No 4 (2020)

Rehabilitation of reproductive function in cancer patients is a complex and steadily growing problem of modern medicine. If clinical recommendations have been developed and patient management tactics determined for some cancers that are most commonly encountered in reproductive-aged women in a number of countries, the presence of a brain tumor is the most unresolved problem in the context of the possibilities of preserving and rehabilitating the reproductive function of patients, which necessitates a thorough study of the problem and a search for methods for its solution.

Objective. To present an update on the analysis of the metabolomics profile of follicular fluid and embryo culture media in patients with external genital endometriosis and on the possible use of a number of metabolites as markers for successful implantation. Materials and methods. The review includes data from foreign and Russian articles found in Pubmed on this topic over the past 10 years. Results. Follicular fluid and culture media for embryos of various development stages are unique objects of study, as they carry information about the peculiarities of the metabolic activity of oocytes and embryos. These studies will be able to identify and introduce additional methods for individualized embryo selection, which will improve outcomes, including those in women with external genital endometriosis. Conclusion. Further investigations and evaluation of the components of follicular fluid and embryo culture media in patients with external genital endometriosis are a promising area in searching for markers for successful embryo implantation with the subsequent development of clinical pregnancy and the birth of a healthy baby. Evidence-based data on the composition of follicular fluid and culture media can let one develop an additional non-invasive method for choosing an embryo for selective transfer and to elaborate an individual management algorithm for women with external genital endometriosis in assisted reproductive technology programs.

The higher infertile marriage rate in economically developed countries has necessitated the emergence and development of assisted reproductive technologies (ART). It should be noted that to date, more than 23% of the ART programs have been implemented in women aged 40years and older. At the same time, the effectiveness of ART techniques using autologous oocytes (AOs) in this age group of patients is about 10%, whereas this indictor for women 45 years of age and older decreases to 1% or less. Over the past 15 years, the number of ART cycles using donor oocytes (DOs) has been steadily increasing. The most common pregnancy complications after cycles using DOs are preterm birth, hypertensive disorders, and preeclampsia. In recent years, there have been data in the literature that the frequency of obstetric complications is higher in patients with DOs than in those with AOs, even after taking confounders into account. That is, the use of DOs is an independent risk factor for obstetric complications. This review of the literature presents current views on the obstetric and neonatal outcomes of ART cycles using DOs.

Aim To determine the most effective way of getting pregnant for patients with a history of initial stages of endometrial cancer. Materials and methods The study comprised 77 patients of reproductive age who were seeking to conceive after achieving remission or required retrieval and cryopreservation of reproductive material before starting cancer treatment. The study participants were divided into groups classified by the presence of stage I endometrial cancer (group 1, n=48) and atypical endometrial hyperplasia (group 2, n=29). Results Seventeen (35.4%) and 6 (20.7%) women in groups 1 and 2, respectively, had polycystic ovary syndrome with severe endocrine and metabolic dysfunctions. There was a lack of unified approaches to counseling and management of this category of patients, which was associated with a high recurrence rate. Procurement of reproductive material after treatment of the present disease resulted in a limited number and poor quality of oocytes/embryos. This observation implied the need for retrieval and cryopreservation of reproductive material before starting treatment. A low pregnancy rate of 21.7% per attempt was probably associated with impaired embryo implantation and endometrial receptivity following exposure to the levonorgestrel intrauterine system. Conclusion The pregnancy rate after 69IVF attempts was 21.7% (15pregnancies). The low pregnancy rate and the questions encountered during the treatment suggest the need for further studies.

Aim. To investigate the feasibility of in vitro maturation (IVM) of human oocytes as a fertility-sparing technology in patients diagnosed with cancer during pregnancy. Materials and methods. Ovariectomy was performed during a cesarean section (CS) or elective surgery. Immature oocyte-cumulus complexes were retrieved from the ovarian medulla and underwent 48-72 h in vitro maturation. All mature oocytes were vitrified. The percentage of matured and degenerative oocytes and the number of cryopreserved oocytes were estimated. Results. In all three cases of patients diagnosed with cancer during pregnancy, oocyte-cumulus complexes were obtained. Six, 20, and 24 oocyte-cumulus complexes were isolatedfrom the first, the second, and the third patient, respectively. The oocyte maturation rate was 33.3%, 30.0%, and 54.2%, resulting in vitrification of 2, 6, and 12 oocytes, respectively. Conclusion. Oocyte-cumulus complexes can be successfully isolated from the ovarian medulla after ovary removal during cesarean section or elective surgery. In vitro-matured oocytes can be vitrified or used for in vitro fertilization (IVF) to preserve fertility.

Objective. To assess the composition of the microorganisms of the uterine cavity of women with chronic endometritis (CE) and idiopathic infertility. Materials and methods. The study included 145 women ofreproductive age with idiopathic infertility. All the patients underwent hysteroscopic examination followed by biopsy histopathological evaluation for immunohistochemical (IHC) and microbiological («Femoflor 16» and «Femoflor Screen» test, DNA-technology, Moscow) studies. Results. According to the results of the IHC study, the CE was detected in 113 (77.9%) patients. The most common microorganisms identified in the uterine cavity were Lactobacilli (66.21%), as well as Staphylococcus (44.83%), Enterobacteriaceae family (22.1%), Ureaplasma spp. (19.3%), Streptococcus spp. (15.2%), Gardnerella vaginalis (11.03%), Atopobium vaginae (10.34%). The presence of Ureaplasma spp. in the uterine cavity significantly increasing the risk of developing CE by 4,5 times (RR=4.483; 95% CI 1.003-20.029). Presence of Atopobium vaginae and Staphylococcus spp. increases the risk of developing pronounced CE by 7 times (RR=6.959; 95% CI 0.856-56.602) and 2.5 times (OS=2.5; 95% CI 1.034-6.043), respectively. Conclusion. The risk of developing CE increases with the persistence of certain microorganisms in the uterine cavity.

Objective. To compare the effectiveness of granulocyte colony-stimulating factor (G- CSF) and autologous platelet-rich plasma (PRP) in patients with “thin” endometrium in frozen embryo transfer programs. Materials and methods. We conducted a prospective cohort study, which included 58 patients with “thin” endometrium. The group with PRP included 37 patients, G-CSF group included 21 patients. All patients received hormone replacement therapy (HRT). Patients in PRP group in addition to HRT were given an intrauterine injection of autologous PRP on the 8-9th, 10-11th, and 12-13th days of the menstrual cycle; patients in G-CSF group in addition to HRT were given an intrauterine injection of recombinant G-CSF on the 5-6th and 12-13th days of the menstrual cycle. The primary outcome was an increase in endometrial thickness greater than 7 mm on the day of embryo transfer, the secondary outcome was pregnancy rates. Results. Endometrial thickness greater than 7 mm on the day of embryo transfer in PRP group was observed in 26 (70.27%) patients, in G-CSF group - in 13 (61.9%) patients, the differences were not statistically significant (p=0.515). The average endometrial thickness on the day of embryo transfer in PRP group was 7.79 (1.42) mm, in G-CSF group - 7.21 (1.42) mm, the difference was not statistically significant (p=0.146). In PRP group embryo transfer was performed in 31 (83.78%) patients, and in G-CSF group in 12 (57.14%) patients, the difference was statistically significant (p=0.026). Pregnancy occurred in 16 (51.61%) patients in PRP group and in 4 (33.33%) patients in G- CSFgroup; the difference was not statistically significant (p=0.282). Conclusion. In our study we did not find statistically significant differences in either an increase in endometrial thickness or in the pregnancy rates between the two groups. Subsequent studies should be conducted to identify differences in the effectiveness of these treatment methods.

Aim. To investigate ovarian reserve using anti-Mullerian hormone (AMH) as a marker of ovarian reserve in patients with rheumatoid arthritis (RA) and infertility, who received or did not receive methotrexate (MTX) therapy. Materials and methods. The observational study comprised 72 patients with infertility. Of them, patients with RA (n=32) constituted the study group, and patients without RA (n=40) made up the control group. Patients with RA were stratified into subgroups based on whether or not they received MTX. The level of AMH was evaluated concerning RA duration and activity, as well as the age at initiation of MTX therapy, dosage, and treatment duration. Results. There was a statistically significant decrease in the level of AMH in RA patients compared with patients with infertility only, and MTX therapy was associated with a reduction in ovarian reserve. No statistically significant differences in the levels of AMH were found regarding RA duration and activity, as well as the total dose and duration of MTX therapy. Conclusions. Patients with RA have lower serum AMH levels. MTX therapy is associated with a more significant decrease in AMH levels. The age at initiation of MTX therapy is negatively correlated with the AMH level.

Objective. To study mitochondrial DNA (mtDNA) content in sperm samples of HIV-infected men receiving antiretroviral therapy (ARVT). Materials and methods. This prospective clinical study included 190patients who presented for the assessment of fertility and achieving conception. The main group consisted of 94 HIV-infected men; the control group included 96 patients without HIV infection. The quantitative assessment of mtDNA deletions (mtDNAdel-), total mtDNA copy number (mtDNAtotal) and their ratio (mtDNAtotal / mtDNAdel-) was carried out in 58 and 96 samples, respectively, using real-time polymerase chain reaction (PCR) method. Results. The median age of HIV-infected men was 37(33; 39) years, duration of the disease was 5 (2; 11) years. The median duration of receiving ARVT was 2 (1; 5) years. The patients of groups were similar in mtDNAdel-(1.9 (0.9; 5.9) and 2.4 (1.9; 5.6); р=0.54), mtDNAtotal (5.4 (3.7; 9.8) and 5.5 (3.5; 8.2); р=0.62) and their ratio mtDNAtotal /mtDNAdel- (2.4(1.5; 3.9) and 1.9 (1.3; 3.0); р=0.09), respectively. In the group with severe sperm abnormality there was a negative correlation between ARVT duration and copy number of mtDNAtotal (r=-0.627; р=0.01), as well as between ARVT duration and mtDNAdel- level (r=-0.542; р=0.04). The pronounced negative correlation was revealed between CD4+ level and ratio mtDNAtotal / mtDNAdel- (r=-0.29; р=0.03). Conclusion. HIV-infected men did not show significant differences in sperm mtDNA copy number in comparison with the men of the control group. HIV-infected men with severe sperm abnormality had inverse relationship between the levels of mtDNAtotal, mtDNAdel- and ARVT duration; mtDNAdel- content was negatively correlated to the immune system state.

Objective. To assess the outcomes of assisted reproductive technologies (ART) depending on molecular genetic profiles of differentially expressed endometrial genes. Materials and methods. The study included 104 patients with tubal and peritoneal factor infertility who were performedpippelle endometrial biopsy in the natural cycle during the implantation window before embryo transfer. Histological and molecular genetic analysis of genes in endometrial samples was conducted using RT-PCR method. Outcomes of ART programs were analyzed afterfrozen-thawed embryo transfer into the uterine cavity. Results. The revealed association between the outcomes of ART programs and endometrial expression profile made it possible to determine additional intermediate stages of secretory endometrial development. Conclusion. The study of expression profiles of mRNA genes LIF, GPX3, AQP3, NDRG1, GNLY, IMPA2, PAEP, IGFBP1, HABP2, DPP4, TAGLN, IL15, POSTN, HLA-DOB, MSX1 allows for identifying the most favorable period for embryo cryotransfer.

Purpose of the study. To specify the role of surgical intervention for the diagnosis and treatment of infertility. Materials and methods. A retrospective study of 1364 women aged 19 - 40 years who underwent the stage of surgical diagnosis and treatment of infertility in the period from January, 2010 to December, 2016. Results. Surgical treatment of infertility facilitates the recovery of reproductive function, mainly at a young age with minimal changes in human pelvic morphology. In addition, the surgery can be considered as a preparatory stage in assisted reproductive technology (ART) programs. There is little possibility for surgical treatment of severe morphological changes in the reproductive organs. Conclusion. Despite the diminishing role of reproductive surgery as the main method of infertility treatment, it continues to be important in the recovery of the fertility and improvement of the effectiveness of ART.

Objective. To evaluate the effect of uterine microbiota on the success of embryo implantation in women undergoing assisted reproductive technology (ART). Patients and methods. The investigation enrolled 80 infertile patients who had undergone IVF programs. Group 1 included 50 patients who had embryos transferred in the stimulation cycle; Group 2 consisted of 30 patients with embryos transferred in the cryo cycle. The women’s mean age was 31.4±1.5 years. The outer walls of an embryo catheter removed from the uterine cavity after embryo transfer were microbiologically tested by culturomics using an expanded set of selective and non-selective culture media. Results. Twenty-seven bacterial species were isolated in Group 1 patients. Pregnancy occurred in 20 (40.0%) women. Lactobacilli, the most abundant bacteria, were detected in 85% of women. Among the opportunistic microorganisms (OMs) in 50.0% of patients, the most common species were Gardnerella vaginalis (G. vaginalis) and Enterococcus faecalis (E. faecalis) in 20.0% of women and Streptococcus anginosus (S. anginosus) in 15.0%. The isolation rate of Lactobacilli was lower in non-pregnant women (60.0%) than in pregnant women (73.3%). The OMs (46.6%), showed a preponderance of G. vaginalis (10.0%) and facultative anaerobic microorganisms, such as S. anginosus (10.0%), Staphylococcus haemolyticus (6.6%), an Actinomyces sp. (6.6%); Haemophilus influenzae (3.3%) is rarely isolated from the genitals. Twenty bacterial species were detected in Group 2 women. Pregnancy occurred in 13 (43.3%) patients. The most abundant bacteria Lactobacilli were isolated in 69.2% of women. The OMs (38.5%) displayed a preponderance of facultative anaerobic microorganisms, such as Escherichia coli and Staphylococcus epidermidis (S. epidermidis) with an equal rate (15.4%). In non-pregnant women (56.7%), the isolation rate of Lactobacilli was 64.7%. Facultative anaerobes, such as S. epidermidis (17.6%) and E. faecalis (11.8%), were most commonly isolated among the OM (41.2%). Bifidobacteria were found in 35.3% of women and Actinomyces neuii were detected in 5.9%. Conclusion. The investigation showed that the best implantation results among 33pregnant women were observed with uterine colonization by only Lactobacilli (42.4%). When the uterus was colonized by Lactobacilli in association with OM, the pregnancy rate was 36.4%, whereas it was 9.1% when it was colonized only by OM. In the absence of endometrial colonization, pregnancy also occurred in only 9.1% of cases.

Objective. To assess the male reproductive potential in recurrent varicocele. Patients and methods. 126 patients aged 23 to 58 years with recurrent varicocele who had been primarily operated on before the age of 18 years or being drafted for military service according to referrals from military registration and enlistment offices (n=59) and in adulthood (n=67) underwent repeat Marmar microsurgical varicocelectomy. Results. By assessing spermogram readings over time, it could be noted that there was significant sperm concentration progress in the patients who had been primarily operated on in both childhood and adulthood. However, there was a considerable effectiveness decrease in the patients who had undergone Palomo surgery in childhood (a sperm concentration increase was observed in 35% of the patients in this group) compared to those who had Ivanissevich’s operation (a sperm concentration increase was seen in 64.1%). The same trend was also noted with direct reproductive results (that is to say, the occurrence of natural pregnancy and the birth of babies), which turned out to be substantially worse in the patients who had primarily undergone Palomo surgery (pregnancy and childbirth occurred in 15% of cases), unlike those who had Ivanissevich’s operation (pregnancy and childbirth occurred in 30.8% of cases). Conclusion. After Ivanissevich’s surgery, the reproductive potential of patients with varicocele recurrences does not depend on the timing of their occurrence. And the natural pregnancy rate after repeat varicocelectomy for a recurrence is statistically lower after Palomo surgery than that after Ivanissevich’s operation.

Objective. To comparatively evaluate the clinical and laboratory effectiveness of different treatment regimens for vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) in pregnant women in the second and third trimesters. Subjects and methods. Sixty-five patients with VVC and BV were examined and treated in the second and third trimesters of pregnancy. Group 1 consisted of 35pregnant women with first diagnosed disease; Group 2 included 30patients with recurrent disease. A short 3-day Gynomax treatment regimen or a long 7-day Gynomax one was used. Results. Before treatment, there were increases in bacterial mass (11.2±1.7Log) and in the number of aerobic and anaerobic microorganisms (6.2 (1.4) Log); as well as obvious Lactobacillus deficiency (3.1 (1.1) Log). Vaginal pH was more than 5.2 in 35/65 (53.8%) women. After applying the seven-day Gainomax treatment regiment, complaints of vaginal discharge and itching persisted in 1/15 (6.6%) women; there were decreases in the total bacterial mass to 7.4 (1.2) Log and in aerobic and anaerobic flora to 2.4 (0.6) Log. Following the three-day use of the drug, pathological discharge and vulvar pruritus persisted in 2/15 (13.3%) of the pregnant women; the bacterial mass was much as 8.2 (1.7) Log; the concentration of aerobic and anaerobic flora was 3.9 (1.5) Log. Conclusion. Both short- and long-course treatment regimens are equally effective during new-onset dysbiosis and VVC in pregnant women in the second and third trimesters. The seven-day regimen has an advantage in recurrent disease.

The literature review discusses two-step treatment for vaginal infections. It presents probative evidence on the efficiency and safety of using the antiseptic Dequalinium chloride (10 mg) in the first stage and the probiotic Gynoflor E that contains at least 107 CFU/g in a tablet of live Lactobacillus acidophilus KS 400 and 0.03 mg of estriol.

The paper gives the results from a meta-analysis of clinical trials using Gainomax (its standard dose is thioconazole 100 mg, tinidazole 150 mg as a suppository or cream) for the therapy of vulvovaginal candidiasis (VVC), bacterial vaginosis (BV), and trichomaniasis (TM). The meta-analysis included 4 clinical trials (covering 209patients). The patients’ mean age was 35±7years (95% CI, 18-52); all the patients used Gainomax suppositories/cream at the standard dose for 7 days or double dose for 3 days. Gainomax therapy substantially increased the chances of clinical cure of BV (by 20 times; OR 20.4; 95% CI 9.5-43.6), microbiological cure of BV (by 16 times; OR 15.5; 95% CI 7.6-31.5), cures of VVC (by 21 times; OR 21.0; 95% CI 8.8-50.2) and TM (by 29 times; OR 28.8; 95% CI 7.4-111.8). Analyzing individual clinical symptoms revealed associations between drug use and a statistically significant reduction in pathological vaginal discharge (by 25 times; OR 0.04; 95% CI 0.02-0.08), inflammation symptoms (by 33 times; OR 0.03; 95% CI 0.02-0.06), and reddening (by 11 times; OR 0.09; 95% CI 0.06-0.15) during treatment. Only one of the four trials included in the meta-analysis described side effects (in 3 out of209patients in the entire sample), no side effects were noted in the remaining trials. Thus, the results of this meta-analysis confirm the high efficacy and safety of the intravaginal use of a combination of tinidazole and thioconazole for the treatment of BV, VVC, and TM.