No 12 (2020)

The paper reviews international clinical recommendations, practical guidelines, and the results of modern evidence-based researches into fetal growth restriction (retardation) (FGR) as one of the main causes of fetal hypoxic complications and perinatal death. It provides evidence that it is necessary to early form a group of pregnant women at high risk for this complication in order to use preventive treatment and describes the prognostic abilities of maternal, biochemical, and biophysical markers and the combined algorithms introduced into clinical practice in our country. The paper describes in detail the novel diagnostic criteria for early- and late-onset FGR, which are common to the whole world, the reference ranges for fetometric parameters and estimated fetal weight in the international INTERGROWTH-21st Project, which are recommended by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). The paper publishes the reference ranges for uterine and umbilical artery pulsatility indices and cerebroplacental ratio, which have been obtained using the results of large-scale European studies and Fetal Medicine Foundation ones. It also presents a stage-based algorithm for the monitoring of FGR cases: the frequency of Doppler measurements, the number of evaluated vessels, and criteria of normality for computerized cardiotocography according to the duration of pregnancy and the presence of preeclampsia, by determining indications for delivery and choosing its method. Conclusion. The introduction of modern predictive algorithms, effective prevention methods, unified diagnostic criteria, and the principles of management of FGR cases, which are based on the results of studies with a high reliable level of evidence, into daily clinical practice will be the basis for a considerable reduction in perinatal morbidity and mortality rates.

The COVID-19 pandemic sweeping around the world has demanded the introduction of emergency lock-down measures, suspended the operation of enterprises, and led to the development of a systemic economic crisis. In a number of countries where governments have taken austerity preventive anti-epidemic measures, the situation could be controlled and a large number of viral infection victims could be prevented. The obstetric service has always been an area of increased responsibility for the life and health of the mother and her child. Each country has operating algorithms, protocols, standards, and guidelines. However, during the epidemic, it can be dangerous to implement the entire package of measures and procedures in the context of COVID-19 infection due to the need to visit outpatient and inpatient healthcare facilities and laboratories. Algorithms for managing pregnancy and childbirth are of particular importance during a viral pandemic. The paper gives an algorithm for the management of pregnant, parturient, and puerperant women with COVID-19 in the Republic of Kazakhstan. The algorithm has been elaborated by the authors on the basis of the experience of the countries that previously faced a true pandemic (China, Italy, and Spain). Along with the traditionally existing orders and recommendations, this algorithm has been introduced in women’s clinics and obstetric hospitals of various regionalization levels in order to preventatively respond to an increase in the number of COVID-19 cases and carriers among pregnant parturient, and puerperant women. In the Republic of Kazakhstan, as of September 1, 2020 COVID-19 cases were registered in 4851 women, of whom there were 3473 pregnant women and 1378 postpartum ones. Spontaneous childbirth occurred in 1247 (90.5%) women; caesarean section was performed in 131 (9.5%) cases. COVID-19 was confirmed in 124 (8.75%) of the 1,420 newborns; of whom 1116 (78.57%) infants were born to puerperas with the confirmed diagnosis and 304 (21.43%) were born to mothers with a negative COVID-19 test.

Based on the literature data, the authors have investigated a number of biomarkers and determined their relationship to the development of preeclampsia in women with pre-gestational diabetes mellitus in the first trimester of pregnancy. Due to the fact that there are similar mechanisms for these conditions, the early diagnosis of preeclampsia is significantly difficult in this patient category. The authors have assessed maternal risk factors and biophysical and biochemical markers and showed their role in the prediction of preeclampsia. It has been established that in the presence of diabetes mellitus, the study of certain hormones and the markers of the inflammatory response, oxidative stress, and lipid metabolism, and adipokines may be of potential value for the prediction of preeclampsia. However, pregnancy-associated proteins and angiogenic and antiangiogenic factors, which are strong predictors of preeclampsia in women without diabetes mellitus, are shown to be a valid diagnostic tool in diabetes mellitus. Despite conflicting data, insufficient experience, and the extent of examinations, it is impossible to draw an unambiguous conclusion about the role of biomarkers in the assessment of preeclampsia in the first trimester of pregnancy complicated by diabetes mellitus. Conclusion. Thus, the active introduction of biomarkers into practice requires further and more detailed study of this area and optimization of research design.

The review presents the latest data on the safety and eff iciency of hormone therapy with estrogens. The authors separate the concepts of "hormone replacement therapy" and "menopausal hormone therapy", focusing on the fundamental differences in approaches to treating reproductive-aged and postmenopausal women with estrogen deficiency. The article discusses the features of therapy selection in women with gynecologic pathology and some chronic diseases. The article contains information about the basic principles of prescribing menopausal hormone therapy to minimize the risks of cancer and adverse cardiovascular events during estrogen treatment that includes the use of transdermal estrogens, 17β-estradiol gel 0.1% in particular, in minimum effective doses and natural progesterone, at the beginning of treatment within the therapeutic time window, a therapy duration of up to five years, by reviewing the benefits/risks of an intervention during treatment over time. The article describes some clinical situations, in which it is recommended to avoid prescribing oral estrogens due to the pharmacokinetic features: hypertriglyceridemia, high basic risks of venous thromboembolic events and strokes, gallbladder diseases, intake of anticonvulsants and thyroxine, female alcoholism, and also probably coronavirus infection. In addition, the review analyzes updated recommendations for hormone replacement therapy in women with premature ovarian failure, by relying on data from international clinical protocols. Conclusion. Hormone therapy is generally a safe pharmacological intervention, since it is prescribed either to reproductive-aged women with ovarian failure/loss of ovarian function or to healthy women with menopausal symptoms aged 40 to 50 years.

One of the main cervical diseases that can be dangerous to a woman’s life is cervical cancer, and its incidence increases every year. High-grade cervical intraepithelial neoplasia (CIN2-3) may precede the development of cervical cancer for several years or even decades. In clinical practice, loop electrosurgical excision procedure (LEEP) has proven to be the most effective method for treating CIN which makes it possible to preserve the functional integrity of the cervix. The article presents a systematic analysis of the results of modern clinical studies devoted to the problem of the development of recurrent CIN after LEEP. This study considers the role of the carriage and persistence of human papillomavirus (HPV), especially HPV16, the age of a woman, and the presence of a positive resection margin in the development of recurrent CIN. The patient undergoes histological examination with the interpretation of its results and dynamic monitoring of the state of the cervix after LEEP. Moreover, HPV vaccination is currently considered by a number of authors as a possible method for preventing the development of recurrent CIN after surgical treatment. The timely detection of opportunistic mixed infections associated with squamous intraepithelial lesions of the cervix is also of great importance. Therefore, the results of studies on the effectiveness and safety of the use of the combined preparation Terzhinan for the treatment of mixed genital infections were analyzed. Conclusion. Despite the high effectiveness of LEEP in the treatment of CIN 2+, the management of women with this pathology requires a comprehensive approach. The predictors of recurrence include the age of a woman over 35 years, the carriage and persistence of HPV, the positive resection margin after excision, and the lack of the subsequent monitoring of the state of the cervix. HPV vaccination should be considered as one of the most effective methods for preventing the development of recurrent CIN.

Objective. To determine the impact of severe preeclampsia on peri- and neonatal outcomes, long-term prognosis for mother and offspring. Materials and methods. A retrospective cohort study including 123 women who had preeclampsia during a current pregnancy. 83 women had severe preeclampsia (PE) and 31 women of them had fetal growth restriction (FGR), the other 40 women had mild PE. The study also included their children who was born between 2012 and 2019. The women were followed for 5-7 years and their infants - for the first year of life. Results.The analysis of neonatal complications revealed statistically significant differences between the groups with severe and mild PE: respiratory distress syndrome (RDS) in newborns - 57.8% and 5%; congenital infectious and inflammatory diseases - 60.2% and 10% including congenital pneumonia in 59.03% and 7.5%. respectively; asphyxia - 18.1% and 7.5%; intraventricular hemorrhage -27.7% and 5%; cutaneous hemorrhagic syndrome -31% and 7.5%, respectively (p<0.05). In the first year of life, children from the group of severe PE had the most negative outcomes. Thus, cerebral palsy (CP) (OR=1,7), speech delay (OR=1,5) and neurotic reactions (OR=1,7), visual disorders (OR=3,2) were most common in this group. Conclusion. Women who had severe early preeclampsia during pregnancy had a threefold risk of developing hypertension and a twofold risk of metabolic syndrome compared to the control group 5-7 years after delivery. Morbidity and mortality of children were significantly higher in the group with severe early preeclampsia compared to mild PE.

Relevance of the issue. High prevalence of pyelonephritis (up to 10%) in pregnant women is an acute problem. The issues of pathogenesis, early diagnosis, prevention of recurrence of the disease remain unsolved. Due to anatomical and physiological changes in the body during pregnancy, urinary tract infection becomes complicated, and effective therapy is especially important. Aim. Optimization of treatment and prevention of recurrent pyelonephritis in pregnant women. Materials and methods. 60 pregnant women with gestational pyelonephritis and acute chronic pyelonephritis, who received standard antibiotic therapy. Additionally, the patients in the main group (n = 30) were prescribed systemic enzyme therapy (Wobenzym). Before and after therapy, all patients underwent Doppler ultrasound examination to determine the blood flow rates in renal and interlobar arteries. Results. The women in both groups were comparable in terms of age, gestation period and clinical characteristics of the disease. Before treatment blood flow indices in renal and interlobar arteries were high in both groups. However, in the group of women, who received Wobenzym, Doppler iindices for blood flow were of normal range in the renal artery (p=0.004) and in the interlobar artery (p=0.001), while standard therapy did not show statistically significant differences. Adding Wobenzym to therapy increased the chances for normalization of the blood flow in renal artery by 7 times (95% CI: 1,38-35,5; p=0,01). Systemic enzyme therapy reduced the recurrence of the disease by 4,5 times (95% CI: 1,09-18,5) compared to the comparison group (p=0.0287). Conclusion. Thus, the use of Wobenzym in complex therapy versus standard therapy had a beneficial effect on statistically significant improvement in renal blood flow and a decrease in the frequency of recurrence of the disease.

Aim. To investigate the hormonal profile and morphofunctional status of the ovaries in women with different clinical forms of premature ovarian failure (POF) and evaluate diagnostic value of new ovarian reserve (OR) markers using 2D and 3D power Doppler sonography. Materials and methods. Baseline evaluation included medical history and clinical assessment. Laboratory testing consisted of measurements of FSH and AMG levels by ELISA. 3D pelvic ultrasound was used to measure antral follicle count (AFC) and intraovarian blood flow, including calculation of vascularization index (VI) and blood flow index (FI). Results. Patients with the initial (biochemical) form of POF had statistically significantly higher FSH and lowered AMH levels than patients with the occult and complete POF forms. Patients with different forms of POF had statistically significantly lower values of all three 3D ultrasound parameters (VI, FI, and AFC) than control subjects. There was a sharp decrease in AFC, VI, and FI in patients with occult POF, suggesting that these characteristics may be promising for early diagnosis of the disease. Conclusion. A comprehensive morphofunctional assessment of ovaries, based on hormonal indicators (AMH and FSH) and ovarian reserve parameters (ovarian volume, AFC, and vascularization and blood flow indexes), determined by three-dimensional ultrasound and Doppler studies may provide a more accurate diagnosis of early forms of POF and, first of all, its occult form.

Objective. To determine the level of sex hormones and evaluate endometrial receptivity in patients with chronic endometritis. Materials and methods. There was an assessment of sex hormone levels, the expression of estrogen (ER) and progesterone (PR) receptors, and the membrane component of the progesterone receptor (PGRMC1) in patients with chronic endometriosis and in the patients of the control group. Results. Patients with immunohistochemical signs of endometritis had significantly higher levels of progesterone in the blood (p=0.006). The analysis of the expression of sex hormone receptors in the endometrium revealed a decrease in the expression of PR and PGRMC1, which indicates an impairment of hormone reception at the molecular level (p<0.001) Conclusion. Patients with chronic endometritis can be administered progestogen therapy only in case of progesterone deficiency.

Currently, thanks to advanced assisted reproductive technologies, as well as improvement of the quality of obstetric and neonatal care, the population of the babies born before 37 weeks of gestation continues to increase. Perinatal brain damage is manifested by disorders affecting the structure and functions of the central nervous system (CNS), and is one of the major factors that contribute to formation of a severe neurological disorder and disability in preterm babies. Intraventricular hemorrhage is the most common form of structural brain damage in premature babies. According to the published data, the incidence of intraventricular hemorrhage is inversely proportional to the gestational age of premature infants and ranges from 15% to 31%. Congenital pneumonia contributes to adverse neurological outcomes of perinatal disorders in preterm babies. Aim. To def ine the correlation between congenital pneumonia in preterm babies and the incidence and severity of hypoxic-hemorrhagic brain damage. Materials and methods. Prospective case-control study was conducted in the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. The study included 271 premature infants born at 28-36 weeks of gestational age in the period from January, 2017 to February, 2019. The infants were stratified into 2 groups: group 1(the main group) - the babies with the signs of congenital pneumonia (n=115); the group 2 (the comparison group) - the babies without these signs (n=156). Results. In group1 the incidence and severity of perinatal disorders of CNS in preterm babies with congenital pneumonia was higher than in the comparison group. Conclusion. According to the obtained data, congenital pneumonia in preterm babies increases the risk of hypoxic-hemorrhagic brain damage.

Objective. To show the acceptability of using ammonium glycyrrhizinate spray in patients with clinical manifestations of papillomavirus infection (PVI) in the presence of bacterial vaginosis (BV) as a therapy aimed at preventing recurrences. Materials and methods. Examinations were made in 78 reproductive-aged patients with BV and PVI, who complained of itching and burning in the genital area, vaginal discharge, dyspareunia, and dysuria. Data were collected from the medical records of all the patients; their somatic and gynecological diseases were taken into account; their clinical symptoms were evaluated; weight and height were determined; and the body mass index was calculated. The Colpo-pH test and extended colposcopy were carried out. Human papillomavirus was detected with PCR; bacterial mass and its components were determined by Femoflor-16 real-time PCR. During therapy with ammonium glycyrrhizinate, PCR and mass spectrometry were used to investigate changes in the vaginal microbiota. Results. 94.9% of the patients had severe/moderate mixed dysbiosis after standard treatment with inosine pranobex for BV and PVI, as indicated in the available recommendations. Complains of itching and burning in the genital area and genital discharge remained in 73.1 and 88.5%, respectively. After the f irst cycle of therapy with the drug, Panavir intim Normaflore was chosen to correct vaginal dysbiosis and PVI; mass spectrometry showed lactobacilli (Lactobacillus rhamnosus) in moderate amounts, clinical manifestations, such as itching and burning, ceased, the discharge practically disappeared, the clinical picture corresponded to moderate dysbiosis; after the second cycle of therapy, a month later, lactobacilli (Lactobacillus crispatus) were abundantly isolated, which corresponded to the microflora of healthy women and after two cycles, there was microbiota normalization and clinical recovery. Conclusion. Two consecutive cycles of therapy with Panavir intim Normaflore in the concentration equal to 3 doses 5 times daily for 15 days contributes to the normalization of the clinical picture, the leveling of the existing complaints, and the normalization of the flora due to the growth of lactobacilli.

The paper deals with the characteristics of the intravaginal route of drug administration that is attractive from two points of view. Firstly, this is the ability to quickly deliver the drug directly into the disease focus. Secondly, the characteristics of the vaginal epithelium (a low metabolic activity against xenobiotics), the relatively favorable aqueous medium for acid-resistant molecules, good organ vascularization, and the entry of absorbed substances into the bloodstream, by passing the liver, create favorable conditions for the use of systemic drugs. Currently, there are many vaginal drug delivery systems: solutions, creams, ointments, gels, tampons, suppositories, capsules, pessaries, sponges, and modified-release vaginal devices (e.g. rings) Despite the ease of use, the vaginal route of drug administration can be associated with certain features, such as differences in the thickness of the mucous membrane in different phases of the menstrual cycle and in different periods of life, variations in the pH of vaginal secretion, the likelihood of dosage form leakage, the effect on the vaginal mucosa and local microbiocenosis, probable discomfort when using certain formulations. The paper describes the anatomical and histological features of the vagina, which affect the absorption of various substances and provides information on the pharmacokinetics of drugs, including those prescribed for the treatment of vaginal infections. Conclusion. Despite its many features, intravaginal administration is one of the most common and widely studied methods of drug delivery. When drugs are prescribed, it is necessary to take into account their pharmacokinetic differences that are observed in both different periods of female patient’s life and different phases of the menstrual cycle, and the associated possible fluctuations in the systemic concentration of drugs. The latter used to achieve an exclusively local effect should be characterized by a minimal systemic absorption and a minimal impact on local immunity and natural vaginal biocenosis.

Insulin resistance (IR) is a trigger for most pathogenetic changes in polycystic ovary syndrome (PCOS). The inositol stereoisomers myo-inositol (MI) and D-chiro-inositol (DCI) are actively involved in showing insulin effects. The MI/DCI ratio varies with tissue metabolic requirements and is under strict control with insulin. The MI/DCI ratio in plasma is 40:1, whereas that in follicular fluid is 100:1. In women with PCOS and IR, the concentration of DCI in insulin-sensitive tissues (muscles, brain, heart, adipose tissue) decreases drastically, which may be due to both a lack of total consumption of inositol and impaired expression/synthesis of epimerase that converts MI into DCI. The ovaries, on the other hand, respond to excess insulin by over-epimerization of MI in DCI and by a decrease in the MI/DCI ratio in follicular fluid to 0.2:1. Experimental and clinical studies have shown that MI in combination with DCI in the 40:1 ratio corresponding to the physiological content in blood plasma is the most optimal therapeutic regimen to reverse metabolic, hormonal, and reproductive disorders in women with PCOS. Regulation of glucose metabolism also occurs independently of inositol with endogenous alpha-lipoic acid (ALA) synthesized in the mitochondria. Conclusion. Supplementation of ALA with inositol improves insulin sensitivity and reproductive function in women with PC OS, especially in those with obesity and a genetic predisposition to diabetes mellitus. Thus, ALA in combination with MI and DCI creates a new comprehensive strategy for overcoming IR and its sequels in women with PCOS.

Background. Placental site trophoblastic tumor (PSTT) is a nonvillous tumor originating from the placental part of trophoblast. This pathology was first described in 1976; only 300 cases of this disease are known to date. PSTT develops in reproductive-aged women and is noted for a relatively slow growth rate; morphologically, it is a monomorphic mass originating from intermediate trophoblast cells with signs of syncytiotrophoblast and cytotrophoblast. PSTT is characterized by a slow rise in blood β-hCG levels. The diagnosis of PSTT remains relevant: the rate of its misdiagnosis amounts to as much as 40%. In addition, there are problems with chemotherapy, which is why surgical treatment comes to the fore. Case report. In 2013, Patient A. aged 30 years had a second premature labor without complications. Her menstrual cycle did not resume after lactation cessation. Diagnostic curettage of the uterine cavity was performed in the National Medical Research Center for Oncology. Histological examination revealed intermediate trophoblast layers in the complete absence of chorionic villi. The histological findings and clinical presentations corresponded to Stage IPSTT. In this connection, an extended extirpation of the uterus with fallopian tubes was recommended. The β-hCG level decreased to 5.6 mIU/ml just 12 days after surgery and it was 0.06 mIU/ml one month later. Conclusion. The diagnosis of PSTT is accompanied by a problem in the medical treatment of this disease due to an extremely low sensitivity to chemotherapeutic agents. It is usually sufficient to carry out uterine extirpation if metastases are absent. In the clinical case demonstrated, the patient’s condition remained stable during the follow-up period of 44 months in the postoperative period and there were no signs of progression. Thus, early diagnosis is of great importance when the tumor is limited to the uterus and can be radically removed.

Background. Genital prolapse (GP) is a disease that has a high recurrence rate after surgical correction. It is based on both the underestimation of the factors leading to GP (connective tissue incompetence, the features of microcirculation and labor course, etc.), and the stereotypes and preferences of a surgeon when choosing a method for GP surgical correction. Phenotypically, patients with GP are prominent representatives of a sarcopenia phenotype. Nevertheless, the literature lacks studies investigating the expression level of the a-1 subunit of the voltage-gated calcium channel CaV1.2 in the smooth muscle tissue of patients with GP, which may be another factor for the latter and its recurrences after surgical correction. Case report. The paper describes a 37-year-old female patient with apical GP, pelvic floor protrusion and relaxation with intact pelvic nerve conduction. The patient has connective tissue dysplasia, an Ehler-like phenotype, with the preponderance of a weak stromal and muscular component: grade 2 mitral valve prolapse, incomplete right bundle branch block, childhood myopia, joint hypermobility, arterial hypotension, minor malformations, etc. The investigators performed physical examinations, genital ultrasound evaluation, Echo-CG, special studies (defetography, pelvic nerve conduction test, sphincterometry, and anorectal manometry), and investigation of the CACNA1C gene expression in the smooth muscles of the round ligament of the uterus, by using real-time PCR. Conclusion. The authors present the combined technique for GP surgical correction, which has been developed for use in patients with hereditary multicompartmental pelvic organ prolapse.

Background. The hemostatic and fibrinolytic systems play a key role in the systemic circulatory adaptation of the woman’s body to pregnancy and childbirth. In the presence of acquired or genetic hemostatic abnormalities (thrombophilia, thrombocytopathy, and coagulopathy), the physiological activation of coagulation processes and systemic inflammation during pregnancy can lead to decompensation in the equilibrium of the hemostatic potential (HP) and thereby provoke obstetric complications. Case report. The paper demonstrates a clinical observation of a female patient with concomitant hemostasiological disorders (thrombocytopathy, a carrier of heterozygous thrombophilia polymorphisms: ITGB3, ITGA2, PAI-1, and MTHFR). She has a history of repeated ineffective ART program attempts. Spontaneous abortion occurred during the early stages of hemorrhagic syndrome when low-molecular-weight heparin was used. An approach to managing this patient was proposed. The principle was the personalized monitoring of the hemostatic system by low-frequency thromboelastography. Owing to the latter, it was possible to have a real-time comprehensive and informative assessment of the parameters of hemocoagulation and fibrinolysis in whole blood. The detected HP disorders was corrected with the targeted therapy: Etamsilat (Lugansk Chemopharmaceutical Plant, Ukraine) was used to correct hypocoagulation at the f irst stage of fibrinogenesis; Tranexam (STADA, Russia) to suppress enhanced fibrinolytic activity; Vessel Due F (sulodexide) (Alfasigma S.p.A., Italy) to correct a hypercoagulable state, which should not have been routinely done in this patient, as thought by the authors. Monitoring the efficiency of the 2P+2D therapy could prolong pregnancy to full term, resulting in the birth of a healthy baby. Conclusion. Thus, the personalized approach to managing the patient with concomitant hemostasiological disorders and IVF contribute to the increased take-home-baby rate.