Vol 68, No 6 (2019)

Actual Health Care Problems
Predictive value of ovarian hormone-producing function assessment in poor responders undergoing assisted reproductive technologies
Merkulova A.I., Dzhemlikhanova L.K., Niauri D.A., Gzgzyan A.M., Kogan I.Y., Krikheli I.O., Tapilskaya N.I., Tkachenko N.N., Mekina I.D., Lesik E.A., Komarova E.M.
Abstract

Hypothesis/aims of study. The management of poor responders to ovarian stimulation for in vitro fertilization (IVF) has always been a challenge. It is difficult for both doctors and patients to make decision to proceed to oocyte donation or abandon fertility treatment. More predictors of successful IVF treatment in poor responders are needed. The aim of this study was to assess hormonal ovarian function in poor responders undergoing ovarian stimulation and to identify predictors of the chance of clinical pregnancy after IVF cycle.

Study design, materials and methods. The study included 45 infertile patients undergoing ovarian stimulation with poor ovarian response according to the Bologna criteria. All patients underwent standard IVF or IVF/ICSI protocol using gonadotropin releasing hormone antagonists. Letrozole (5 mg/day) was administered during the first 5 days of stimulation in standard antagonist FSH/hMG protocol to 13 of the patients included in the study, with standard antagonist FSH/hMG protocol being only administered to other 32 patients. Serum and follicular fluid were collected at the time of follicle aspiration, and the concentrations of total testosterone, estradiol and androstenedione were determined.

Results. Follicular fluid concentrations of testosterone and androstenedione were higher and serum estradiol level was lower in the letrozole group. The serum concentrations of testosterone and androstenedione were comparable in both groups, while the serum estradiol/testosterone ratio was lower in the letrozole group. The threshold level of estradiol/testosterone ratio × 1000 on the day of oocyte retrieval above which pregnancy and implantation rates were increased was 1532.68 (odds ratio — 7.0 (95% CI 1.39–35.35), р = 0.02).

Conclusion. Evaluating of the serum estradiol / testosterone ratio has been shown to determine aromatase activity of ovarian preovulatory follicles and to predict IVF outcome in poor responders undergoing assisted reproductive technology.

Journal of obstetrics and women's diseases. 2019;68(6):7-18
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Urinary tract infections in obstetrics and gynecology: current issues of diagnosis and antibiotic therapy
Khusnutdinova T.A.
Abstract

Urinary tract infections are among the most common infectious diseases in women and often complicate the course of pregnancy. This article reviews current scientific and methodical literature on the management of pregnant women with urinary tract infection. Aspects of clinical importance of urinary tract infections during pregnancy (epidemiology, clinical manifestations, and complications) are discussed, with current recommendations for diagnosis and management of urinary tract infections summarized. Special attention is paid to the problem of antibiotic resistance of urinary tract infection pathogens.

Journal of obstetrics and women's diseases. 2019;68(6):19-28
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Original Researches
Vaginal and intestinal microbiocenosis composition in pregnant women
Bezmenko A.A., Sadovaya N.D.
Abstract

Hypothesis/aims of study. It is assumed that intestinal dysbiosis, as well as bacterial vaginosis, may be one of the risk factors, and in some cases, the direct cause of pregnancy complications. This study was aimed to assess the intestinal and vaginal microbiocenosis composition in women with threatened miscarriage and normal pregnancy.

Study design, materials and methods. The study involved 68 women aged 18 to 35 years (mean age 27.6 ± 0.7 years) in pregnancy from 6 to 18 weeks. The main group consisted of 38 women with threatened miscarriage. The control group included women (n = 30) with normal pregnancy. Patients of the main and control groups were examined in accordance with the requirements of the Ministry of Health order No. 572n. In addition, a qualitative and quantitative microbiological analysis of vaginal discharge and feces was performed using the real-time polymerase chain reaction method.

Results. Vaginal dysbiosis was detected in 60.5% of pregnant women of the main group and only 13.3% of women of the control group. In the main group, grade II dysbiosis was found in 23.7% of cases, and grade I dysbiosis in 36.8% of cases, while in the control group, these grades were found only in 3.3% and 10% of cases, respectively. Intestinal dysbiosis was diagnosed in 100% of the examined pregnant women. In patients of the main group, intestinal dysbiosis was detected as follows: grade I in 29% of cases, grade II in 52.6% of cases, and grade III in 18.4% of cases. In patients of the control group, the disorders corresponded mainly to grade I (83.4%) and, to a lesser extent, grade II (16.6%) dysbiosis, there being no cases of severe dysbiosis revealed.

Conclusion. Women with threatened miscarriage had the most pronounced dysbiotic changes in vaginal and intestinal microflora compared to the control group. Vaginal dysbiosis was combined with intestinal dysbiosis in 100% of cases in patients of the main and control groups, and the degree of dysbiotic changes in the vaginal microflora was directly proportional to the degree of intestinal dysbiosis.

Journal of obstetrics and women's diseases. 2019;68(6):29-36
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Use of androgens and aromatase inhibitors in poor responders undergoing in vitro fertilization
Merkulova A.I., Dzhemlikhanova L.K., Niauri D.A., Gzgzyan A.M., Kogan I.Y., Krikheli I.O., Tapilskaya N.I., Mekina I.D., Lesik E.A., Komarova E.M.
Abstract

Hypothesis/aims of study. Poor ovarian response is still considered one of the most challenging tasks in reproductive medicine. Poor responders have decreased circulating androgens during spontaneous cycles. Androgens are known to play an important role in follicular growth and development. Hence, the use of various androgens and androgen inhibitors in poor responders undergoing ovarian stimulation for IVF has been proposed to improve efficacy of treatment. This study was aimed to examine the efficacy of aromatase inhibitors and androgens in infertility treatment in patients with poor response.

Study design, materials and methods. This prospective cohort-controlled clinical trial included 204 patients under 42 years of age with infertility and poor response to ovarian stimulation. In vitro fertilization treatment with an antagonist FSH/hMG protocol with letrozole (5 mg/day) was administered in the first group of patients (n = 26) during the first 5 days of stimulation. Patients of the second group (n = 38) were applied testosterone (25 mg/day) transdermally, starting from the 5th day of the menstrual cycle preceding controlled ovarian stimulation for in vitro fertilization. The third group of patients (n = 18) was administered dehydroepiandrosterone (100 mg/day) for 3 months prior to controlled ovarian stimulation for in vitro fertilization.

Results. Improved response to FSH stimulation with letrozole co-treatment was evidenced, with parameters of stimulation efficacy and embryo development being better in the testosterone group. No significant improvement in ovarian response markers, ovarian response to gonadotrophin stimulation and in vitro fertilization outcomes were found in poor responders receiving pre-treatment dehydroepiandrosterone.

Conclusion. Further studies are necessary to improve approaches of testosterone and aromatase inhibitors use in poor responders undergoing in vitro fertilization.

Journal of obstetrics and women's diseases. 2019;68(6):37-46
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Analysis of the timing and delivery methods, clinical and laboratory indicators of hiv-infected pregnant women in Saint Petersburg
Mozaleva O.L., Samarina A.V.
Abstract

Assessing the timing and delivery methods, clinical and laboratory indicators of HIV-infected pregnant women is important for organizing effective care for this group of patients and further reducing the frequency of perinatal transmission of HIV infection. In 2014–2017, in Saint Petersburg, there were 2,524 childbirths in HIV-infected women, who were observed during pregnancy mainly in the Center for the Prevention and Control of AIDS and Infectious Diseases (AIDS Center). The average frequency of perinatal HIV transmission in the city over the study period was 1.3%, which is lower than the average for Russia (2.5%). A retrospective and prospective analysis of 1,858 medical records of HIV-infected women observed during pregnancy at the AIDS Center in 2014–2017 was performed. An annual decrease in the proportion of chronic viral hepatitis C coinfection was found, which was proportional to a decrease in parenteral HIV transmission in the study group. Due to the increase in HIV testing coverage, the frequency of detection of infections in pregnant women in antenatal clinics during registration was reduced. This allows conducting a thorough examination, counseling and a timely initiation of antiretroviral therapy (ART) during pregnancy planning. The vast majority of HIV-infected women are committed to follow-up in medical facilities during pregnancy, to receive antiretroviral prophylaxis (ARP) and, as a result, to give birth to a healthy child. The rate of preterm birth among HIV-infected women is higher than in HIV-seronegative women. This determines the timely initiation of ARP/ART during pregnancy for prevention of preterm delivery. The proportion of births through the birth canal increases annually, but the operative delivery rate remains above the population.

Journal of obstetrics and women's diseases. 2019;68(6):47-56
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Activity of catalase in surgically induced endometrial-like lesions in rats
Razygraev A.V., Petrosyan M.A., Baziyan E.V., Polyanskikh L.S.
Abstract

Hypothesis/aims of study. There is a link between the activities (and polymorphisms of genes) of antioxidant enzymes and endometriosis. It is also known that progesterone induces some antioxidant enzymes in the endometrium and that progesterone analogs are effective for reduction of endometrial lesions. In addition to morphometric and histological estimations of endometriosis regression, it could be useful to assess the activity of antioxidant enzymes within endometriotic foci. The present study is aimed at estimating the activity of catalase, a hydrogen peroxide-detoxifying enzyme, in surgically induced endometrial-like lesions with a variable degree of reduction.

Study design, materials and methods. The study was carried out on 12 mature female rats of Wistar strain. Endometrial-like lesions were induced by autotransplantation of uterine tissue fragments on the abdominal wall. After 35-37 days, the endometrial foci were extracted. Catalase activity in the ectopic endometrium was determined by the Beers & Sizer method modified as follows: recording hydrogen peroxide concentration decrease at 250 nm and using 3-amino-1,2,4-triazole (AT) to assess specificity. The correlation between the specific catalase activity and protein amount in the ectopic endometrium was estimated.

Results. At the wavelength of 250 nm, a relatively weak interference of AT with other components of the reaction mixture was observed, which allows using the specific catalase inhibitor to indicate the enzyme activity. The activity is measured in a short period of incubation (less than 1 minute) and is proportional to amount of the endometrial tissue extract in the reaction mixture. As a rule, the most reduced endometriotic foci (with the lowest weight) possessed a higher catalase activity (the Spearman’s rho was –0.66 with p < 0.025).

Conclusion. The method for determining catalase activity was adapted to work with endometriotic foci. With p < 0.025, we can accept that a low weight of endometriotic foci is linked with a relatively high catalase activity within their tissue. The results allow suggesting the involvement of catalase in reduction of endometrial lesions.

Journal of obstetrics and women's diseases. 2019;68(6):57-63
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A model for predicting the risk of preeclampsia in women with different somatotypes
Tomayeva K.G., Gaydukov S.N.
Abstract

Hypothesis/aims of study. Preeclampsia is a serious pregnancy-specific multi-organ disease of complex etiology. It affects 3–6% of expectant mothers worldwide and it persists as a leading cause of maternal and fetal morbidity and mortality. This study aimed at analyzing the frequency of preeclampsia in women with different somatotypes and at developing a prediction model to determine the risk of this disease.

Study design, materials and methods. 390 women were examined, of whom 110 were of the macrosomatic type, 173 of the mesosomatic type, and 107 of the microsomatic type. Somatometry was performed according to R.N. Dorokhov in women in early pregnancy (before 9–10 weeks of gestation). The urinary excretion of markers for podocyte injury (nephrin, podocalyxin, and VEGF) was measured using ELISA spectrophotometric methods.

Results. Preeclampsia has been found to be significantly more prevalent among the representatives of the macrosomatic type, compared to women of the meso- and microsomatic types. Urine nephrin, podocalyxin and VEGF levels were significantly higher in women of the macrosomatic type, as compared to those of the meso- and microsomatic types. Using multiple regression analysis, we obtained the regression equation (formula), which predicts the development of preeclampsia in women of different somatotypes.

Conclusion. Carrying out calculations according to the presented formula allows predicting the occurrence of preeclampsia with high accuracy, as well as forming high-risk groups among patients already in the first trimester of pregnancy when a pregnant woman is registered in the women’s consultation, long before the disease develops. This will contribute to more effective implementation of therapeutic measures to prevent the development of this complication.

Journal of obstetrics and women's diseases. 2019;68(6):65-72
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Reviews
Features of the placenta structure in post-term pregnancy
Burkitova A.M., Polyakova V.O., Bolotskikh V.M., Kvetnoy I.M.
Abstract

This review deals with the formation and structure of the placenta in the full-term gestational period and during post-term gestation. The results of various morphological and immunohistochemical studies are analyzed, highlighting changes in the placenta during post-term gestation and the role of expression of immunohistochemical markers, such as CD34, NO synthase, and collagen.

Journal of obstetrics and women's diseases. 2019;68(6):73-86
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Squamous intraepithelial lesions of the cervix: a modern view of etiology, pathogenesis, and diagnosis
Zhukova A.B.
Abstract

Squamous intraepithelial lesions of the cervix are one of the most common pathologies of the female reproductive system, mainly affecting patients of reproductive age. The progression of this pathology can result in the development of cervical cancer. As a rule, cervical cancer does not occur immediately, but develops over a long period of time, going through a series of stages. Dynamic monitoring and identification of squamous intraepithelial lesions progression markers are necessary to prevent the development of cervical cancer. The article presents current data on the etiology, pathogenesis, and diagnosis of this pathology.

Journal of obstetrics and women's diseases. 2019;68(6):87-98
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Current understanding of selective estrogen receptor modulators
Polyanskikh L.S., Petrosyan M.A., Morozkina S.N., Baziyan E.V.
Abstract

Despite the variety of selective estrogen receptor modulators of different classes of compounds and their active use for the treatment of hormone-dependent breast cancer, climacteric conditions, and polycystic ovary syndrome, as well as for ovulation stimulation and for prevention and treatment of postmenopausal osteoporosis and vertebral fractures, there are a number of serious side effects, such as thromboembolic disorders, uterine cancer and endometrial cancer. Among the selective estrogen receptor modulators used in clinical practice, it is worth noting: Raloxifene, for the prevention and treatment of postmenopausal osteoporosis and vertebral fractures; Tamoxifen, for the treatment of breast cancer; Toremifene, for the treatment of metastatic breast cancer in postmenopausal women; Lasofoxifene, for the treatment of osteoporosis; Bazedoxifene, for the treatment and prevention of postmenopausal osteoporosis; Clomiphene, for the treatment of anovulatory infertility; Ospemifene, for the treatment of moderate to severe dyspareunia associated with postmenopausal syndrome. An ongoing search for an effective and safe selective estrogen receptor modulator for the treatment of endometriosis is currently underway.

Journal of obstetrics and women's diseases. 2019;68(6):99-106
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Inflammatory response and its role in antenatal transformation of the cervix
Prokhorova O.V., Olina A.A.
Abstract

Understanding how the cervical tissue changes before childbirth is one of the most significant issues of modern-day obstetrics. This article reviews current original research findings by domestic and foreign authors in the field of antenatal cervical transformation mechanisms. Cellular and humoral components of inflammation in the cervix are presented as the most significant causes of morphological changes in cervical tissues. The perspectives of further research in the field have been stated in this review.

Journal of obstetrics and women's diseases. 2019;68(6):107-114
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