No 7 (2023)

To date, the use of platelet-rich autoplasma (PRA) has become one of the new areas used in the assisted reproductive technology programs. Platelets contain a large number of growth factors and different types of proteins that are released after their activation. These factors accelerate cell mitosis, promote angiogenesis of endothelial cells, induce anti-inflammatory modulators, and support the production of fibrinogen that is essentially a framework for tissue regeneration. The intraovarial and intrauterine PRA administration has been used in reproductive medicine for the thin endometrium, premature ovarian insufficiency, and a low ovarian reserve.

In preparing this review, we sought literature over the past 10 years to identify studies on the use of PRA therapy in the assisted reproductive technology programs.

Conclusion: The use of PRA is a new and rather promising method for infertility treatment in some women who are resistant to standard therapy. However, there is a need for additional prospective randomized controlled trials involving more participants to more significantly demonstrate the benefits of PRA therapy in clinical practice.

Mitochondria are the only cell organelles that have their own DNA. It has been shown that the mitochondrial DNA (mtDNA) level can vary significantly among different cell types and depend on the cell's need for energy in accordance with changing environmental conditions. Researchers consider the mtDNA level as a possible marker of the potential of gametes for fertilization, development of the embryo and its implantation.

The review presents and analyzes the domestic and foreign trials that study the mtDNA level in gametes, cumulus cells and embryos, as well as in the spent (collected after culturing the embryo) culture medium, depending on the outcomes of assisted reproductive technologies programs. A summary table of mtDNA studies in the spent culture medium is presented separately.

On the one hand, according to the literature, there is a trend that determines an increased potential for development, implantation, and the onset of clinical pregnancy for: embryos obtained from oocytes with an increased mtDNA level, blastocysts with a reduced mtDNA level in the cells of the trophectoderm and inner cell mass and an increased mtDNA level in the spent culture medium. On the other hand, a significant controversies remain in the literature regarding the effectiveness of mtDNA determination as an additional method for assessing the quality of gametes and embryos.

Conclusion: The question of the possibility of recommending the widespread use of mtDNA level assessment in one way or another remains unresolved. Therefore, additional large-scale well-designed studies are required.

Relevance: Multiple pregnancies carry a higher risk of perinatal morbidity and mortality. In pregnancies complicated by intrauterine death of one of the co-twins, the perinatal outcome of the surviving fetus depends on the type of placentation.

Objective: To investigate the impact of dichorionic and monochorionic twin pregnancies complicated by single fetal demise on perinatal outcomes.

Materials and methods: A retrospective study was conducted at V.I. Kulakov NMRC for OG&P from 2014 to 2022, analyzing 113 twin pregnancies and neonatal outcomes of 99 newborns. The study subjects were divided into groups of dichorionic and monochorionic twin pregnancies. The groups were compared in terms of the course of the antenatal period and outcomes of the neonates.

Results: The study analyzed 20 dichorionic and 93 monochorionic twin pregnancies. Pregnancy rates resulting from assisted reproductive technologies were higher in dichorionic twins (40%) compared to monochorionic twins (18.3%; p<0.05). The mean gestational age at intrauterine death of one co-twin was significantly lower in monochorionic twins (21.9 weeks) compared to dichorionic twins (29.6 weeks; p<0.01). Discordance in body weight of newborns was more prevalent in monochorionic twins (51.6%) compared to dichorionic twins (25%; p<0.05). Low Apgar scores in the 1st minute were more common in monochorionic twins (24%) than in dichorionic twins (10%; p=0.03). However, there was no statistically significant difference in overall morbidity between the two groups (p=0.61).

Conclusion: Monochorionic placentation, compared to dichorionic placentation, is associated with specific complications in twin pregnancies complicated by single fetal demise. In monochorionic twins, the occurrence of single fetal demise happened much earlier than in dichorionic twins. Furthermore, monochorionic placentation was associated with cases of second fetal death and spontaneous demise of one of the co-twins in uncomplicated pregnancies. Neonatal mortality and morbidity rates were similar between the two groups. However, monochorionic placentation was characterized by severe central nervous and cardiovascular complications, as well as sepsis.

Objective: To investigate gene transcription profiles and identify differences in gene expression between different forms of fibrocystic breast disease (FBD).

Materials and methods: We studied 128 formalin-fixed, paraffin-embedded breast tissue samples obtained at the time of surgery with histologically confirmed non-proliferative FBD, typical ductal hyperplasia, atypical ductal hyperplasia, ductal carcinoma in situ, and normal tissue. The expression profiles of the 46 candidate genes were analyzed by real-time quantitative PCR.

Results: Depending on the histological type of the sample, we established the general patterns of mRNA expression of the genes studied in different forms of FBD, and the spectra of differentially expressed genes in proliferative FBD with atypia (18 genes) and non-proliferative forms of FBD (14 genes).

Conclusion: Proliferative FBD with atypia, which carries the highest risk of developing breast cancer, is characterized by a statistically significant increase in the mRNA expression of MKI67, CCNB1, KIF14, PTTG1, ANLN, TMEM45B, TPX2, PRLR, FGFR4, MMP11, GATA3, EXO1, TYMS, and NAT1, and a decrease in the mRNA expression of MYC, RANK, TNFA, and MMP9.

Objective: To assess the expression of the Epha1 receptor on the epithelial cell membrane of the glands of the eutopic and ectopic endometrium in women without endometrial pathology, with endometriosis of varying severity and endometrial cancer.

Materials and methods: The study included 46 patients of reproductive age who were treated in the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation from 2020 to 2021. The patients were divided into four groups: Group 1 included 20 women with deep endometriosis (DE), Group 2 included 21 patients with peritoneal endometriosis (PE), Group 3 (comparison group) included 6 patients with endometrial cancer (EC), and Group 4 (control) included 9 patients without endometriosis (no pathological changes in the endometrium) and operated on for tubal-peritoneal infertility factor. The groups were additionally divided into subgroups depending on the phase of the menstrual cycle on the day before the operation. Semi-quantitative evaluation of EphA1 expression on the epithelial cells of the glands of the uterine mucosa was performed by immunohistochemistry, using rabbit polyclonal antibodies ab217363 and the ImageJ open source program for image analysis and processing.

Results: We have shown for the first time that in healthy endometrium, a significantly higher expression of the ephrin receptor EphA1 on the surface of glandular cells is observed in the secretory phase of the menstrual cycle (MC), compared to the proliferative one. The same pattern of receptor expression was found in the eutopic endometrium of patients with PE - higher in the secretory than in the proliferative phases. In the eutopic endometrium of patients with DE, a significantly increased level of EphA1 expression was found in the proliferative and secretory phases of MC compared to patients without endometriosis or with PE. In foci on the peritoneum in both PE and DE, a higher level compared to the norm was found only in the proliferative phase of the cycle. The highest hyperexpressed level was found on the membrane of the glandular cells of the endometrium affected by cancer and in deeply infiltrative foci on the intestine with DE in both phases of the cycle.

Conclusion: Overexpression of the ephrin receptor EphA1 in glandular cells of endometrial tissue in EC and DE makes it a promising target for the development of new technologies for the diagnosis and treatment of these diseases.

Modern methods of diagnosing endometrial receptivity which have been introduced into clinical practice (ERA, Igenomix; ER-Map, iGLS; ERPeak, CooperGenomics), are based on transcriptome analysis of invasively obtained endometrial tissue; therefore, embryo cannot be transferred in the same cycle when endometrial biopsy is performed.

Objective: To evaluate endometrial receptivity by determining the number of small non-coding RNAs (ncRNAs) in uterine fluid (UF) on the day of cryopreserved embryo (CE) transfer in women receiving cyclic hormone therapy (CHT) and to develop a logistic regression model for calculating the optimal endometrial receptivity for embryo implantation by comparing the UF transcriptome from patients with positive and negative outcomes of the ART program.

Materials and methods: The study included 54 women whose UF was aspirated in a volume of 5–50 µl depending on the level of its secretion immediately before the CE transfer with the help of a catheter (COOK, Australia). Small ncRNAs isolated from UF with the miRNeasy Serum/Plasma Kit (Qiagen) were analyzed using deep sequencing on the NextSeq 500/550 platform (Illumina, USA); the obtained data were subsequently validated with real-time quantitative PCR using the miScript II RT Kit and miScript SYBR Green PCR Kit (Qiagen, Hilden, Germany).

Results: The UF samples were classified into two groups: receptive endometrium and non–receptive endometrium depending on the results of the ART program (the presence and absence of implantation, respectively). Seven logistic regression models were developed on the basis of the small ncRNAs profile in the UF samples and endometrial thickness at the time of embryo transfer into the uterine cavity. The most accurate model appears to be the combination of content of miR-1180-3p in UF and endometrial thickness (71% sensitivity, 88% specificity) due to the lack of dependence of the variables using Spearman correlation analysis (r=0.02, p=0.9) and the statistical significance of all values included in the model (p<0.05).

Conclusion: The effectiveness of ART treatment can be improved owing to the individual approach in determining the implantation window during IVF in women receiving CHT and identifying the level of small ncRNAs in UF. The use of the logistic regression model which was developed in this study is limited in clinical practice due to the lack of information about the implantation potential of the blastocyst transferred into the uterine cavity. It is the poor quality of the embryo itself rather than the absence of the receptive endometrium that may result in a negative outcome of the ART program. Simultaneous determination of endometrial receptivity and embryo implantation potential on the basis of the small ncRNA profile can lead to a decrease in the percentage of false-negative results and improve the quality of the model. It is necessary to increase the training set of participants and to check the accuracy of the constructed models on an independent test set.

Objective: To evaluate the effectiveness of complex treatment of patients with endometriosis and chronic pelvic pain (CPP) considering the preliminary diagnosis of their sensitization to progesterone.

Materials and methods: The study included 100 women of reproductive age with confirmed endometriosis and CPP. The patients of the main group were divided into four subgroups depending on the results of the diagnosis of sensitization to progesterone and on the administered hormone therapy with dienogest and dydrogesterone (group 1: sensitization to progesterone – surgical treatment+dienogest; group 2: sensitization to progesterone – surgical treatment + dydrogesterone; group 3: without sensitization to progesterone – surgical treatment+dienogest; group 4: without sensitization to progesterone – surgical treatment+dydrogesterone). Six months after surgery and therapy there was an assessment of the dynamics of pain intensity using a visual analogue scale (VAS).

Results: There was a statistically significant decrease in pain on the VAS scale in all four subgroups of patients who had experienced CPP, dysmenorrhea, and dyspareunia. A decrease in CPP and dyspareunia in patients with sensitization to progesterone was more significant in the subgroup that was treated with hormone therapy with dydrogesterone. A decrease in dysmenorrhea was not different in patients who were treated with dydrogesterone and dienogest.

Conclusion: The most effective option for postoperative treatment of endometriosis for patients with CPP and sensitization to progesterone is the therapy with dydrogesterone. The high selectivity of dydrogesterone to progesterone receptors provides clinical efficacy and a favorable safety profile of the medication.

Objective: To present own experience of complex treatment of bacterial vaginosis during pregnancy.

Materials and methods: The study included 46 patients with a pregnancy at 22–36 weeks’ gestation with confirmed bacterial vaginosis. All patients were divided into two equal groups: women of group 1 received treatment with an antibiotic in com-bination with the immunomodulatory medication Superlymph, patients of group 2 received only antibiotic therapy. Efficacy was evaluated by the analysis of clinical manifestations, microbiological and microscopic examination of vaginal dis-charge, vaginal pH, pro-inflammatory cytokines.

Results: In both groups there was a decrease in the number of epithelial cells and leukocytes during the treatment, key cells were not detected after the treatment; however, the improvement was more significant in group 1. There was also a de-crease of the titer in both groups. But despite the treatment, the average titer of Gardnerella vaginalis was >10⁴ CFU/ml in 17.4% (n=4). The growth of Lactoba-cillus spp. in both groups was evidence of the effectiveness of the therapy while the value of this microorganism was higher in group 1. Moreover, there was a statisti-cally significant decrease of pro-inflammatory cytokines to normal values in the main group. The most favorable results for obstetric and perinatal outcomes (preterm rupture of membranes, preterm labor, asphyxia, intrauterine infection of newborns, etc.) were obtained in group 1.

Conclusion: Immunomodulatory medication Superlymph combined with antibacte-rial drugs improves the effectiveness of the treatment for bacterial vaginosis during pregnancy.

Objective: To evaluate the efficiency of treatment for chronic nonspecific cervicitis (CNSC) by ultrasound cavitation and altered tissue radiowave excision compared to empirical antibacterial treatment.

Materials and methods: Based on standardized included criteria, 50 reproductive-aged patients with CNSC were enrolled in the investigation and were available for analysis. They were equally divided into 2 groups: a study and a comparison group. After colposcopic examination, each group was divided into subgroups A (in terms of the presence of cervical deformity) and B (in terms of its absence). At the first stage, all the study patients (n=25) underwent 5 sessions of treatment of the cervix with 0.05% chlorhexidine solution cavitated by ultrasound. The comparison group patients (n=25) received only empirical treatment with a single dose of 1.0 g azithromycin. After 3 months, the study group patients (n=17) who had impaired cervical histoarchitectonic abnormalities as old ruptures, the consequences of destructive treatment or ectropion, and who did not meet the criteria for cure by the time cutoff of 3 months, an additional intervention (electrosurgical (radiowave) excision of the altered cervical tissue) was performed. No additional interventions were done in the control group patients. The effect of therapeutic interventions was evaluated following 1, 3, and 6 months according to the criteria: satisfaction with treatment (a subjective effect) and the criterion of cure (an objective one).

Results: After a month, the disappearance of the main symptoms of CNSC according to the objective criteria was noted in most patients, in both patients with normal (1B, 2B) and in those with the impaired cervical (1A, 2A) histoarchitectonics, in both the study (cavitation) group and control (azithromycin) groups. Antibiotic therapy with azithromycin showed no statistically significant differences in efficiency compared with ultrasound cavitation, neither in the patients with the normal cervical histoarchitectonics (1B and 2B) after 1, 3, and 6 months (p=0.55; 0.262; 0.3, respectively), nor in the patients with the impaired cervical histoarchitectonics after 1 and 3 months (p=0.29; 0.06, respectively). Ultrasound cavitation for the treatment of CNSC was not inferior in the effectiveness of antibacterial therapy in the short term. However, there was a resumption of the symptoms of CNSC after 3 and 6 months, which was especially pronounced in patients with the impaired histoarchitectonics of the cervix uteri. Additional surgical excision of its altered tissue in patients with the impaired cervical histoarchitectonics (1A) led to the cure criteria in 15/16 (93,8%) patients compared with the identical (azithromycin) group 2A, where after 6 months only 1/18 (5,6%) met the cure criteria (OR 157.7 [11.5; 10051.4]; p<0.001). There was a high treatment satisfaction on average 4 [3; 4] scores when evaluating after 1 month in all the groups, with its subsequent decrease, except for Group 1A (cavitation, then excision following 3 months), in which at the cut-off of 6 months, there was a higher treatment satisfaction than that in Group 2A (4 [4; 4] vs 2 [2; 2]; p<0.001; 0.676 [0.5; 0.817]).

Conclusion: The main reason supporting the chronic inflammatory process is the impaired cervical histoarchitectonics. Empirical antibiotic therapy is not effective in treating CNSC in the long term, having only a temporary effect. Ultrasound cavitation therapy has a positive permanent effect in patients with the normal cervical histoarchitecnonics, but most patients with the impaired cervical exhibited a resumption of the symptoms of CNSC. Only additional surgical removal of the altered cervical tissue after ultrasound cavitation therapy in patients with the impaired cervical histoarchitectonics can achieve the cure of CNSC in most cases.

It is useful for clinicians to be aware of the risks, limitations, and outcomes of laser therapy. This article analyzes the development of laser fractional thermolysis in medicine and substantiates its use in gynecology. Definitions of key terms for working on laser devices are pressented. The stages of the use of fractional lasers in dermatology are described, the features of the physics of a laser on living tissues are explained, and the choice of the type of laser and the options for selecting its parameters are analyzed in detail, with the rationale for choosing the parameters of a CO₂-laser for various gynecological diseases. The mechanism of induction of tissue regeneration during fractional photothermolysis due to the effects of photobiomodulation has been substantiated. The indications and contraindications for CO₂-fraction laser thermolysis in aesthetic gynecology and urogynecology with examples from systematic reviews and meta-analyses are described, and ready-to-use protocols for working on a CO₂-laser platform are presented. The examinations necessary before CO₂-fraction laser thermolysis of the vagina and vulva are discussed.

Conclusion: Many professionals are concerned about the lack of published full and operational laser parameters to enable the clinician to use lasers for a safe and effective outcome. This article describes the basics of the interaction of a CO₂-fraction laser with tissue and shows how different parameters of laser fractional thermolysis can be applied to various conditions in gynecology and urogynecology.

Background: Uterine leiomyomas are not uncommon in adolescence; however, an unusual growth model, such as diffuse uterine leiomyomatosis (DUL), has been registered in single cases. The differential diagnosis of DUL is made with common multiple uterine leiomyomas and nodular adenomyosis. In view of the fact that the early diagnosis is difficult and there is no universal approach to the tactics of patient management, uterine masses frequently reach large sizes and motivate organ-removing operations.

Case report: The paper presents a review of literature data and an extremely rare clinical case of DUL in a 14-year-old girl. The patient visited a gynecologist with complaints of severe lower abdominal pain increasing in the last days of menstruation, which has been bothering her for the past year. She was suspected of diffuse nodular adenomyosis or multiple uterine myoma and was referred to be admitted to Gynecology Department Two, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation. The Department made an instrumental and laboratory additional study, diagnosed uterine leiomyomatosis and external genital endometriosis of the pelvic peritoneum, ruled out other sites of possible leiomyomatosis; oncomarkers were obtained within the reference values. The girl received surgical treatment (laparoscopy, adhesiolysis, removal of a subserous leiomyomatous node, corpus uteri biopsy, coagulation of the foci of external genital endometriosis, and diagnostic hysteroscopy. Morphological examination confirmed uterine leiomyomatosis with hyalinosis. Immunohistochemical study of a myometrial biopsy sample revealed that the expression of estrogen receptors was 3 scores and that of progesterone receptors was 4 scores (according to the Allred scale; that of the proliferation marker Ki-67 was 20%. The patient was discharged home; after 3 months during therapy with gestagens (norethisterone), pelvic organ ultrasound indicated no substantial changes in the uterine sizes. Therapy and a follow-up were continued.

Conclusion: DUL is extremely rare in pediatric practice and is frequently detected late, which determines the relevance of timely preventive examinations and early diagnosis in order to maximize the organ-sparing tactics of management.

Background: The present-day social conditions set new trends in changing the age model of birth rates with the implementation of reproductive function at a later stage, which creates a number of medical and social problems. проблем. Late reproductive aged women the most frequently face failures in the treatment of infertility by assisted reproductive technologies (ART). In addition, the women of this age cohort have high rates of pregnancy complications and perinatal morbidity.

Case report: The paper describes a clinical case of a favorable outcome of infertility treatment by ART methods using the standard short protocol with gonadotropin-releasing antagonists in a married couple of late reproductive age (the wife is 44 years; the husband is 58 years).

Conclusion: This case shows the possibility of achieving clinical pregnancy with the birth of a healthy baby in even female patients of late reproductive age, which emphasizes the need to optimize ovulation stimulation protocols and to choose the most appropriate method of infertility treatment for each married couple individually. At the same time, it is necessary to provide these married couples with information about the extremely low chances of clinical pregnancy and live birth in the treatment of infertility with ART methods and their own oocytes, as well as about the fertility preservation opportunities, including those using deferred motherhood at an earlier reproductive age.