The role of various matrix metalloproteinases (MMP)--such as gelatinases, stromelysins, matrilysin, collagenase-3, and membrane-bound MMP (MB-MMP)--in tumor invasion and metastasis is discussed. Data suggesting significance for malignant growth of the expression level of these enzymes and also of their activators and inhibitors are presented. It is concluded that at different stages of tumor progression the activity of different MMPs is displayed, which is regulated by various growth factors and oncogenes. Different malignancies are characterized by changes in activities of specific MMPs. Data are presented which show significance of the ratio between the MMP activity and that of tissue inhibitors of metalloproteinases (TIMP) in tumor invasion and metastasis, especially in connection with a dual role of TIMP as both MMP inhibitors and activators.
Polycystic ovarian syndrome (PCOS) is a fairly common disease that occupies one of the leading positions among the reasons of endocrine infertility. Women with this diagnosis have an increased risk of developing diabetes mellitus, cardiovascular disease, metabolic syndrome (dyslipidemia, decreased sensitivity to peripheral tissue insulin, hyperinsulinemia). Currently, a step-by-step and individual approach to treatment has been applied, including both conservative treatments and surgical ones.
INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the urgent problems of gynecological endocrinology. The main signs of PCOS include a violation of menstrual and/or ovulatory function and clinical and/or biochemical hyperandrogenism, as well as polycystic ovarian morphology according to the ultrasound results. PCOS leads to infertility, obesity, and cardiovascular system diseases. PCOS is an important symptom complex in the diagnosis, which directly affects the reproductive function of females, hence the percentage of fertility. This study aimed to analyze the features of clinical, laboratory, and instrumental parameters in females with a previously established PCOS diagnosis referred for surgical treatment. The obtained results were studied from the point of view of the clinical guidelines of the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology (2003), International PCOS Network (2018), and the Ministry of Health of the Russian Federation (2021). MATERIALS AND METHODS: The study included 121 females who were admitted to hospitals in Moscow for surgical treatment. Among the gynecological surgical hospitals, the following medical institutions were allocated: the city clinical hospital, the research center, and the commercial clinic we conditionally divided into three levels. The city clinical hospital had 54 females (1st group) aged 2137 years, the research center with 48 females (2nd group) aged 2242 years, and the commercial clinic with 19 females (3rd group) aged 2541. Before the ovarian surgery for PCOS, all patients underwent an additional examination, including the collection of anamnesis, particularly, features of menstrual and generative function, anthropometric indicators, body weight, and height study. Based on these parameters, the body mass index (BMI) was calculated, the clinical signs of hyperandrogenism (acne, excessive hair growth on the body and face, and the degree of hirsutism) were assessed, and the hormonal profile was determined to detect biochemical hyperandrogenism (free testosterone). Additionally, the level of glucose and insulin in the blood plasma was determined in all patients, and a pelvic ultrasound examination (ultrasound) was performed. RESULTS: Menstrual irregularities were revealed, of which complaints were presented by a total of 49.5% of patients. The results of the preliminary selection of patients with PCOS for surgical treatment revealed that 108 (89.2%) had primary and secondary infertility, of whom 64 (52.9%) had BMI within the normative values, 29 (23.9%) were overweight, and 25 (20.6%) were obese. Clinical manifestations of hyperandrogenism were present in 61 (50.4%) patients included in the study. The level of free testosterone above the normative values (2.85 pg/ml) was diagnosed only in 9 (7.4%) patients out of 121 who are included in the study. Additionally, this parameter was within the upper limit of the norm (average value of 2.780.36 pg/ml) in 112 females but was combined with clinical manifestations of hyperandrogenism. Black acanthosis was noted in 6 (5.0%) patients with free testosterone levels in 3.013.64 pg/ml. Increased blood glucose levels were combined with obesity in 3 (5.5%) patients of 1st group and 1 (2.1%) in 2nd group. Insulin levels significantly exceeded the upper limit of the norm in 6 (5.0%) patients. The ultrasound result in all patients (n=121) revealed the presence of echographic signs of PCOS in PCOS was confirmed by ultrasound in 54 females in 1st group, 48 females in 2nd group, and 19 females in 3rd group. CONCLUSION: Our results suggest an unreasonably broad interpretation of PCOS diagnosis. Therefore, PCOS diagnosis should be primarily remembered as a diagnosis-exception. Only repeated, extended, thorough, and comprehensive examination of patients with a presumed PCOS diagnosis will allow you to better navigate the individual characteristics of patients and offer adequate methods for correcting the symptom complex to improve the overall health, fertility, and quality of life.
BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common and to some extent mysterious diseases falling under the competence of gynecologists. PCOS occurs in 510% of women of reproductive age. This paper presented the long-term results of surgical treatment of patients with PCOS. AIM: This study aimed to determine the efficiency of surgical treatment of the ovaries to restore reproductive function in women with PCOS. MATERIALS AND METHODS: The initial diagnosis of PCOS was made at the outpatient examination. The study included 121 women of reproductive age diagnosed with PCOS when other factors of infertility and menstrual dysfunction were excluded. Patients with PCOS as an initial diagnosis for hospitalization and absence of tubal-peritoneal infertility and male infertility were included. All patients (n = 121) underwent surgical treatment and histological examination. Patients were referred for treatment to gynecological surgical hospitals. In particular, 54 (group 1), 48 (group 2), and 19 (group 3) women were treated in a municipal clinical hospital, research center, and commercial clinic, respectively. Statistical data analysis was performed with the STATISTICA Base software package using parametric and nonparametric methods. Arithmetic mean, standard deviations, medians, and percentiles of the indices were calculated. Confidence limits to the arithmetic mean were calculated based on Students distribution. The exact 95% confidence limits to frequencies and the reliability of differences in frequencies between the groups were determined using binomial distribution and the chi-square test, respectively. In addition, the MannWhitney (U) and Wilcoxon nonparametric tests were used because several indicators had significantly normal distributions. Differences were considered statistically significant at p 0.05. RESULTS: Of the total number of patients (n = 121), 108 (89%) became pregnant postoperatively, and 13 (11%) did not. Moreover, 47 (39%) of the total number of patients became pregnant for up to 1 year and 61 (50%) for over a year, and 48 (39.6%) of 108 patients became pregnant post-in vitro fertilization (IVF, 12 attempts in 37 (32%) and more than 3 attempts in 11, or 9% patients). PCOS was confirmed in 6 (14%) patients; of these, spontaneous pregnancy occurred in 5 (83%), including 4 patients in the first year and 1 in over a year. These patients had clinical and biochemical signs of hyperandrogenism and insulin resistance. PCOS-like conditions were diagnosed in 37 (86%) patients; of these, pregnancy occurred in 33 (89%), including spontaneous pregnancy in 10, or 27% (4 within 1 year and 6 over 1 year) patients. Post-IVF pregnancy was diagnosed in 23 (62%) patients (12 attempts in 20, or 54.1%, and more than 3 attempts in 3, or 8.1% women). CONCLUSIONS: Surgical treatment of patients with PCOS is an independent treatment of this gynecological and metabolically burdened disease. This method has both indications and contraindications, and it has specific types, which require certain patient preparations, such as weight loss, blood glucose control, hyperinsulinemia analysis, and compensation of arterial hypertension, to increase treatment efficiency.
INTRODUCTION: Polycystic ovarian syndrome (PCOS) is currently one of the most common diseases in women. Ovarian dysfunction (irregular menstrual cycle and anovulation), hyperandrogenism, and polycystic ovarian morphology are the most frequent manifestations of the syndrome. Its main macroscopic sign is bilateral enlargement of the ovaries with multiple cystic and atretic follicles. Moreover, an ovarian biopsy is usually performed in addition to clinical examination allowing for an accurate diagnosis and management. AIM: In this study, we sought to analyze the morphological verification of PCOS. MATERIALS AND METHODS: We analyzed 121 patients admitted to Moscow hospitals for surgical treatment diagnosed of PCOS by pathologists. Initially, PCOS was diagnosed at the outpatient examination. Thus, 121 women of reproductive age were included in the study after excluding tubal-peritoneal factors, male infertility factors, and menstrual dysfunction. Intraoperatively, all patients (n=121) were sampled for histological examination. The patients were referred to different gynecological hospitals: a municipal clinical hospital (group 1, n=54), a research center (group 2, n=48) and a commercial clinic (group 3, n=19). We processed data using parametric and non-parametric me thods in the STATISTICA Base software package. Arithmetic means, standard deviations, medians, and percentiles were equally determined. Confidence intervals for the arithmetic mean were determined using on the Student-t distribution. Moreover, we determined the 95% confidence intervals to the frequencies and the significance of differences in frequencies between the groups using binomial distribution and the Chi-square test, respectively. Some indicators exhibited significantly different distributions from the norm; therefore, non-parametric Mann-Whitney (p2) and Wilcoxon criteria were further applied. Differences were considered significant at p 0.05. RESULTS: Histological findings in 121 (100%) women of reproductive age with a clinical diagnosis of PCOS after surgical treatment were analyzed. After primary analysis, the clinical diagnosis was not confirmed in 78 (64%) patients, and histological findings of PCOS or PCOS that could not be excluded were obtained for only 43 (36%) women. Re-examination of histological samples from these 43 women let to the identifying of two groups of patients: group 1 with a typical histological pattern of PCOS (n=6, 14%) and group 2 with the so-called PCOS-like conditions (n=37, 86%). CONCLUSIONS: Significant differences were found between the morphological pattern of true PCOS and PCOS-like conditions. Thus, the final diagnosis should made clinically and through imaging, as well as through mandatory morphological examination of ovarian biopsy specimens after surgical treatment.
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