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Background. Epithelial-mesenchymal transition (EMT) is a conserved mechanism in the process of morphogenesis and organogenesis. EMT provides cells with migratory and invasive properties, which is a necessary condition for the formation of endometrioid heterotopias. Aim. To confirm the presence of EMT features in different types of endometriosis. Materials and methods. During a period of five years (2012–2017) we analyzed 43 cases of extragenital endometriosis: appendix (3 case), colon (5 cases), ileum (1 case), abdominal scar endometriosis after caesarean section (24 cases), and inguinal hernia (10 cases). The material was processed according to histological and immunohistochemical technique using monoclonal E-cadherin and polyclonal Vimentin antibodies to assess local invasiveness. Results. In peritoneal endometriosis, the ratio of E-cadherin to Vimentin expression was 10.3, in the colon = 9.1, in the appendix 8.6, in the ileum 5.5, in the hernial sac 4.2. Thus, in diffuse infiltrative forms of endometriosis, the lesion phenotype is characterized by low expression of E-cadherin, while expression of Vimentin is at a high level (p0.05). Conclusion. The results of our study confirmed involvement of the epithelial-mesenchymal transition process in the pathogenesis of extragenital endometriosis lesions, on the one hand, and they certify its invasive potential in these localizations, on the other hand.

Aim. To identify clinical and history features of patients with recurrent deep endometriosis (RDE). Materials and methods. A retrospective study of clinical and history data of 200 patients with DE undergoing surgical treatment at the Department of General Surgery of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in 2020–2021. Group 1 included 80 patients with RDE, group 2 included 120 patients with newly diagnosed DE. All patients underwent surgical treatment followed by immunohistochemical examination and DE confirmation. Results. An association was found between the young age of the patient at the time of the first surgery and the type of endometriosis. It was found that women with a history of endometriosis surgery in early reproductive years (29.22±5.3 years) are at risk of recurrent endometriosis. Two or more surgeries were reported in 33.7% of RDE patients. In 90.2% of patients, endometriosis recurred with clinical manifestations; in 9.8%, it was asymptomatic and diagnosed on pelvic ultrasound. The group of RDE patients showed a longer period of infertility (5.432±3.53 years) than the group with newly diagnosed DE (2.953±1.29 years). It was found that the surgeries performed in RDE patients were longer, more complex, and associated with more blood loss. Intestinal resection, ureterolysis, adhesiolysis, and salpingectomy were significantly more common in the RDE group than in patients without a history of endometriosis surgery. Conclusion. In most cases, RDE is clinically manifested, rarely asymptomatic and diagnosed by visualization methods. Patients with a history of surgery at a younger age are at risk of RDE, and their surgical interventions are more complicated with more blood loss. Currently, surgical treatment of DE is the optimal method; however, it has serious disadvantages with severe and even life-threatening postoperative complications.

Aim. To analyze the profile of anti-Mllerian hormone (AMH) and the expression level of the transmembrane AMH receptor type II (AMHRII) in the eutopic and ectopic endometrium of patients with deep infiltrative endometriosis (DIE). Materials and methods. A comparative analysis of AMHRII expression in epithelial and stromal cells of eutopic and ectopic endometrial samples and the level of serum AMH in patients of reproductive age with DIE (n=50) and tuboperitoneal infertility (n=9) was performed. Results. AMHRII expression in eutopic endometrial stromal cells of DIE patients was significantly higher compared to glandular cells in all study groups (p0.5). AMHRII expression was found to be significantly higher in glandular cells of the eutopic endometrium compared to the ectopic endometrium of pelvic peritoneal foci in DIE patients: 1.600.77 and 1.090.68 points, respectively (p=0.001). Conclusion. The inhibitory effect of AMH on cell proliferation and the proven expression of AMHRII by eutopic and ectopic endometrioid cells may indicate the role of AMH in the pathogenesis of endometriosis and endometriosis-associated infertility.

Aim. To study the regulation of apoptosis in the endometrium of women with chronic endometritis (CE) and external genital endometriosis (EGE) based on the study of the expression of its regulators such as transcription factor (NF-), Bcl-2 and Caspase-8. Materials and methods. The study evaluated the expression of apoptosis factors such as Caspase-8, NF-B transcription factor, and Bcl-2, in patients with chronic endometritis (CE, n=23), external genital endometriosis (EGE, n=20), and intact endometrium (control group; n=7). Statistically significant differences were found for all test markers (p0.05). Results. The increased expression of apoptosis factors is probably related to high endometrial pro-inflammatory activity in both CE and EGE. For EGE, this effect is more pronounced at the transcription level in the form of an increase in the expression of the transcription factor NF-B in both glandular and stromal endometrial cells. It is probably due to the systemic nature of the chronic inflammatory process. For CE, despite the antiapoptotic activity of Bcl-2, an increase in Caspase-8 expression in the endometrium may also indicate a predominance of innate immunity activation. Conclusion. The imbalance of pro- and antiapoptotic factors can be an inducer of both cytotoxic and cytoprotective mechanisms of EGE and CE. However, it requires further research.

Aim. To assess the reproducibility of cytological diagnoses in evaluating liquid cervical smears and immunocytochemical co-expression of p16/Ki-67 using manual and automatic methods. Materials and methods. Cytological smears prepared using the liquid cytology method on the Becton Dickinson device (SurePath technology) were studied. An immunocytochemical study was carried out using a Ventana BenchMark Ultra automatic immunostainer with a commercial CINtec kit (determination of p16/Ki-67 co-expression). In total, 100 cytological slides (50 pairs of Pap-smears and immunocytochemical slides) were studied. The diagnostic kit was reviewed by five cytologists independently, and the cytologic slides were evaluated using four categories according to the Bethesda system (2014) and according to the categories of normal/abnormal. The co-expression of p16/Ki-67 was assessed per the manufacturer's recommendations (Roche) using the manual method (light microscope) and the automatic Vision Cyto Pap ICC system. Statistical processing of the results was performed using the SPSS software package version 26.0.0.0 with the calculation of the reproducibility indices of Cohen's kappa and Fleiss' kappa. Results. When assessing the reproducibility of four categories of cytological diagnoses according to the Bethesda system (2014), Cohen's kappa was 0.0480.265. The overall Fleiss' kappa between all cytologists was 0.103. When only two categories (normal/abnormal) were used, the reproducibility ranged from 0.058 to 0.377. When assessing the co-expression of p16 and Ki-67, Cohen's kappa reproducibility was from 0.196 to 0.574, while the overall Fleiss' kappa was 0.407. When comparing the evaluation results of each of the cytologists with the neural network, Cohen's kappa reproducibility ranged from 0.103 to 0.436. Conclusion. The reproducibility of cytological diagnoses according to the Bethesda system (2014) and two categories (normal/abnormal) based on the Pap smear study was low. Such results are primarily due to a large number of abnormal smears in the study. The immunocytochemical method has diagnosis reproducibility three times higher, indicating the need to measure the co-expression of p16 and Ki-67 to increase the sensitivity and specificity of the cytological method. Similar reproducibility when comparing the manual and automatic evaluation of the "double label" suggests that the neural network algorithm can currently help in decision support rather than replace the cytologist at the diagnostic stage.

Aim. To analyze the incidence and types of adverse outcomes and complications of laparoscopic myomectomies. Materials and methods. This work is a retrospective study based on data from the Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology. We analyzed 711 case histories of patients diagnosed with uterine myoma who received surgical treatment in the Department of Innovative Oncology and Gynecology from 2015 to 2019. The frequency of malignant neoplasms, verified by pathomorphological examination, and the characteristics of surgical interventions performed in these patients were comparatively evaluated. Results. Surgical interventions for uterine myoma are leading in gynecology due to the high prevalence of such disorders. Conservative myomectomy remains the "gold standard" in organ-sparing surgery. However, during surgeries for suspected benign neoplasms, there is a risk of morcellation of the malignant tumor, significantly worsening patient survival outcomes. In our study, the incidence of uterine leiomyosarcoma in suspected benign neoplasms was 0.98%. The probability of parasitic myomas or disseminated perineal leiomyomatosis after myomatous nodule morcellation is 0.19%. Conclusion. No reliable information about the malignant potential of the tumor and its proliferative activity can be obtained until a definitive pathomorphological examination. The above considerations warrant the routine use of prophylactic measures to prevent tumor cell dissemination.

Introduction. The main function of the endometrium is to create the optimal environment for embryo implantation, controlled by multicomponent signaling pathways. They are modulated by progesterone and estradiol acting through related estrogen receptors (ER) and progesterone receptors (PR). Alteration in steroid hormone, follicle-stimulating hormone (FSHR), and luteinizing hormone (LGHR) receptor expression are underlying factors in the development of various reproductive disorders. Therefore, understanding the physiological features of receptors expression and localization in tissues is extremely important for a proper comprehensive assessment of the endometrial condition. Materials and methods. The expression of ER, PR, FSHR, and LGHR in endometrial samples of healthy females from different menstrual periods, who applied for assisted reproductive technologies (ART) due to male infertility, was assessed by immunofluorescence. Results. The increase in immunoreactivity of ER, PR, FSHR, and LGHR in the glands and stroma of the endometrium is initiated during the early proliferation stage and reaches its maximum during the late proliferation stage. Subsequently, ER expression in the glands and stroma gradually decreases throughout the early and middle stages of secretion; PR immunoreactivity in the stroma and FSHR and LGHR in all endometrial components persists throughout the secretion stage. Conclusion. The correspondence between the change of the studied receptors' expression and endometrium structural features at different stages of the menstrual cycle was demonstrated. The increased expression of ER, PR, FSHR, and LGHR in the endometrium at the proliferation stage coincides with the growth period of the uterine body mucosa, and the increased immunoreactivity of PR, FSHR, and LGHR during the secretion stage is associated with its decidual transformation and seems to create conditions for successful implantation and embryo development if pregnancy occurs.

Aim. To conduct a comparative analysis of the results of organ-preserving laparoscopic operations performed for uterine fibroids with the use of plastic containers for morcellation and without it. Materials and methods. We examined 57 patients with a diagnosis of uterine fibroids who were admitted to the Department of Innovative Oncology and Gynecology of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology for organ-preserving surgical treatment. To achieve the goal of the study, the patients were divided into the following groups: the main group 29 patients who underwent laparoscopic myomectomy and morcellation of removed nodes using plastic containers. The control group consisted of 28 patients who underwent morcellation during laparoscopic myomectomy without the use of plastic containers. Results. The duration of laparoscopic operations performed using plastic containers main group was 85.6925.87 minutes. Laparoscopic conservative myomectomies, performed without the use of limiting systems, took a slightly longer amount of time control group 88.7530.36 minutes. There were no statistically significant differences, but in the second group, more prolonged sanitation of the abdominal cavity and removal of small fragments of myomatous nodes after morcellation outside the sacs were required. Autoinfusion was used in 6 (20.69%) patients in the main group, in 7 (25%) patients in the control group. Blood transfusion was not used in any case. Average blood loss was 120.6967.50 ml in the main group, 125.0099.54 ml in the control. The duration of hospitalization in the main group was 4.661.76 days, in the control group 5.793.62 days. In the main group, histological examination revealed leiomyoma in all cases, leiomyoma was detected in 96.4% (27 patients) of cases in the control group, and leiomyosarcoma in 1 patient (3.6%). Conclusion. In all groups of patients, there was a favorable course of the postoperative period, early activation of patients. In the group of laparoscopic operations, one patient (3.6%) after morcellation of the myomatous node without the use of a plastic container was found to have leiomyosarcoma. The use of plastic containers in our study did not increase the duration of operations and did not affect the volume of blood loss, the frequency of intra- and postoperative complications. In contrast, the operation time was slightly higher among patients who were operated without the use of containers. In all likelihood, this was due to the fact that the morcellation stage itself took longer, since it was required to extract small fragments of myomatous nodes, as well as thorough and prolonged sanitation of the abdominal cavity. It should be noted that the use of plastic containers, of course, requires the development of certain skills from the surgeon, taking less and less time in parallel with the learning curve. Of course, further studies are required to assess the risk of tumor spread in patients undergoing surgery using plastic containers, but preliminary data indicate that ablastic morcellation can and should be used in organ-preserving surgery for uterine myoma.

Aim. To conduct a retrospective analysis and evaluate the morphological methods for HPV-related intraepithelial lesions detection in women of reproductive age. Materials and methods. The data of cytological diagnosis, as well as the results of histological reports were analyzed for the period from 2018 to 2019. A comparative analysis was performed in 415 patients with HPV-related intraepithelial lesions, who applied to the scientific and polyclinic department of the Kulakov National Research Medical Center at the age of 19 to 45 years. Morphological examination was carried out by specialists of the 1st pathology department of the Center. Results. According to the results of a comparative analysis of cytological and histological conclusions, 3 groups were formed: 1 the group of coincidence (agree) of cytological and histological conclusions; 2 group of minor discrepancies (minor under/ over) between cytological and histological finding; 3 group of major discrepancies (major under/ over) between cytological and histological findings. Cytological and histological compliance was achieved in 194 (46.74%) patients. The total number of minor nonconformities was 192 (46%) cases. The total number of significant discrepancies between cytological and histological findings was 29 (6.9%) patients: 20 (4.8%) cases were found in the group NILM, hr. cervicitis HSIL and 9 (2.1%) cases in the group HSIL hr. cervicitis according to the results of histological examination. Conclusion. Cervical screening reduces the risk of breast cancer due to cytological examination of the cervix, but histological examination is crucial in making a correct diagnosis, since its result determines the choice of treatment method. The comparative analysis showed that in all groups there were cases of hypo- and hyperdiagnostics during cytological examination although the major discrepancies which can change treatment algorithm, were found only in 6.8% cases.

Aim. To evaluate the endometrial glyotype in the implantation window in patients with infertility in assisted reproductive technologies (ART) programs and to develop criteria for assessing endometrial receptivity based on the analysis of complex changes in the functional groups of glycans in the main endometrial epithelial to use in clinical practice. Materials and methods. The study included 32 infertile patients who took part in ART programs. Pipelle endometrial biopsy was performed during the implantation window in the cycle preceding the cycle of ovarian stimulation and embryo transfer. Using lectin histochemistry and immunohistochemistry, glycans levels in the glycocalyx of endometrial surface epithelium (SE) and glandular epithelium (GE) was studied. Results. Differences in the expression of mannose-rich glycans in SE and N-acetylgalactosamine--terminated glycans in the GE of the endometrium were revealed, as well as the link between the expression of lectin staining glycans: ConA, VVL, UEA-I, SNA, MAL-II, ECL and monoclonal antibodies: anti-MECA -79 mAb and anti-LeY mAb in SE and GE of the endometrium was assessed in patients with infertility, depending on the outcome of the ART program. The estimated threshold levels in glycan expression and the odds ratio for pregnancy occurrence allow to characterize the diagnostic value for the studied glycomarkers and to develop criteria for assessing endometrial receptivity. Conclusion. Based on a comprehensive evaluation of glycans in the main endometrial epithelial structures in the cycle preceding the ART cycle, criteria for assessment of the likelihood of pregnancy have been developed, which can increase the effectiveness of ART programs in patients with infertility.

Female urethral diverticulum is a fairly rare pathology, the frequency of which ranges from 0.02 to 6.00% of women worldwide. The stones inside urethra diverticulum even more rare. The most common reasons of urethral diverticula are frequent bladder catheterizations, labour trauma, infections. Clinically is may present with the dysuria, dyspareunia, dribble, urinary incontinence, vaginal discomfort. Voiding cystourethrography and cystourethroscopy are the most accurate methods of diagnosis for urethral diverticula. The presented article describes the clinical case in women with urethral diverticulum who complained on the vaginal discomfort, dyspareunia and presentation of the brown stones in vagina and underwent surgical excision of diverticulum with urethral reconstruction.

Aim. To analyze the literature data on modern approaches to morcellation of myomatous nodes in laparoscopic surgery and to highlight this area in a historical aspect. To form an idea of the main difficulties associated with morcellation, which contributed to and contribute to the improvement of the technique of this manipulation. Materials and methods. The review includes data from foreign articles published in the elibrary.ru and PubMed databases on this topic. Results. It describes both modern trends in the surgical treatment of patients with uterine myoma, and historical aspects of improving methods aimed at reducing risks, reducing the time of surgical intervention and improving its safety. Analyzed data on the use of electromorcellation, carried out both with the use of plastic containers, and without them. Conclusion. High requirements for surgical interventions contributed to the emergence of such a method of intracorporeal fragmentation of drugs, such as morcellation, which led to a significant reduction in the proportion of laparotomic operations in the treatment of patients with my uterus. The introduction of laparoscopy in the surgical treatment of uterine myoma allowed to achieve a fundamentally new high level of rehabilitation of patients. Removing removed drugs from the abdominal cavity is associated with a certain risk. Despite the significant number of proposed methods and devices for morcellation, they all require further improvement, since it is necessary to completely exclude contact of the myoma node tissue with abdominal organs in the extraction process. Currently, active research continues on ways to realize all the benefits of minimally invasive technologies in compliance with the rules of oncological safety.

Objective - to evaluate the structural features of the external and internal genital organs in girls with aplasia of the vagina and uterus. Materials and methods. The study included 64 adolescent girls aged 15-18. The examination included a general and gynecological with an assessment of the structural features of the perineum, external genital organs and urethra, including using a specially designed measurement scheme for anatomical landmarks. An ultrasound study was performed with the aiming assessment of uterine horns and, when identifying signs of functioning, laparoscopic removal of them with histological study. In order to optimally assess the type of tissue lining the vaginal fossa zone, an analysis was carried out of the material obtained by scraping from the studied zone using liquid cytology. Results. Every third patient (34.3%) was diagnosed with urinary system pathology. In most patients, the external opening of the urethra was typical. Almost everyone had hymen (95%). Gynecological examination showed that in the vast majority of patients in the area of intended vaginal entry, was a blindly ending vaginal fossa (95.3%). The length of the fossa was on the average 1.7±0.1 cm. According to the smear scrapings from the vaginal fossa, flat cells of the superficial, intermediate, and parabasal and basal types were present. Representatives of the lactobacillus and coccal microflora were revealed. A topographic-anatomical analysis of the orientations of the perineum in girls with aplasia of the vagina showed that the depth of the vaginal fossa weakly depended from the age of the patients and did not depend on any of the suggested guide points. According to the results of instrumental methods of investigation of the pelvic organs, 68.75% of the girls had a muscular cord at the uterus place. Moreover, 22% of girls had signs of the functioning of rudimentary horns. Ovaries, as a rule, were located high, at the entrance to the small pelvis. Laparoscopy was performed in all patients with cyclic pain syndrome and closed functioning uterine rudiments, removal of the uterine horns with fallopian tubes were prefered. Histological examination of the obtained preparations was characterized by the detection of endometrial stroma and active endometrial glands. Summary. The authors emphasize that a multilateral examination of this cohort of patients is extremely important for the diagnosis and optimized treatment.

The goal is to assess the sensitivity and specificity of transvaginal ultrasound (USI) in the diagnosis of localization of foci of deep infiltrative endometriosis. Materials and methods. The study included 142 patients with deep infiltrative endometriosis, who underwent surgery in the surgical department of the V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of Russian Federation in the period 2014-2016. Criteria for inclusion in the study: informed agreement of the patient, the reproductive age (from 18 to 44 years), deep infiltrative endometriosis with a confirmed histological conclusion. Exclusion criteria were malignant tumors of the pelvis and abdomen, refusal to undergo surgical treatment of deep infiltrative endometriosis, and malformations of the urogenital system. Results. Transvaginal echography in identifying the localization of foci of deep infiltrative endometriosis is highly sensitive in the diagnosis of colorectal endometriosis (88.9%) and endometriosis of the bladder (96%) with a relatively low specificity of the study (35%). The sizes of endometrial infiltrates of the intestine, retrocervical endometriosis, and bladder intraoperatively were large in comparison with the data obtained with transvaginal ultrasound. When assessing the accuracy of the diagnostic method, it was found that transvaginal ultrasound evaluates retrocervical endometriosis with an accuracy of 41.5%, endometriosis of the intestine - 37.7%, bladder - 54.8%. Conclusion. Transvaginal echography, based on a quantitative assessment of the characteristic curve by calculating the area under it, the size of the infiltrate and their localization, showed that our study have middle diagnostic quality and visualization of DIE lesions with enough specify.

Abnormal uterine bleeding (AUB) is one of the most common indications for hysteroscopy. Most of the AUB cases occur due to endometrial or myometrium pathology. Among it, endometrial polyps (EP) and chronic endometritis (CE) prevalent in reproductive age, while endometrial hyperplasia (EH) and EP dominate in perimenopause. It was determined that EP and CE are characterized with menorrhagia and metrorrhagia approximately equally, whereas EH reveals AUB with oligomenorrhoea. Verification of exact endometrial pathology by ultrasound examination is hindered, that results in deviations of ultrasound and histological diagnosis. The usage of ultrasound data and AUB’s characteristics may improve the diagnostic accuracy on preadmission period.

Among ovarian tumors, germinogenic tumors occur in 25.9% of cases, develop from the polypotent highly specialized germinogenic epithelium of the gonads. Most germinogenic tumors are mature (benign) cystic teratomas (95%), malignant germinogenic tumors occur in only 3-5% of cases. The only reasonable method of treating these tumors is surgery, which is associated with losses of the ovarian reserve. The article presents the clinical and anamnestic characteristics of girls aged 7 to 17 years with ovarian teratomas, describes the structure of the surgical interventions (access, volume of operations) with the analysis of the histological conclusion of the remote formations.

The article presents a clinical case of cryopreservation of ovarian tissue in a patient 15 years with the bulk formation of a single ovary, is made on the basis of V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation.