COMPARATIVE EFFECTIVENESS OF TWO SCHEDULES OF GYNESTRIL ADMINISTRATION IN TREATMENT OF UTERINE FIBROIDS

Modern options of uterine fibroids pharmacotherapy allow for individual selection of therapy. Aim. To compare the effectiveness of uterine fibroids treatment with administration of mifepristone (Gynestril) on the basis of a differentiated approach to the assignment of two treatment schedules in various dosages: 25 mg or 50 mg per day for three months.Materials and methods. A prospective comparative study was conducted at the clinical bases of Department of Obstetrics and Gynecology with the Course of Perinatology of the Peoples’ Friendship University of Russia (Moscow) and the Department of Obstetrics, Gynecology and Perinatology of the Kuban State Medical University (Krasnodar). 160 women with uterine myoma were enrolled in the clinical groups. Randomization was carried out by a double-blind method using envelopes.Results. Administration of mifepristone (Gynestril) at a dosage of 50 mg per day for 12 weeks and 25 mg per day for 24 weeks has comparable efficacy.Conclusion. Due to the assessment of subjective and objective criteria of drug tolerance, an individual dose selection of mifepristone is possible without compromising the achievement of the therapeutic effect

A clinical and immunological rationale for ultrasonic cavitation use in the complex treatment of infertility in chronic endometritis

Aim.To prove the safety and efficacy of using the ultrasonic cavitation of saline to restore the endometrial receptivity, local immune balance, and antioxidant status in females with chronic endometritis (CE) and a history of reproductive losses. Materials and methods. Fifty females aged 29.957.65 years (range 2338 years) with histologically and immunohistochemically confirmed CE were examined. The control group included 45 female patients aged 28.989.9 years (range 2338 years) with infertility of tubal-peritoneal genesis without histochemical studies confirming CE and with no history of reproductive losses. Transvaginal pelvic ultrasound was used in the study. All the patients had histological, immunohistochemical examination of endometrial scrapings, including quantification of CD138+, CD20+, CD56+, progesterone receptors (PR), and estrogen receptors (ER) in the stroma and glands. The following cytokines were measured in protein-free fractions of uterine cavity contents by ELISA: interleukin (IL)-2, IL-10, IL-8, tumor necrosis factor-, IL-1, interferon-, interferon-. The activity of lipoperoxidation factors and antioxidant system enzymes (catalase, superoxide dismutase, glutathione peroxidase) was detected by spectrophotometry. As a part of the treatment, irrigation of the uterine cavity with sonicated 0.9% sodium chloride solution was applied twice in 6 sessions consecutively within three months. Results. According to transvaginal pelvic ultrasound, the endometrial thickness before treatment was 6.541.2 mm. An increase in endometrial thickness up to 9.02 (7.6210.42) mm in the luteal phase of the next cycle and up to 9.34 (8.1210.56) mm in the two subsequent luteal phases was observed within three months after irrigation of the uterine cavity with sonicated normal saline. The normalization of the ЕR/PR ratio and decrease in CD138+, CD20+, and CD56+ cells in the endometrial stroma and glands were noted. Mature pinopods were revealed in 71.25 (67.2974.46)% of patients, which is 2.95 times more than the respect value before the treatment, 24.55 (21.4327.75)%. After treatment, a recovery of cytokine production was noted: IL-2, IL-10, tumor necrosis factor-, IL-8, IL-1, interferon-, interferon-; concentration of primary, secondary and tertiary products of lipoperoxidation decreased; superoxide dismutase enzyme activity increased by 36.98 (32.8841.18)%, catalase by 15.32 (14.1316.51)%, glutathione peroxidase by 12.32 (11.1214.2)%; р0,005. Reduced colonization rate of Streptococcus spp, Enterococcus faecalis, Escherichia coli, elimination of Mycoplasma genitalium, Ureaplasma urealyticum, and increased of Lactobacillus spp. were reported. Conclusion. Using the cavitated normal saline restores the endometrium structure, normalizes the ЕR/PR ratio, reduces the colonization by opportunistic and pathogenic microorganisms in the uterine cavity and normalizes the cytokine balance and the content of pro-oxidative and anti-oxidative factors. High clinical and immunological efficacy supports cavitated solutions in the complex treatment of infertility in females with CE

Патогенез опущения влагалища с формированием ректоцеле

To carry out a systematic analysis of the data available in the modern literature on the pathogenesis of the formation of vaginal prolapse with the formation of rectocele rectum. The failure of the pelvic floor, namely its posterior compartment with the formation of a rectocele against the background of the lowering of the posterior vaginal wall, continues to be one of the most common gynecological diseases. This article presents an analysis of current literature data on the pathogenesis of pelvic organ prolapse with the formation of rectocele. Analyzing the above-mentioned data, it can be noted that the research data of recent years have significantly expanded the understanding of the etiology and pathogenesis of pelvic organ prolapse in its posterior compartment. However, the issues of etiology and pathogenesis of genital prolapse in patients of reproductive age, the role of individual risk factors and their combinations, pathogenetic mechanisms of development are still far from being resolved. Unfortunately, none of the above theories fully explains all the reasons for the formation of pelvic organ prolapse in its posterior compartment.Проведен систематический анализ данных, имеющихся в современной литературе, относительно патогенеза формирования опущения влагалища с формиро- ванием ректоцеле. Несостоятельность тазового дна, а именно заднего компартмента с формированием ректоцеле на фоне опущения задней стенки влагалища, продолжает оставаться одним из наиболее распространенных гинекологических заболеваний. В статье представлен анализ современных данных литературы о патогенезе пролапса тазовых органов (ПТО) с формированием ректоцеле. Исследования последних лет заметно расширили представления об этиологии и пато- генезе ПТО в его заднем компартменте. Однако вопросы этиологии и патогенеза генитального пролапса у пациенток репродуктивного возраста, роли отдельных факторов риска и их сочетаний, патогенетические механизмы развития все еще далеки от окончательного решения. К сожалению, ни одна из существующих теорий полностью не объясняет все причины формирования ПТО в его заднем компартменте

Efficacy of laser remodeling in the genitourinary syndrome of menopause: A review

The real-world treatment of genitourinary syndrome of menopause has several limitations: contraindications to topical estrogen therapy, which is currently recognized as the "gold standard" treatment for vulvovaginal atrophy (VVA), fear of the systemic effects of topical estrogens or/and carcinophobia, and poor compliance of patients to intravaginal agents. Therefore, there is an unmet need for alternative noninvasive or minimally invasive therapies, mostly non-hormonal. A PubMed, Cochrane Library, Science Direct, and ELibrary databases were searched for the keywords CO2-laser, Er:YAG-laser, vulvovaginal atrophy, genitourinary syndrome of menopause, treatment, postmenopausal age for 20122022. Remodeling microablative laser therapy using carbon dioxide (CO2) is a promising method for treating VVA, acting pathogenetically and symptomatically. CO2 laser relieves VVA symptoms and improves the condition of the vaginal mucosa by enhancing regeneration and restoring vaginal pH. However, evidence of the efficacy and long-term safety of the method, obtained in high-quality studies, is needed before the method can be introduced into widespread clinical practice. Aim. To analyze and summarize the evidence-based and experimental data on the efficacy and safety of laser therapy for VVA and genitourinary syndrome of menopause

Vulvovaginal atrophy in the peri- and post-menopause: relevance and impact on quality of life

Vulvovaginal atrophy (VVA) is detected in more than 50% of postmenopausal women, and at 4049 years of age, 15-19% of women have relevant signs. Atrophic changes in the female urogenital system are associated with hypoestrogenism, which results in the defective synthesis of collagen and elastin due to reduced functional activity of fibroblasts. Although the symptoms of genitourinary syndrome of menopause significantly impair the quality of life, women rarely seek medical help for urogenital symptoms, considering them a normal condition for the period of aging. We searched Cochrane Library, PubMed, Science Direct, and ELibrary databases for the keywords vulvovaginal atrophy, genitourinary syndrome of menopause, quality of life, epidemiology, and postmenopausal age for 20122022. The literature review suggests that the prevalence of VVA is extremely high but underestimated due to the infrequent seeking of medical care by female patients with relevant symptoms. The genitourinary syndrome of menopause dramatically impacts patients' quality of life, but not all women eligible for treatment receive it. One of the reasons for refusing hormonal treatment is patients' fear of the systemic effects of hormonal drugs. There is an unmet need for alternative non-hormonal therapies. The objective is to analyze and systematize the scientific data accumulated over the past ten years on the epidemiology of VVA, its impact on patients' quality of life, and the challenges in diagnosing and treating the disease

The Immune Profile of the Endometrium in the "Uterine Factor" of Infertility

Background: This study aimed to investigate the endometrial characteristics (pathomorphological and immunological) of women with infertility. Methods and Results: Data from an immunohistochemical study of endometrial biopsies (TNF-α, IL-10, GM-CSF, CXCL16, BCA1, TGF-β1) collected during the “implantation window” and microbiota studied by real-time polymerase chain reaction in 171 patients (21 women with unexplained infertility, 36 - chronic endometritis, 74 - tubal-peritoneal infertility, 22 - external genital endometriosis, 8 - "thin" endometrium, and 10 healthy fertile women from the comparison group) were analyzed to identify molecular signatures. Chronic endometritis was verified morphologically and immunohistochemically. Each group revealed different immune endometrial phenotypes. The basis of the "normal" phenotype was a controlled immune inflammation and a Lactobacillus-dominant microbiota (LDM) type. In contrast to the comparison group, in the group with the phenotype of chronic inflammation, an excessive immune response (overexpression of TNF-α, GM-CSF, CXCL16, BCA1, and a decrease in IL-10 and TGF-β1 in glandular epithelium and stroma) was determined on the background of non-Lactobacillus-dominated microbiota (NLDM) type (63.3%) (P<0.001). The peculiar feature of a dysplastic phenotype was a "poor" immune response, with maximal TGF-β1 overexpression (P<0.001) and a NLDM type (47.1%). We determined an excessive immune response in the proliferative endometrial phenotype (GM-CSF overexpression by 1.2 times in the glandular epithelium and stroma [P<0.001 in both cases] and a decrease in IL-10 by 1.6 times in the glandular epithelium and 1.2 times in the stroma [P<0.001 in both cases]). Uterine microbiome disorders were detected less frequently than in patients with the inflammation phenotype (31.6%) (P=0.01). In the phenotype with impaired immune status, there was a decrease in GM-CSF, BCA1, CXCL16, TNF-α, and IL-10 markers in both endometrial compartments (P<0.001) with a LDM type (81.2%). Conclusion. The molecular signatures of the endometrium are due to the heterogeneity of immune factors and microbiota. Aberrant expression of immune factors may contribute to the formation of a microenvironment unfavorable for blastocyst implantation

Metabesity: pathogenetic bases and predictive capabilities. A review

One of the most pressing problems of our time is obesity, recognized by the WHO as a pandemic of the XXI century. It is important to remember that obesity is a full-fledged nosological entity, but many women think that obesity is just a problem of beauty and aesthetics. It is important to note that this nosology has a number of serious consequences, starting with the development of cardiovascular disease and ending with cancer. However, the “problem in the problem” is the so-called “metabesity” – a new term that reflects a number of diseases, the pathogenesis of which is based on the metabolic syndrome. Obesity, metabolic syndrome and metabesity seem to be different concepts, but the absolute identity of the pathogenetic basis characterizes them as successive stages of one global process. In this regard, it is necessary to highlight the key mechanisms of the development of the described disorders and to consider the concept of clinical management of patients in this cohort

Pathogenetic Mechanisms of Pelvic Prolapse

Пролапс тазовых органов (ПТО) – периферическое смещение матки и/или стенок влагалища в результате растяжения фасциальных структур малого таза. Цель исследования: проанализировать патогенетические механизмы лежащих в основе ПТО. Для формирования обзора предпринят анализ баз данных PubMed, EMBASE, MedLine, Cochrane и отобраны международные обзоры авторов с наиболее крупными морфологическими и молекулярными исследованиями в этой области. Ключевую роль в формировании ПТО, помимо таких признанных факторов как беременность и роды, травма промежности, длительное повышение внутрибрюшного давления и возраст, играют биохимические особенности состава соединительной ткани, количество и качество в ней коллагена различных типов, эластина, и их соотношение, а так же действие на ее структуры различных биологически активных веществ, (MMP-2, TIMP-2 и TGF-β1) что, по мнению многочисленных исследователей, регулируется генетически, а так же способность клеток соединительной ткани, в частности фибробластов, переносить окислительный стресс.Pelvic organ prolapse (POP) is a peripheral displacement of the uterus and/or vaginal walls as a result of stretching of the fascial structures of the pelvis. The purpose of the study: to analyze the pathogenetic mechanisms underlying POP. An analysis of the PubMed, EMBASE, MedLine, Cochrane databases and selected international reviews of authors with the largest randomized controlled trials in that area is made with the aim of forming the review. A key role in the formation of POP, in addition to such recognized factors as pregnancy and childbirth, perineal trauma, increased intra-abdominal pressure and age, is played by the biochemical features of the composition of connective tissue, the amount of collagen of various types, elastin, and their ratio, as well as their effect on the structure of various biologically active substances (MMP-2, TIMP-2 and TGF-β1), which, according to numerous researchers, is regulated genetically, as well as the ability of connective tissue cells, in particular fibroblasts, to undergo oxidative stress

Mystery Solved: The Identification of the Two Missing Romanov Children Using DNA Analysis

One of the greatest mysteries for most of the twentieth century was the fate of the Romanov family, the last Russian monarchy. Following the abdication of Tsar Nicholas II, he and his wife, Alexandra, and their five children were eventually exiled to the city of Yekaterinburg. The family, along with four loyal members of their staff, was held captive by members of the Ural Soviet. According to historical reports, in the early morning hours of July 17, 1918 the entire family along with four loyal members of their staff was executed by a firing squad. After a failed attempt to dispose of the remains in an abandoned mine shaft, the bodies were transported to an open field only a few kilometers from the mine shaft. Nine members of the group were buried in one mass grave while two of the children were buried in a separate grave. With the official discovery of the larger mass grave in 1991, and subsequent DNA testing to confirm the identities of the Tsar, the Tsarina, and three of their daughters – doubt persisted that these remains were in fact those of the Romanov family. In the summer of 2007, a group of amateur archeologists discovered a collection of remains from the second grave approximately 70 meters from the larger grave. We report forensic DNA testing on the remains discovered in 2007 using mitochondrial DNA (mtDNA), autosomal STR, and Y- STR testing. Combined with additional DNA testing of material from the 1991 grave, we have virtually irrefutable evidence that the two individuals recovered from the 2007 grave are the two missing children of the Romanov family: the Tsarevich Alexei and one of his sisters

CHRONIC ENDOMETRITIS: CURRENT ASPECTS

Aim. To broaden the understanding of chronic endometritis (CE) pathogenesis on the basis of the reception study of steroid hormones and markers of cell proliferation/apoptosis in its different types depending on the nature of microbial colonization of the uterine mucosa.Materials and methods. A group of 345 patients with early reproductive losses (non-developing pregnancy, spontaneous abortion, artificial abortion, in vitro fertilization (IVF) failure for up to 6 months after intrauterine intervention) who had histologically revealed chronic endometritis was prospectively examined. The following studies were performed: microbiological (PCR diagnostics, bacteriological examination of the cervical canal, mucous uterus); instrumental (hysteroscopy). Vacuum suction biopsy of the endometrium was performed on the 7th-9th days of the menstrual cycle (m.c.) during hysteroscopy and on the 22nd-24th days of the m.c. with the purpose of clarifying the condition of the mucosa, including pathomorphological examination. CE verification was carried out with macrotypes identification (hysteroscopic evaluation of mucosal thickness, in the dynamics of the cycle, and its color – the presence of hyperemia or pallor, focal or diffuse hyperemia, micropolyps, vascular responses): hyper-, hypoplastic and mixed. Immunohistochemical study of the endometrium included evaluation of the expression of estrogens and progesterone receptors (Dako, Denmark), marker of mucosal proliferation (Ki-67) and apoptosis (CPP32).Results. Inflamed mucous uterus remodelling is realized in pathomorphosis and homoeokinesis characteristics of each macro-type caused by the variability of the balance of the processes of cell proliferation and apoptosis. The morphological basis of the hyperplastic macrotype is dystrophic-atrophic changes of the endometrium, mixed type reveals alternation of sites of dystrophy and fibrosis, hyperplastic – induction of micro-polypoid growths on the background of a lymphocytic infiltration of the mucosa. The rate of uterine mucosa cellular renewal in CE cases is detected by the activity of persistent infections in the endometrium: with endometrial dystrophy – the diagnostic titers of opportunistic strains (Escherichia coli, enterococcus, anaerobes, bacteroides), with mucosal mosaicism – mycoplasmas and their associations with HSV2 and opportunistic strains, with hyperplastic macrotypes – chlamydia, HSV2 and their combinations.Conclusion. The study of signalling chain markers of control over proliferative cascades at the endometrial level in comparison with the response to the introduction of a pathogenic infection and morphological transformations promotes the expansion of the concept of pathogenetic CE variants, and therefore, the choice of differentiated therapy for the purpose of restoring the fertile potential after reproductive losses