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Vol 71, No 3 (2022)

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Original Research

The effectiveness of the application of modern diagnostic criteria of cervical pathology

Kazakova A.V., Lineva O.I., Kiyashko I.S., Dufinets I.E., Chechko S.M., Mishina A.I.


BACKGROUND: Cervical cancer is one of the four most common cancers today and is the second most common cancer among women in developing countries. According to World Health Organization estimates, in 2018, the number of new cases in these countries was 570,000 (84% of all new cases globally). About 311,000 women died of cervical cancer in 2018, with more than 85% of these deaths occurring in low- and middle-income countries. The detection of the disease in its later stages has not significantly reduced since 2018 (32.6% of all cases).

AIM: The aim of this study was to compare the information contents of conventional and liquid cytology methods in women with verified human papillomavirus of high oncogenic risk.

MATERIALS AND METHODS: We retrospectively analyzed 50 outpatient records of women aged 23 to 65 years who underwent colposcopy (cervical biopsy) based on the results of cervical screening. To establish the diagnosis, all patients underwent examination of smears from the cervix and cervical canal using conventional (n = 25) and liquid (n = 25) cytology methods. A molecular genetic study was carried out to detect high-oncogenic human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 56, 58) in scraping of the cervix by real-time polymerase chain reaction. Women in the both study groups also underwent colposcopy with histological examination of the cervical biopsy specimen. The analysis of the obtained data was carried out using methods of parametric and nonparametric statistics. Inclusion criteria included cytological examination, verified human papillomavirus of high oncogenic risk, and colposcopy. Exclusion criteria included pregnancy and acute infectious diseases.

RESULTS: According to the results of histological examination, the percentage of coincidence of cytological and histological diagnosis in the group of women who underwent conventional cytological examination was 48%. The total number of discrepancies in this group was 13 (52.0 ± 9.99%). The number of women infected with human papillomavirus in the both study groups was almost the same (18 in the conventional cytology group and 19 in the liquid cytology group). The most common types of human papillomavirus among the examined patients were the 16th type (9 women) and the 18th type (6 women).

CONCLUSIONS: To date, cytological research methods have not lost their relevance, the liquid cytology method being a reliable screening test with high specificity, which reduces the number of unsatisfactory preparations for analysis and false negative results. The most informative for women with type 2 or type 3 of transformation zone is the use of the liquid cytology method.

Journal of obstetrics and women's diseases. 2022;71(3):5-12
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Pathogenetic significance of antiphospholipid antibodies in the development of placenta-associated complications in pregnant women with thrombocytopenia

Mysik O.L., Zainulina M.S., Klikunova K.A., Orlova E.S.


BACKGROUND: Thrombocytopenia is one of the most common cytopenic syndromes that complicate pregnancy. It is considered a typical hematological criterion and the second most common manifestation of antiphospholipid syndrome. In recent years, the relationship between the development of thrombotic and placenta-associated pregnancy complications and the circulation of antiphospholipid antibodies has been actively studied, which makes it necessary to search for new methods for hemostasis correction and for prevention of the development of obstetric complications.

AIM: The aim of this study was to assess the incidence of antiphospholipid antibodies in pregnant women with thrombocytopenia in order to determine the risk of obstetric complications and adverse pregnancy outcomes depending on the presence of antiphospholipid antibodies in the examined women.

MATERIALS AND METHODS: 299 pregnant women were included in this multicenter prospective study: the main study group (n = 249) consisted of patients with thrombocytopenia, and the control group (n = 50) comprised women with normal platelet counts during a physiological pregnancy. All participants underwent a complete clinical and anamnestic examination and a study of the hemostasis system. To determine antibodies to cardiolipin, beta-2 glycoprotein 1, annexin V, and prothrombin (IgG/IgM/IgA), we performed enzyme-linked immunosorbent assay in 84 pregnant women with thrombocytopenia and in 25 women in the control group. Lupus anticoagulant was determined in 123 pregnant women of the main group and 25 women in the control group using an ACL-200 coagulometer (Instrumentation Laboratory, Spain).

RESULTS: A comparative analysis of antiphospholipid antibodies detection has shown that in pregnant women with thrombocytopenia, lupus anticoagulant was detected in every third case (35.8% of cases, 44/123 women), which is more common than in the control group (8.0% of cases, 2/25 women; p = 0.008). Antibodies to beta-2 glycoprotein 1 were detected in pregnant women with thrombocytopenia in every fourth case (27.4% of cases, 23/84 women), and in the control group only in 4% of cases (1/25 women; p = 0.013). Antibodies to cardiolipin were also more often detected in pregnant women with thrombocytopenia (23.8% of cases, 20/84 women) compared to the control group (4% of cases, 1/25 women; p = 0.040). Based on the data obtained with V Cramer, we established medium-strength direct correlations between criterial antiphospholipid antibodies circulation and the development of placenta-associated complications of pregnancy (p < 0.05; 0.2 < V < 0.4). We also identified statistically significant risks of developing placenta-associated complications in pregnant women with circulating antiphospholipid antibodies (95 % confidence interval excludes 1).

CONCLUSIONS: Thrombocytopenia during pregnancy develops more often in women with antiphospholipid antibodies. Antiphospholipid antibodies circulation elevates coagulation potential and activates intravascular coagulation, resulting in an increased risk of placenta-associated complications of pregnancy, which requires hemostasis correction.

Journal of obstetrics and women's diseases. 2022;71(3):13-20
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Postoperative scar endometriosis: the clinical course, diagnosis, treatment, and the morphological examination of surgical material

Pechenikova V.A., Akopyan R.A., Danilova A.S., Petrovskaia N.N.


BACKGROUND: Postoperative scar endometriosis is diagnosed in 0.03–1.5% of women and is 0.42–4.0% of the total number of endometriosis lesions. The increase in the frequency of surgical delivery and the difficulties of early clinical diagnosis determine the relevance of clinicopathologic analysis of postoperative scar endometriosis.

AIM: The aim of this study was to conduct a comprehensive comparative analysis of the clinical course, diagnostic criteria, results of surgical and combined treatment, as well as morphological and morphofunctional features of postoperative scars endometriosis.

MATERIALS AND METHODS: We analyzed complaints, anamnesis, general clinical, gynecological and instrumental examination data, as well as results of the morphological examination of the surgical material from 21 patients with postoperative scar endometriosis. Immunohistochemical study of the surgical material was performed according to the avidin-biotin complex method using monoclonal mouse antibodies to alpha-smooth muscle actin (Dako, Denmark).

RESULTS: The average age of patients with postoperative scar endometriosis was about 33.6 ± 6.3 years. In 19 out of 21 patients (90.47%), this pathology occurred in the scar after caesarean section. The main clinical manifestation of the disease was pain syndrome. All patients complained of periodic pain in the area of the postoperative scar, which worsened on the eve and during menstruation. According to its nature and intensity, the patients characterized the pain as dull (33.3%), aching (14.3%), paroxysmal (19.1%), or “twitching” (33.3%). In some cases (28.6%), the pain syndrome was accompanied by nausea and vomiting. Many women (71.4%), in addition to the pain, noted the appearance of dark brown (bloody) discharge from the scar during menstruation. In macro- and microscopic examination, postoperative scar endometriosis foci formed nodes of different sizes without a clear capsule. This was due to proliferation of connective tissue fields found in all observations with a large number of collagen fibers located around and between heterotopias. Immunohistochemical study of postoperative scar endometriosis revealed perifocal proliferation of myofibroblasts, which surrounded endometrioid heterotopias in the form of “couplings” and was characterized by positive expression of alpha-smooth muscle actin. Concentric myofibroblast proliferates in the form of nodules were found in the cytogenic stroma of endometriosis foci.

CONCLUSIONS: Early diagnosis and treatment of endometriosis are important in terms of preventing the fibrosis and sclerosis of the affected tissues and organs, which lead to their deformation and dysfunction.

Journal of obstetrics and women's diseases. 2022;71(3):21-30
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The effectiveness of the Dr. Arabin cervical pessary in the prevention of extreme preterm birth and very preterm birth in twins

Sargsyan G.S., Pachuliia O.V., Bespalova O.N.


BACKGROUND: Multiple pregnancy remains a serious obstetrical problem, as it is a high risk factor for miscarriage/preterm birth at any gestational age. On average, in 54% of patients with twins, pregnancy ends in preterm birth, regardless of the economic situation and the level of perinatal care in the state, and is characterized by high childhood morbidity and mortality.

AIM: The aim of this study was to identify risk factors for spontaneous preterm birth and to evaluate the effectiveness of a cervical pessary in pregnant women with twins and a short cervix.

MATERIALS AND METHODS: This prospective, open, randomized cohort study included 91 women with twins, a short cervix (<25‰ according to the L.J. Salomon scale) and a threatened miscarriage / preterm birth in the second and third trimesters of pregnancy, who received the Dr. Arabin cervical pessary. We analyzed pregnancy outcomes and identified risk factors for spontaneous preterm birth.

RESULTS: Based on the pregnancy outcomes, all patients were categorized into two main groups after 16 pregnant women with induced preterm birth were excluded from further study. The study was continued by 75 pregnant women, with term birth in 40 (53.3%) women in group I and spontaneous preterm birth in 35 (46.7%) women in group II.

The average period of pregnancy prolongation was statistically different between groups II and I (8.86 ± 4.86 and 12.32 ± 4.38 weeks, p < 0.01). The average gestational age of labor initiation was 37.73 ± 0.62 weeks in group I and 34.24 ± 2.08 weeks in group II (p < 0.001). We found no extreme preterm birth (22-27 6/7 weeks) in group II, the perinatal mortality of newborns being the highest at this gestational age. Labor at a gestational age of 28-33 6/7 weeks was in 14 (18.67%) women and of 34-36 6/7 weeks in 21 (28.00%) women. The detailed analysis of the course and outcomes of pregnancy and labor in high-risk groups identified two factors that affect the occurrence of spontaneous preterm birth in twin pregnancies: the Bishop score > 5 points (p = 0.03579; odds ratio 4.93, 95% confidence interval 1.23–19.74) and cervical length on bimanual vaginal examination < 20 mm (p = 0.014; odds ratio 4.67, 95% confidence interval 1.47–14.82).

CONCLUSIONS: The use of a cervical pessary in the group of pregnant women with twins and at a high risk of spontaneous preterm birth not only allows for prolonging pregnancy and excluding the birth of extremely premature babies, but also reduces the number of spontaneous extreme and very preterm births.

Journal of obstetrics and women's diseases. 2022;71(3):31-42
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Preterm birth: the impact of risk factors on pregnancy outcomes

Khalitova R.S., Ziganshin A.M., Mukhametdinova I.G., Mudrov V.A.


BACKGROUND: Despite the achievements of modern obstetrics and neonatology, the problem of preterm birth remains one of the most pressing.

AIM: The aim of this study was to evaluate the influence of risk factors on the outcome of threatened preterm birth.

MATERIALS AND METHODS: This prospective cohort study included the analysis of clinical and anamnestic data of 130 patients delivered at various gestational ages. The main group comprised 68 women with preterm delivery, with the control group consisting of 62 women with timely delivery.

RESULTS: The outcome of preterm birth is adversely affected by overweight in the group of modifiable risk factors, by history of premature birth in the immediate family in the group of non-modifiable risk factors, and by a previous COVID-19, anemia and autonomic nervous system disorders in the group of potentially modifiable risk factors. The most reliable prognostic marker for the development of preterm labor was the shortening of the cervical length of less than 2.5 cm according to ultrasound.

CONCLUSIONS: The formation of risk groups based on the analysis of clinical, anamnestic, medical, and social data, as well as somatic and gynecological diseases can help avoid the development of adverse outcomes of preterm birth.

Journal of obstetrics and women's diseases. 2022;71(3):43-52
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Melatonin in the pathogenesis of preeclampsia

Evsyukova I.I., Kvetnoy I.M.


The review presents the results of experimental studies that have revealed the molecular mechanisms underlying implantation and placentation controlled by cytokines, chemokines, adhesion molecules, hormones, as well as transcription and growth factors, and have indicated the key regulatory and protective role of melatonin. It has been shown that low production of the hormone and lack of its circadian rhythm underlie the disruption of endogenous antioxidant protection and contribute to oxidative stress leading to the development of preeclampsia. The necessity of using melatonin as a neuroimmunoendocrine marker of pathology is emphasized in this review article, which will allow for developing new approaches to its use for the prevention and treatment of preeclampsia, as well as its adverse consequences, such as obesity, type 2 diabetes mellitus, renal failure, and cardiovascular pathology.

Journal of obstetrics and women's diseases. 2022;71(3):53-64
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Dominant Lactobacillus spp. in different conditions of vaginal microbiocenosis

Kalinina N.A., Sulima A.N., Rumyantseva Z.S., Rybalka A.N., Baskakov P.N., Voronaya V.V., Lyashenko A.S.


The vaginal microbiota is a primary non-specific barrier that protects against various bacterial, viral and fungal pathogens. A normal microflora of the female genital tract is represented by aerobes, facultative and strict anaerobes. Bacteria of the genus Lactobacillus spp. dominate the majority of women of reproductive age. They have high protective properties against other microorganisms. Lactobacillus spp. prevent an excessive reproduction of opportunistic and pathogenic microorganisms in the vaginal biotope due to the synthesis of short-chain acids that maintain the pH value in the normal range. As a rule, one or two species of Lactobacillus spp. dominate in the vaginal biotope, which are responsible for ensuring homeostasis of the vaginal microflora. At the same time, various Lactobacillus spp. differ in their protective properties. L. crispatus is a marker of the stability of the vaginal microflora. With the dominance of this type of lactobacillus, the authors of the studies observed a low risk of bacterial vaginosis, aerobic vaginitis, and unwanted obstetric complications during pregnancy and in assisted reproductive technology protocols, as well as a reduced risk of infection with sexually transmitted infections and human papillomavirus. L. gasseri and L. iners were more often detected in women with intermediate microflora or with dysbiosis. L. iners, unlike L. crispatus, has reduced protective properties and is widespread in dysbiotic conditions of the vaginal microflora. The detection of L. iners can serve as a prognostic sign of the development of pathological conditions of the vaginal microflora.

Journal of obstetrics and women's diseases. 2022;71(3):65-76
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Assisted reproductive technology and uterine cancer risk. A systematic review and meta-analysis

Klyukina L.A., Sosnova E.A., Ishchenko A.А.


BACKGROUND: The problem of infertility has not only medical, but also socio-demographic significance. To date, the global scale of the spread of various forms of infertility is beyond doubt among specialists around the world. This, in turn, causes an increase in the frequency of prescribing assisted reproductive technologies, but the question of the relationship between the prescribing of drugs used to treat infertility and the risk of developing cancer of the uterine body remains poorly understood.

AIM: The aim of this study was to assess the possible relationship between in vitro fertilization, the use of ovulation stimulation drugs and the risk of developing uterine cancer in women with infertility.

MATERIALS AND METHODS: This literature systematic review is based on resources from the following databases: Medline, ClinicalKey, Google Scholar, Embase, the Cochrane Library, and eLIBRARY for the period 1999–2022. The search for publications was carried out using keywords defined in accordance with the PICO principle (P, population or patients; I, intervention; C, comparison; O, outcomes): “female”, “women”, “infertility”, “infertility treatment”, “in vitro fertilization”, “IVF”, “assisted reproductive technology”, “ART”, “ovarian stimulation”, “ovarian hyperstimulation”, “clomiphene citrate”, “hCG”, “hMG”, “tamoxifen”, “uterine”, “endometrial”, “cancer”, “carcinoma neoplasm”, “uterine neoplasm”. The following SQL operators were used during the search: AND and OR.

RESULTS: The search resulted in 37 representative publications, with eight studies selected for meta-analysis.

CONCLUSIONS: This systematic review and meta-analysis have demonstrated the ambiguity of the design and results of studies on the possible relationship of uterine cancer and assisted reproductive technology methods published to date. The issue under review is urgent due to the high frequency of infertility and an increase in the frequency of gynecologic cancers. The conducted studies confirm that it is impossible to evaluate the carcinogenic effect of ovulation inducers or in vitro fertilization methods without adjusting for the infertility factor, as well as risk factors for uterine cancer. There is still a high need for further research, particularly for studying the safety profile of infertility treatment methods in relation to long-term cancer risks.

Journal of obstetrics and women's diseases. 2022;71(3):77-86
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The role of pre-pregnancy care for women with pregestational diabetes mellitus for improving maternal and perinatal outcomes

Misharina E.V., Yarmolinskaya M.I., Tiselko A.V.


The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus can have various adverse consequences for the mother, fetus, child, and pregnancy. Pregnancy planning in women with pregestational diabetes mellitus significantly improves the outcomes of pregnancy and childbirth. The introduction of diabetes self-control skills, the use of human insulin and insulin analogues, the use of constant subcutaneous insulin infusion and family planning allows for optimal glycemic control in early pregnancy and reduces the incidence of fetal congenital anomalies and perinatal mortality. Lifestyle optimization, weight loss, taking adequate doses of folic acid, discontinuation of teratogenic medications, and quitting smoking are essential components of preconception care. Of significant clinical value is the training of women planning pregnancy at the “Diabetes school”, training in self-control and insulin therapy skills, consultation with an endocrinologist, an obstetrician-gynecologist, an ophthalmologist, a nephrologist, and a nutritionist.

The aim of this study was to present current data on pre-pregnancy care in patients with pregestational diabetes mellitus and to show its possibilities in reducing the frequency of obstetric and perinatal complications. We analyzed 74 domestic and foreign literature sources using the following databases: PubMed, PubMed Central, Google Scholar, and UpToDate.

Journal of obstetrics and women's diseases. 2022;71(3):87-100
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Maternal pregestational diabetes as an factor in the genesis of congenital malformations of the fetus

Shengelia N.D., Bespalova O.N., Shengelia M.O.


This review article summarizes the results of modern clinical studies performed domestically or abroad, which provide information on maternal pregestational diabetes (type 1 or 2) shaping a spectrum of congenital malformations of the fetus. Advances in the treatment of diabetes mellitus have reduced the risk of fetal congenital malformations in pregnant women with the disease, but an increase in its incidence among women of childbearing age indicates that this cause of congenital malformations is becoming more relevant every year. This review article presents four diabetes-mediated pathways for the genesis of fetal congenital malformations: those associated with metabolic imbalance or oxidative stress, genetically mediated and caused by insufficient inhibition of apoptosis. Thus, based on clinical studies and meta-analysis over the past ten years, it has been demonstrated that women with pregestational diabetes mellitus are at the highest risk of developing fetal congenital malformations. Achievement of diabetes compensation and physiological nutritional status in such patients determines the favorable course of all stages of pregnancy.

Journal of obstetrics and women's diseases. 2022;71(3):101-110
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History of medicine

The Northern School of Obstetricians and Gynecologists: the scientific legacy of E-A.Ya. Krassovsky, N.V. Yastrebov, K.F. Slavyansky, and D.O. Ott

Andreyeva A.V., Samburov G.O., Baranov A.N., Revako P.P., Burenkov G.M.


This article provides information on the Northern School of Obstetricians and Gynecologists established in the city of Arkhangelsk, Russia thanks to the scientific legacy of E.-A.Ya. Krassovsky, N.V. Yastrebov, K.F. Slavyansky, D.O. Ott and V.V. Preobrazhensky. World-famous scientists, as heads of obstetric and gynecological clinics in St. Petersburg, Russia made a huge contribution to the creation and future development of the northernmost medical institute not only in the European Arctic Russia, but also in the world, as well as to the opening of the Department of Obstetrics and Gynecology in 1934. In 2022, the Northern State Medical University (formerly Arkhangelsk State Medical Institute, Arkhangelsk State Medical Academy) is to celebrate its 90th anniversary.

Journal of obstetrics and women's diseases. 2022;71(3):111-118
pages 111-118 views

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