Introduction. In the structure of gynecological diseases, uterine myoma occupies one of the leading places and is accompanied by abnormal uterine bleeding, anemia, hemodynamic and hemostasiological disorders. Purpose. To optimize the management of the perioperative period in patients with uterine myoma and iron deficiency anemia (IDA) using methods of patient blood management (PBM). Materials and methods. The study group consisted of 94 patients with uterine myoma and IDA, who were examined and treated at the Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology. Of these, 74 patients made up the first, prospective group, who received IDA treatment with intravenous administration of ferric carboxymaltose during the perioperative period and during surgical treatment (laparoscopy / laparotomy and myomectomy), they underwent intraoperative autologous blood transfusion (IABT) using the cell salvage with Cell Saver 5+ apparatus. 20 women with myoma uterine and IDA constituted a comparison group (retrospective) who did not receive intravenous iron therapy in the perioperative period and did not undergo IABT. During surgical intervention (laparoscopy / laparotomy and myomectomy) or in the postoperative period, they received transfusion of donor erythrocyte-containing blood components according to indications. Results. All patients underwent surgical treatment in the amount of laparoscopy / laparotomy and myomectomy. During the operation, 74 patients of the main group underwent IABT in an average volume of 467.4 ± 327.8 ml. In the postoperative period, the patients of the main group continued to receive anemia therapy with intravenous administration of ferric carboxymaltose. And blood transfusions were not required in any patient of the main group. In patients of the second group, two (10 %) patients received donor erythrocyte suspension in an average volume of 358.2 ± 85.8 ml. Infectious and inflammatory complications: fever, inflammation of the postoperative suture, parametritis occurred in 6.8 % of women in the main group; in the comparison group – in 15 % of patients. Conclusions. Introduction into clinical practice of modern methods of blood management in patients with uterine myoma and IDA: the Infusion of intravenous high-dose ferric preparationsin the perioperative period, the use of Cell Saver devices for intra-operative autologous blood transfusion, helps to reduce the time of therapy, minimize transfusions of donor erythrocytes, reducing the frequency of infectious and inflammatory complications.

Миомэктомия нередко сопряжена с техническими сложностями, которые можно минимизировать путем медикаментозной предоперационной подготовки, направленной на уменьшение размеров миоматозных узлов, остановку связанных с наличием миомы обильных менструальных кровотечений, купирование анемического синдрома. ЦЕЛЬ ИССЛЕДОВАНИЯ Обосновать эффективность медикаментозной подготовки с применением препарата улипристала ацетат на основании результатов органосохраняющего хирургического лечения пациенток репродуктивного возраста с миомой матки, сопровождающейся обильными менструальными кровотечениями и анемией. МАТЕРИАЛ И МЕТОДЫ В исследование включены 75 пациенток репродуктивного возраста с лейомиомой, обильными менструальными кровотечениями и анемией. В 1-ю группу включены 40 женщин, которым проводилась предоперационная подготовка с применением препарата улипристала ацетат в течение 3 мес, а затем выполнена лапароскопическая миомэктомия. Во 2-ю группу включены 35 пациенток, которым хирургическое вмешательство проводилось без предоперационной подготовки. Выполнен проспективный сравнительный анализ клинико-лабораторных данных, интраоперационных и послеоперационных параметров, патоморфологических изменений в узлах и эндометрии. РЕЗУЛЬТАТЫ У всех пациенток 1-й группы на фоне терапии препаратом улипристала ацетат прекратились обильные менструальные кровотечения, размер миоматозных узлов сократился в среднем на 25% по данным эхографии (p<0,05), уровень гемоглобина и ферритина достиг нормальных значений (p<0,01). У пациенток 1-й группы отмечалось снижение длительности операции (p=0,043) и объема кровопотери (p=0,021) по сравнению с пациентками 2-й группы. В послеоперационном периоде у пациенток 1-й группы выявлен более высокий уровень гемоглобина (p=0,038), а также появилась тенденция к снижению длительности госпитализации. В отдаленном послеоперационном периоде большинство пациенток отметили улучшение общего состояния, отсутствие обильных менструаций, снижение болевого синдрома. Уровень гемоглобина через 6 мес после операции соответствовал норме практически у всех пациенток. В эндометрии пациенток 2-й группы после терапии выявлен лекарственный патоморфоз, оказавшийся доброкачественным и обратимым. ВЫВОДЫ Тактика ведения пациенток репродуктивного возраста с миомой матки, сопровождающейся обильными маточными кровотечениями и анемией, должна включать комплексную дооперационную диагностику, патогенетически обоснованную предоперационную подготовку, направленную на уменьшение размеров миоматозных узлов и коррекцию анемии, что создает благоприятные условия для проведения органосохраняющих операций.

Objective: To compare the effectiveness of two different treatment regimens of dydrogesterone in the management of endometriosis-related chronic pelvic pain. Design: Observational, prospective cohort study over six months. Setting: Twenty gynecology clinics in the Russian Federation. Patient(s): Three hundred fifty women from 18 to 45 years of age with endometriosis and chronic pelvic pain with or without dysmenorrhea. Intervention(s): Dydrogesterone 10 mg 2 or 3 times daily, either between the 5th and 25th days of the menstrual cycle (prolonged cyclical treatment regimen) or continuously (continuous treatment regimen). For all patients, the data cutoff was at six months of treatment. Main Outcome Measure(s): Intensity of chronic pelvic pain on the 11-point numerical rating scale (after 6 months). Result(s): A marked reduction in chronic pelvic pain was observed with both the prolonged cyclical and continuous treatment regimens (mean +/- standard deviation change from baseline -3.3 +/- 2.2 and -3.0 +/- 2.2, respectively), with no significant difference between the two groups. With both regimens, patients experienced significant improvements in the intensity of chronic pelvic pain, number of days in which analgesics were required, severity of dysmenorrhea, sexual well-being, and health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no serious adverse drug reactions were reported during the study. Conclusion(s): Prolonged cyclical and continuous treatment regimens of dydrogesterone therapy both demonstrated a pronounced and similar reduction in the severity of chronic pelvic pain and dysmenorrhea and led to marked improvements in all study parameters related to quality of life and sexual well-being. (C) 2021 by American Society for Reproductive Medicine.

The article is devoted to the extremely pressing issue of the treatment of endometriosis, which is the object of a thorough study by scientists around the world. There is no drug that is 100% effective against endometrioid heterotopias and has no pronounced side effects either in our country, or abroad. In addition, the quality of evidence base generated on the basis of randomized clinical trials on the effectiveness of drug therapy for endometriosis is not sufficient in terms of research methodology. The Russian clinical guidelines for the management of endometriosis postulate that operational intervention is the main stage in the treatment of this disease. The treatment of endometriosis is aimed to remove the endometriotic lesion, reduce pain intensity, treat infertility, prevent progression or recurrences of the disease. There is currently no universal drug therapy for endometriosis, and the drug therapy used to treat it is nonspecific and primarily aims to reduce the severity of existing symptoms. The drug therapy for endometriosis is chosen on case-by-case basis, depending on the extent of the disease, clinical symptoms and the patient’s needs. In addition to the above, the choice of hormone therapy for endometriosis should take into account the efficacy of a drug, its individual tolerance, the cost of treatment, the doctor’s experience in using this drug, the patient’s compliance with the doctor’s recommendations. The article presents possible algorithms for choosing strategies in the treatment of endometriosis using surgical and pharmaceu-tical methods. The authors discussed the principles and mechanisms of action of hormonal drugs intended for the treatment of endometriosis. The review and analysis of modern clinical data on the problem of treatment of endometriosis is presented.

Aim: To assess the efficacy and safety of ulipristal acetate (UA) use in uterine myoma patients before surgical treatment. Material and methods: 78 patients of reproductive age with uterine bleeding and anemia, who underwent laparoscopic myomectomy, were included in the study. Patients were divided into two groups: the first group consisted of 43 women who received 5 mg of ulipristal acetate daily for 3 months before the operation and the second group consisted of 35 patients without ulipristal treatment. A comparative analysis was made between clinical laboratory data groups, pathomorphological changes in myoma and endometrial nodes, and long-term treatment results. Results: As a result of UA therapy uterine bleeding stopped in all patients of the first group, the size of myoma nodes decreased by 25% according to visual diagnostics data, hemoglobin content normalized without iron-containing drugs. Duration of the operation and volume of intraoperative blood loss were less in the first group of patients in comparison with such parameters in the second group. Conclusion: Use of ulipristal acetate for preoperative assessment of patients with uterine myoma of reproductive age suffering from uterine bleeding and anemia is effective and safe.

Recent research revealed that tissue spray mass spectrometry enables rapid molecular profiling of biological tissues, which is of great importance for the search of disease biomarkers as well as for online surgery control. However, the payback for the high speed of analysis in tissue spray analysis is the generally lower chemical sensitivity compared with the traditional approach based on the offline chemical extraction and electrospray ionization mass spectrometry detection. In this study, high resolution mass spectrometry analysis of endometrium tissues of different localizations obtained using direct tissue spray mass spectrometry in positive ion mode is compared with the results of electrospray ionization analysis of lipid extracts. Identified features in both cases belong to three lipid classes: phosphatidylcholines, phosphoethanolamines, and sphingomyelins. Lipids coverage is validated by hydrophilic interaction liquid chromatography with mass spectrometry of lipid extracts. Multivariate analysis of data from both methods reveals satisfactory differentiation of eutopic and ectopic endometrium tissues. Overall, our results indicate that the chemical information provided by tissue spray ionization is sufficient to allow differentiation of endometrial tissues by localization with similar reliability but higher speed than in the traditional approach relying on offline extraction. Graphical Abstract ᅟ.

Study Objective To introduce a method for the rapid assessment of endometriotic tissues using direct mass spectrometry (MS)-based lipidomics. Design A prospective observational cohort study (Canadian Task Force classification II2). Setting Department of Operative Gynecology of the Research Centre for Obstetrics, Gynecology and Perinatology. Patients Fifty patients with ovarian cysts and peritoneal endometriosis who underwent laparoscopic surgery between 2014 and 2016. Intervention Differences in mass spectrometric profiles of ectopic endometria (endometriosis) and eutopic endometria were analyzed for each patient in combination with morphohistologic evaluation. The lipidomic approach was applied using a direct high-resolution MS method. Measurements and Main Results Of 148 metabolites, 15 showed significant differences between endometriotic tissue and a healthy endometrium of the same patient, considered as a control in this study. The main lipids prevalent in endometriotic tissues were phosphoethanolamine (PE O-20:0), sphingomyelin (SM 34:1), diglycerides (DG 44:9), phosphatidylcholines (PC 32:1, PC O-36:3, PC 38:7, PC 38:6, PC 40:8, PC 40:7, PC 40:6, PC 40:9, and PC O-42:1), and triglycerides (TG 41:2, TG 49:4, and TG 52:3). Using partial least squares discriminant analysis models, MS showed that the lipidomic profile of endometriotic tissue (peritoneal endometriosis and ovarian endometriomas) was clearly separated from the eutopic endometrium, indicating tissue-type differentiation. Conclusion Our results suggest that direct MS may play an important role for endometriotic tissue identification. Such an approach has potential usefulness for real-time tissue determination and differentiation during surgical treatment. Lipids of 3 important classes, sphingolipids, phospholipids, and the fatty acids (di- and triglycerides), were identified. Validation is required to determine whether these lipids can be used to discriminate between patients with endometriosis and those with other gynecologic diseases.

Objectives of the study: improve early non-invasive diagnosis of external genital endometriosis (EGE) using the mass spectrometry method, and determine the risk factors for recurrence of EGE after surgical treatment. Material and methods: a prospective cohort study included 100 patients with EGE who underwent surgical treatment during the 2014 to 2016 period. The EGE diagnosis was made on the basis of diagnostic and therapeutic laparoscopic findings and finally confirmed at histological exam. All patients underwent blood sampling before and after surgical treatment to detect recurrence of endometriosis using direct mass spectrometry method. Results: recurrences of EGE were diagnosed in 22% of patients at 18–36 months postoperatively. High incidence of recurrent EGE was reported in the group of patients who did not receive post-surgical hormonal therapy. The hormone therapy with dienogest 2 mg for 6-9 months, as well as with goserelin 3.6 mg for 3-6 months showed the greatest efficacy for the prevention of recurrent EGE. Significant predictive factors of recurrence after surgical treatment for EGE include intensive acyclic pelvic pain; presence of surgical interventions for the history of EGE; infertility; stimulation of ovulation with hormonal drugs as part of the Assisted Reproductive Technologies Program; degree 3-4 disease spread; pronounced adhesions of the small pelvis; infiltrative forms of endometriosis; endometrioid cysts of large size; bilateral ovarian lesions. The plasma lipid profile including determination of phosphatidylcholines, phosphoethanolamines, diglyceride and sphingomyelin in the patients with endometriosis provides an approach for noninvasive early diagnosis of recurrence of this disease by mass spectrometry (sensitivity 93%, specificity 95%). Conclusion: This study developed an individual comprehensive approach to the prevention of recurrent EGE, including surgical treatment, hormonal therapy and diagnosis of the disease at an early stage of development. Timely administration of a-GnRH or dienogest 2 mg at the post-surgery stage is associated with a minimal or total absence of recurrent EGE. The administration of COCs showed no efficacy in preventing the recurrence of EGE, and therefore COCs cannot be recommended as a prophylactic drug, but exclusively for contraceptive use.

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare premalignant cervical lesion that combines the structural features of cervical intraepithelial neoplasia (CIN) and endocervical adenocarcinoma in situ (AIS).AIM:to analyze archival materials for the detection of SMILE and its subsequent morphological and immunohistochemical characterization.MATERIAL AND METHODS:Cervical cone specimens from 53 women with histologically verified CIN3 were examined. The diagnosis of SMILE was based on the positive mucicarmine staining and weak focal expression of p63. The samples containing SMILE were further immunohistochemically examined using the biomarkers P16, Ki-67, Oct4, CD117, CD34, p53, EMA, and CK15. SMILE was detected in 2 of the 53 patients and concurrent with CIN3 in both cases. SMILE was characterized by the stratified arrangement of atypical cells containing mucin, the positive mucicarmine staining of the entire layer of the atypical epithelium, weak focal p63 expression, high Ki-67 expression, and diffuse р16Іnk4а staining. Both SMILE samples showed weak diffuse p53 expression in the presence of single cells with the pronounced nuclear staining pattern for p53 in one female patient. Weak focal CK15 expression was visualized in SMILE. The expression of the stem cell markers Oct4 and CD117 and the angiogenic marker CD34 was absent in the examined cervical epithelial preparations. The diffuse and intense expression of the marker EMA, which was not different from that in the endocervical and stratified squamous epithelium, and CIN3 was established in SMILE.RESULTS:The findings suggest that SMILE is morphologically and immunohistochemically similar to CIN3. In this investigation, these abnormalities differed only in the mucicarmine staining and expression of p63. This may be indicative of the underdiagnosis of SMILE, attendant СIN3 in the routine practice of a clinical pathologist, as the diagnosis of CIN3 is primarily based on the results of assessment of only the preparations stained with hematoxylin and eosin; the expression of p16 and Ki-67 is evaluated in some cases, which fails to differentiate SMILE and CIN3 in a number of preparations.CONCLUSION:The diagnosis of SMILE can be made only by immunohistochemical examination.

Objective: assessment of the feasibility and safety of the use of ulipristal acetate on the basis of the clinical and morphological study.Materials and methods: the study involved 78 women with leiomyoma, abundant menstruation and anemia. Group I – 43 patients who underwent ulipristal acetate therapy for three months and then laparoscopic myomectomy. Group II – 35 patients who were myomectomyed without presurgical preparation. A comparative analysis was made of the clinic-laboratory data, operational parameters, pathomorphological changes in the nodes and endometrium. According to the original clinical laboratory study groups I and II were almost homogeneous.Results: in the case of ulipristal acetate therapy in all group I patients uterine bleeding ceased, the size of the myomatous nodules decreased by an average of 25 per cent according to the ultrasound and the MRI (p < 0.05), the haemoglobin and the ferritin levels reached normal values (p < 0.01). In group I there was a decline in the duration of the operation and blood loss compared to group II. Some leiomyoma reduction mechanisms have been identified. In endometrium of group I patients drug pathomorphosis after therapy was diagnosed. However, the immunohistochemical study made it possible to establish that these changes were benign and reversible.Conclusions: presurgical treatment by ulipristal acetate of reproductive age patients with myomas, uterine bleeding and anaemia is appropriate, safe and pathogenetically justified. The possibility to use repeated courses of the drug, which may eventually postpone or cancel the need for surgical treatment is promising.

Objective: assessment of the feasibility and safety of the use of ulipristal acetate on the basis of the clinical and morphological study. Materials and methods : the study involved 78 women with leiomyoma, abundant menstruation and anemia. Group I – 43 patients who underwent ulipristal acetate therapy for three months and then laparoscopic myomectomy. Group II – 35 patients who were myomectomyed without presurgical preparation. A comparative analysis was made of the clinic-laboratory data, operational parameters, pathomorphological changes in the nodes and endometrium. According to the original clinical laboratory study groups I and II were almost homogeneous. Results : in the case of ulipristal acetate therapy in all group I patients uterine bleeding ceased, the size of the myomatous nodules decreased by an average of 25 per cent according to the ultrasound and the MRI (p < 0.05), the haemoglobin and the ferritin levels reached normal values (p < 0.01). In group I there was a decline in the duration of the operation and blood loss compared to group II. Some leiomyoma reduction mechanisms have been identified. In endometrium of group I patients drug pathomorphosis after therapy was diagnosed. However, the immunohistochemical study made it possible to establish that these changes were benign and reversible. Conclusions : presurgical treatment by ulipristal acetate of reproductive age patients with myomas, uterine bleeding and anaemia is appropriate, safe and pathogenetically justified. The possibility to use repeated courses of the drug, which may eventually postpone or cancel the need for surgical treatment is promising.

Obtaining fast screening information on molecular composition of a tissue sample is of great importance for a disease biomarkers search and for online surgery control. In this study, high resolution mass spectrometry analysis of eutopic and ectopic endometrium tissues (90 samples) is done using direct tissue spray mass spectrometry in both positive and negative ion modes. The most abundant peaks in the both ion modes are those corresponding to lipids. Species of three lipid classes are observed, phosphatidylcholines (PC), sphingomyelins (SM) and phosphoethanolamines (PE). Direct tissue analysis gives mainly information on PC and SM lipids (29 species) in positive ion mode and PC, SM and PE lipids (50 species) in negative ion mode which gives complementary data for endometriosis foci differentiation. The biggest differences were found for phospholipids with polyunsaturated acyls and alkils. Although, tissue spray shows itself as appropriate tool for tissue investigation, caution should be paid to the interpretation of mass spectra because of their higher complexity with more possible adducts formation and multiple interferences must be taken into account. The present work extends the application of direct tissue analysis for the rapid differentiation between endometriotic tissues of different foci.

Цель исследования — создание методики неинвазивной экспресс-диагностики наружного генитального эндометриоза, основанной на анализе молекулярного состава эндометриоидных тканей методами масс-спектрометрии и иммуногистохимии. Материал и методы. Исследование проводилось на операционном материале, полученном от 20 пациенток с установленным во время лапароскопической операции и подтвержденным гистологическим диагнозом наружного генитального эндометриоза. Анализу подвергались перитонеальные очаги эндометриоза, капсулы эндометриоидных кист с прилежащими интактными тканями и соскоб эндометрия. Образцы тканей делились на две части: основная часть тканей отправлялась для морфологического исследования, остальная (меньшая часть) — для масс-спектрометрического анализа. Иммуногистохимическое исследование проводили на парафиновых срезах по стандартному протоколу с использованием мышиных моноклональных антител к нейрофиламентам и Ki-67. Масс-спектрометрический анализ тканей проводили методом электрораспылительной ионизации. Результаты. При расчете коэффициента корреляции нейрофиламентов и Ki-67 с уровнем липидных пиков наиболее значимыми оказались спектры следующих липидов: PC 38:6, PC 40:6, TG 49:4, DG 44:9, PE O-20:0, SM 34:1, экспрессия которых увеличилась пропорционально в перитонеальных очагах и капсулах эндометриоидных кист и не показала значимости в эутопическом эндометрии. При этом, чем выше содержание нейрофиламентов и Ki-67 в эндометриоидных тканях, тем выше оказались пики вышеперечисленных липидов. Выводы. Дальнейшая верификация вышеперечисленных липидов в качестве серологических биомаркеров может привести к созданию неинвазивной диагностики для пациентов с подозрением на наружный генитальный эндометриоз, оценить предикторы возникновения рецидива заболевания, повысить безопасность и эффективность хирургического вмешательства, а также уменьшить потребность в диагностической лапароскопии.