Vol 66, No 4 (2017)

Molecular mechanisms of regulation of uterine leiomyoma growth
Antsiferova Y.S., Voronin D.N., Sotnikova N.Y., Malyshkina A.I.

Background: to elucidate the molecular mechanisms, regulating growth and proliferation of leiomyoma cells, the estimation of the activity of PR-A and PR-B isoforms of progesterone receptor and PI3K/Akt and MAPК kinases, participating in signal transduction from sex steroids and growth factors, has the special interest.

Aim of the work: to investigate the character of the expression of mRNAs of PR-A and PR-B isoforms of progesterone receptor in leiomyomas of different size and different intensity of cellular proliferation, and to elucidate the relationship between the PR-A and PR-B synthesis and activation of PI3K/Akt and MAPК signaling pathways in tumour tissue.

Materials and Methods. The examination of the PR-A, PR-B, Akt, PTEN, ERK and Ki67 mRNAs expression in normal myometrium and leiomyoma tissues of 29 women with uterine leiomyoma was performed using RP-PCR.

Results. It was found that in general the leiomyoma tissue was characterized by the high level of PR-A, PTEN and ERK mRNAs expression comparing to the miometrium. Distinctive characteristic of the small leiomyomas and leiomyomas with low proliferative activity was the highest synthesis of PR-A isoform of progesterone receptor. In large leiomyomas and in proliferating Ki67+ leiomymas the significant increase of ERK mRNA expression was seen.

Conclusion. Activation of the PR-A isoform of progesterone receptor and MAPK/ERK signaling pathway associated with the inhibition of PI3K/Akt signaling due to high synthesis of PTEN plays the important role in mechanisms, regulating leiomyoma growth.

Journal of obstetrics and women's diseases. 2017;66(4):7-13
Features of pregnancy with gestational diabetes mellitus and prediction of diabetic fetopathy
Akhmetova E.S., Lareva N.V., Mudrov V.A., Gergesova E.E.

Gestational diabetes mellitus (GDM) and its consequences for the mother and child represent a serious not only medical, but also an economic problem. The urgency of studying this problem also lies in the fact that the number of pregnant women suffering from this disease is progressively increasing. The aim of the study was to study the risk factors and features of the course of pregnancy and childbirth in women with gestational diabetes mellitus, as well as to improve methods for diagnosing and predicting the development of diabetic fetopathy (DF). The work was carried out in 3 stages: 1 — prospective study of the course of pregnancy and childbirth in 104 women with GDM and in 50 pregnant women without GDM (control group); 2 — determination in the peripheral blood of the pregnant women of both groups of the level of glycemia, C-peptide, insulin, calculation of the insulin resistance index (HOMA-IR) with an assessment of the prognostic significance of these markers in the development of diabetic fetopathy; 3 — prediction of the development of diabetic fetopathy using a mathematical model that includes risk factors, the results of laboratory and instrumental research methods for this pathology. It was found that the violation of carbohydrate metabolism during pregnancy promotes the development of a large number of obstetric complications and in 36.5% of cases leads to the birth of children with diabetic fetopathy, which is manifested to a greater degree by macrosomia (30%), which increases the risk of perinatal complications and worsens the course of the period newborn in the future. An increase in the level of C-peptide was diagnosed in 87% of pregnant women with gestational diabetes, and an increase in the insulin resistance index in 93%, in contrast to the control group, where these indicators were 4 and 6%, respectively (p < 0.05). Using discriminant analysis, it was determined that the threshold for predicting the development of DF should be considered an increase in HOMA-IR above 7 with a confidence of 73%, but the level of C- peptide does not have a predictive value. The mathematical model, including risk factors, data of laboratory and instrumental methods for studying carbohydrate metabolism in the mother and fetus, created using regression analysis, reflects the probability of development of diabetic fetopathy in pregnant women with gestational diabetes with an accuracy of 91.4%, which will help to prevent this complication in at an earlier stage through insulin therapy.

Journal of obstetrics and women's diseases. 2017;66(4):14-24
Pregnancy planning in women with diabetes mellitus type 2
Borovik N.V., Glavnova O.B., Tiselko A.V., Suslova S.V.

The aim of the study: to evaluate the role of pregnancy planning in patients with diabetes mellitus type 2 in improvement of pregnancy and birth outcomes.

Material and methods. 80 women with type 2 diabetes mellitus who were referred to the centre “Diabetes mellitus and pregnancy” in Ott’s Research Institute of Obstetrics and Gynecology were examined.

Results. In the group of women who underwent pre-pregnancy counseling, the course and outcome of pregnancy were significantly better. Since the frequency of gestosis was lower (60%) than in the group without pregnancy planning (86.7%), there was no gestosis of severe degree in the group of women who underwent pre-pregnancy counseling (in the group without pregnancy planning the rate of gestosis of moderate and severe degree was 25%). Frequency of preterm delivery was lower (15%) in the group of women who underwent pre-pregnancy counseling than in the group without pregnancy planning (38.3%). Also in the group of women who underwent pre-pregnancy counseling there were no fetal congenital malformations, neonatal hypoglycemic events and hypertrophic cardiomyopathy (in the group without pregnancy planning these indicators were respectively − 3.4; 28.8; 3.4%. Also in the group of women who underwent pre-pregnancy counseling there were no perinatal mortality (in the group without pregnancy planning this indicator was 3.4%.

Conclusion: pregnancy planning in patients with diabetes mellitus significantly improves the course and outcome of pregnancy.

Journal of obstetrics and women's diseases. 2017;66(4):25-31
The contents of progesterone in the blood of pregnant in I and II trimesters of gestation with an unfavorable outcome of the pregnancy
Voskresenskiy S.L., Trishina V.L.

Relevance. Progesterone is the only hormone in the body, the main function of which is the development and maintenance of pregnancy, while its other properties are duplicated by other hormones. The hormone deficiency is part of the general mechanism of spontaneous abortion, and not its cause [1].

The aim of the study was to establish a connection between the content of the level of progesterone and its metabolites in the blood of pregnant women and the developmental disorders of pregnancy in order to determine the possibility of laboratory confirmation of pathology.

Materials and methods. The study included 31 patients with pathological pregnancy, hospitalized in the hospital, in the first and second trimesters of gestation and 34 women with physiological pregnancy in the first trimester of gestation. Pregnant women with infertility in history, severe somatic pathology, acute infectious diseases, oncological processes, with endocrine disorders, with malformations of the genital organs, endometriosis, pregnant women taking gestagens or other hormonal medications before entering the study are excluded from the study. Each patient hospitalized in a hospital and women with a physiological pregnancy had, in addition to a general clinical examination, performed a blood serum test for hormones (progesterone, cortisol, DHEA-C, 17-OH, estradiol) and ultrasound (VOLUSON 730, GENERAL ELECTRIC in 2007) using transvaginal 4-8 MHz and transabdominal 2–5 MHz sensor. Progesterone, cortisol, estradiol was determined by enzyme-linked fluorescence analysis using reagents from bioMerieux (France) using a VIDAS device from bioMerieux, France (2012). The analysis is based on a combination of a two-stage enzyme-linked immunoassay (sandwich method) and a fluorescent determination of the reaction products. The DHEA-C and 17-OH study was carried out using the ELISA method on equipment: the Freedom EVO75 laboratory automated laboratory for laboratory diagnostics produced in Switzerland (2008) using ANALYSIS MED reagents, Belarus. The statistical processing of the results of the study was carried out using the application statistical packages Statistica 6.0.

Results. It was found that with the termination of pregnancy in both I and II trimesters, the level of progesterone and estradiol statistically significantly decreased. The content of DHEA-S and 17-OH progesterone varied depending on the gestation period. The concentration of cortisol also decreased, but it was not statistically significant. It was also found that after the death of the embryo and spontaneous abortion, functional fragments of the fetal egg remain in the uterine cavity.

Conclusion. The priority of hormones in the development of pregnancy in the I and II trimester is different. If in the first trimester the most dependent on the gestation period are progesterone, estradiol, DHEA-C, then in the II trimester — progesterone, estradiol, 17-progesterone. And also that cortisol during pregnancy is predominantly synthesized outside the fruiting and amniotic complex, which explains the absence of its statistically significant changes in the unfavorable termination of pregnancy in both I and II trimester of gestation.

Journal of obstetrics and women's diseases. 2017;66(4):32-39
Pelvic organ prolapse in women: what are the patient expectations of the prospective treatment?
Korshunov M.Y.

Background. Personalized approach to the issue of pelvic organ prolapse in women assumes a detailed analysis of the patient’s expectations from the surgical treatment ahead.

Aim: detailing the treatment goals for patients with POP.

Materials and methods: Four hundred eighty six patients (mean age 54.3 ± 9.5 years) participated in a survey designed based on content from verbal reports of women with POP seeking medical help.

Results: Out of 9 presented options patients indicated 2–7 treatment goals. The most frequently specified main goals of the treatment were: cure of urinary incontinence (48.6%), correction of vaginal wall prolapse (27.1%), and improvement of quality of sexual life (10.3%).

Conclusion. Patients with POP indicate numerous objectives of surgical treatment. Treatment of urinary incontinence is the most frequently sought out main goal.

Journal of obstetrics and women's diseases. 2017;66(4):40-45
The problem of "thin" endometrium in reproductive medicine: experience of application of recombinant Interleukin-2 to prepare patients to assisted reproductive technologies programs
Lysenko O.V., Rozhdzestvenskaya T.A.

Introduction. “Thin” endometrium is known affect negatively to reproductive function. Treatment of “thin” endometrium remains a problem and subject of future major studies.

Aim. To justify the possibility of applying of recombinant interleikina-2 person late reproductive age patients with “thin” endometrium before using assisted reproductive technologies.

Matherials and Methods. We examined a total of 64 late reproductive age women. Three groups of patients were analyzed. The first investigated group included 25 women with histologically proven chronic endometritis; the comparison group included 20 patients with endometrium of the early proliferative phase; the second investigated group included 19 patients with “thin” endometrium, with indications for the conduct of in vitro fertilization. Interleukin 2, interleukin-4, tumor necrosis factor alpha, interleukin-1β, Interleukin-6, interleukin-8, interleukin-10, IFN-γ concentrations were determined by enzyme linked immunosorbent assay in serum and aspirates from the uterine cavity in first investigated group and comparison group. Vaginal ultrasonic examination was made for women of second investigated group in first and second phase of menstrual cycle before and after recombinant human interlejkinom-2 treatment. Statistical data processing was performed using application software package Statistica 6.0 (StatSoft, Ink. 1994–2001), adapted for biomedical research. P < 0.05 was considered significant.

Results. Were found that concentrations of interleukin 2, interleukin-10 significantly reduced and concentrations of tumor necrosis factor alpha, interleukin-1β, Interleukin-6 and interleukin-8 significantly increased in aspirates from the uterine cavity in women of late reproductive age with chronic endometritis. All changes occur at the local level in chronic endometritis. Endometrial thickness a statistically significant increase after use of recombinant human interlejkinom-2 in patients with infertility and chronic endometritis.

Conclusions. Application of recombinant interleukin-2 in patients with “thin” endometrium can become optimal schema therapy, which requires further study.

Journal of obstetrics and women's diseases. 2017;66(4):46-50
Compared diagnostic value of proteinuria definition applying different methods at pregnants with preeclampsia
Mozgovaya E.V., Androsova N.E., Dorofeicov V.V.

Colorimetric method of protein determination in urine with use of pyrogallol red (PGR) has certain advantages over a routine method of proteinuria determination with use of sulfosalicylic acid (SSA) which is still applied in most clinics in the Russian Federation. For the purpose to determinate the diagnostic significance of proteinuria estimation by different methods at pregnants with preeclampsia, conducted a comparative research of proteinuria levels at 68 pregnants with preeclampsia and at 15 healthy pregnant by two methods: with sulfosalicylic acid and with pyrogallol red. At the same patients the diagnostic significance of protein/creatinine ratio was evaluated when using the method with PGR. It was revealed that proteinuria determination with PGR- method had authentically higher sensitivity, and proteinuria indices when using this method corresponds to the criteria for evaluation of preeclampsia severity specified in the Ministry of Health Russian Federation Order No. 572n 2012 and the Clinical Recomandations “Hypertensia during pregnancy. Preeclampsia. Eclampsia” (2012). In case of proteinuria determination by method with SSK it is necessary to consider lower sensitivity of the method and adhere to earlier classification of preeclampsia (gestosis) where proteinuria more 1 g/l was regarded as the symptom of severe preeclampsia. Confirmation of the diagnostic significance of protein/creatinine ratio needs further researches.

Journal of obstetrics and women's diseases. 2017;66(4):51-56
Criteria for diagnosis of bacterial vaginosis using the test Femoflor-16
Nazarova V.V., Shipitsyna E.V., Gerasimova E.N., Savicheva A.M.

Background. Bacterial vaginosis is disturbance of the balance of the vaginal microflora, associated with a number of infectious diseases of the urogenital tract and adverse pregnancy outcomes. In this country, for the detection of vaginal dysbiotic conditions, the test Femoflor-16 (DNA-Technology, Moscow) is widely used, however interpretation algorithms of this test do not include the category of BV.

Aim. The study aimed to elaborate diagnostic criteria for the detection of BV using Femoflor-16 test.

Materials and methods. Women of reproductive age addressing a gynecologist with vaginal discharge were enrolled in the study. For clinical diagnosis of BV, the Amsel criteria were used, laboratory analysis for BV was performed via microscopic investigation of vaginal discharge using the Nugent score. Samples of vaginal discharge from all women were analyzed with the test Femoflor-16, intended for characterizing vaginal microbiocenosis using multiplex quantitative real-time PCR.

Results. A total of 280 women were included in the study. BV was diagnosed in 86 women (31%) using the Amsel criteria, and in 81 women (29%) using the Nugent score. All groups of anaerobic bacteria included in Femoflor-16 test were shown to be associated with BV, with the exception of bacteria of the genus Mobiluncus, which are detected together with phylogenetically related but not BV-associated bacteria of the genus Corynebacterium. A low amount of lactobacilli (< 10% of total bacterial load) coupled with an elevated amount of Gardnerella vaginalis/Prevotella bivia/Porphyromonas (> 1%) and/or Eubacterium (> 2%) and/or Sneathia/Leptotrichia/Fusobacterium (> 0.1%) and/or Megasphaera/Veillonella/Dialister (> 0.1%) and/or Lachnobacterium/Clostridium (> 0.1%) and/or Peptostreptococcus (> 0.1%) and/or Atopobium vaginae (> 0.2%) detected BV with a sensitivity of 99% and specificity of 93%.

Conclusions. Criteria for BV diagnosis using the test Femoflor-16 have been elaborated, which enable to detect BV or exclude it with a sensitivity of 99% and specificity of 93%. These criteria for BV and criteria of the test manufacturers for severe anaerobic dysbiosis determine to a large extent the same category of the vaginal microbiocenosis.

Journal of obstetrics and women's diseases. 2017;66(4):57-67
Pathogenetic justification of possibility of antidiuretic hormone use in incontinent women
Osipova N.A., Niauri D.A., Gzgzyan A.M.

Hypothesis/aims of study. Urine incontinence seems to include several pathogenetic forms, as efficient therapy is provided by different medications. Commonly used in the treatment of female patients with overactive bladder and nocturnal polyuria is desmopressin which normalizes the water excretion of the kidney, which is disturbed by a presumed inverted rhythm of vasopressin secretion in these patients. The current analysis was undertaken to evaluate the clinical efficiency of desmopressine in incontinent patients with nocturnal polyuria and polyuria.

Study design, materials and methods. A total of 84 patients with complaints of urinary incontinence, polyuria (24-urine volume of 40 mL/kg bodyweight or above) or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above) and 14 control subjects were included. Mean patient age was 43.6 ± 4.6 years, in control subjects 38.5 ± 6.4 (p > 0.05). All participants performed 24h-urinecollection to determine the voided volumes and the levels of creatinine, osmolality, sodium, magnesium and potassium for each sample. A blood sample was taken during the 24-urinecollection to determine the levels of creatinine, osmolality, sodium, magnesium and potassium. The examination of patients with polyuria and nocturnal polyuria was performed twice: in the initial state and one month after the start of treatment with optimal dose of desmopressin. Optimal dose was established through an open-label dose-titration using 0.1 mg, 0.2 mg and 0.4 mg of desmopressin (Minirin). Safety parameters assessed included incidence of adverse events, vital signs and serum sodium levels.

Results. In patients with polyuria and nocturnal polyuria the glomerular filtration rate was normal, whereas diuresis and solute (sodium, magnesium, potassium) excretion in night samples in nocturnal polyuria and both in night and day samples in polyuria were increased. The higher diuresis and the higher solute excretion observed in nocturnal polyuria and polyuria are accompanied by an increase of free water reabsorption. In nocturnal polyuria and polyuria a high correlation was found between the free water reabsorption and solute excretion. This occurs against the background of the high night and day osmotic concentration. The statistically significant recovery of renal function occurred in 12 incontinent women with polyuria and 18 with nocturnal polyuria. In these papients there was a statistically significant decrease in diuresis, osmolar clearance and excretion of sodium, potassium and magnesium.

Concluding message. As desmopressin affects cells of the thick ascending limb of Henle’s loop, it is likely that nocturnal polyuria and polyuria result from a disturbed regulation of the function of these cells. Normalization can be achieved by desmopressin administration to stimulate V2-receptors, which increase water permeability and water reabsoption in collecting ducts as well as ion reabsorption by cells of the thick ascending limb of Henle’s loop.

Journal of obstetrics and women's diseases. 2017;66(4):68-78
The case of abdominal delivery in acute heteroimmune drug indused thrombocytopenia
Shirokov D.M., Bolotskikh V.M., Dzhanashia M.M., Eremeeva D.R., Korostelev Y.M., Vartanova I.V., Blinov A.E.

The secondary gravida pregnant patient with uterine scar after previous cesarean section was treated with parenteral methamizol sodium due to renal colic and acute thrombocytopenia suddenly occurred. There were supposed that this condition had been drugs induced heteroimmune thrombocytopenia. The indications for planned cesarean section were breech presentation of large fetus in patient with uterine scar. However, uterine contractions appeared in 38/39 weeks and it was decided to deliver the patient urgently after appropriate preparing. The treating of severe thrombocytopenia was substitutive — thromboconcentrate and plasma transfusion and pathogenetic — using of dexamethasone and human immunoglobulin. After transfusion of one dose of thromboconcentrate and two doses of plasma the level of thrombocytes had reached of 21 × 109/л and it was decided to start cesarean section which was performed successfully in conditions of total combined anesthesia with tracheal intubation and pulmonary ventilation. The recovery of thrombocytes quantity occurred in postoperative period with continuing using of steroid therapy.

Journal of obstetrics and women's diseases. 2017;66(4):79-83
Procedure for specialized anesthesium-renamatological assistance in case of massive obstetric bleeding
Shirokov D.M., Korostelev Y.M., Vartanova I.V.

The clinical protocol outlines the procedure for the provision of specialized anesthesia-resuscitation assistance in the case of massive obstetric hemorrhages, adopted in the Department of Anaesthesiology and Reanimation of the Ott. Institute of Obstetrics, Gynecology and Reproductology. The protocol emphasizes that the provision of full-fledged assistance with massive obstetric hemorrhages and hemorrhagic shock (GSH) is possible only in conditions of deployed operating room. The recommendations on the implementation of infusion-transfusion therapy (ITT), including venous access and the composition of ITT, on the use of vasoactive therapy, the choice of the method of anesthesia and drugs for its conduct. Other pharmacotherapy with GSH is indicated, including the features of the application of uterotonic drugs. The tactics of respiratory support, as well as the volume of hardware and laboratory monitoring, are presented. Recommendations for the management of patients in the post-shock period are given. The effectiveness of this clinical protocol is confirmed by many years of practice of the department.

Journal of obstetrics and women's diseases. 2017;66(4):84-89
Endometrial receptivity in women with disoders in reproductive system
Ponomarenko K.Y.

Infertility and miscarriage are unresolved problems of obstetric and gynecological practice. Endometrial dysfunction is considered to be one of the most important factors in pathogenesis of reproductive losses. The usefulness of hormone-dependent cyclic transformation of the endometrium depends on the adequacy of the molecular interaction of sex hormones with specific receptors in the endometrium. The last also play an important role in the implementation of the correct “dialogue” between the blastocyst and endometrium. This review presents recent data on the role of the receptor apparatus of the endometrium in the genesis of reproductive dysfunctions.

Journal of obstetrics and women's diseases. 2017;66(4):90-97

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