No 2 (2017)

The review gives an update on the analysis of embryo metabolic products in nutrient media and on the possible use of a number of metabolites as markers for successful embryo implantation. Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic. Results. The media for the cultivation of embryos at various stages of development are a unique study object, as they carry information about the energetic and metabolic activities and the signaling systems of the embryo. The study of the aspects of human embryo life is a fundamental task and it is of undoubted interest because it will be able to expand our understanding of the processes of early development, to develop new technologies improving the outcomes of assisted reproductive technology (ART) programs, and to introduce them into clinical practice. Conclusion. Further studies and assessment of the molecular components of nutrient media are a promising area in searching for the markers of successful embryo implantation with the subsequent development of a clinical pregnancy and the birth of a healthy baby to enhance the efficiency of treatment using ART techniques. Scientifically substantiated evidence on the molecular composition of cultivation media will be able to develop an additional noninvasive procedure to choose an embryo for selective transfer, which will make it possible to elaborate an individual management algorithm for women in ART programs.

Objective. To investigate the impact of lymphocyte immunotherapy on the level of cytokines (tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10), fibrinolytic responses (PAI-I level and activity, t-PA antigen, plasminogen levels, Factor XII-dependent f ibrinolysis time), and pregnancy course and outcomes. Subjects and methods. A prospective cohort study was conducted in 233 patients, including 69 pregnant women with recurrent miscarriage who had received lymphocyte immunotherapy, 73 women with recurrent miscarriage who had conventional treatment, and 91 gynecologically healthy patients. Cytokine levels and fibrinolytic indicators were determined at 7-8 weeks of gestation. Results. Immunochemotherapy increases the activity of the regulatory cytokine IL-10 (p=0.0001), reduces the proinflammatory cytokine response of TNF-α (p=0.0001) and the level (p=0.0001) and activity (p=0.0173) of PAI-1, and raises the content of t-PA (p=0.0413), without changing the integral indicator (Factor XIIa-dependent fibrinolysis). Lymphocyte therapy declines the number of fetal growth retardation cases by 2.5 times (p < 0.05). Conclusion. Therapy with allogeneic lymphocytes from the partner can be regarded as prevention of late pregnancy complications.

Objective. To conduct a comprehensive study of a mother’s psychoemotional state over time during the postpartum period after very early preterm birth (VEPB). Subjects and methods. On days 3 and 30 after birth, a comprehensive psychological case-control study was performed in a study group (n = 23) after VEPB (an average of 26.8±0.28 weeks) and in a control group (n = 23) following full-term birth (an average of 39.4±0.01 weeks). The methods included an interview using the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale (HDRS). Results. On 3-5 days after VEPB, anxiety levels were three times higher than that following full-term birth (36.1 versus 14.4 scores; p<0.05), which persisted at 30 days after birth. On days 3-5 and 30 after VEPB, HDRS depression scores were 1.7 and 2.3 times higher, respectively, than following full-term birth. Symptoms of severe postpartum depression were noted in 28.6% of the women in the study group on days 3 and 30 after birth. Conclusion. Delivery at 22-27 6/7 weeks of gestation is a predictor of severe postpartum depression with manifestations of anxiety. There is a need to organize psychological adaptation of women and their family members in the first month after VEPB.

Objective. To study the significance of vitamin D receptor (VDR) gene polymorphism as a molecular genetic marker for estimating the rate of implantation and clinical pregnancy and the patterns of oogenesis and embryogenesis in assisted reproductive technology programs. Subjects and methods. A total of 142 patients who had undergone an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) program with superovulation and embryo transfer in this cycle were examined during a prospective study case-control study. Serum 25-hydroxyvitamin D levels and VDR gene polymorphism were ascertained in all the patients. The women were divided into 3 groups according to the level of vitamin D; 1) blood vitamin D deficiency (<10 ng/ml); 2) blood vitamin D insufficiency (10-29 ng/ml); 3) normal blood vitamin D levels (30-100 ng/ml). Results. Analysis of the association of VDR gene polymorphism with serum vitamin D levels established that the patients with A/G and A/A genotypes of VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) [rs 10735810] had serum vitamin D deficiency in 13.4% of women, vitamin D insufficiency in 70.1%, and normal vitamin D levels in 16.5% of the women included in the study. At the same time, the patients with G/G genotype of VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) were found to have blood vitamin D deficiency in 40% and insufficiency of this vitamin in 60%. The findings suggest that the carriage of G/G genotype of this polymorphism more than doubles the risk of serum vitamin D deficiency. The analysis of the association of VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) with the quality of the embryos obtained from women with different serum vitamin D levels revealed that the carriage of G/G genotype of the polymorphism (compared to A/A and A/G genotypes) reduced the risk of having poor-quality embryos by more than 3 times. Conclusion. VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) [rs 10735810] is an independent factor that can predict the serum vitamin D level that affects the outcomes of assisted reproductive technology programs and embryo quality and can complement the arsenal of already existing markers.

Objective. To determine the in vivo molecular mechanisms of action of ulipristal acetate on the cell apoptosis of myomatous nodules and on the proteolysis of extracellular matrix components and to identify the features of a tumor cell response to the drug during its therapy showing varying clinical efficacy. Subjects and methods. A total of 32 women with uterine leiomyoma (17 had not been preoperatively prepared and 15 women had preoperatively received ulipristal acetate 5 mg daily for 3 months) were examined. PCR was used to determine XIAP, PPARγ, PTEN, and MMP-2 mRNA expression levels in the biopsies of the myometrium and myomatous nodules. Results. The drug-untreated patients showed a higher XIAP, PPARγ, PTEN, and MMP-2 mRNA expression in the myomatous nodes than in the myometrium. The synthesis of XIAP and MMP-2 decreased and the expression of PPARγ mRNA increased in the leiomyomas of the treated women as compared to those of the untreated ones. The ulipristal acetate-induced reduction in nodular sizes was associated with the highest rates of PPARγ and PTEN synthesis in the tumor. Conclusion. The ulipristal acetate-induced reduction in uterine leiomyoma sizes occurs due to the induction of apoptosis in the tumor, by increasing the synthesis of the pro-apoptotic factors PPARγ and PTEN.

Objective. To estimate the capabilities of comprehensive magnetic resonance imaging (MRI) in the differential diagnosis of ovarian tumors. Subjects and methods. In 2011 to 2015, a total of 256patients with 289 ovarian masses underwent small pelvic and abdominal MRI (if necessary) to clarify the pattern and extent of the tumor process. MRI was performed on a 1.5 Tl scanner. The MRI protocol was to obtain T2-weighted images (WI) in three projections, STIR, T1-WI, DWI with b-factors 0, 1000м/мм2, to calculate the values of the diffusion coefficient, and to make the diffusion maps Dynamic 3D FatSat. Postprocessing involved an analysis of signal intensity-time curves in a given area of interest (8-45 pixels). MRI findings were compared with intraoperative tumor histological structural data or verified during a follow-up for at least 6 months. Results. The pattern of detected abnormalities was as follows: true ovarian tumors (71%), endometriomas (16%), cysts (11%), and tubo-ovarian abscesses (2%). Among the true tumors, there were serous epithelial tumors (51%), mucinous epithelial tumors (26%), endometrioid cysts (2%), dermoid cysts (6%), clear-cell carcinomas (2%), granulosa cell tumors (6%), fibromas (4%), Brenner tumors (1%), and metastatic tumors (3%). The degree distribution of the tumors identified was the following: benign tumors (49%), borderline tumors (12%) (occurring only in a group of epithelial tumors), and malignant tumors (39%). FIGO staging of the borderline ovarian tumors classified as Stages IA (66%) and IC (34%). That of the malignant tumors classified as Stages IA (7.3%), IIA (17%), IIB(12.2%), IIC(17%), IIIB (21.9%), IIIC(14.6%), and IV(9.7%). Quantitative estimation of the parameters of perfusion images showed that the amplitude of contrast agent accumulation was significantly higher in malignant tumors (167% (115.2-212.5%)) than in benign tumors (61.2% (41.2-99.0%)) (P < 0.001) and borderline ones (85.7% (58.3-138.2%)), (P < 0.01); the signal intensity semi-elevation period was significantly longer in benign tumors (35.1 sec (30.8-42.5sec)) than in borderline tumors (27.9sec (23.5-29.8 sec) (P < 0.05), and malignant ones (23.1 sec (20.5-30.9 sec)) (P = 0.01). The largest curvature (inflection) of the curve (%/sec) amounted to 1.78 (1.0-2.6); 2.86 (2.01-3.95), and 6.1 (4.19-9.46) for benign, borderline, and malignant tumors, respectively, and it was significantly higher in invasive carcinomas (P < 0.01). Malignant tumors have significantly lower mean apparent diffusion coefficients (ADC) than benign tumors (1.012±0.18 and 1.54±0.25 mm2/sec x 10-3, respectively); the value intervals did not intersect. The threshold ADC value of malignant ovarian tumors was lower than 1.139 mm2/sec x 10-3. The information values of advanced MRI techniques were an accuracy of 92.1%, a sensitivity of 93.6%, and a specificity of 91.2%. Conclusion. The incorporation of MRI with quantitative evaluation of perfusion parameters and diffusion-weighted images in a comprehensive examination algorithm allows differentiation of the degree of malignancy of ovarian tumors with a high degree of accuracy, by determining the opportunities for optimizing management tactics for patients.

Objective. To evaluate the efficiency of treatment in patients with the hypoplastic type of chronic endometritis (CE) by uterine cavity irrigation with cavitation drug solutions exposed to low-frequency ultrasound (LFUS). Subjects and methods. 128 women diagnosed with the hypoplastic type of CE were examined. hypoplastic option. 64 patients of a study group (Group 1) received drug therapy and irrigation with a 0.05% cavitation chlorhexidine solution exposed to LFUS and with an immunomodulator solution (a total of 3 cycles). 64 patients of a comparison group (Group 2) had drug therapy only. The results were assessed by the time course of changes in the size of M-echo, endometrial histological examination before and after treatment, the occurrence of pregnancy and its outcomes. Results. The pretreatment endometrial thickness (M-echo data) was 5.8±0.8 mm in Group 1 and 5.8±0.5 mm in Group 2 (p = 0.899), the posttreatment one was 8.6±0.3 and 6.4±0.9 mm, respectively (p = 0.000). In the patients of the study group, the histological pattern in the endometrial biopsy specimens was observed to normalize in 11 (17.2±0.05) and 64 (100%) patients after cycle treatments 2 and 3, respectively. In the comparison group, the endometrium after 4 and 6 months of treatment corresponded to the phase of the cycle in 2 (3.1%±0.02) and 18 (28.1%±0.06) women, respectively. In the first year after the end of therapy, pregnancy occurred substantially more commonly in Group 1 than in the comparison group (45.3 versus 28.15%). Pregnancy ended in childbirth in 89.7% of the patients in Group 1 and in 44.4% in Group 2; in these groups, there were miscarriages in 10.3 and 55.6%, respectively. Conclusion. Thus, LFUS used in patients with the hypoplastic type of CE promotes the adequate growth of the endometrium and the creation of favorable conditions for ovum implantation.

Objective. The Russian and foreign experience with indole-3-carbinol, a substance with proven multitargeted antitumor activity, in the treatment of benign breast diseases and in the prevention of breast cancer was summarized. There are results of foreign experimental and clinical studies, and the randomized, double-blind, placebo-controlled trial of the efficacy of a drug based on indole-3-carbinol (Indinol forto) in treating cyclic mastalgia (mastodynia) and benign breast dysplasia (fibrocystic mastopathy), which was conducted in the Russian Federation in 2010-2013. Subjects and methods. This clinical trial included 62 patients aged 20 to 45 years. 30patients received indole- 3-carbinol 400 mg/day and 32 took placebo during 6 menstrual cycles. After 6 months of therapy, its efficiency was found to be, in terms of breast tenderness, significantly higher in the Indinol forto group than in the placebo group (83.3% vs 50.3%; p = 0.002). Following 6 months of treatment, breast tenderness reduced or disappeared in 83.0% of the patients in the mastopathy subgroup (in 47.0% in the placebo group; p = 0.004). The Indinol forto group also showed an increment in the plasma level of sex steroid-binding globulin and a statistically significant rise in the ratio of urinary estrogen metabolites (2-hydroxyestrone/16α-hydroxyestrone). Results. The investigation provided evidence that the new multitargeted drug Indinol forto was effective in treating patients with cyclic mastalgia (mastodynia) and mastopathy. Considering that the known mechanisms of action of indole carbinol characterize it as an agent having a protective effect against cancer, this result is particularly important in the terms of the prevention of breast cancer in patients with cyclic mastalgia. The results of studies demonstrating the positive effect of indole-3-carbinol and 3,3’-diindolylmethane on the clinical markers of an increased risk for breast cancer (mastalgia, mastodynia, and other manifestations of fibrocystic breast disease) confirm the important role of these molecules as preventive strategies to reduce the risk of breast cancer. Conclusion. These findings have led to the conclusion that Indinol forto may be recommended for the treatment of patients with both cyclic mastalgia (mastodynia) and mastopathy.

Objective. To analyze the results of the International Congress dedicated to chlamydial infection, by simultaneously analyzing the scientific literature on the topic. Material and methods. The reports of the 8th Congress of the European Society for Chlamydia Research and the data of the studies found in international databases on this topic were examined. Results. The molecular biology and genomics of Chlamydia, the diagnosis and immunology of its infection, as well as the efficiency of antibiotic therapy were the main issues considered at the Congress. Conclusion. The efficacy of azithromycin in treating chlamydial infection and patients’ adherence to this type of therapy were substantiated.