No 11 (2018)

The investigators have carried out a systems analysis of the data available in the modern literature on the role of cumulus cells, autologous embryo-cumulus cell co-culturing in the treatment of infertility with assisted reproductive technologies (ART). The paper describes the role of cumulus cells in the embryo implantation process using autologous co-culturing and cumulus-aid embryo transfer, which allows the ART programs to be individualized. The results of investigations confirm the relevance of the use of autologous embryo-cumulus cell co-culturing in the ART programs. Cumulus cells can become a reliable model for understanding the components of oocyte quality, for stimulating the ovaries, for assessing embryo development, and the rates of clinical pregnancy and healthy births in the ART programs.

Objective. To investigate the relationship of the levels of preactivated (primed) neutrophils in the peripheral blood of pregnant women with preeclampsia. Subjects and methods. The investigation enrolled 14 women with preeclampsia (a study group, Group 1), 15 women with physiological pregnancy (a control group, Group 2), and 11 non-pregnant women (to obtain normative values). Formyl peptide, Ficoll-Hypaque (1.077 and 1.119 g/ml) gradients, lucigenin, Roswell Park Memorial Institute (RPMI) 1640medium, Hanks medium, and fetal calf serum (Sigma-Aldrich) were determined in the peripheral blood. Neutrophils were isolated from the blood samples obtained from the ulnar vein (the anticoagulant heparin 35 IU/ml) using a two-step Ficoll-Hypaque gradient. Red blood cells were destroyed by hypotonic lysis. Neutrophils in the suspensions were at least 96%. The live cells tested with trypan blue were 94%. Suspensions containing 1^106 cells/ml were prepared. Formyl-methionyl-leucyl-phenylalanine (fMLP, 2 pM) was used as a stimulant. The formation of oxygen radicals was recorded in imp/sec, by using the luminophor lucigenin (30 pM) on a Biotox-7 chemiluminometer (Russia). The maximum radical formation amplitude, the time of its achievement, and the light sum were determined for a fixed time period. Results. The cell suspensions from non-pregnant women showed a monotonic spontaneous increase in oxygen radical formation at a very low rate. The rate increased by 1.3 times in healthy pregnant women (p > 0.05). The rate of spontaneous oxygen radical generation rose sharply in pregnant women with preeclampsia. In this group, the formation of oxygen radicals reached maximum values and plateaued at 24±7 min. The spontaneous radical formation might be due to the stimulation of initially primed neutrophils as a result of their adhesion on the cell walls. To test this assumption, the standard stimulant fMLP that strongly stimulates the neutrophil generation of oxygen radicals were added to the suspensions from the women with preeclampsia. It should be noted that in both non-pregnant women and healthy pregnant women, fMLP significantly increased the level of radicals compared to the responses of neutrophils in women with preeclampsia. Conclusion. The potentiated response to formyl peptide due to spontaneous neutrophil stimulation in pregnant women with preeclampsia suggests that their peripheral blood contain primed cells. This total response may suggest that the mechanism of stimulation of neutrophils due to their adhesion on the cell wall and to fMLP stimulation is different, additive in nature, and is carried out by different processes

Objective. To assess the features of somatic, obstetric and gynecologic histories and the course of pregnancy in order to determine factors and to identify a risk group for delayed labor. Subjects and methods. The study included 957 healthy primiparas and secundiparas and their newborns. The data of family, somatic and obstetric/gynecologic histories were analyzed to clarify differences in the course of pregnancy and childbirth during timely and delayed childbirth. Results. Post-term pregnancy was found to be more common in some types of extragenital pathology, such as diseases of ENT (p = 0.01), urinary system (p = 0.01), and visual organs (p = 0.01), and a male fetus (p = 0.0001). The significant risk factors of post-term pregnancy included the birth of a pregnant woman herself (OR = 4.6; 2.5-8.3; p < 0.0001) or that of the father of the child (OR = 3.8; 1.7-8.1; p = 0.0005) due to delayed labor, a history of post-term pregnancy (OR = 2.2; 1.2-4.1; p = 0.01), and birth canal unreadiness for childbirth in primiparas at 284 days or more (p < 0.0001) and in secundiparas at 283 days or more (p < 0.0001). Taking into account the gender of a fetus and medical history data, a prognostic model was created using the binary logistic regression method. Conclusion. The most significant risk factors for post-term pregnancy are diseases of ENT, urinary system, and visual organs, a male fetus, birth of parents from delayed labor, a history of post-term pregnancy, birth canal unreadiness for childbirth in primiparas at 284 days or more and in secundiparas at 283 days or more.

Objective.To investigate the prevalence of urogenital infections and status of the cervical-vaginal microbiota in pregnant women with threatened preterm birth using real-time polymerase chain reaction (PCR). Material and methods. We conducted a cross-sectional study of300pregnant women at 27 to 32 weeks’ gestation, of which 118 were diagnosed with threatened preterm labor, and 182 had a late uncomplicated pregnancy (control group). We analyzed the results of antenatal screening for urogenital infections, which included real-time PCR detection of etiologically significant pathogens associated with bacterial vaginosis, vulvovaginal candidiasis, aerobic vaginitis, and the causative agents of four sexually transmitted infections (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis). All study participants attended antenatal clinics. Results Among pregnant women with threatened preterm birth and women in the control group, the prevalence of mixed infections, bacterial vaginosis, aerobic vaginitis, vulvovaginal candidiasis, and infection caused by Mycoplasma genitalium was 14% and 4% (p <0.01), 17% and 7% (p <0.05), 12% and 3% (p < 0.05), 16% and 9% (p = 0.08), and 2% and 1% (p > 0.05), respectively. No women in the control group had chlamydial infection and gonorrhea, while they were found in 3% (p < 0.05) and 0.8% (n = 1) (p < 0.05) among patients with threatened preterm labor, respectively. The vaginal concentration of Lactobacillus spp. was significantly higher in the women in the control group compared with the patients with threatened preterm birth (8.24 ± 0.67 and 7.38 ± 1.27GE/ml;p <0.001). Conclusion Real-time PCR screening for female genital tract infections revealed significantly higher rates of mixed infections, bacterial vaginosis, aerobic vaginitis, chlamydial infection among pregnant women with threatened preterm birth.

Objective. To study the safety and efficiency of transplantation of the developed tissue-engineered prosthesis based on polydioxanone and cultured multipotent stromal cells (MSC) from the umbilical cord. Material and methods. In vivo biocompatibility of prostheses was evaluated in outbred rats, by modeling a full-layer defect of the anterior abdominal wall, the edges of which was sutured with a polydioxanone prosthesis that was unpopulated and populated by the cultured cells. A prosthesis based on the decellularized dermis (Permacol) was used in the comparison group. The animals were withdrawn from the experiment at 3, 10, 30, 60, and 180 days after surgery. Macroscopic, tensiometric, histomorphometric, and immunohistochemical studies were conducted. Results. The polydioxanone-based prostheses were found to be more effectively integrated and grow their own tissues. The biomechanical properties of tissues in the field of transplantation in the long-term periods did not differ between the groups and the native tissue of the anterior abdominal wall. When a tissue-engineered construct was transplanted, there was a lower inflammatory response due to macrophage M2 polarization, as well as a more pronounced angiogenesis. The transplanted cells did not differentiate into blood vessel cells and were totally eliminated by a recipient’s macrophages. The registered effects appeared to be shown via paracrine mechanisms. Conclusion. The addition of cultured MSCs to the prosthesis could substantially reduce the severity of an inflammatory response to rejection of a foreign body and stimulate angiogenesis and the rate of replacement by the recipient’s own tissues.

Objective. To investigate the expression of syndecan-1 and heparanase in the lining of the ovarian endometrioma capsule in reproductive-aged women in the proliferative phase of the cycle, by assessing the severity of inflammatory infiltration and the correlation with pain syndrome. Subjects and methods. Twenty patients aged 27.7 ± 5.3 years with Stage III ovarian endometrioid cysts were examined using a semiquantitative immunohistochemical assessment of the expression of syndecan-1 and heparanase in the capsule of resected endometriomas, as well as a statistical analysis. Results. The expression of heparanase in the epithelial nuclei with sufficient statistical significance (p < 0.0001) shows a strong positive correlation with a visual analog scale pelvic pain scores of 3-5 (r = 0.902) and with subepithelial inflammatory infiltration (r = 0.887), as well as a strong negative correlation with the manifestations of cytogenic stromal fibrosis (r = -0.902). Conclusion. The pronounced heparanase expression in the epithelium of ovarian endometriomas is associated with inflammatory cell infiltration and the presence of pain syndrome; no significant regularities were found for syndecan-1.

Objective. To improve cervical cancer screening programs via clinical introduction of a diagnostic vaginal swab self-sampling test for the detection of high-risk human papillomavirus (hrHPV). Subjects and methods. A total of 455 residents of the Lipetsk Region were examined; vaginal swabs tested for HPV were taken both independently by a woman with a Qvintip device and by a gynecologist with a universal urogenital probe. The women were asked whether it was convenient for them to self-collect a vaginal swab. Results. In the surveyed sample of 455 women, there were 35 (7.7%) cases of hrHPV identified on the swabs collected by the Qvintip and 38 (8.4%) women with hrHPV detected on those taken by the physician, out of them 26 (68.5%) women had atypical squamous cells of undetermined significance. 70.3% of women preferred the Qvintip self-sampling method. Conclusion. The Qvintip self-sampling method for hrHPVtesting shows high diagnostic efficiency, simplicity, and ease-to-use. The method may be recommended for the detection of hrHPV to increase cervical cancer screening coverage.

Objective. Study of the effectiveness of determining the sFlt-1/PIGF ratio in the diagnosis of pre-eclampsia at the preclinical stage and in cases of erased/atypical course. Subjects and methods. The investigation included 206 pregnant women with suspected PE. According to the sFlt-1/PlGF ratio, all the patients were divided into 2 groups: 1) 118patients with a sFlt-1/PlGF ratio of <38 (a negative test); 2) 88 with a sFlt-1/PlGF ratio of >38 (a positive test). Results. In Group 1, 6 (5.4%) patients were found to have moderate PE; 112 (96.4%) patients did not develop PE. In Group 2, 32 (36.4%) patients were diagnosed with severe PE; moderate PE was present in 23 (26.1%) patients, PE was absent in 33 (37.5%). In Group 2, the sFlt-1/PlGF ratio in the patients with severe PE was significantly higher than that in those with moderate and no PE: 268 (128-540) vs 80.5 (61.9-116.4) vs 57.5 (42.5-110), P1 < 0.0001 and P2 < 0.0001. Comparing the examined groups in perinatal outcomes and clinical symptoms of PE ascertained that adverse perinatal outcomes (antenatal and postnatal fetal death) and symptoms indicating the development of a critical situation (transient ischemic attack, epigastric pain, and acute renal failure) occurred only in Group 2patients. Conclusion. Determination of the sFlt-1/PlGFratio can serve as an additional method to diagnose PE, to evaluate the severity of preeclampsia, and to predict adverse perinatal and maternal outcomes.

Objective. To evaluate the pharmacoeconomic feasibility and validity of using a long-acting recombinant follicle-stimulating hormone (rFSH) for the stimulation of ovulation in IVF protocols using gonadotropin-releasing hormone antagonists versus the daily administration of rFSH. Material and methods. The analysis included data on 613 patients who had undergone ovulation stimulation with different FSH preparations in the IVF protocols using gonadotropin-releasing hormone antagonists in 15 regional assisted reproductive technology (ART) centers of Russia (613 IVF cycles), by applying quality of life questionnaires (EQ-5D-3L and visual analog scale (VAS)). According to the used rFSH preparation to stimulate ovulation, the patients were divided into 4 groups. Mathematical modeling for cost analysis, cost-effectiveness analysis, budget impact analysis, and cost-utility analysis was carried out using data on the regional tariff agreements of the Compulsory Health Insurance Fund (CHIF) and the Federal State Statistics Service; clinical guidelines and published clinical trial results, as well as the regulatory acts of the Ministry of Health of Russia were analyzed. Results. Analysis of the comparative clinical efficacy of a long-acting recombinant follicle-stimulating hormone (rFSH) revealed no substantial differences in the main clinical performance indicators, such as the number of obtained MII oocytes. In the long-acting recombinant follicle-stimulating hormone (rFSH) group, there was the highest proportion (75%) of the patients who had undergone embryo/blastocyst transfer, while in the the daily administration of rFSH.groups, the transfer was carried out in 67 and 70% of cases, respectively. The cost-effectiveness in the cost of a cycle with a long-acting recombinant follicle-stimulating hormone (rFSH) was 29 and 12% lower than that with the daily administration of rFSH respectively. Conclusion. The prescription of a long-acting recombinant follicle-stimulating hormone (rFSH) provides the most effective use of the CHIF tariff for IVF and has the lowest share in the cost of this tariff.

Urinary disorders in women with recurrent urinary tract infections (UTI) are a serious problem that has not yet been solved despite that there are a large number of papers on this topic. Pregnant women who have experienced acute urinary tract infection and those who have been treated for asymptomatic bacteriuria should be followed up until delivery, by examining their urine to prove the efficiency of antibacterial therapy that can threaten their pregnancy. It is necessary to emphasize the importance of prevention, timely detection of signs of UTI in pregnant women and the correct choice of antibiotic therapy in the developed UTI.

Objective. To generalize and systematize recommendations for the prevention and correction of PIP in obstetric and gynecological practice on the basis of literature data and the authors’ own experience. Materials and methods. The paper describes the results of a prospective analysis in 40 cases of PCP of varying severity in puerperas after cesarean section and long-term delivery. Results. Based on the analysis, the authors identified main risk factors for PIP in obstetrics, gave recommendations for its prevention, and proposed an algorithm for the intensive therapy of PIP of varying severity. Conclusion. To comply with the algorithm for the intensive therapy of PIP with the currently available prokinetics can achieve the regression of clinical and laboratory symptoms and prevent bowel obstruction.