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Vol 72, No 2 (2023)

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Original Research

Prognostic value of anti- and proangiogenic factors in severe preeclampsia

Vasileva M.Y., Smirnov I.V., Ishkaraeva V.V., Yakovleva N.Y., Vasilyeva E.Y., Chepanov S.V., Kalosha L.V., Tamakhina O.N., Selkov S.A., Zazerskaya I.E.

Abstract

BACKGROUND: Over the years, preeclampsia has remained a common pathology of pregnancy. Its severe form poses a significant threat to the health of the woman and the fetus. To assess the risk of developing preeclampsia, biochemical screening for placental growth factor and soluble tyrosine kinase-1 is carried out. The soluble glycoprotein endoglin, which regulates angiogenesis by influencing cell activation, adhesion, and migration, can supplement the idea of the imbalance of vascular factors in severe preeclampsia. A holistic study of anti- and proangiogenic factors can significantly complement the diagnosis of preeclampsia at the preclinical stage and a look at the course and treatment of this pregnancy complication.

AIM: The aim of this work was to evaluate the concentrations of anti- and proangiogenic factors (soluble glycoprotein endoglin, soluble tyrosine kinase-1, placental growth factor) and compare the obtained data with the clinical manifestations of severe preeclampsia.

MATERIALS AND METHODS: This case-control study included 81 pregnant women. The main group consisted of patients with severe preeclampsia (n = 41), while the control group comprised individuals with normal pregnancy (n = 40). To determine soluble glycoprotein endoglin levels in biological fluids, we used a new ELISA kit developed in the Laboratory of Hybridoma Technology, Academician A.M. Granov Russian Research Center for Radiology and Surgical Technologies (Saint Petersburg, Russia). placental growth factor and soluble tyrosine kinase-1 concentrations were assessed by electrochemiluminescence immunoassay using commercial Roche Diagnostics kits. Statistical analysis was performed using the StatTech v.3.0.6 program (Stattech Ltd., Russia).

RESULTS: When analyzing the concentrations of anti- and proangiogenic factors (soluble glycoprotein endoglin in the blood serum and urine, soluble tyrosine kinase-1, placental growth factor and the ratio of these factors), depending on the study group, statistically significant results were obtained (p < 0.05). The diagnostic significance of serum and urine soluble glycoprotein endoglin levels in predicting the probability of severe preeclampsia was assessed by the method of ROC curve analysis. Statistically significant differences (p < 0.05) were found in the analysis of the concentrations of anti- and pro-angiogenic factors depending on the clinical manifestations such as systolic blood pressure ≥ 160 mm Hg (except for placental growth factor level), a multiple increase in urine soluble glycoprotein endoglin level with massive proteinuria, an increase in soluble glycoprotein endoglin levels in biological fluids with an increase in edematous syndrome. Correlation analysis revealed a significant relationship between anti- and proangiogenic factors and the term of delivery, as well as urine soluble glycoprotein endoglin level and the duration of the treatment.

CONCLUSIONS: The data obtained complement the concept of severe preeclampsia. Knowing the concentrations of soluble glycoprotein endoglin in the blood serum and urine allows for predicting the timing of delivery and the possible duration of treatment, which is critical in the management of patients with severe preeclampsia.

Journal of obstetrics and women's diseases. 2023;72(2):5-17
pages 5-17 views

Labor in women with the new coronavirus infection (COVID-19) and HIV infection

Gareyeva A.I., Kovalchuk A.S., Lioznov D.A., Sudakov D.S., Nesvit E.M., Kucheryavenko A.N.

Abstract

BACKGROUND: HIV and COVID-19 remain some of global health problems today. Complications of these diseases, pregnancy and labor, as well as the perinatal condition of newborns can make a significant contribution to the deterioration of the demographic situation in this country. Summarizing the foreign and domestic literature, one may assess the impact of each individual pathogen on the condition of the pregnant woman and the fetus. However, we have not found data on the associative or antagonistic form of symbiosis of these pathogens, as well as on the joint effect on the pregnancy, labor and the condition of newborns in the available literature.

AIM: The aim of this work was to analyze the outcomes of labor in women with the new coronavirus infection (COVID-19) and HIV infection.

MATERIALS AND METHODS: We performed a retrospective analysis of birth histories of 63 women who were delivered in S.P. Botkin Clinical Infectious Diseases Hospital (Saint Petersburg, Russia) in the period from April 2020 to March 2022. Of these, 26 birth histories are of women with a combination of HIV infection and COVID-19, and 37 birth histories of women with HIV infection alone. We assessed the severity of COVID-19 in pregnant women with HIV infection, the course of labor, complications during childbirth and the condition of newborns.

RESULTS: The groups did not differ in the duration of labor, the frequency of labor abnormalities, the volume of blood loss during delivery, the frequency of postpartum complications and the condition of newborns after one and five minutes on the Apgar scale. The duration of the anhydrous interval was significantly longer in women with HIV infection who did not suffer from COVID-19. The frequency of cesarean section was significantly higher in pregnant women with HIV infection and COVID-19. According to pathological examination, inflammatory changes in the placenta and signs characteristic of viral infection occurred more often in the group of women with HIV infection and COVID-19.

CONCLUSIONS: The presence of COVID-19 affects the course of labor in patients with HIV infection. However, the frequency of caesarean section in the group of patients with HIV infection and COVID-19 was significantly higher due to obstetric reasons, and was not related to the severity of the mother’s condition and the prenatal state of the fetus due to the infectious process. Inflammatory changes in the placenta and signs of a viral infection are more common in patients with COVID-19 and HIV infection. These data suggest that the combined course of these diseases may have a greater negative impact on the fetus than in women with HIV infection who do not suffer from COVID-19.

Journal of obstetrics and women's diseases. 2023;72(2):19-29
pages 19-29 views

Principles of treatment of intrahepatic cholestasis of pregnant women

Zhestkova N.V., Aylamazyan E.K., Kuzminykh T.U., Marchenko N.V.

Abstract

BACKGROUND: Intrahepatic cholestasis of pregnancy occupies a leading place in the structure of hepatoses associated with pregnancy. As with many other diseases that debut during gestation, all the symptoms of intrahepatic cholestasis of pregnancy disappear after delivery and have no consequences for the mother, unlike, for example, acute fatty degeneration of the liver. However, the fetal prognosis remains serious due to the high incidence of preterm birth and the toxic effect of bile components on the developing fetus, which both lead to perinatal complications. Especially fatal is the situation when intrahepatic cholestasis of pregnancy is combined with intrauterine infection, placental insufficiency, severe preeclampsia, diabetes mellitus, or other extragenital pathology. Until recently, it was believed that the only correct solution for intrahepatic cholestasis of pregnancy development was early delivery. Only in recent decades, attempts have been made to therapeutic correction of this pathology in order to prolong pregnancy to full term and reduce the frequency of perinatal complications. So far, tangible results have been achieved with the use of ursodeoxycholic acid preparations and the introduction of efferent methods of therapy into obstetric practice.

AIM: The aim of this study was to develop optimal schemes for pathogenetic therapy of intrahepatic cholestasis of pregnancy using hepatoprotectors from the ursodeoxycholic acid group, as well as ademetionine, essential phospholipids, and membrane plasmapheresis.

MATERIALS AND METHODS: This study included 150 pregnant women with intrahepatic cholestasis of pregnancy. Group I (n = 50) comprised patients who were treated only with ursodeoxycholic acid. Group II (n = 50) included individuals who were given combined drug therapy with ursodeoxycholic acid, ademetionine, and essential phospholipids. Group III (n = 50) consisted of women whose treatment included efferent therapies (membrane plasmapheresis) in combination with ursodeoxycholic acid or ademetionine preparations. All pregnant women before the start of therapy were determined the blood levels of bile acids, total and direct bilirubin, and transaminases (alanine aminotransferase, aspartate aminotransferase). Blood parameters were monitored once every seven days. All the patients were also monitored for the condition of the fetus (fetometry, dopplerometry, cardiotocography).

RESULTS: The use of ursodeoxycholic acid not combined with other hepatoprotectors (group I) was possible only in cases of increased blood levels of bile acids of not more than 40 mmol/L, preparations of ademetionine and essential phospholipids as monotherapy being ineffective. With an increase in the blood levels of bile acids of more than 40 mmol/L and transaminases by two to three or more times from the upper limit of the norm (group II), the most effective was the combined use of ursodeoxycholic acid, ademetionine and essential phospholipid preparations. The most significant decrease in the blood levels of bile acids and hepatic cytolysis parameters (transaminases) was observed when plasmapheresis was used in combination with ursodeoxycholic acid or ademetionine (group III).

CONCLUSIONS: The choice of treatment regimen depends on the level of increase in bile acids and the severity of cytolytic syndrome. With an increase in the level of bile acids to 40 mmol/L, ursodeoxycholic acid preparations can be used only. With an increase in bile acid level of more than 40 mmol/L, the complex use of the above hepatoprotectors is necessary. The most effective treatment regimen is the use of membrane plasmapheresis in combination with ursodeoxycholic acid or ademetionine.

Journal of obstetrics and women's diseases. 2023;72(2):31-38
pages 31-38 views

Extended combined screening for preeclampsia prediction in women with diabetes mellitus

Kapustin R.V., Tcybuk E.M., Kopteeva E.V., Alekseenkova E.N., Chepanov S.V., Shelaeva E.V., Arzhanova O.N., Korenevsky A.V., Kogan I.Y.

Abstract

BACKGROUND: Early screening for preeclampsia has shown high efficiency for low-risk groups, however, the presence of systemic vascular disease in patients with diabetes mellitus complicates their use and requires the development of additional approaches to predicting preeclampsia in this group of patients.

AIM: The aim of this study was to evaluate the effectiveness of early prediction of preeclampsia with extended combined screening in patients with pregestational types of diabetes mellitus.

MATERIALS AND METHODS: This study included 75 pregnant women: 40 patients with type 1 diabetes mellitus, and 35 patients with type 2 diabetes mellitus. To determine the risk of further preeclampsia development, we evaluated biochemical, biophysical and anamnestic factors, along with the serum levels of placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin at 11+0 to 13+6 gestational weeks. The main outcome assessed was the development of preeclampsia.

RESULTS: In patients with further development of preeclampsia (35% in type 1 and 40 % in type 2 diabetic women), we observed higher soluble fms-like tyrosine kinase 1 / placental growth factor ratios, as well as elevated serum soluble endoglin (type 1 diabetes mellitus) and soluble fms-like tyrosine kinase 1 (type 2 diabetes mellitus) levels. Isolated determination of placental growth factor showed no significant differences in the levels of this angiogenic factor in preeclampsia. A multivariate predictive model for preeclampsia demonstrated high prognostic parameters: for patients with type 1 diabetes mellitus, area under the curve was 0.96 (95% confidence interval 0.93–1.00), with positive predictive value 76.7% and negative predictive value 90.1%; for patients with type 2 diabetes mellitus, area under the curve was 0.94 (95% confidence interval 0.86–1.00), with positive predictive value 88.5% and negative predictive value 97.1%.

CONCLUSIONS: Specific biochemical and biophysical markers of preeclampsia combined with maternal risk factors and assessment of carbohydrate metabolism can increase the predictive value of early screening studies for preeclampsia in women with pregestational diabetes mellitus.

Journal of obstetrics and women's diseases. 2023;72(2):39-50
pages 39-50 views

Analysis of the impact of uterine fibroids of different locations and sizes on the perfusion and metabolic characteristics of the endometrium

Polenov N.I., Yarmolinskaya M.I., Zakuraeva K.A., Krutikova V.Y., Potapova E.V., Kogan I.Y., Shengelia N.D.

Abstract

BACKGROUND: Uterine fibroids are the most common benign tumor of the female reproductive system. A number of factors affect endometrial receptivity in patients with uterine fibroids such as transcription factors HOXA10 and HOXA11, cytokines (growth factors and inflammatory markers), etc. The negative effect of myomatous nodes, which deform the uterine cavity, on endometrial receptivity has been well studied and is beyond doubt, while the influence of intramural and intramural-subserosal fibroids on the endometrium is debatable. An important point is to define clear criteria that justify myomectomy in patients without clinical symptoms of the disease who are planning pregnancy, in particular, with the help of assisted reproductive technology. This article presents the results of studies on the impact of uterine fibroids of different locations on the endometrium. The data were obtained from foreign literature sources and such electronic databases as PubMed, CyberLeninka, and Google Scholar in the period from 2000 to 2022. This survey also reflects the main aspects of federal clinical recommendations and demonstrates the results of our own research.

AIM: The aim of this study was to determine the effect of intramural and intramural-submucosal myomatous nodes nodes on the perfusion and metabolic characteristics of the endometrium.

MATERIALS AND METHODS: We conducted a comprehensive examination of 20 patients of reproductive age with uterine fibroids who underwent surgical treatment in Gynecological Department One with Operating Unit of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott (Saint Petersburg, Russia) and the Gynecological Department of N.A. Semashko City Hospital No. 38 (Saint Petersburg, Russia). Two groups were formed: group I consisted of 10 patients with multiple uterine fibroids (FIGO types 2 and 3); group II included 10 patients with intramural and intramural-subserosal myomatous nodes (FIGO types 4 to 6). Studies of endometrial perfusion and metabolism were carried out using a fiber optic system that implements fluorescence spectroscopy and laser Doppler flowmetry, including the LAKK-M diagnostic complex (Lazma Ltd., Russia) and a laparoscopic fiber optic probe, followed by registration of optical signals.

RESULTS: In the group of patients with uterine fibroids that deform the uterine cavity, we revealed a statistically significant decrease in the microcirculation index in endometrial tissues and an increase in fluorescence signals at a wavelength of 365 nm. This may indicate hypoxic phenomena in endometrial tissues of patients with FIGO types 2 and 3 fibroids. These findings are some of the significant pathogenetic causes of implantation disorders and abnormalities in the physiological course of pregnancy in patients of this study group.

CONCLUSIONS: The data obtained substantiate the need to continue research in this direction in order to develop perfusion-metabolic criteria that allow for optimizing the choice of treatment strategies in patients with uterine fibroids.

Journal of obstetrics and women's diseases. 2023;72(2):51-62
pages 51-62 views

Reviews

Pregnancy and childbirth in patients with endometriosis

Bezhenar V.F., Rogatinskaya E.V., Dyachenko D.T., Fedosova D.V.

Abstract

This review of modern literature presents data on the effect of endometriosis on the course of pregnancy and childbirth. It covers studies related to the relationship of pregnancy complications such as preeclampsia and hypertension with previous treatment of endometriosis. Attention is also paid to complications of the postpartum period and the frequency of premature birth. The directions of further development of the problem, which is pregnancy in patients with endometriosis, are determined.

Journal of obstetrics and women's diseases. 2023;72(2):63-70
pages 63-70 views

Topical issues of surgical treatment of pelvic floor dysfunction. A literature review

Bezhenar V.F., Plekhanov A.N., Bezhenar F.V., Epifanova T.A.

Abstract

This article presents a review of the current literature on the problem of omission and prolapse of the internal genitalia in women. Patients diagnosed with pelvic organ prolapse need pelvic floor plastic surgery. Currently, in spite of the extensive experience in managing this category of patients, there is still no single and unambiguous approach to the choice of surgical treatment tactics.

This review describes the latest information on the etiopathogenesis of pelvic floor supporting apparatus lesions, namely, systemic connective tissue dysplasia as the main development factor. Prospective development of genetic and immunohistochemical marker diagnosis is the key to individual selection of treatment options for this multidisciplinary problem. The results of interventions are characterized by extreme variability in terms of both effectiveness and the frequency of intra- and postoperative complications. The treatment of rare forms of prolapse after surgery for rectal cancer also raises many questions. The current multitude of types of surgical interventions for genital prolapse and variants of pelvic floor defect closure is constantly being modified. To date, there is no universal treatment option, and all available techniques have both advantages and disadvantages, as well as limited application due to the risk of somatic complications, high recurrence rate, and the need for expensive equipment and a highly qualified surgeon.

New research is needed, taking into account the current knowledge about the cellular and molecular mechanism of the lesion of the pelvic floor supporting apparatus. All of this will improve the methods of correction of pelvic organ prolapse in both typical and rare forms caused by iatrogenic factors. As a result, this may lead to an improvement in the quality of life of such patients.

Journal of obstetrics and women's diseases. 2023;72(2):71-84
pages 71-84 views

Tocolytics in obstetric practice

Ziganshin A.M., Akbulatova E.V.

Abstract

Preterm birth remains a leading cause of perinatal mortality and morbidity in preterm infants and leads to significant annual health care costs. A special role in preventing premature birth belongs to tocolytic therapy, which allows for prolonging pregnancy and avoiding various complications. However, questions arise about the efficacy and safety of this therapy, which can be manifested by various isolated and combined side effects. The aim of the study was to assess the effectiveness and complications of tocolytic therapy. We analyzed the literature on eLibrary, Medline, Scopus, Cochrane Library, PubMed, ScienceDirect, etc.

Journal of obstetrics and women's diseases. 2023;72(2):85-93
pages 85-93 views

Recurrent genital endometriosis: risk factors and possible prevention strategy

Semenova V.O., Yarmolinskaya M.I.

Abstract

Endometriosis is one of the most common gynecological diseases in women of reproductive age, which is characterized by a relapsing course. The recurrence rate varies greatly among literary sources. This review covers symptoms and types of endometriosis, laboratory tests, options for hormonal therapy, as well as features of surgical approaches that may be associated with the disease recurrence risk. The aim of this article was to analyze and summarize current literature on the definition of endometriosis recurrence, risk factors and prevention strategy. Despite advances in the study of various mechanisms for the development of endometriosis and the use of combined treatment, a high recurrence rate remains an unsolved problem for this disease. All of this underscores the need to develop new methods for early diagnosis and treatment, taking into account the risk group and a personalized approach.

Journal of obstetrics and women's diseases. 2023;72(2):95-103
pages 95-103 views

Theory and Practice

Use of combined hormonal contraceptives in women with uterine fibroids: opinions of practitioners

Aganezova N.V., Aganezov S.S., Shilo M.M.

Abstract

BACKGROUND: Uterine fibroids are increasingly diagnosed in patients of reproductive age. Combined hormonal contraceptives provide reliable protection against unwanted pregnancy and help to reduce or eliminate various clinical manifestations of uterine fibroids. In practice, obstetrician-gynecologists have “barriers” to prescribing combined hormonal contraceptives to patients with uterine fibroids.

AIM: The aim of this work was to study the features of the clinical approach of obstetrician-gynecologists to the management of patients with uterine fibroids interested in combined hormonal contraception.

MATERIALS AND METHODS: The method of voluntary anonymous questioning was applied to 366 obstetrician-gynecologists. The work experience of 62.1% (n = 227) of doctors was 10 years or more. The questionnaire included questions about various aspects of the use of combined hormonal contraceptives for contraception in women with uterine fibroids.

RESULTS: Only every second (47.5%; n = 174) obstetrician-gynecologist correctly assigns uterine fibroids to the first category of acceptability for combined hormonal contraceptives. The presence of an asymptomatic submucous myomatous node (FIGO 1–2) or dysmenorrhea in women with uterine fibroids is considered by 29.0% (n = 106) and 5.7% (n = 21) of obstetrician-gynecologists, respectively, as a contraindication to the use of combined hormonal contraceptives. Every ninth participant (11.4%; n = 42) believes that the presence of uterine fibroids limits the duration of use of combined hormonal contraceptives for contraception to 1–5 years. Almost half (45.6%; n = 167) of the respondents believe that combined hormonal contraceptives have various effects on uterine fibroids (cause regression or growth of fibroids, increase the risk of new fibroids). More than half (53.3%; n = 195) of the respondents are not informed about the reduction in the risk of developing uterine fibroids when using combined hormonal contraceptives for five years or more.

CONCLUSIONS: In the analyzed cohort of experienced obstetrician-gynecologists, we identified their “barriers” to prescribing combined hormonal contraceptives for contraception for women with uterine fibroids. Those are incomplete awareness of the acceptance criteria for combined hormonal contraceptives and insufficient awareness of the lack of effect of combined hormonal contraceptives on the size of existing myomatous nodes and a decrease in the risk of developing uterine fibroids when using combined hormonal contraceptives for five or more years.

Journal of obstetrics and women's diseases. 2023;72(2):105-112
pages 105-112 views

Organ-preserving treatment in progressive cervical pregnancy. A clinical case

Sulima A.N., Gunar Z.V., Adamov A.M., Gordeychik A.E., Mkrtchian A.A., Davydova A.A., Tkacheva N.Y.

Abstract

This article describes a rare clinical case of progressive ectopic pregnancy in the cervix in a female patient of reproductive age, the incidence of which is less than 1% of all ectopic pregnancies. The exact etiopathogenetic mechanism of cervical pregnancy is still unknown. Misdiagnosis of cervical pregnancy can lead to a fatal outcome with massive bleeding and is associated with the risk of hysterectomy and complete loss of fertility in patients of reproductive age.

This article presents the results of a pathoanatomical study confirming the diagnosis and adequacy of the performed therapeutic measures. We demonstrated the complexity of diagnosing this pathology, as well as the possibility and conditions for performing an organ-preserving surgery. The presented clinical case will allow doctors of various specialties to know more about this rare form of ectopic pregnancy, to suspect and successfully diagnose cervical pregnancy in the early stages of gestation, which will avoid or reduce the development of severe and sometimes life-threatening complications.

Journal of obstetrics and women's diseases. 2023;72(2):113-120
pages 113-120 views

History of medicine

In memory of Nikolay Alexandrovich Sosnin, a pioneer of endoscopic operative gynecology in the Arkhangelsk region (to the 70th anniversary of his birth and the 100th anniversary of N.A. Semashko Northern Medical Clinical Center, Arkhangelsk, Russia)

Andreeva A.V., Baranov A.N., Kazakevich E.V., Kozyr O.F., Samburov G.O., Tuchina T.A., Dyachkov S.K.

Abstract

This article presents information about Nikolay Alexandrovich Sosnin, a pioneer of endoscopic operative gynecology in the Arkhangelsk region. On March 10, 2022, he would have turned 70 years old. For more than 30 years, he was the head of the gynecological department of N.A. Semashko Northern Medical Clinical Center (Arkhangelsk, Russia). N.A. Sosnin introduced laparoscopic technology into the practice of gynecologists in the Arkhangelsk region.

Journal of obstetrics and women's diseases. 2023;72(2):121-128
pages 121-128 views


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