No 4 (2021)

The review summarizes the results of current clinical and experimental studies of renal function and venous hemodynamics in physiological pregnancy and in two types of preeclampsia (PE): early-onset PE that occurs between 20 and 34 weeks’ gestation and late-onset PE that is observed after 34 weeks’ gestation. It is shown that the trophoblast cells not only invade into the uterine spiral arteries, but also into the lymphatic vessels and veins to create an open channel of communication with the intervillous space. As this takes place, remodeling occurs earlier in the venous segment than in the arterial one, which is of great importance for the development of pregnancy pathology. Ultrasound Doppler studies show that the venous system works close to the peak of its capabilities even in physiological pregnancy. The pathological type of venous blood flow signals is more frequently observed in early-onset PE than in late-onset PE, but is not seen in gestational hypertension. This type is characterized by the appearance of wave A that is associated with retrograde pressure through the vein in the right atrial systole, and is a sign of increased pressure in the venous system of a woman. Conclusion. The authors show the relationship between venous hypertension and renal dysfunction in PE. They discuss the commonness of maternal and fetal venous system and kidney dysfunctions in PE, which could be important for the programming of fetal cardiovascular and renal diseases in later life.

Endometrial hyperplasia (EH) is one of the main causes of abnormal uterine bleeding (AUB), which reduces quality of life in women and is a significant risk factor for malignant transformation of the endometrium, which together determines the importance of the problem, especially in developing cancer prevention programs. The current issue is to standardize morphological classifications to level the subjectivity of making histological diagnoses and to search for biomarkers that can predict the pathological process. The literature review discusses treatment options for EH, in particular the principles of hormone therapy that remains a generally recognized treatment option aimed at reversing the pathological process, preventing AUB and disease progression to endometrioid adenocarcinoma (EA), and restoring normal endometrial function and fertility. Worthy of separate attention is the management tactics for reproductive-aged patients with atypical EH, especially with unrealized generating function. Conclusion. The clinical protocols for the management tactics in patients with EH, which have been proposed to clinicians over the past 5 years, can standardize approaches to solving the problem. However, despite the substantial recent progress in the development of the discussed problem, there remain unresolved problems, one of the main ones is to search for reliable predictors for EH, its possible progression in EA, and to predict disease relapses and therapy response.

Endometriosis is one of the acute problems of modern gynecology; it is a gynecological disease characterized by the presence of heterotopias that are identical in structure and function with the endometrium outside the boundaries of the normal mucous membrane of the uterus. The incidence of endometriosis varies widely from 12% to 50% according to different authors. Despite a significant number of studies, the etiology and pathogenesis of various forms of endometriosis have not yet been established, which leads to different approaches to diagnosing and treating this disease. Adenomyosis (or internal endometriosis) occupies a special place among all types of endometriosis. The specif ic frequency of internal endometriosis of the corpus uteri (adenomyosis) in the structure of genital endometriosis varies from 9 to 70% according to different researchers, reaching 70-90% in some publications. Adenomyosis is used to denote the form of endometriosis, the morphological manifestation of which is the spread of the components of the glandular and stromal layer of the endometrium into the myometrium. Despite the fact that this term is far from new and is widely used in clinical practice; specialists do not cease discussions. The review discusses the etiology and pathogenesis, diagnosis, clinical features, and current approaches to the management of patients with infertility in adenomyosis. Conclusion. The impact of adenomyosis and its stage on the outcomes of IVF programs, the need for and methods for preliminary treatment of patients before IVF are debatable.

Endometriosis is considered to be a chronic progressive recurrent disease that affects every 10 reproductive-aged women, which has a negative impact on various aspects of quality of life in patients. Treatment for endometriosis should minimize the progression of the disease, preserve fertility, and relieve pain syndrome in the patient. Surgical and medical treatments should not be contrasted. Medical treatment includes the use of nonsteroidal anti-inflammatory drugs, neuromodulators, and hormone therapy (gonadotropin releasing hormone agonists, progestins which are considered as first-line therapy), levonorgestrel intrauterine system, and combined oral contraceptives*. Conclusion. Based on experimental models, randomized clinical trials, and real clinical practice studies, the authors have obtained data on the favorable safety profile, efficacy, and good tolerability of dienogest in the treatment of different types of genital endometriosis, which allows this progestogene to be regarded as a rational strategy for long-term therapy and prevention of disease relapses.

Aim. To investigate the value of immunological testing for platelet functional activity in patients with gestational thrombocytopenia in the setting of hemostatic system activation. Materials and methods. This multicenter prospective study involved 299pregnant women in the third trimester of pregnancy divided into the study group (n=249), including patients with thrombocytopenia and the control group (n=50) comprised of women with a healthy pregnancy and normal platelet counts. We used flow cytometry with FITC- and PE-labeled antibodies against GP Ilb/IIIa receptors and P-selectin to determine the number of GP IIb/IIIa receptors and P-selectin expression on the platelet surface and conducted an association with the principle of ADP activation, which is used in standard induced aggregation. Results. After ADP activation, the study group patients with thrombocytopenia had almost 40-fold higher P-selectin expression and significantly higher number of GP IIb/IIIa receptors on the platelet surface than women in the control group (p=0.0001; p=0.001). This indicates platelet hyper-aggregation, hemostatic system activation and suggests the feasibility of using acetylsalicylic-acid- containing drugs and low molecular weight heparins in this specific patient category to prevent obstetric complications. Conclusion. The flow cytometry can be used as a new laboratory criterion for assessing platelet hyper-aggregation in pregnant women with thrombocytopenia. The findings also support the administration of acetylsalicylic acid and low molecular weight heparins in this patient category.

Materials and methods. A retrospective case-control study included 180 women and their newborns. The levels of pH, lactate (Lac), base deficit (BD), partial oxygen pressure (pOJ, and partial carbon dioxide pressure (pCO) in umbilical cord arterial blood were determined using an ABL800 FLEX gas analyzer (Radiometer Medical ApS, Denmark). Results. Neonates with HIE had significantly lower pH [6.966 (0.309) versus 7.269 (0.074), p <0.001] and higher BD and Lac levels than neonates in the control group [18.1 (6.8) versus 7.9 (4.1), p <0.001 and 12.0 (5.1) versus 5.8 (2.7) mmol/L, p <0.001], respectively; pCO2 was significantly higher in newborns with HIE [59.7 (32.3) versus 41.7 (8.8), p=0.049], while pO2 was higherin the control group [28.1 (28.3) versus 21.3 (11.0), p <0.001]. The arterial umbilical cord blood pH was significantly lower, and BD was higher in newborns with grade II-II HIE than in those with grade I HIE [6.861 (0.309) versus 7.033 (0.163), p=0.04 and 21.7 (6.7) versus 16.2 (6.1)], p=0.02. Lac, pO2, and pCO2 levels were not associated with HIE severity. The predictors of moderate and severe HIE of hypoxic origin were pH <7.03 and BD> 19.2. The severity of HIE was associated with the incidence of adverse long-term outcomes. In 10 HIE cases (27.7%), ABB parameters at birth did not confirm the presence of metabolic acidosis. Conclusion. Determination of the pH and BD in umbilical cord arterial blood allows prediction of the development and severity of HIE. The proposed model for predicting moderate and severe HIE has a sensitivity and specificity of 94.7% and 90.9%, respectively. In 27.7% of cases, HIE was diagnosed in neonates with normal pH and BD in umbilical cord arterial blood, suggesting that there are causes of encephalopathy other than intrapartum fetal hypoxia.

Materials and methods. The study included 982 women: 193 women with uterine fibroids combined with endometrial hyperplasia and 789 healthy controls. Five polymorphic loci of growth factor genes were chosen for the study: EGFc.-38M>G rs4444903, TGFp-1 c.-1347T>C rs1800469, IGF1 c.*2716GM rs6214, VEGFc.-958C>T rs833061, FGFR2 c.109+906T>C rs2981582. The study was carried out using the polymerase chain reaction method. Results. Polymorphic loci were found to be associated with the development of uterine fibroids combined with endometrial hyperplasia. Genotype CC rs2981582 FGFR2 increases the risk of developing uterine fibroids combined with endometrial hyperplasia (OR=1.38). The combination of alleles A rs4444903 EGF and C rs1800469 TGFfi-1 is also a risk factor for the development of the disease (OR=1.50). The combination of G rs4444903 EGF, C rs1800469 TGFfi-1, G rs6214 IGF1, and T rs2981582 FGFR2 can play a protective role in the development of the disease (OR=0.59). These polymorphisms have a significant regulatory potential and affect the expression level of eight different genes; they are located in the areas of exonic splicing enhancers and they are the binding sites of transcription factors. Conclusion. Polymorphic loci of the genes PGR c.1415-11113G>T rs1042838, ESR1 c.*1029T>C rs3798577, ESR1 c.453-397T>Crs2234693, ESR1 c.453-35M>Grs9340799 are associated with the development of uterine fibroids combined with endometrial hyperplasia.

Objective. To study the correlation between polycystic ovary syndrome (PCOS) and polymorphism in genes associated with metabolic dysfunction, impaired androgen biosynthesis and folliculogenesis. Materials and methods. The study included 163 patients with PCOS (mean age is 25.2 (4.6) years, mean body mass index (BMI) is 23.9 (5.3) kg/m2) and 135 healthy controls who had no reproductive disorders or signs of androgenization (mean age is 49.8 (5.8) years, mean BMI is 27.4 (5.8) kg/m2). The examination of patients with PCOS included pelvic ultrasound, assessment of androgen levels, AMH, LH, FSH, and a two-hour glucose tolerance test with the evaluation of glucose and insulin levels. All patients were genotyped for 45 loci. Results. PCOS was found to be associated with polymorphism of six genes. The genes Rub5B/SUOX (rs705702), THADA (rs12468394), OCT1 (rs6282031), SLCO1B1 (rs4149056) are supposed to be linked with insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus. Impaired function of the genes DENND1A (rs10818854) and YAP1 (rs1894116) may result in hypothalamic-pituitary dysfunction and hyperandrogenism. The genes Rub5B/SUOX, SLCO1B1, and OCT1 are associated with an increase in glucose and insulin levels, and gene YAP1 is correlated with hyperandrogenism. Conclusion. These results can serve as the basis for further associative and functional studies on the genetic characteristics of PCOS in the population of the Russian women. The development of an individual genetic risk scale for the diagnosis of PCOS in adolescent girls and women is promising.

Objective. To evaluate the effectiveness of long-term dydrogesterone therapy for 12 months after surgical treatment of external genital endometriosis in reducing the intensity of endometriosis-associated pain, improving the quality of life, overcoming infertility and preventing the recurrence of the disease. Materials and methods. The study included 51 patients aged 21 to 43 years (median age 32.23+4.0 years) with endometriosis which was confirmed laparoscopically and histologically; the patients experienced endometriosis-associated pain and received hormone-modulating therapy with dydrogesterone in the postoperative period. After 12 months of combined treatment, the dynamics of pain relief, improvement in the quality of life, and pregnancy rate in infertile women were evaluated. Histological and immunohistochemical studies were used to determine the characteristics of endometrioid infiltrates and intact peritoneum in patients with pelvic pain of varying intensity. Results. After 12 months of combined treatment of endometriosis (surgical and dydrogesterone therapy), there was a statistically significant decrease in pain intensity (NRS, points): the intensity of dysmenorrhea before surgery was rated as 8 (6;9), after surgery it scored 1 (0;2), the intensity of dyspareunia - 5 (2;7) and 0 (0;0.5), chronic pelvic pain - 6 (1;6) and 1 (0;2), respectively (p<0.0001). There was a statistically significant improvement in the quality of life and satisfaction with sexual life (p<0.05), as well as high pregnancy rate in patients with infertility: 10 (62%) patients became pregnant spontaneously, and 3 (19%) patients became pregnant using ART. Conclusion. The study proves the need for combined surgical and prolonged hormonal treatment of endometriosis; long-term dydrogesterone therapy for 12 months appears to be highly effective in the treatment of endometriosis-associated pain, infertility, and prevention of the recurrence of the disease. Dydrogesterone has a favorable safety profile and allows doctors to personalize the treatment of endometriosis depending on the current needs of patients.

Background. The main factor for placenta increta is the presence of a uterine scar after cesarean section. Placenta increta with no scar is extremely rare, which is due to the absence of specific diagnostic signs. This type of ingrowth is most often detected only during surgery and is confirmed only postoperatively by pathomorphological verification. Placenta increta with no scar occurs in pregnant women with a family obstetric and gynecological history (uterine curettage or manual examination of the postpartum uterus, which leads to damage and chronic inflammation of the myometrium). This is associated with a high massive blood loss risk, hysterectomy, and maternal mortality. Case report. The paper describes three clinical cases of placenta increta with no uterine scar after cesarean section. One patient underwent organ-sparing surgery, such as metroplasty using tourniquet hemostasis by autoerythrocyte reinfusion, infusion of fresh frozen plasma and red blood cells for the controlled reduction of blood loss. Two patients underwent hysterectomy. Conclusion. Placenta increta without uterine scarring after cesarean section has no pathognomonic symptoms or typical diagnostic signs, which increases the risk of intraoperative and postoperative complications, their most formidable ones are massive blood loss and hysterectomy.

Background. Thanks to the current advances in hematologic oncology, the healthcare system faces a task of preserving the reproductive potential in surviving patients. The high efficiency of specific treatment for malignant blood diseases (MBD) and similar conditions is associated with high risks for reproductive disorders. Pediatric and adolescent patients occupy a special place. In 2017, the number of children with any cancer was 88.1 per 100,000 people in the Russian Federation. At the same time, global statistics show that in girls aged 0 to 14 years, acute leukemias account for up to 40% of cancers, which is 2.6 times higher than those in women aged 15-44 years. Case report. The paper deals with the pattern and features of gynecological diseases characteristic for girls with MBD and similar conditions. Information is provided on the degree of gonadotoxicity of different classes of chemotherapy drugs, the procedures of gonadal shielding, and an individual approach to preventing uterine bleeding, as well as indications for and options of hormonal correction of estrogen deficiency. The paper presents a clinical case of a complication of medication-induced menses suppression in a 16-year-old patient, describes a case of extramedullary (ovarian) leukemic relapse in a 12-year-old girl, and gives an example of management of a 17-year-old patient with genital manifestations of grade III graft-versus-host disease. It considers the features of genital inflammatory diseases in girls with MBD: the high incidence of the torpid course of purulent vulvovaginitis; isolation of bacteria resistant to most antibiotics; the susceptibility of these patients to soft tissue infections; a prolonged course of vulvovaginal candida infection. The paper provides an example of vulvar lesion in a 3.5-year-old child with Langerhans cell histiocytosis. Conclusion. The literature data and the authors’ own observations contained in the article provide an opportunity to get an idea of the peculiarities of a gynecologist’s work with this specific group of patients as children with MBD and similar conditions.