№ 12 (2018)

The paper analyzes the data available in the modern scientific literature on the possibility of human umbilical cord tissue cryopreservation and its further clinical application. It describes protocols to obtain various biomedical products (vascular matrix, Wharton jelly-based grafts, and multipotent stromal cells) from the frozen umbilical cord, as well as prospects of their clinical use. The analysis of the literature data may be indicative of the active development of a promising cell biotechnology area, such as human umbilical cord cryopreservation.

The paper carries out a systems analysis of the data available in the current literature on menarche as a pubertal stage and its molecular genetic determinants. It presents studies of menarche formation during pubertal development, as well as molecular genetic factors for its determinants. According to the literature, age at menarche is an important indicator of pubertal development in a woman and has molecular genetic determinants.

Objective. To investigate the feasibility of using cardiotocography (CTG) in the 2nd trimester of pregnancy to assess the fetal functional state and identify criteria for characterizing fetal hypoxia in this period of gestation. Material and methods. This study analyzed the features of CTG in the 2nd trimester in 100 pregnant women with a physiological course of pregnancy and childbirth and 40 pregnant women with adverse perinatal outcomes. Results. The following CTG parameters were characteristic of pregnant women with physiological pregnancy in the second trimester: STV more than 3.2 ms, LTV more than 37 ms, EHV more than 5, ELV less than 4 minutes, and fewer than three decelerations. The patients with gestational complications had the following CTG findings: an STV decrease below 3.2 ms; LTV below 37 ms; the combination of a decrease in EHV of less than 5 minutes with an increase in ELV of more than 5 minutes, and more than three decelerations. Conclusion. The criteria for the pathological type of CTG in the 2nd trimester of pregnancy cannot be used to diagnose fetal hypoxia but may help predict the development of gestational complications.

Objective. To elaborate new approaches to therapy for cervical dysplasia in pregnant women, by correcting the expression of innate immunity factors. Subjects and methods. A study group included 30 patients with cervical dysplasia [low-grade squamous epithelial lesion (TSIT) (43.33%) and high-grade squamous epithelial lesion HSIT (56.67%)]; a comparison group consisted of 11 patients without cervical disease. The patients’ age was 31.6 + 1.7 years in the study group and 31.9 + 2.2 years in the comparison group. Real-time PCR was used to investigate the expression of innate immunity factors (TNF-a, TLR9, TLR2, and HBD-1) in the cervical canal epithelium and in the vagina. The HPV titer was determined using the digene HPV test. Results. During cytokine therapy, there were 1.2- and 1.8-fold reductions in the viral loads of HPV of Groups A9 andA7, respectively. There was a 2-fold increase in the expression of TNF-a and a 10-fold rise in that of NBD-1 and TLR9 and TLR2 in the cervical canal. In the vaginal epithelium, the level of TLR9 increased 5.3-fold. Conclusion. The Syperlymph-induced change in the viral load correlates with innate immunity activation in both the cervical canal mucosa and the vagina due to the activation of the expression of the TIR2 and TIR9 genes and the effector molecules TNF-a and HBD-1.

Objective. To investigate the outcomes of IVF/ICSI in patients with anovulatory infertility depending on ovarian aromatase activity. Materials and methods. This prospective cohort study comprised 98 patients with anovulatory infertility. Depending on ovarian aromatase activity, patients were divided into Group I (low activity, n = 60), Group II (normal activity, n = 24), and Group III (high activity, n = 14). The outcomes of IVF/ICSI were analyzed. Results. The proportion of mature oocytes was significantly higher in the Group II than in Group I [89.0% (80-100) vs. 78.5% (69-86), p <0.05] and did not differ from Group III [89.0%o (67-100)]. The fertilization rate in the Group II was significantly higher than in Group I [(73%) (56-86) vs. 59% (49-75), p = 0.04] and did not differ from Group III [71%) (43-80)]. The biochemical and clinical pregnancy rates and live birth rate per embryo transfer in Group II were higher than in Group I [45.5% vs 10.0% (p = 0.005); 40.9% vs 10.0% (p = 0.01), and 31.8% vs 10.0% (p = 0.05), respectively], and did not differ from Group III, where these rates were 35.7%; 35.7% and 28.6%, respectively. Hyperergic response to ovarian stimulation was observed in 55%, 25%, and none of the patients in Group I, Group II, and Group III, respectively. Conclusion. In patients with normogonadotropic anovulation with low ovarian aromatase activity, embryo transfer in fresh cycles is associated with a high risk of ovarian hyperstimulation syndrome and results in a low pregnancy rate.

Objective. To investigate of the efficacy of the selective progesterone receptor modulator in treating uterine fibroids of different types and sizes Subjects and methods. The investigation enrolled 30 women with uterine fibroids who experienced pain and heavy menstrual periods. The patients took ulipristal acetate, a synthetic selective progesterone receptor modulator, at a dose of 5 mg/day for 12 weeks. Intensity of pain syndrome, volume of bleeding, volume of the uterus and dominant nodules, and sizes of nodules were assessed according to sonographic and Doppler findings before and after a therapy cycle. Conclusion. After completing a treatment cycle, pain intensity decreased from 6.6 to 4.4 scores due to the absence of patients reporting unsufferable and severe pain. 85.7%o of patients who complained of heavy menstrual periods achieved uterine bleeding control on day 7 after treatment initiation. After the first cycle of therapy with uliprystal acetate, there were decreases in the uterine volume exceeding 3-5-fold the normal values (p < 0.05) and in the nodular sizes that had been larger than 6 cm before treatment (p < 0.05). This resulted in a 1.9-fold decline in the number of cases of nodules greater than 100 cm3. Such alterations stemmed from drug- induced changes in nodular blood flow. There was a significant increase in vascular resistance and a decrease in blood flow, especially in mosaic one, indicating a decline in the number of arteriovenous anastomoses between the newly formed vessels.

Objective. To study protein oxidative modification (POM) processes in patients with hyperandrogenism and obesity. Material and methods. The intensity of tissue POM was assessed using the R.L. Levine method modified by E.E. Dubinina: the method is based on the interaction of carbonyl groups and aminogroups of oxidized amino acid residues with 2,4-dinitrophenylhydrazines (2,4-DNPH) to give rise to 2,4-dinitrophenylhydrazones having a specific absorption spectrum in the ultraviolet and visible regions. Results. There was a statistically significant increase in spontaneous POM products in obesity; POM levels did not change in hyperandrogenism. Secondary markers for POM were observed to increase in hyperandrogenism; the ratio of primary and secondary markers of oxidative stress was unchanged in obesity. There was a reduction in the reserve-adaption potential in obese patients. Conclusion. Obesity is accompanied by an increase in POM and a decrease in the reserve-adaptive potential of the body. Hyperandrogenism occurs with an increase in secondary oxidative stress markers.

Objective. Evaluate the features of phenotypic variants of PCOS during adolescence with regard to body mass index and insulin resistance (IR). Materials and methods. A study in parallel groups was conducted. The total of 95 girls with PCOS from 15 to 17 years old were divided into four groups according to the presence or absence of IR and excessive body weight. The control group consisted only of lean healthy girls without IR with regular menstrual cycle. All participants underwent full clinical and instrumental examination, assessment of the level of С-reactive protein, leptin. Results. The obese insulin resistant PCOS group in comparison with lean nonIR PCOS group was characterized with the most unfavorable atherogenic lipid prof ile and biochemical hyperandrogenism due to the decreased level of sex hormone binding protein (SHBP), more pronounced pro-inflammatory activation according to higher levels of CRP (p = 0.0011), leptin (p= 0.0004) and white blood cell count (p=0.0235), platelets (p = ft. 0012), neutrophils (p = 0.0440) and ESR (p = 0.0036). The obese insulin resistant PCOS group compared with the control group characterized not only by significantly higher values of HOMA-IR (p = 0.0026), fasting glucose (p = 0.0021), higher TG levels (p = 0.0237), atherogenic coefficient (p = 0.0010) and cardiovascular risk by the VAI index (p = ft. 0105), lower HDL content (p = ft. 0459), and higher value of CRP (p = ft. 0239) and leptin (p = 0.0034) levels. Lean PCOS insulin resistant group significantly differed from lean nonIR PCOS group with a higher iron content (p = 0.0423), higher TG (p = ft. 0056) and atherogenic coefficient values (p = ft. 0262), lower levels of HDL (p = 0.0391), which proved dyslipidemia, despite the normative В ML in this group. Lean PCOS insulin resistant group differed significantly from the control group with higher levels of total and direct bilirubin (p = 0.0076 and p = 0.0155, respectively) and iron (23.8 ± 8.0 versus 16.6 ± 6, 8, p = 0.0343), and higher atherogenic coefficient values (p = 0.0206). Obese PCOS nonLR group differed from lean PCOS nonLR group with higher levels of CRP (p = 0.0226) and leptin (p = 0.0267), which indicates thatproinflammatory activation occurs in PCOS patients with excessive weight already in adolescence even in the absence of metabolic disorders. Lean PCOS nonLR group differed from the control group with a higher content of total protein (p = 0.0431) and direct bilirubin (p = ft. 0251). Conclusions: the combination of excessive body weight and metabolic disorders since adolescence is associated with increasing dyslipidemia and atherosclerosis, proinflammatory activation as well as an unfavorable cardiovascular risk.

Objective. To investigate whether 99mTc-technephyte can be used as a radiopharmaceutical agent (RPA) in the intraoperative scintigraphic search for sentinel lymph nodes (SI. N) in breast cancer (BC). Subjects and methods. Examinations were made in 90 patients aged 31 to 82 years with BC, who were treated at the Academician V.l. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology. RPA was injected intradermaily paraareolarly from 4 time points (at 12-15-18-21 hours) 2-24 hours prior to surgery. Thirty minutes after RPA injection, some [36 (40%)] patients underwent scintigraphy, the results of which were used to determine the number and localization of RPA-accumulating lymph nodes. SLNs were intraoperatively sought using a Gamma Finder II handheld gamma probe. When detected, SIN was removed and sent for urgent histological examination. Results. SLNs were visualized in 31 (86.1%) of the 36 patients undergoing scintigraphy and successfully intra-operatively identified in 86 (95.6%) patients. Regardless of scintigraphy results, all the patients underwent SLN biopsy. SLNs could not be visualized in 4 patients, which was the reason to perform axillary lymph node dissection. Urgent histological examination diagnosed SLN métastasés in 24 (27.9%) patients. Axillary lymph node dissection was performed in 17.patients. The mean follow-up period was 18 months. No regional recurrences were reported during this period. Conclusion. SLN biopsy is an effective procedure that can reduce the scope of regional lymph node surgery in patients with early breast cancer and can accordingly improve substantially quality of life in these patients under high locoregional control.

Objective. To compare the outcomes of combination therapy in patients with pelvic inflammatory diseases (PIT)) who use longidase (Bovhyaluronidase azoximer) with those of therapy in patients who do not use of this drug. Subjects and methods. An open-label multicenter comparative study was conducted in 240 patients with acute or exacerbated chronic PID. Group 1 of 170 women used longidasa (Bovhyaluronidase azoximer) 3000-IU suppository once every 3 days in the combination therapy of PID with a total cycle of 20 administrations. Group 2(n = 70) received basic therapy. Results. In Group 1, lower abdominal pain syndrome was relieved much faster and detected in a larger number of patients: only 11 (6.5%) women in the study group continued to notice it after 2 months of treatment while there were 56 (80%) women in Group 2 (p < 0.001). Tenderness was reduced by palpation and cervical traction in all (100%) patients in the study group, while this symptom continued to be noted by 25.7% of women in the basic therapy group (p < 0.001). After performed therapy, the proportion of patients who were observed to have increased uterine dimensions decreased by 56% in Group 1 and only by 15.7% in Group 2 (p < 0.001). During 2-month follow-up, the number of patients with normal white blood cell counts in the cervical canal smear increased more than 3-fold in the study group, whereas 1.03-fold from the baseline in Group 2, and by the end of the follow-up, this was noted in 170(100%) and 59(84.3%) patients in Groups 1 and 2, respectively. Conclusion. longidasa (Bovhyaluronidase azoximer) increases the efficiency of combination treatment for PID, contributes to early improvement of the clinical status of patients, making appropriate use of the drug since the cycle of antibacterial therapy is initiated.

Objective. To conduct a comparative analysis of the effectiveness of an improved imidazole derivative (2% clotrimazole cream) as part of complex therapy with standard treatment regimens for the development of bacterial vaginosis and vulvovaginal candidiasis. Materials and methods. The study included 90 women who had combinations of Atopobium vaginae, GardnereUa vaginalis and Candida krusei. These pathogens caused not only the development of an infectious process in the lower part of the urogenital tract, but also its complicated course. Results. The study showed that the use of the improved imidazole derivative (2% clotrimazole cream) could arrest the main symptoms of the disease after the first use. The drug is highly effective against difficult-to-cultivate pathogens of bacterial vaginosis and Candida non-albicans, and also does not adversely affect the amount of lactobacilli in vaginal biocenosis. Conclusion. The experience of using the improved imidazole derivative shows that the drug is no less effective in inflammatory diseases of the lower parts of the urogenital tract than its counterparts. Its purpose is appropriate in the complex therapy of complicated bacterial vaginosis and vulvovaginal candidiasis.

Objective. To assess changes in cognitive function and quality-of-hfe indicators in menopausal women receiving different types of menopausal hormone therapy (MITT). Subjects and methods. Eighty postmenopausal women with neurovegetative and psychoemotional symptoms were divided into 4 groups: 1) 17-β estradiol 1 mg, drospirenone 2 mg; 2) transdermal 17-β estradiol 0.06% gel, oral micronized progesterone 200 mg; 3) monotherapy with transdermal 17-fi estradiol 0.06% gel; 4) no MET. The Kupperman index, NGF, MoCA test, SF-36 scale, and Beck Depression Inventory were applied to examined the women’s status. Results. NGF levels were significantly increased and the neurovegetative, psychoemotional status improved in Group 1 versus Group 2. Changes were absent in Group 3; cognitive impairment progressed in Group 4. Conclusion. The systemic administration of 17-fi estradiol 1 mg, drospirenone 2 mg versus transdermal 17-fi estradiol 0.06% gel, oral micronized progesterone 200 mg or estrogen monotherapy is effective in restoring cognitive functions and quality of life in early postmenopause.

Abnormal vaginal discharge is one of the most common symptoms in women in outpatient practice. The purpose of this review is to combine the analysis of the results of current studies concerning vaginal microbiota and its disorders. The impaired vaginal microbiota composition leads to the degradation and depletion of the components of the mucosal protective barrier. The main causes of vaginal discharge in women are bacterial vaginosis, vulvovaginal candidiasis, and aerobic vaginitis. Current approaches to diagnosing and treating these diseases are considered.