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Endometriosis affects about 10% of women of reproductive age and can negatively impact their quality of life (QoL). Due to the heterogeneity of symptoms or even their absence, early diagnosis is difficult. Therefore, it is necessary to comprehensively assess the patient's complaints, including a thorough review of medical history, the results of imaging studies, and risk factors for endometriosis. Early diagnosis enables preemptive treatment and avoids surgical intervention. The article presents data on managing patients with endometriosis in outpatient settings, describing methods for non-invasive imaging diagnosis of endometriosis. Current options of pharmacotherapy aimed at controlling the development of the disease and improving the QoL of patients in the long term are addressed. Timely initiated drug treatment improves the QoL of patients, in some cases, leads to a regression of the lesions, and improves the prognosis for the reproductive function. A shift in focus to clinical diagnosis, combined with non-invasive imaging, shortens the time between the first consultation and the final diagnosis. According to the current view of Russian and international professional societies, therapy should be long-term; therefore, selecting treatment with predictable responses and monitoring the course of the disease is necessary.

Endometriosis is a prevalent chronic inflammatory disease characterized by a considerable delay between initial symptoms and diagnosis through surgery. The pressing need for a timely, non-invasive diagnostic solution underscores the focus of current research efforts. This study examines the diagnostic potential of the menstrual blood lipidome. The lipid profile of 39 samples (23 women with endometriosis and 16 patients in a control group) was acquired using reverse-phase high-performance liquid chromatography–mass spectrometry with LipidMatch processing and identification. Profiles were normalized based on total ion counts. Significant differences in lipids were determined using the Mann–Whitney test. Lipids for the diagnostic model, based on logistic regression, were selected using a combination of variance importance projection filters and Akaike information criteria. Levels of ceramides, sphingomyelins, cardiolipins, triacylglycerols, acyl- and alkenyl-phosphatidylethanolamines, and alkenyl-phosphatidylcholines increased, while acyl- and alkyl-phosphatidylcholines decreased in cases of endometriosis. Plasmenylphosphatidylethanolamine PE P-16:0/18:1 and cardiolipin CL 16:0_18:0_22:5_22:6 serve as marker lipids in the diagnostic model, exhibiting a sensitivity of 81% and specificity of 85%. The diagnostic approach based on dried spots of menstrual blood holds promise as an alternative to traditional non-invasive methods for endometriosis screening.

Aim. To evaluate the effectiveness of the intrauterine levonorgestrel-releasing device (LNG-IUD) in the treatment of atypical hyperplasia and the use of LNG-IUD in combination with a gonadotropin-releasing hormone analog (3.6 mg goserelin depot) in the treatment of stage Ia highly differentiated endometrial adenocarcinoma in women wishing to preserve childbearing function, and to assess reproductive outcomes after treatment in these women. Materials and methods. A prospective and retrospective series of cases included all patients treated with LNG-IUD or LNG-IUD combined with goserelin 3.2 for atypical hyperplasia or early endometrial cancer (EC) treated in the Department of Innovative Oncology and Gynecology of the Institute of Oncogynecology and Mammology of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology from January 2018 to March 2022. Response rates and the relationship of the response with clinical and pathological factors were calculated. Results. Fifty-six patients diagnosed with atypical hyperplasia or stage Ia highly differentiated endometrial adenocarcinoma were treated with LNG-IUD and LNG-IUD combined with 3.2 mg of goserelin. Of the 56 patients who completed a 6-month course of hormonal treatment, 42 (82%) showed a complete response: 22 (91.7%) with atypical endometrial hyperplasia (AEH) and 20 (74.1%) with EC. In 4 (7.8%) patients, a partial response was reported: 2 (8.3%) with AEH and 2 (7.4%) with EC. No response was noted in 5 (9.8%) patients in the EC group only. Childbirth was reported in 13 (23.2%) women: 8 (29.6%) with AEH and 5 (17.2%) with EC. Two (3.6%) women were in the second trimester of pregnancy, and 17 (30.4%) women had an early pregnancy loss; 7 (25.9%) of them had AEH, and 10 (34.5%) had EC. The positive response rate was 90.2% at 6 months: 24 (100%) patients with atypical hyperplasia and 22 (81.5%) with EC. Patients with EC in combination with polycystic ovary syndrome and obesity and patients with the non-obese EC phenotype had a lower therapy efficacy. Conclusion. LNG-IUD therapy for the conservative treatment of atypical hyperplasia and LNG-IUD therapy combined with goserelin 3.2 for early EC led to a morphological cure in most patients and can be considered for women planning pregnancy.

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.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective of the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96). Conclusion: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome.

Background. According to the modern concept of surgical treatment of ovarian cancer (OC) it is necessary to perform cytoreductive surgery (CRS) without residual tumor in order to achieve more favorable oncological prognoses. However, the possibilities of achieving it with a disseminated process (stages IIIIV) are limited, and therefore, for some patients, neoadjuvant chemotherapy (NACT) is the optimal initial treatment. Aim. To compare the duration of progression-free survival (PFS) of patients with advanced OC after treatment, as well as to assess the value of the prognostic nutritional index (PNI) in predicting this outcome. Materials and methods. We conducted a retrospective cohort study of 78 patients with stages IIIIV OC, who received combined treatment between January 2016 and March 2020 (54 patients after primary CRS (PCRS)+platinum-based chemotherapy (CT), 24 patients after NACT+interval CRS (ICRS)+postoperative CT. The predictive value of the PNI was calculated. Results. The complete PCRS is associated with increased PFS: after complete PCRS 3211.21 months (95% confidence interval CI 10.0953.97); after optimal PCRS 223.46 months (95% CI 15.2128.79); after suboptimal PCRS 147 months (95% CI 0.2827.72). Performing a complete ICRS is associated with decreased PFS compared to PCRS, even if the complete CRS is achieved: after complete ICRS 143.34 months (95% CI 7.4620.54); after optimal ICRS 172.16 months (95% CI 12.7721.23); after suboptimal ICRS 7 months. PNI27.86 correlates with an increased probability of complete PCRS in patients with advanced PCR (AUC 94.3, sensitivity 80%, specificity 91.7%; p0.001). Conclusion. Achieving complete PCRS in patients with disseminated OC leads to an improvement in the oncological outcome. The prognostic value of pre-treatment calculation of PNI has been revealed: an increased PNI is associated with more favorable perioperative outcomes. Objective criteria should be developed for a strictly reasoned refusal to carry out the first stage of surgical treatment due to the obviously less favorable prognosis of the tactics of "NACT+ICRS+CT".

The objective of the study was to evaluate the profile of serum autoantibodies and their diagnostic and pathogenetic significance in ovarian endometrioma (OEM) and deep infiltrative endometriosis (DIE). The study enrolled 74 patients with endometriosis (Group 1), including 53 patients with OEM (Subgroup 1a); 21 patients with DIE without ovarian lesions (Subgroup 1b); and 27 patients without endometriosis (Group 2). The diagnosis was confirmed by laparoscopic surgery and histologic examination of resected tissues. Antibodies (M, G) to tropomyosin 3 (TPM), tropomodulin 3 (TMOD), α-enolase (ENO), estradiol (E2), progesterone (PG), and human chorionic gonadotropin (hCG) were identified in blood serum using modified ELISA. In endometriosis, antibodies to endometrial antigens, hormones, and ENO were detected more often than antiphospholipid and antinuclear antibodies. Higher levels of IgM to TPM, hCG, E2, and PG and IgG to TMOD, ENO, E2, and hCG were found in Subgroup 1a compared to Group 2. IgM to TPM, hCG, E2, PG, and IgG to E2 and ENO had a high diagnostic value for OEM (AUC > 0.7), with antibodies to TPM having the highest sensitivity and specificity (73.6% and 81.5%). In Subgroup 1b, only the levels of IgM to TPM and hCG were higher than in Group 2. These antibodies had a high diagnostic value for DIE. Thus, endometriosis is associated with autoantibodies to endometrial antigens, α-enolase, steroid, and gonadotropic hormones. A wider spectrum of antibodies is detected in OEM than in DIE. These antibodies have a high diagnostic value for OEM and DIE and potential pathogenetic significance for endometriosis and associated infertility.

The review presents a critical analysis of data on the role of immune factors in the pathogenesis of endometriosis. The research results accumulated by now convincingly demonstrate that an abnormal subclinical inflammatory response and disorders in the immune control system play a significant role in the onset, progression and persistence of endometriosis. In spite of the fact that many studies are concentrates on particular components of immune disorders in the pathogenesis of endometriosis, there is still no overall picture summarizing these data. Further research is needed to find immunological parameters that can be used as markers for clinical use in non-invasive diagnosis of this disease. The search for specific immune markers that could be used for target immunotherapy of endometriosis also remains relevant.

The solution of many clinical problems, including the issues of the origin of pain as a component of individual pathologies, lies in the plane of quantitative objectification of the underlying disease and elucidation of the role of pain syndrome (PS) in it. The analysis of literature data on methods of pain assessment, including quantitative scales and questionnaires, biochemical and instrumental studies, was carried out. Various PS correlates used in fundamental and applied research are considered. The neurophysiological mechanisms of pain formation and specific methods for assessing PS in endometriosis were studied.

Background. Ovarian cancer is the first fatal malignancy of the female reproductive system. Early detection is associated with better outcomes, but is significantly difficult because of asymptomatic or low-symptomatic course. Aim. To study the possibility of detecting of OC in early stages (IaIc) by the lipid profile of blood serum obtained using high-performance liquid chromatography with mass spectrometric (MS) detection. Materials and methods. An observational "case-control" study was conducted in period November 2019 July 2020 in the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. 41 patients were included: group 1 (main) 28 patients with histologically verified high grade serous ovarian cancer of IIV FIGO stage, group 2 (control) 13 conditionally healthy women. Venous blood samples were collected immediately before the operation. Extracts of serum lipids were obtained in accordance with the modified Folch method. The composition of the samples was analyzed by electrospray ionization MS. Using the method of discriminant analysis and orthogonal projections to latent structures (OPLS-DA) were building OPLS-models based on profile of significant lipids. The comparison based on the non-parametric MannWhitney test. Results. The presence of 128 lipids in blood serum samples makes a major contribution to the OPLS-models, that are different for patients with IIV OC stage and controls. The OPLS-model parameters are: R2=0.87 and Q2=0.80, the area under the ROC curve reached 1, sensitivity and specificity of the model 100%. The second OPLS-model was developed to assign patients to 13 blood serum samples of the control group or to 5 blood samples of patients with I-II stages of OC: 108 lipids made the main contribution to this model (R2=0.97, Q2=0.86). The third OPLS-model was constructed to distinguish patients with earlier (IaIa stages; n=5) and advanced (IIaIVa; n=23) stages: R2=0.96 and Q2=1.00, AUC=0.99. Diglycerides, triglycerides, phosphatidylcholines, ethanolamines, sphingomyelins, ceramides, phosphatidylserines, phosphoinositols and prostaglandins significantly differ in the blood serum samples of patients with IaIc stages of OC and patients with IIIV stages and controls, that indicates the diagnostic value. Conclusion. It is possible to distinguish a healthy person from patient with IaIc or IIIV stages of OC. Serum oncolipids profile obtained by high-performance liquid chromatography with MS detection can be used as markers of early stages of OC, that are associated with better prognosis.

A significant part of pregnant and lactating women have a lack of several micronutrients at once (vitamin D, group B, iodine, iron, etc.). The secretion of vitamins A, E, D, C, B1, B2, B6, B12, iodine and selenium into breast milk decreases with their insufficient consumption and insufficient provision of the nursing mother. The content of folates, calcium, magnesium, phosphorus in breast milk is maintained even if they are insufficient in the mother, however, enriching the diet with them during breastfeeding, improving the status of the mother, prevents the depletion of reserves in her body. The iron and zinc content in breast milk is determined by the mothers status during pregnancy. The intake of vitamin-mineral supplements or food products enriched with micronutrients during the pregravid period, during pregnancy and lactation leads to an improvement in the provision of a woman and her child by increasing the content of vitamins, iodine and selenium in breast milk. The use of vitamin-mineral supplements is an effective way not only to eliminate multiple micronutrient deficiencies in the diet and improve the status of a lactating woman, but also to optimize the vitamin composition of breast milk and the provision of an exclusively breastfed baby.

The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (p = 0.007, p = 0.009, p = 0.002, p = 0.008, respectively). At the same time, there was a noted increase in the CD10 protease expression by peritoneal macrophages (p = 0.044). Correlation analysis showed a positive correlation of ghrelin and GLP-1 levels with CD86 macrophage expression (p = 0.044, p = 0.022, respectively) in the study group; a positive correlation was also found between the levels of GLP-1, glucagon, and visfatin with CD26 macrophage expression (p = 0.041, p = 0.048, p = 0.015, respectively) in PF. No correlations were found in the control group. These results indicate that a decrease in the levels of ghrelin, GLP-1, glucagon, and visfatin in PF may contribute to endometriosis development through their impact on the expression of pro-inflammatory markers of PF macrophages.

The myocardium of children with tetralogy of Fallot (TF) undergoes hemodynamic overload and hypoxemia immediately after birth. Comparative analysis of changes in the ploidy and morphology of the right ventricular cardiomyocytes in children with TF in the first years of life demonstrated their significant increase compared with the control group. In children with TF, there was a predominantly diffuse distribution of Connexin43-containing gap junctions over the cardiomyocytes sarcolemma, which redistributed into the intercalated discs as cardiomyocytes differentiation increased. The number of Ki67-positive cardiomyocytes varied greatly and amounted to 7.0–1025.5/106 cardiomyocytes and also were decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity of cardiomyocytes in children with TF were demonstrated. The proportion of interstitial tissue did not differ significantly from the control group. The myocardium of children with TF under six months of age was most sensitive to hypoxemia, it was manifested by a delay in the intercalated discs and myofibril assembly and the appearance of ultrastructural signs of dystrophic changes in the cardiomyocytes. Thus, the acceleration of ontogenetic growth and differentiation of the cardiomyocytes, but not the reactivation of their proliferation, was an adaptation of the immature myocardium of children with TF to hemodynamic overload and hypoxemia.

Abstract A new cell type, interstitial Cajal-like cell (ICLC), was recently described in different organs. The name was recently changed to telocytes (TCs), and their typical thin, long processes have been named telopodes (Tp). TCs regulate the contractile activity of smooth muscle cells and play a role in regulating vessel contractions. Although the placenta is not an innervated organ, we believe that TCs are present in the placenta. We studied placenta samples from physiological pregnancies and in different variants of preeclampsia (PE). We examined these samples using light microscopy of semi-thin sections, transmission electron microscopy, and immunohistochemistry. Immunohistochemical examination was performed with primary antibodies to CD34, CD117, SMA, and vimentin, and TMEM16a (DOG-1), the latter was used for the diagnosis of gastrointestinal stromal tumours (GIST) consisting of TCs. We have identified a heterogenetic population of ТСs in term placentas, as these cell types differed in their localization, immunophenotype and ultrastructural characteristics. We assume TMEM16a could be used as the marker for identification of TCs. In PE we have revealed telocyte-like cells with ultrastructural signs of fibrocytes (significant process thickening and the granular endoplasmic reticulum content was increased) and a loss of TMEM16a immunohistochemical staining.

Endometriosis is characterized by the formation and development of endometrial tissues outside the uterus, based on an imbalance between proliferation and cell death, leading to the uncontrolled growth of ectopic foci. The potential target for the regulation of these processes is the endocannabinoid system, which was found to be involved in the migration, proliferation, and survival of tumor cells. In this paper, we investigated the effect of endocannabinoid-like compounds from the N-acyl dopamine (NADA) family on the viability of stromal cells from ectopic and eutopic endometrium of patients with ovarian endometriosis. N-arachidonoyldopamine, N-docosahexaenoyldopamine, and N-oleoyldopamine have been shown to have a five-times-more-selective cytotoxic effect on endometrioid stromal cells. To study the mechanisms of the toxic effect, inhibitory analysis, measurements of caspase-3/9 activity, reactive oxygen species, and the mitochondrial membrane potential were performed. It was found that NADA induced apoptosis via an intrinsic pathway through the CB1 receptor and downstream serine palmitoyltransferase, NO synthase activation, increased ROS production, and mitochondrial dysfunction. The higher selectivity of NADA for endometriotic stromal cells and the current lack of effective drug treatment can be considered positive factors for further research of these compounds as possible therapeutic agents against endometriosis.

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures. A comparative multiplex analysis of the secretomes revealed a significant increase in the secretion of pro-inflammatory mediators, including IL6, IFN-γ, and several chemokines associated with inflammation by the stromal cells of ectopic lesions. The results demonstrate that the stromal cells of endometrioid heterotopias display enhanced pro-inflammatory and immunosuppressive activities, which most likely impact the pathogenesis and progression of the disease.

Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.