No 5 (2018)

Objective. To search and analyze the literature devoted to the study of possible markers and predictors of preeclampsia (PE), with the use of post-genomics technologies in particular. Material and methods. Articles were searched in the database Pubmed. The review includes the data of foreign and Russian articles published in the past 15 years. Results. The markers identified so far are shown to relate to early PE. The paper presents the results of postgenomics studies based on omics technologies. It shows the possibility of using the urine congophilia phenomenon as a new screening method. Conclusion. It is necessary to conduct further investigations to develop a panel of non-invasive markers for PE in biological fluids, by using a proteomic and further urinary peptidome analysis as an example, which, reflecting the multifactorial pattern of PE, can simultaneously serve as both a predictor and a tool for monitoring the course of the disease, being a key component of personalized medicine.

Objective. To carry out a systems analysis of the data available in the current literature on cell technologies used to restore the normal endometrium in Asherman’s syndrome (AS) refractory to traditional treatments. Material and methods. The review includes the data of foreign and Russian articles published in the biomedical literature database Pubmed and the database ClinicalTrials.gov on this topic in the past 10 years. Results. The paper gives the data available in the literature, suggesting the molecular and biological properties of the endometrium in AS. It analyzes various aspects of cell therapy, ranging from the type of stem cells and their sources to the alleged mechanisms of therapeutic action. The authors consider the results of experimental studies and clinical trials, which demonstrate a positive effect in restoring endometrial functional activity and regenerative properties. Conclusion. Cell technologies are shown to have high therapeutic efficiency and prospects for their use for endometrial regeneration in AS. Nevertheless, it is necessary to conduct further investigations aimed at developing well-defined protocols for isolating stem cells from various sources, for unifying the procedure for their identification and phenotyping, as well as the schemes and ways of their insertion.

Objective. To analyze the peculiarities of reproductive function realization in HIV-infected men, the impact of human immunodeficiency virus (HIV) infection and antiretroviral therapy (ARVT) on the quality of gametes and the outcomes of assisted reproductive technology (ART) programs. Material and methods. The review includes more than 50 foreign and Russian publications. Results. The impact of HIV infection and ARVT on fertility, the quality of spermatozoa, and the effectiveness of ART programs is discussed in HIV-infected men. Conclusion. It becomes necessary to use of ART in serodiscordant couples with a HIV-positive man mainly to reduce the risks of vertical and horizontal transmission. To date, there is no clear evidence of the impact of HIV infection and ARVT on fertility, the quality of spermatozoa and their mitochondrial potential, and there remains debate about the outcomes of ART programs in married couples and a HIV-positive man.

Aim To compare the effectiveness and safety of nifedipine and atosiban in women with threatened preterm labor. Material and methods The study comprised 111 pregnant women presenting with threatened preterm labor between 30 and 34 weeks of gestation, who were assigned to receive tocolysis with either nifedipine (n=54) or atosiban (n=57). The effectiveness of tocolysis was determined by the duration of pregnancy prolongation (for 48 hours, 7 days, more than 14 days). The primary outcome was the rate of pregnancy prolongation for 48 hours. The safety of tocolytics was assessed by the rate of adverse events in mothers and the neonates. Results Tocolysis failed in eight women receiving nifedipine (14.8%) and two treated with atosiban (3.5%) (p <0.05), and labor occurred within thefirst 24 hours after beginning treatment. In 46 women receiving nifedipine (85.1%) and 55 treated with atosiban (96.5%) pregnancy was prolonged for more than 48 hours (p<0.05). Among them, all births occurred more than 7 days after the initiation of tocolysis. Two women of the atosiban group underwent a second complete treatment course. Full-term births occurred in 15 (27.8%) and 19 (33.3%) women in nifedipine and atosiban group, respectively (p> 0.05%). Mean duration of pregnancy prolongation after the tocolysis with atosiban was 9.2 days longer than after nifedipine (p <0.05). Women receiving nifedipine were more likely to have hot flushes, palpitations, dizziness and hypotension (p <0.01) requiring a dosage reduction and increasing the interval between doses in 14.8% of cases. Eight women in the nifedipine group did not complete the tocolysis protocol due to poor drug tolerance. Of them, in five women tocolysis was ineffective, and they progressed to delivery within 24 hours after admission. After exclusion from the analysis women failing to follow the treatment protocol, no differences were found in the effectiveness of tocolysis with nifedipine and atosiban. After adjusting the groups for multiple pregnancies, the rates of singleton pregnancy prolongation for 48 hours were 88.46% and 95.56% in the nifedipine and atosiban groups, respectively, and did not differ significantly (p> 0.05). However, the duration of pregnancy prolongation was significantly longer in women receiving atosiban (29.37 ± 14.95 days) than nifedipine (20.30 ± 11.95 days) (p <0.01). Conclusion The effectiveness of nifedipine and atosiban in pregnancy prolongation for 48 hours in threatened preterm labor is comparable. However, lower tolerability of nifedipine limits its applicability. Another advantage of atosiban is a longer period of pregnancy prolongation. Further studies are needed to clarify the effectiveness and safety of these drugs in the management of the threatened preterm labor in multiple pregnancies.

Objective. To estimate changes in glucose and glutamate levels in the culture media of 5-day-old embryos with fluorimetric detection and to determine the association between the studied indicators and the quality and ploidy of embryos. Material and methods. A cross-sectional parallel-group study was conducted to examine 68 embryo samples from the culture media of different morphological quality embryos from 21 patients less than 45 years of age who underwent IVF (ICSI) using gonadotropin preparations and preimplantation genetic screening with comparative genomic hybridization, as indicated. Glucose and glutamate consumption in the culture media of 5-day-old embryos was analyzed with fluorescence photometry using the Amplex Red Glucose Assay kit and the Amplex Red Glutamic Acid Assay kit (Molecular Probes, Life technologies). Results. The investigation established that the proposed methodological approaches allow the recording of glucose consumption by embryos after five days of cultivation. The embryos demonstrating the higher rates of development at the time of the study were shown to have an increased glucose consumption level. It was also found that the embryos with a normal and aneuploid karyotype did not show significant differences in glucose uptake on day 5 of cultivation. Estimation of the implantation potential and glucose levels in culture media showed that the embryos with higher glucose consumption are more likely to develop pregnancy after their transfer. Conclusion. On the basis of the findings, the proposed method for measuring the concentration of glucose may be recommended as an additional noninvasive investigation for the selective transfer with similar morphological parameters.

Aim. To compare surgical treatments for tamoxifen associated endometrial pathology in patients in late postmenopause. Material and methods. The study comprised 136 postmenopausal women with breast cancer, who were taking tamoxifen, had concurrent endometrial pathology confirmed by ultrasound examination, and/or complained of genital bleeding. Patients were divided into three groups: 54 patients underwent monopolar endometrial ablation (group I), 32 patients received bipolar endometrial ablation (group II), and 50 patients had hysteroscopy, diagnostic fractional curettage, and polypectomy without endometrial ablation (group III). The results of the study were evaluated within 12 months after surgery. Results. The incidence of recurrent endometrial pathology in group I and group II was 1.8% and 0%, respectively. In the non-ablative group, the recurrence rate during the first year was 60%. Conclusion. In breast cancer patients receiving adjuvant tamoxifen therapy, endometrial ablation significantly reduces the incidence of recurrent tamoxifen-associated endometrial pathology. Our study findings suggest that the effectiveness of mono- and bipolar ablation is significantly higher than hysteroscopy, diagnostic fractional curettage and polypectomy (98.2, 100 and 40%, respectively).

Objective. To investigate the efficiency and safety of bacterial vaginosis (BV) monotherapy with 100 mg of lactic acid as vaginal suppositories. Subjects and methods. In 2015 to 2016, an open-label randomized placebo-controlled study was conducted to investigate the efficacy and safety of vaginal suppositories containing 100 mg of lactic acid (femilex), by covering 116 women diagnosed with BV, which were divided into 2 representative groups. Group 1 (a study group) consisted of 64 women with BV who received monotherapy with one lactic acid (femilex) suppository intravaginally once daily (overnight) for 10 days. A comparison (control) group included 52 patients who used placebo vaginal suppositories without lactic acid (containing only polyethylene oxide as their base) in the same cycle schedule. All the patients underwent conventional gynecological examination. Results. A posttreatment analysis of main indicators established that in Group 1 the changes from the vaginal pH level to the normal one were convincing at relevant visits: 6.84, 4.28, and 4.34 (p < 0.001) while the pH level did not change significantly in the control group. The same can be said for the detection rate of a positive amino test at relevant visits: 95.3, 0, and 3.13% in Group 1 (p < 0.001) and 92.3 and 86.54% in Group 2 (p > 0.05). There was a similar trend in the detection of key cells by microscopy of vaginal smears: 100, 7.81, and 10.94% in the study group (p < 0.001) and 98.1 and 94.23% in the control group (p > 0.05).

Objective. To report the clinical experience of treatment in 7 patients who have undergone open heart surgery with extracorporeal circulation (EC) in the second and third trimesters of pregnancy. Subjects and methods. The mean age of the patients was 31(20-36) years; the mean gestation period was 32.5 (27-34) weeks. Cardiac surgery was repeated in four patients. Four urgent, two immediate, and one salvage surgeries were performed in a patient admitted to the hospital with the clinical presentations of interstitial pulmonary edema due to prosthetic mitral valve dysfunction. Results. Cesarean section (CS) was performed simultaneously with cardiac surgery in 6 cases. In one case, pregnancy was prolonged and ended in elective CS at 38 weeks of gestation and in the birth of a boy with an Apgar score of 7/8. EC in all the patients was performed at a perfusion flow rate of 2.6-2.8 l/min/m2, in a normothermic state (venous blood temperature, 36.6-36.9°C), by using the pulsatile blood flow. The mean time of EC was 96 (58-137) minutes; that of aortic ligation was 61 (44-107) minutes. Pharmacological cold cardioplegia with histidine-tryptophan-ketoglutarate (HTK) solution was used for myocardial protection. Cardiotocography was employed to monitor fetal cardiac activity and uterine contractility. To prevent obstetric hemorrhage, the internal iliac arteries were ligated prior to heparin administration and EC. The early postoperative period was complicated by bleeding from the pericardial cavity in two cases; one woman required pacemaker implantation; no uterine inflammatory changes or intestinal failure were noted. Female reproductive function was maintained in all the cases. All the patients were discharged from hospital in a satisfactory condition. Preterm newborn infants were transferred to a specialized neonatal intensive care unit and were subsequently discharged in a satisfactory condition. Conclusion. Management of pregnant patients who need cardiac surgery is a serious ordeal for obstetricians/ gynecologists, cardiac surgeons, anesthesiologists/resuscitators. The exchange of experience and well-coordinated collective work are an essential component of a successful pregnancy outcome in a woman and a fetus.

Objective. To compare the eff icacy of micronized progesterone formulations, such as prajisan and utrogestan as vaginal capsules in supporting the luteal phase in in vitro fertilization (IVF) cycles. Subjects and methods. This was a single-center observational retrospective study. Women who had been planned to have IVF were randomized to use prajisan or utrogestan in a daily dose of 600 mg as vaginal capsules. The main parameter of achieving the goal was to estimate the number of positive pregnancy tests on day 15 after embryo transfer, as well as abdominal and transvaginal ultrasound findings. Results. The investigation enrolled 264 patients, of whom 149 women received prajisan and 115 had utrogestan. Pragisan was as effective as the latter: the cumulative pregnancy rate was 42.95% (64) and 41.74% (48) in the prajisan and utrogestan groups, respectively. The rate of pregnancy ending in childbirth was 32.21% (48) and 33.04% (38) in these groups, respectively. Prajisan and utrogestan had a similar safety profile. No undesirable adverse reactions were recorded in the patients of both compared groups. Conclusion. The study demonstrated that intravaginal prajisan was as effective as intravaginal utrogestan. Prajisan can successfully support the luteal phase in IVF programs.

Objective. To carry out a systems analysis of the data available in the current literature on the effect of herpes simplex virus (HSV) and human papillomavirus (HPV) on the reproductive health of a couple, on the ability to conceive, on the course of pregnancy, and on the efficacy of valacyclovir in pregravid preparation. 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 paper describes the role of viral infections in the occurrence of inflammatory diseases of the pelvic organs, leading to subfertility and infertility in both women and men, in the reduction of the eff iciency of assisted reproductive technologies, and in the development of pregnancy complications. It presents data on the need for pregravid preparation using valacyclovir. Conclusion. Pregravid preparation should be done in couples with HPV/HSV infections. Valacyclovir has shown benefits in the treatment of HSV.

Objective. To carry out a systems analysis of the data available in the current literature on the pathogenesis, therapy, and prevention of vaginal infections caused by the pathogens of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). 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 paper highlights the main pathways of pathogenesis and the causes of recurrent vaginal coinfection. It describes methods for the treatment of women with BV and VVC and presents the optimal therapy and prevention schemes for recurrent vaginal infectious diseases, which have evidence-based effectiveness. Conclusion. The features of a microbial portrait and immune status predispose to recurrent BV and VVC, the presence of which results in coinfection. The cause of the latter is also repeated therapy for recurrent monoinfection. First-line therapy for BV is recognized to include metronidazole and clindamycin; the advantages of the latter are a wider spectrum of activity against the microorganisms that are diff icult to identify. To treat coinfection and to prevent VVC in patients with BV, it is advisable to use fluconazole that also remains a first-line treatment option for vaginal infection caused by Candida albicans.