No 1 (2019)

The mainstay of treatment for precancerous cervical neoplastic diseases caused by human papillomavirus (HPV) continues to be surgical techniques (laser destruction, loop electrosurgical excision, cryodestruction, and coldknife conization) that are accompanied by high complication and recurrence rates and negatively affect female reproductive function. The etiopathogenetic therapy of cervical intraepithelial neoplasia (CIN), which affects the key mechanisms for the hyperproliferation and tumor transformation of HPV-infected cervical epithelial cells, is becoming increasingly important now. Cervicon-DIM is the world’s first and only 3,3’-diindolylmethane-based drug used to treat CIN, regardless of whether HPV infection is detected by PCP. Acting locally, Cervicon-DIM versus placebo stimulates apoptosis of virus-infected and -transformed cells and substantially increases the likelihood of regression of cervical dysplasia.

The paper presents a systems analysis of the data available in the current literature on the use of ozone therapy in obstetric and gynecological practice and its benefits. It considers data on the possibilities of using medical ozone in gynecology, obstetrics, and other fields of medicine, as well as the potential risks and benefits associated with ozone therapy. The basic mechanisms of action of medical ozone and the methods and procedures for its use in practice are described. Medical ozone has shown itself to good advantage in treating gynecological and other diseases, especially when it is used as part of combination therapy. The potential risks associated with the toxicity of ozone should be taken into account in determining its dosages and administration methods. It is necessary to continue investigations of the application of ozone therapy in medical practice and to elaborate well-defined algorithms for its use.

The data available in the literature on the clinical and economic effectiveness of accelerated recovery protocols that can be used in the perioperative management of patients with deep infiltrating endometriosis (DIE) are analyzed. The paper presents the pathophysiological principles underlying the concept of accelerated postoperative recovery. It describes the main stages, methods and features of preoperative preparation and inpatient management of surgical patients within the concept. The clinical introduction of accelerated postoperative recovery protocols can serve as a reserve for reducing drug load, discomfort in patients, length of hospital stay, and economic expenditures, without lowering the efficiency of surgical treatment in patients with DIE.

Objective. The review gives the data available in the modern literature on the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and embryo cultivation in the medium containing the factor in the treatment of infertility using assisted reproductive technology (ART) techniques. Material and methods. The review includes data from foreign and Russian articles found in Pubmed on this topic. Results. The paper describes the role of GM-CSF in early embryonic development and subsequent implantation when using the GM-CSF-containing medium and discusses the effectiveness of this approach in ART programs. Conclusion. The results of the investigations performed confirm the relevance of using the GM-CSF-containing medium for in vitro embryo culturing, which can create conditions for obtaining better quality embryos, increasing the frequency of pregnancy, and preventing its termination, and giving birth to healthy babies due to the use of ART programs.

Material and methods. The study comprised 58 pregnant patients of reproductive age at 28- 40 weeks’ gestation. Of the 29 patients in the study group, 11 were diagnosed with severe PE, and the remaining 18 had moderate PE. Twenty-nine women with normal pregnancy were enrolled in the control group. Plasma markers were determined by quantitative enzyme immunoassay using Renin (active) ELISA kits (IBL International GMBH, Germany), Angiotensin 1-7(Ang 1-7) (Cloud-Clone Corp., USA), and Human ANGIIEIA (RayBiotech, Inc., USA). Results. The level of angiotensin II in severe PE (24.0 ± 5.0 pg/ml) was significantly higher than in moderate PE (15.3 ± 1.2 pg/ml; p = 0.046) and in normal pregnancy (14, 7 ± 1.9 pg / ml; p = 0.023). The level of angiotensin (1-7) in severe PE(424.0 ± 16.6 pg/ml) was higher than in moderate PE(361.1 ± 26.7 pg/ml;p = 0.051) and in normal pregnancy (390.7 ± 13.86 pg/ml); p = 0.095. In severe PE, the angiotensin (1-7) / angiotensin II ratio was significantly lower than in normal pregnancy (21.8 ± 3.1 vs. 29.4 ± 2.6 pg/ml, p = 0.049). There were no significant differences in renin concentrations between the study groups (p > 0.05). Conclusion. Severe pre-eclampsia is associated with a pronounced increase in the production of the vasoconstrictor angiotensin II concomitantly with an insufficient increase in the production of angiotensin (1-7). The absence of differences in plasma renin concentrations suggests the need for further studies to clarify the underlying mechanisms and causes of elevated plasma angiotensin II levels in patients with severe and moderate preeclampsia.

Objective. To evaluate the profile of differentially expressed microRNAs associated with oxidative stress and placental vascular dysfunction in fetal growth restriction (FGR). Materials and methods. Real-time quantitative RT-PCR was used to evaluate the placental tissue expression of microRNAs: miR-16-5p, miR-26b-5p, miR-100-5p, miR-125b-5p, miR-146a-5p, miR-182-5p, miR-199a-5p, miR-221-3p, miR-451a, and miR-574-3p in pregnant women with early- and late-onset FGR and control groups in the corresponding period. Results. Placental tissues from pregnant women with FGR were found to have signif icant changes in the expression levels of the microRNAs playing an important role in the regulation of oxidative stress: miR-125b-5p, miR-221-3p, miR-451a, and miR-574-3P in early-onset FGR and miR-451a and miR-574-3p in late-onset FGR. The DAVID database.v.6.8 could identify the potential targets of the above microRNAs that are determined as the key participants of a number of biological pathways: TGFβ-, TNFα-, VEGF-, HIF1α-, FOXO-, and MAPK-signaling pathways. Conclusion. The evaluation of the expression of the tissue-specific microRNAs regulating the balanced work of pro- and antioxidant system genes allows further determination of their diagnostic potential in the umbilical cord plasma and blood from pregnant women with FGR.

Material and methods. The study comprised 80 patients, including 47 women with spontaneous preterm labor (study group) who were divided based on gestational ages as follows: 22-27weeks and 6 days (10), 28-33 weeks and 6 days (13) and 34-36 weeks and 6 days of gestation (24). Thirty-three women with normal pregnancies and full-term labor were enrolled in a control group. The levels total and fetal cell-free DNA in blood plasma was estimated by quantitative PCR by determining the concentration of the promoter of the RASSF1A gene and its hypermethylatedportion. The analysis included measurements of IL-2, IL-4, IL-6, IL-10, GM-CSF, IFNγ and TNFα concentrations using the multiplex method. The predictive value was determined by logistic regression. Results. Patients in the study group had increased levels of IL-6 at 22-27week and 6 days gestation, and in 60% (p = 0.003) of cases, there were signs of intrauterine infection. The level of IL-8 was significantly increased in the study group at 28-33 weeks and 6 days and 34-36 weeks and 6 days gestation. There were no differences between groups in the rates of intrauterine infection at 28-33 week and 6 days. In the study group, intrauterine infection was diagnosed in 37.5% of cases (p = 0.01) at 34-36 weeks and 6 days. The concentration of fetal cell-free DNA was increased at 28-33 week and 6 days gestation. The most predictive of preterm labor at 22-27 weeks and 6 days, 28-33 weeks and 6 days, and 34-36 weeks and 6 days was combined testing of IL-6 and cfDNA (AUC 0.925; 95% CI, 0.83-1), IL-8 and cffDNA (AUC 0.92; 95% CI, 0.85-1), and IL-8, cfDNA, and cffDNA (AUL 0.92; 95% CI, 0.85-1), respectively. Conclusion. Combined testing of cell-free DNA and cytokines is a promising approach for predicting preterm labor.

Objective. Based on the amended list of risk factors for genital tuberculosis, to conduct an operational study of active identification of women at risk of reproductive disorders associated with genital tuberculosis. Material and methods. The study was conducted at the Research Center for Problems of Family Health and Human Reproduction (Irkutsk), G.D. Dugarova Republican Tuberculosis Clinical Hospital (Ulan-Ude), and Republican Clinical Gynecological Hospital (Ulan-Ude) in 2011-2017. The study analyzed the incidence of female genital tuberculosis in 2011 among patients of maternity clinics of City Polyclinic No. 6 and City Polyclinic No. 4. Obstetrician-gynecologists providing outpatient care at the City Polyclinic No. received a course of six once-monthly lectures. The developed algorithm for genital tuberculosis risk stratification was introduced with subsequent referrals of patients to G.D. Dugarova Republican Tuberculosis Clinical Hospital, Ulan- Ude since the beginning of February 2012. After the intervention, the incidence of genital tuberculosis was assessed in the control and experimental health care facilities (2015). Results. An extended list of risk factors for genital tuberculosis in women with reproductive disorders has been proposed and introduced into clinical practice. The list included new and updated criteria: chronic pelvic pain, a history of failed IVF attempts, specific types of menstrual disorders, temporary criteria for treatment failure of menstrual dysfunction and pelvic inflammatory diseases. The operational study estimated the implementation of an algorithm for active identification of risk factors of female reproductive disorders associated with genital tuberculosis, which resulted in 3.6-fold improvement of diagnosis of genital tuberculosis in outpatient settings. Conclusion. The operational study of the active introduction of the extended list of risk factors in outpatient settings increased the effectiveness of early diagnosis of female reproductive disorders associated with genital tuberculosis: 14 out of390 (3.6%), which corresponds to 0.5 per 100 000population versus zero incidence without intervention.

Objective. To estimate the level of α-microglobulin (α2-MG) of fertility in patients after a missed miscarriage (MM) and during treatment over time. Subjects and methods. Ninety patients after MM were divided into 3 groups: 1) 30 patients who received antibiotics, uterine cavity irrigation with cavitated solutions, and peloid therapy; 2) 30 patients who had antibiotics and peloid therapy; and 3) 30patients who took antibiotics only. A control group (Group 4) included 28 healthy individuals. Menstrual blood α2-MG levels [Mean (SD)] were determined. Results. The study groups exhibited low α2-MG levels: 12.6 (2.9), 9.3 (2.5), and 9.3 (2.4) μg/ml, respectively; and the control group had 40.3 (2.4) μg/ml (p = 0.001). The post-treatment α2-MG levels were 44.1(8.2) μg/ml in Group 1 (p = 0.001), 2 times lower than 24.2 (3.3) μg/ml in Group 2 (p = 0.05), and unchanged in Group 3. Conclusion. Comprehensive treatment leads to a significant increase in AMGP level and the restoration of endometrial receptivity.

Objective. To determine the effectiveness of the homeopathic herbal preparation Mastodynon (Bionorica SE, Germany) in treatment of benign breast diseases concurrent with mastalgia in reproductive-aged patients and its effect on the level of gonadotropins and estrogen metabolites. Subjects and methods. A prospective, open-label, monocenter study was conducted in a small group (n = 20) to assess results before and after a course of therapy. The patients mean age was 32.8 ± 3.1 years. The assessment points were a pain level on a visual analogue scale (VAS); breast tissue density determined by ultrasound; the blood levels of follicle-stimulating hormone, prolactin, and estradiol and the urinary levels of 6 estrogen metabolites (4- OHE1, 2- OHE1, 2- OHE2, 16α- OHE1, 2- OMeE1, and 4- OMeE1), as well as 2- OHE1+2- OHE2/16α-OHE1 and 2- OHE1/2- OMeE1 ratios. Results. The breast pain intensity according to VAS ranged from 40 to 95 mm (52.76 ± 15.38 mm) at baseline; 27.42 ± 11.78 mm at a month after therapy initiation (p = 0.0001) and 7.4 ± 8.5 mm after 90 days of therapy (p < 0.0001); mastalgia completely disappeared in 40% of cases. After the course of therapy, an improvement in the breast structure was noted in 80.0%, signif icantly more often in mastopathy with a predominance of the glandular component (80% and 30%; p = 0.004). All the patients had normal baseline blood estrogen concentrations however in 60% of cases it was showed a higher urinary levels of a number of estrogen metabolites; after the course of therapy, the profile of estrogen metabolites in all the patients returned to normal; the 2-OHE1+2-OHE2/16α-OHE1 ratio increased 2.4-fold(2.4 ± 1.03 and 5.76±6.9;p = 0.02). Conclusion. The 90-day use of Mastodynon in patients with benign breast diseases concurrent with mastalgia leads to a 7.1-fold decrease in its severity, to an improvement in the breast structure diagnosed by ultrasound in 80.0% of cases, and to a 2.4-fold increase in the 2-OHE1+2-OHE2/16α-OHE1 ratio.

Objective. To determine the predictors of miscarriage and to evaluate the efficacy of a dome-shaped obstetric pessary and surgical cerclage in the management of pregnancy in a group at high risk for miscarriage. Resu1ts. First-trimester threatened miscarriage was observed in 29.8% (48/161) of cases in Group 1 and in 37.9% in Group 2. Postpartum hemorrhage was diagnosed in 8.1% (13/161) of the puerperas in the study group and in 22.8% (18/79) in the comparison group (χ2 = 6.500; p = 0.011). Surgical cerclage is more preferable for isthmic-cervical insufficiency of organic origin, a cervical length less than 15 mm, and a large isthmic myomatous nodule. Pessary placement enables preterm birth to be reduced by 1.7 times. Conclusion. An integrated approach to pregnancy management allows a reduction in the number of premature births.

Objective. To carry out a systems analysis of the data available in the modern literature on organ-sparing operations for early cervical cancer, on their technical features and the advantages and disadvantages of various procedures. Materials and methods. Includes the data of foreign and Russian articles published in the past 7 years and found in Pubmed and eLIBRARY on this topic. Results. The efficiency of organ-sparing surgery was evaluated; cases, in which this surgery could not be performed, were described. The data on preserved reproductive function in women who had received this treatment were studied. Conclusion. To date, the use of radical trachelectomy has proven improved quality of life in women undergoing this surgical intervention. Further investigation is needed in this area.

Background. The genetic determinants of ovarian hyperstimulation syndrome (OHSS) are relevant due to the fact that the prediction of this complication by routine clinical and laboratory markers is not always objective. The emergence of spontaneous forms of the OHSS is associated just with the peculiarities of the genotype. Description. The paper presents a clinical case of OHSS in a patient with spontaneous pregnancy and shows the relationship of this condition to the OHSS risk genotypes identified in the study of genetic features of the development and course of OHSS in ART programs. Conclusion. The development of OHSS in spontaneous pregnancy and the detection of the genotype characteristics of this condition in this patient emphasize the contribution of genetics to the development of this complication and the relevance of searching for new markers to personalize ART programs. Genetic testing is a highly specific technique that can minimize the risks associated with the development of OHSS.