective: To evaluate the efficacy of distal tourniquet hemostasis combined with vaginal balloon tamponade using a Zhukovsky vaginal catheter during delivery of pregnant women with placenta accreta spectrum to reduce intraoperative blood loss. Materials and methods: A prospective observational study enrolled 164 pregnant women with histologically confirmed placenta accreta spectrum and underwent distal tourniquet hemostasis. The patients were divided into Group 1 (study group, n=133) and Group 2 (control group, n=31) who had and did not have vaginal balloon tamponade in addition to distal tourniquet hemostasis, respectively. Results: All patients in Group 1 (n=133) underwent organ-sparing surgery. The median blood loss was 959 (699; 1651) mL in Group 1 and 1549 (899.5; 2098) mL in Group 2. Patients in Group 1 did not require a transfusion of donor blood components. The volume of autotransfusion in the study group was 208 ml versus 485 ml in the control group. Conclusions: Distal tourniquet hemostasis combined with vaginal balloon tamponade using a Zhukovsky vaginal catheter was highly effective in surgical delivery in patients with placenta accreta spectrum and allowed significant reduction in intraoperative blood loss. The findings of the study give reason to recommend the use of this technique in daily clinical practice to guide the delivery strategy in pregnant women with this pathology.
Obstetrics and Gynecology. 2022;(10):58-66
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Social and demographic predictors of postpartum depression in women in Slovakia

Kelcikova S., Mazuchova L., Maskalova E., Malinovska N.

Abstract

Postpartum depression can negatively affect the overall quality of life in mothers and child’s emotional, cognitive, and behavioral development. Objective: Estimation of the prevalence of postpartum depression and the study of relationship between the risk of postpartum depression and socio-demographic factors in women in Slovakia. Materials and methods: A randomized study of newborns’ mothers (n=584; the mean age 30.9 (4.8) years) was conducted in two University maternity hospitals in Slovakia from 2019 to 2020. The first data of the study were obtained at baseline level (2-4 days after childbirth, stage I), and the next data were obtained from the subsequent follow-up (6-8 weeks after childbirth, stage II). Depression symptoms were measured using Slovakians version of the Edinburgh Postnatal Depression Scale. Moreover, some issues in the study were dedicated to detection of social and demographic risk. Threshold value 10 and higher indicated a high risk for depression symptoms. Multiple logistic regression model was used for statistical analysis. Results: Prevalence of postpartum depression was 12.74% at stage I, and 22.05% at stage II. Regression analysis with regard to social and demographic factors showed that i) primiparous women; ii) unemployment before pregnancy; and iii) insufficient financial security were statistically significantly associated with the symptoms of postpartum depression in the first days after childbirth (p<0.05). Six weeks after childbirth, the relationship between postpartum depression and i) insufficient financial security; ii) unemployment in the postpartum period (р<0.05) was identified. Conclusion: Among puerperant women, significant differences in the level of depression were identified with respect to the sodal and demographic factors. These factors need to be further explored and should be taken into account when planning intervention and prevention strategies for women.
Obstetrics and Gynecology. 2022;(10):67-75
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BRCA1 pathogenic variants in women with premature ovarian failure

Rshtuni S.D., Chernukha G.E., Bystritskiy A.A., Tabeeva G.I., Krasheninnikova R.V., Marchenko L.A.

Abstract

The role of BRCA1 pathogenic variants in the genesis and development of premature ovarian aging has been discussed in the literature in recent years. Objective: To identify the proportion of female carriers of BRCA1 pathogenic variants among patients with premature ovarian failure (POF). Materials and methods: This was an observational longitudinal study which included 142 women with POF who underwent BRCA testing. The patients were aged from 18 to 39 years (median age is 35 years (Q1-Q3 29-38). The control group consisted of150 women with timely menopause (median age is 54 years (Q1-Q3 46-71); they underwent BRCA testing optionally. Results: During the study we identified two cases of the most frequent BRCA1 pathogenic variants (loci 3819del GTAAA and 5382insC) which constitute 1.4% (95% CI: 0.4-5.0%) in POF pathology. Conclusion: BRCA1 pathogenic variants are associated not only with an increased risk of oncopathology, but also with a diminished ovarian reserve; therefore, the principles of cancer prevention in patients with POF should be revised. In case of diminished ovarian reserve, it is necessary to carry out not only primary standard cancer screening, but one should also carefully take a family history of cancer with the subsequent administration of BRCA genetic testing.
Obstetrics and Gynecology. 2022;(10):76-82
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Analysis of treatment satisfaction in patients with premature ovarian failure

Averkova V.G., Yureneva S.V.

Abstract

Objective: To analyze treatment satisfaction in patients with premature ovarian failure (POF) and to study the frequency and severity of symptoms of estrogen deficiency in patients with POF taking hormone replacement therapy (HRT). Materials and methods: A cross-sectional study which was carried out on the basis of the National Medical Research Center for Obstetrics, Gynecology and Perinatology, included 223 patients diagnosed with POF. Treatment satisfaction was assessed using a structured survey; the severity of estrogen deficiency symptoms was determined using a questionnaire (Greene Climacteric Scale). Results: Most of the study participants (86.3%) received HRT medications containing a standard dose of estradiol (E2): 2 mg were administered orally and 1 mg of 1% gel was administered via the transdermal route. Low-dose HRT was taken by 2.2%, combined oral contraceptives (COC) were received by 1.8%. Higher doses of E2 were taken by 2.2% of the participants. The survey of the women showed that 53.8% were satisfied and 41.3% were not satisfied with the therapy. The lowest indicators of treatment satisfaction were obtained by patients who took low-dose HRT (p=0.022) and COC (p=0.048). The patients who took higher doses of E2 as part of HRT were satisfied with the treatment in 100% of cases. The average severity of climacteric syndrome among the participants was 12 points according to the Greene Climacteric Scale. The ROC analysis of the dependence of the negative assessment of therapy on the total score on the Greene Scale showed that the area under the ROC curve was 0.809 (0.031) with 95% CI: 0.748- 0.870 (p <0.001). The threshold value of the total score on the Greene Scale at the cut-off point was 14 points; the cut-off point corresponded to the highest value of the Yuden index. Conclusion: The high percentage of patients dissatisfied with therapy as well as persistent symptoms of estrogen deficiency associated with HRT administration indicate the need to revise approaches to the management of patients with POF.
Obstetrics and Gynecology. 2022;(10):83-92
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Micronutrient status of women with impaired reproductive function in the Northwestern region of Russia

Bespalova O.N., Zhernakova T.S., Shengelia M.O., Zagaynova V.A., Pachulia O.V., Kogan I.Y.

Abstract

Background: In the modern world, the global population experiences metabolic syndrome pandemic as a result of micronutrient deficiencies. Intake levels of vitamin D, folates and polyunsaturated fatty acids vary in different populations. This issue is understudied among women with reproductive losses and infertility. Objective: To assess the micronutrient status (25-hydroxyvitamin D [25(OH)D], folic acid, omega-3 PUFAs) in the cohort of women in the Northwestern region of Russia, who have various reproductive impairments in history and evaluate relationship between impairments and the parameters of immunological profile. Materials and methods: The study included 299 women who had infertility in history. Their anamnestic data were obtained from the database of D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology (St. Petersburg) from 2017 to 2022. The patients were divided into 2 groups depending on their reproductive anamnesis. Group I (n=131) consisted of women with primary infertility. Group II (n=168) was comprised of women with secondary infertility, who had both emergency childbirth and one or more cases of reproductive loss (spontaneous abortion or missed miscarriage) in history. Further, at the stage of pregnancy planning (3 months before getting pregnant), different parameters of the micronutrient status in blood plasma and serum and immunological profile in the peripheral blood were evaluated in these groups of women. The micronutrient status was evaluated using the following techniques: chemiluminescent microparticle immunoassay was used to assess 25(OH)D circulating form of vitamin D levels in serum samples; chemiluminescent microparticle immunoassay (CMIA) was used to evaluate plasma homocysteine levels (the Laboratory of D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology); and gas chromatography-mass spectrometry was used to perform the Omega-3 Index test (the laboratory “Hemotest”). The assessment of immunological profile was performed by measuring the functional activity and the level of natural killer (NK) cells (the percentage (%) of NK cells (CD3-CD(16+56)+, the percentage (%) of NKT (CD3+CD(16+56)+, spontaneous NK cell activation (CD107a), activation of NK cells (CD107a) by flow cytometry. Antiphospholipid antibodies - lupus anticoagulant, antibodies against cardiolipin, β2 -glycoprotein, phosphatidylserine, phosphatidylic acid, phosphatidylinositol, annexin, prothrombin and the level of a human chorionic gonadotropin IgG (hCG IgG) antibodies were measured by ELISA (in the Department of Immunology and Intercellular Interactions, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology). The following target values were determined for the patients of reproductive age: vitamin D≥30 ng/ml; homocysteine concentration <7 μmol/L; Omega-3 Index ≥ 8%. Results: In the group of women with primary infertility vitamin D level (n=55) was 31.90 (20.65; 40.75) ng/ml, whereas in the group with secondary infertility (n=74) it was 24.70 (18,00; 34,00) ng/ml. In both groups, median values of homocysteine were above target values and reached 7.7(6.0; 9.0) μmol/L (n=79) and 7.3(5.9; 3.6) μmol/L (n=100) in group I and group II, respectively. Omega-3 Index was 6,5 (5.1; 7.6)% in the group of women with primary infertility (n=14), and 5,2 (4,4; 5,9)% in the group of women with secondary infertility (n=42). However, there was no statistical difference between the groups (p<0.062). There was no statistically significant difference in the levels of vitamin D and homocysteine between the groups. Due to this, the subsequent analysis of these parameters was performed entirely regardless of the type of infertility in the general cohort of patients. Thus, in the general cohort of patients with infertility, vitamin D deficiency (<20 ng/ml) was in 38/129 (29,46%) women, insufficiency (20-30 ng/ml) was in 35/129 (27.13%), normal level was in 56/129 (43.41%) women. The target level of homocysteine (<7 μmol/L) was in 79/179 (44.13%) women, and non-target values (>7 μmol/L) were in 100/179 (55.87%) women. Omega-3 Index was critically low (<4%) in 5/56 (8.93%) women, insufficient (4-8%) in 46/56 (82.14%), and optimal (>8 %) in 5/56 (8.93%) women. Correlation analysis showed direct relationship between the mean values of vitamin D and Omega-3 Index (rs=0.5; p<0,01) and the level of homocysteine and human chorionic gonadotropin (hCG) antibodies (rs=0.5 p<0.01), as well as inverse relationships between vitamin D and immunological parameters: β2-glycoprotein antibodies (rs=-0.34; p=0,04), percentage (%) of NK (rs=-0.4; p=0.03); and Omega-3 Index and cardiolipin antibodies (rs=-0.47 p=0.03). There was no significant correlation between the other values. It has been shown, that the value of Omega-3 Index changes depending on the level of vitamin D (H=12.5; p=0.002). So, in women with vitamin D deficiency, the median level of Omega-3 Index was the lowest and reached 4.2 (3.8; 4.6) %, and was statistically significantly lower than in women with vitamin D insufficiency and reached 5.5 (4.6; 7.1)% (p=0.012), and it was lower than in patients with normal level of vitamin D, and this value was the highest and reached 5.85 (5.2; 6.9)% (p=0.002). In women with serum vitamin D level <20 ng/mL, there was a risk of identifying critically low level of Omega-3 level (OR=14.4 (1.23-168.51), p<0.05). Conclusion: According to the data in our study, the cohort of women with reproductive failures and infertility had a high prevalence of vitamin D deficiency, high level of homocysteine and low Omega-3 Index. Correlations between the micronutrient status and immunological profile were identified, which may be a factor that contribute to reproductive dysfunction
Obstetrics and Gynecology. 2022;(10):93-102
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Does sexual intercourse during IVF/ICSI cycle affect endometrial thickness in the presence of immunohormonal markers of stress in the seminal plasma?

Nikolaeva M.A., Babayan A.A., Arefieva A.S., Chagovets V.V., Starodubtseva N.L., Frankevich V.E., Kalinina E.A., Krechetova L.V., Sukhikh G.T.

Abstract

Men’s stress may alter the concentration of immunological and hormonal factors in seminal plasma, which, on entering the female reproductive tract during sexual intercourse, may affect endometrial development. Objective: To investigate the relationship between endometrial thickness in women having intercourse during the proliferative phase of the IVF/ICSI cycle and the content of immunological and endocrine stress markers in the partner's seminal plasma. Materials and methods: This prospective study included 71 couples with tubal infertility factor having unprotected intercourse during the proliferative phase of IVF/ICSI cycle, supplemented with intravaginal injection of seminal plasma on the day of transvaginal ovarian puncture. The retrospective pilot study included couples with IVF/ICSI success (group 1, n=7) and IVF/ICSI failure (group 2, n=9). They were comparable by clinical, demographic and laboratory parameters, but differed in the content of immunohormonal stress markers in the partner's seminal plasma. The groups were formed based on the content of cytokines IL-18 and IL-1P, steroid hormones, their precursors and seminal plasma metabolites. Endometrial thickness was measured by transvaginal ultrasound on the day of ovulation trigger. The cytokine content in seminal plasma was assessed by flow cytofluorometry and fluorescent microspheres using FlowCytomix technology. The concentration and total amount of steroids in seminal plasma were determined using a combination of high-performance liquid chromatography and tandem mass spectrometry. Results: Prospective and retrospective studies revealed a reduced endometrial thickness in the group of patients with an increased content of immunoendocrine stress markers in seminal plasma. There was a negative correlation between endometrial thickness and concentration and/or total amount of 17-a-hydroxypregnenolone, testosterone, progesterone, and cytokines IL-18, IL-1P in seminal plasma. The cortisol/DHEA ratio was positively associated with endometrial thickness. Conclusion: The study's finding suggested that stress-related seminal immunological and hormonal factors in the seminal plasma entering the female reproductive tract during sexual intercourse in the proliferative phase of the IVF/ICSI cycle may negatively impact endometrial development. However, further research is necessary to establish a causal link between the composition of seminal plasma and the endometrial status.
Obstetrics and Gynecology. 2022;(10):103-114
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The impact of COVID-19 on the outcomes of assisted reproductive technology programs

Dolgushina N.V., Ermakova D.M., Lomova N.A., Menzhinskaya I.V., Vtorushina V.V.

Abstract

Objective: To investigate the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19 of various severity. Materials and methods: This prospective study enrolled 240 infertile patients. They were divided into group 1 comprising patients without a history of COVID-19 (n=105) and group 2 (n=135) including patients who less than 12 months before the ART cycle had mild (subgroup 2a, n=85) or moderate (subgroup 2b, n=50) COVID-19. The level of specific antibodies to SARS- CoV-2, parameters of oogenesis, early embryogenesis, and clinical outcomes of HRT were evaluated. Results: The parameters of oogenesis and embryogenesis, pregnancy and delivery rates did not differ between groups 1 and 2. A weak negative correlation was detected between the level of IgG-antibodies to SARS-CoV-2 and the number of obtained oocytes and embryos. Patients with an interval between COVID-19 and ART cycle 46 months had a significantly higher relative number of poor-quality blastocysts than women with >6 months interval. Patients who experienced moderate COVID-19 had a high early miscarriage rate of (12%). Conclusion: COVID-19 can adversely affect reproductive outcomes, lead to a decrease in the number of oocytes and embryos obtained in ART cycles and their quality, and increase the risk of early miscarriage. More research is needed to investigate the mechanisms underlying the adverse effects of COVID-19 and the post- COVID syndrome.
Obstetrics and Gynecology. 2022;(10):115-122
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The impact of COVID-19 on the ovarian reserve in women

Ermakova D.M., Dolgushin G.O., Ivanets T.Y., Vtorushina V.V., Dolgushina N.V.

Abstract

Objective: To investigate ovarian reserve and menstrual function in women with COVID-19 of various severity. Materials and methods: This prospective study analyzed parameters of ovarian reserve (AMH, FSH, and the AFC) and menstrual cycle (cycle length, menstrual duration) in 41 patients before and after COVID-19 disease. The interval between measurements was 6-12 months. Mild and moderate COVID-19 was observed in 31 (group 1) and 10 (group 2) patients. The inclusion criteria were age 18-45 years, preserved menstrual function. Non-inclusion criteria were decreased ovarian reserve before the onset of COVID-19 (AMH<1.2 ng/mL, AFC<5), a history of COVID-19 vaccination, pregnancy and lactation, severe somatic and infectious comorbidities affecting ovarian reserve. Results: In patients of late reproductive age (LRA) (>35 years), COVID-19 was associated with a reduction in ovarian reserve. Furthermore, patients with more severe COVID-19 had a more pronounced decrease in AFC. When simultaneously assessing the effect of infection severity and age on ovarian reserve, it was found that LRA patients with a more severe form of infection had the biggest decrease in ovarian reserve. The menstrual cycle did not change significantly. Conclusion: The study findings reflect the impact of both age and severity of COVID-19 on ovarian reserve in women. In women of LRA, a decrease in ovarian reserve can occur spontaneously, and the time difference can be very significant. Therefore, one cannot accurately state that ovarian reserve reduction was due to the disease. Nevertheless, the effect of infection severity on the degree of ovarian reserve reduction suggests an adverse effect of SARS-CoV-2 on ovarian function in women.
Obstetrics and Gynecology. 2022;(10):123-128
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Androgen profile in infertile women undergoing treatment with assisted reproductive technologies depending on the ovarian response

Gavisova A.A., Kindysheva S.V., Starodubtseva N.L., Frankevich V.E., Dolgushina N.V.

Abstract

Objective: To evaluate the androgen profile in infertile women undergoing treatment with assisted reproductive technologies (ART) depending on the ovarian response. Materials and methods: The study included 150 women who underwent IVF/ICSI treatment at the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, and met the inclusion criteria. The groups were stratified depending on the ovarian reserve on the basis of the POSEIDON classification and ovarian response to the stimulation in accordance with the Bologna criteria: group 1 included 50 patients with diminished ovarian reserve (AMH<1.2 ng/ml, CAF<5) and poor ovarian response to stimulation (≤3 oocytes during transvaginal puncture); group 2 consisted of 100 patients with normal ovarian reserve (AMH≥1.2 ng/ml, CAF≥5), among them there were 50 patients with normal ovarian response (>9 oocytes) and 50 patients with reduced ovarian response (<9 oocytes). The androgen profile in the follicular fluid and blood serum was studied using mass spectrometry data. Results: Depending on the decrease in the ovarian reserve and ovarian response, there was a statistically significant decrease in the concentration of total testosterone and androstenedione in the blood. The women with reduced ovarian response had a statistically significant decrease in the blood level of total testosterone and androstenedione compared to women with normal ovarian reserve and normal response. There was also a decrease in the concentration of DHEA-C in the follicular fluid associated with a decrease in ovarian reserve and ovarian response. However, there was a reverse trend for androstenedione in the follicular fluid: women with normal ovarian response and normal ovarian reserve had lower levels of androstenedione. Conclusion: This study was the first comparative assessment of the androgen profile in infertile patients using mass spectrometry which is considered to be the gold standard. This analysis indicates changes in the levels of androgens and confirms their role in the emerging androgen deficiency. Our study also confirms the hypothesis about the influence of androgens on the processes of folliculogenesis and their significant contribution to the ovarian response. It is possible to explain pathogenetically the value of studies on the effect of hormonal priming in women with infertility and diminished ovarian reserve in order to block apoptosis of follicles and increase sensitivity to FSH.
Obstetrics and Gynecology. 2022;(10):129-137
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Comparative study of the equivalence of the biosimilar follitropin alpha preparation (solution for subcutaneous injection) and the original follitropin alpha preparation (lyophilisate for preparation of solution for subcutaneous administration) in women with different responses to ovarian stimulation in an in vitro fertilization program: results of a phase IV clinical trial

Perminova S.G., Nazarenko T.A., Korneeva I.E., Bashmakova N.V., Mityurina E.V., Alimova O.A., Belova I.S., Ershov A.V., Khramtsova A.Y., Dzhalilova E.R.

Abstract

The efficacy and safety of any medication should be proven in randomized prospective clinical trials. However, the data obtained in real clinical practice are important for the formation of the evidence base and make the results of the study on the effectiveness and safety of the medications available to a wide population of patients. Objective: To determine the equivalence of the biosimilar follitropin alpha preparation (Primapur, solution for subcutaneous administration) and the original follitropin alpha preparation (Gonal-F, lyophilisate for preparation of solution for subcutaneous administration) in women with different responses to ovarian stimulation in an in vitro fertilization program. Materials and methods: This is a retrospective, non-interventional (observational), cohort, comparative, multicenter study of the efficacy and safety of the biosimilar follitropin alpha preparation (Primapur, solution for subcutaneous administration, IVFarma, Russia), and the original follitropin alpha preparation (Gonal-F, lyophilisate for preparation of solution for subcutaneous administration, Merck-Serono, Italy). A total of 240 patients were included in the study: 120 patients received Primapur, a solution for subcutaneous administration, and 120 patients used Gonal-F, lyophilisate for preparation of solution for subcutaneous administration. The patients were stratified depending on the parameters of the ovarian reserve and the expected ovarian response. Results: The results of the study confirmed the therapeutic equivalence of the biosimilar follitropin alpha preparation (Primapur, solution for subcutaneous administration) and the original follitropin alpha preparation (Gonal-F, lyophilisate for preparation of solution for subcutaneous administration) in women with different responses to ovarian stimulation in an in vitro fertilization program. There were no statistical differences in the parameters of the stimulated cycle: in the initial, daily and total dose of drugs, in the number of aspirated and mature oocytes, zygotes, blastocysts, blastocysts of good quality and cryopreserved embryos in the compared groups. The outcomes of in vitro fertilization programs (the rate of biochemical pregnancy, clinical pregnancy, early reproductive losses and ongoing pregnancy) were also comparable in the subgroups with hypo-response, normal response and hyper-response and did not differ statistically. Conclusion: The biosimilar follitropin alfa preparation (Primapur, solution for subcutaneous injection) can be recommended for a wide use in clinical practice in various categories of patients in the in vitro fertilization programs, regardless of the parameters of the ovarian reserve and the type of ovarian response.
Obstetrics and Gynecology. 2022;(10):138-149
pages 138-149 views

Modifying the risk of ascending uterine cavity infection during gynecological procedures

Dobrokhotova Y.E., Borovkova E.I., Burdenko M.V., Zaidieva Z.S., Amiryan D.S., Marakhovskaya E.

Abstract

Objective: To modify the risk of ascending uterine cavity infection during gynecological procedures by preventive medical vaginal sanitation. Materials and methods: A prospective cohort study was conducted in 80 patients who required outpatient gynecological procedures (hysterosalpingography, office hysteroscopy). There were 2 randomized groups: a study group who before the manipulation received a 6-day cycle of sanitizing therapy with a multicomponent local agent; a comparison group had no therapy. The formed groups were matched by age, parity, anamnestic data, and gynecological history. The Femoflor-16 PCR-RT assay was used to assess the microbiocenosis of the vagina and uterine cavity. Results: The total vaginal bacterial mass in the patients of both groups was lg 6.3 and 6.2 GE/sample (p=0.94). After the sanitizing therapy, the study group showed a decrease in the total vaginal bacterial contamination to lg 4.8 (Q1-Q3: 4.4-5.05) (p=0.03). The total uterine bacterial mass was lg 2.3 GE/sample (Me, IQR 2.05- 2.95) and lg 4.8 GE/sample (Me, IQR 4.25-5.2) in the study and comparison groups, respectively (p<0.001). Comparing the indicators of uterine bacterial contamination with those of vaginal biocenosis after sanitation revealed a decline in the number of Peptostreptococcus spp., Veilonella spp. and Mobiluncus spp. in 17.5% of patients (p=0.018), Staphylococcus spp. (p=0.043) and Atopobium vaginae in 12.5% (p=0.042), Streptococcus spp. in 20% (p=0.012), Gardnerella vaginalis in 27.5% (p=0.003), and members of the Enterobacteriaceae family in 35.5% (p=0.01). Uterine cavity biocenosis could be characterized as lactobacillus-dominant in 98% of patients in the study group; the dominant lactobacillus type of biocenosis was detected in 42.5% of those in the comparison group. Before and after the therapy, the correlation between the total vaginal bacterial mass was statistically significant (p=0.03; r =0.63) (Spearman's rank correlation coefficient) and had a noticeable tightness in accordance with the Chaddock scale. There were statistically significant direct correlations between the total vaginal bacterial mass after the therapy and the amount of Lactobacillus spp. (ry=0.514; p=0.02) and Gardnerella vaginalis (ry=0.55;p=0.01) in the uterine cavity. Conclusion: Preoperative sanitizing therapy can reduce the overall bacterial contamination of the vagina and uterine cavity by 2 times.
Obstetrics and Gynecology. 2022;(10):150-158
pages 150-158 views

The effect of a new contraceptive with estetrol on the thrombotic safety profile of hormonal contraception

Akinshina S.V., Koloda Y.A.

Abstract

Thromboembolic complications are rare but potentially life-threatening adverse events associated with combined hormonal contraceptives (CHCs). The thrombogenic safety of CHCs is an issue that customarily causes the greatest concern among specialists and patients when choosing a birth control method, whereas the need to design new contraceptives with a minimal adverse effect on the hemostatic system has always remained relevant. Esteretta is the first CHC containing estetrol, a selective estrogen, which belongs to a fundamentally new class of estrogen with selective action in tissues and has a neutral metabolic profile and a minimal effect on the hemostatic system. The paper presents the current guidelines for selection of hormonal contraception in patients at high thrombotic risk; a review on the effect of various combined hormonal contraceptives on the hemostatic system; an analysis of the effects of the new contraceptive Esteretta on the parameters of the hemostatic system and on the risk of thromboembolic complications in the view of an obstetrician/gynecologist and hematologist. Conclusion: Despite a more favorable safety profile with regard to the hemostatic system, contraindications to the use of Esterette are the same as to that of other CHCs, while the thrombotic safety of this drug remains to be analyzed from the results of studies involving a large number of patients and in terms of real clinical practice.
Obstetrics and Gynecology. 2022;(10):159-168
pages 159-168 views

Non-developing pregnancy in the history of a married couple: risk factors and rehabilitation

Posiseeva L.V.

Abstract

Genetic, anatomical, infectious, endocrine, and immune factors are identified as main risk ones for nondeveloping pregnancy (NDP). The latter is commonly caused by the abnormal development of the zygote, embryo, and fetus, or by structural abnormalities in the genetic program for placental development. Most pregnancy losses result from infection, mainly from persistent viral infection along with opportunistic microorganisms. Particular attention is paid to chronic endometritis that is an autoimmune disease, as well as to alloimmune disorders. About 40% of NDPs are of uncertain origin. The role of male factor for NDP is considered. Male sperm pathology may be characterized by increased viscosity, reduced motility of spermatozoa, their agglutination and aggregation, abnormal morphology, low sperm glycodelin levels, elevated sperm fragmentation, and viral infection. The negative influence of male factor is exhibited via sperm pathology, which is associated with the genetic risk of conception and ovum defects, whereas which is related to the risk of embryo chorionic insufficiency when the genetic program is undisturbed. Conclusion: Rehabilitation of married couples with NDP involves the consistent exclusion of possible causes, including sperm pathology. If the cause is identified, these factors need to be corrected. A set of measures for the rehabilitation of male reproductive health is considered to incorporate inositols as effective agents to improve fertility.
Obstetrics and Gynecology. 2022;(10):170-176
pages 170-176 views

Rationale for the choice of menopausal hormone therapy if treatment switching is needed in the context of a personalized approach

Tapilskaya N.I., Bespalova O.N., Kogan I.Y.

Abstract

Timely and personalized menopausal hormone therapy (MHT), as is indicated, is a key method for maintaining health and quality of life in women and for preventing menopause-related diseases. The benefits of MHT outweigh possible risks in somatically healthy women, but the situation becomes more complicated in comorbid patients. At the same time, active ageing is a new expectation of mankind today. MHT should be selected in terms of the severity of menopausal symptoms, the presence of concomitant diseases, drug tolerance, and other personal characteristics of the patient; it is alsi important to consider the availability of prescription medicines in the country for their long use. In practice, physicians and patients often face the situations requiring that MHT should be switched. A correct algorithm of the physician’s actions will largely ensure treatment efficiency and safety and the woman’s adherence to the prescribed therapy. This aspect demonstrates the relevance of elaborating and introducing an algorithm of actions into practice when a demand arises for MHT drugs to be switched. The paper presents an update on rational MHT. Particular attention is paid to the efficacy, tolerability and safety of combination MHT containing estrogen and progestogen on the basis of the results of relevant studies and in the context of national and international clinical practice guidelines. A tactic in managing menopausal women is demonstrated, by describing clinical cases as an example. The presented algorithms of the physician’s actions, when a demand rises for MHT drugs to be switched, reflect the current approaches to personalizing patient care in real clinical practice and are an effective practical solution. Among the drugs intended for the correction of menopausal symptoms, the estradiol/didrogesterone combination meets all the criteria for MHT according to the International Menopause Society (IMS), the European Menopause and Andropause Society (EMAS), and the National Institute for Health and Care Excellence (NICE). The range of different estradiol/didrogesterone combination dosages and regimens allows personalizing the therapy for menopausal disorders as much as possible and provides an opportunity to manage the patient throughout the period from peripause to postmenopause, without changing the progestogen. Conclusion: The current tactics of managing patients with menopausal symptoms and the algorithm for replacing hormonal drugs give the physician and patient the chance to have the maximum efficiency and safety of therapy and high adherence to treatment and to prevent long-term complications.
Obstetrics and Gynecology. 2022;(10):178-184
pages 178-184 views

The importance of a multidisciplinary approach to the delivery and subsequent management of patients with placenta increta

Gritskevich A.A., Baitman T.P., Simonov A.D., Melnikov M.V., Chuprynin V.D., Karelskaya N.A.

Abstract

Background: Placenta increta is an abnormal partial or complete attachment of placental villi to the uterine wall. The main etiological factor of placenta increta is uterine traumatization, in particular during repeat caesarean sections or intrauterine surgical interventions. With a rise in the frequency of these operations, the prevalence of the pathology under consideration also increases by more than 10 times over the past 30 years. Undiagnosed placenta increta is associated with a high risk for massive blood loss and maternal mortality in delivery. Case report: The paper describes a clinical case of placenta increta first detected during caesarean section (a third childbirth). The delivery was complicated by uterine and urinary bladder rupture, ureteral traumatization, and massive blood loss. Hysterectomy and bladder wall defect suturing were done as vitally indicated. The early postoperative period was complicated by urinary peritonitis that made sanitation and drainage of the abdominal cavity and small pelvis, fistuloplasty and ureteral reimplantation to be performed. At 3 months when urine resumed to flow into the bladder, vesicovaginal fistula formation and microcystis were diagnosed due to dislocation of one of the nephrostomes. Cystectomy and orthotopic vesiculoplasty were electively carried out. An 8-month follow-up demonstrated improvements in general condition of the patient and her quality of life. Conclusion: Placenta increta increases the risk of life-threatening intra- and postoperative complications, which makes a multidisciplinary approach to preoperative preparation, perioperative management and delivery of the patients at high risk for placenta increta particularly important.
Obstetrics and Gynecology. 2022;(10):186-194
pages 186-194 views

To the Jubilee of E.A. Chernukha

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Obstetrics and Gynecology. 2022;(10):195-195
pages 195-195 views

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