Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

PURPOSE: To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. METHODS: This retrospective cohort study included women aged 18 years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. RESULTS: A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2 months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. CONCLUSION: In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

Brazilian Portuguese Translation and Validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA revised.

INTRODUCTION AND HYPOTHESIS: Condition-specific sexual questionnaires are important patient-reported outcome measures. The aim of this study was to translate and validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association Revised (PISQ-IR) into Brazilian Portuguese and to clinically validate it in a Brazilian Portuguese-speaking population. METHODS: Translation and validation of the PISQ-IR was performed according to the International Urogynecological Association-recommended process and guidelines. For external validity, PISQ-IR subscales were compared with the clinical measures, Pelvic Organ Prolapse Quantification system (POP-Q) stage, pelvic floor muscle tone, and Oxford Grading Scale (Pearson correlations). Descriptive statistics, internal consistency (Cronbach's alpha coefficient), and test-retest reliability (interclass correlation coefficient) were calculated for all PISQ-IR subscales. RESULTS: A total of 120 sexually active and 106 not sexually active women were enrolled in the study between March 2015 and July 2019. Internal consistency was acceptable, with Cronbach's alpha values 0.60-0.80, except for the sexual arousal and orgasm, sexual arousal and partner-related issues, sexual arousal and condition-specific issues, global rating of sexual quality and condition impact subscales. PISQ-IR demonstrated good reliability (α > 0.6, CIC = 0.996). The agreement for each individual questionnaire item also individually presented substantial agreement between the assessments (κ 0.61-0.8). There was a correlation between PISQ-IR and POP, mixed, stress and fecal incontinence diagnosis and a positive correlation with pelvic floor muscle function according to the Oxford Scale in sexually active women. For sexually inactive women there was a correlation between PISQ-IR and mixed urinary symptoms. CONCLUSIONS: The Brazilian Portuguese version of PISQ-IR is a reliable and valid tool that can be easily used for the identification and assessment of sexual function in Brazilian Portuguese-speaking women with pelvic floor disorders.

Analysis of two reperfusion techniques in uterine transplantation in an experimental model.

INTRODUCTION: Uterine transplantation was developed for the treatment of absolute uterine factor infertility. As it is a new modality of transplantation, there is still room for technical improvement. A factor that impacts graft survival in organ transplantation is the warm ischemia time. In uterine transplantation specifically, at least two vascular anastomoses are performed on each side of the uterus, and the graft revascularization takes place when the vascular clamps of the arteries and veins are released on both sides simultaneously. For this reason, the warm ischemia time in uterine transplant is expected to be considerably long. The purpose of this study was to compare the sequential technique of uterine graft revascularization, which aims to reduce the warm ischemia time of the procedure, with the simultaneous revascularization technique. MATERIAL AND METHODS: For the procedure, the uterine auto-transplantation technique was performed using 10 non-pregnant adult ewes weighing about 45 kg, divided into two groups: simultaneous revascularization group (5 animals) and sequential revascularization group (5 animals). To evaluate the groups, we analyzed the procedure and warm ischemia times, graft macroscopy, hemodynamic, laboratory, and histological parameters of the uterus. RESULTS: The sequential revascularization technique group had similar surgical procedure times, and the warm ischemia time was significantly shorter with medians of 32 min in the sequential group versus 72 min in the simultaneous group (p < 0.008). The graft macroscopy and hemodynamic, laboratory, and histological parameters evaluated were similar between the groups. CONCLUSIONS: The sequential revascularization technique proved to reduce the warm ischemia time in the sheep uterine auto-transplantation model without compromising graft viability.

Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles.

OBJECTIVE: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested. DESIGN: Prospective pilot study. SETTING: Perola Byington Hospital Reference for Women's Health. SUBJECTS: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study. INTERVENTION: Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval. MAIN OUTCOME MEASURES: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration. RESULTS: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed. CONCLUSION: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. OBJECTIVE: To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. METHOD: From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. RESULT: Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). CONCLUSION: Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Skin-sparing mastectomy for the treatment of breast cancer.

BACKGROUND: Skin-sparing mastectomy (SSM) is a surgical technique that aims to maximize skin preservation, facilitate breast reconstruction, and improve cosmetic outcomes. Despite its use in clinical practice, the benefits and harms related to SSM are not well established. OBJECTIVES: To assess the effectiveness and safety of skin-sparing mastectomy for the treatment of breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 9 August 2019. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-randomized or non-randomized studies (cohort and case-control) comparing SSM to conventional mastectomy for treating ductal carcinoma in situ (DCIS) or invasive breast cancer. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome was overall survival. Secondary outcomes were local recurrence free-survival, adverse events (including overall complications, breast reconstruction loss, skin necrosis, infection and hemorrhage), cosmetic results, and quality of life. We performed a descriptive analysis and meta-analysis of the data. MAIN RESULTS: We found no RCTs or quasi-RCTs. We included two prospective cohort studies and twelve retrospective cohort studies. These studies included 12,211 participants involving 12,283 surgeries (3183 SSM and 9100 conventional mastectomies). It was not possible to perform a meta-analysis for overall survival and local recurrence free-survival due to clinical heterogeneity across studies and a lack of data to calculate hazard ratios (HR).  Based on one study, the evidence suggests that SSM may not reduce overall survival for participants with DCIS tumors (HR 0.41, 95% CI 0.17 to 1.02; P = 0.06; 399 participants; very low-certainty evidence) or for participants with invasive carcinoma (HR 0.81, 95% CI 0.48 to 1.38; P = 0.44; 907 participants; very low-certainty evidence). For local recurrence-free survival, meta-analysis was not possible, due to high risk of bias in nine of the ten studies that measured this outcome. Informal visual examination of effect sizes from nine studies suggested the size of the HR may be similar between groups. Based on one study that adjusted for confounders, SSM may not reduce local recurrence-free survival (HR 0.82, 95% CI 0.47 to 1.42; P = 0.48; 5690 participants; very low-certainty evidence).  The effect of SSM on overall complications is unclear (RR 1.55, 95% CI 0.97 to 2.46; P = 0.07, I2 = 88%; 4 studies, 677 participants; very low-certainty evidence). Skin-sparing mastectomy may not reduce the risk of breast reconstruction loss (RR 1.79, 95% CI 0.31 to 10.35; P = 0.52; 3 studies, 475 participants; very low-certainty evidence), skin necrosis (RR 1.15, 95% CI 0.62 to 2.12; P = 0.22, I2 = 33%; 4 studies, 677 participants; very low-certainty evidence), local infection (RR 2.04, 95% CI 0.03 to 142.71; P = 0.74, I2 = 88%; 2 studies, 371 participants; very low-certainty evidence), nor hemorrhage (RR 1.23, 95% CI 0.47 to 3.27; P = 0.67, I2 = 0%; 4 studies, 677 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the risk of bias, imprecision, and inconsistency among the studies. There were no data available on the following outcomes: systemic surgical complications, local complications, explantation of implant/expander, hematoma, seroma, rehospitalization, skin necrosis with revisional surgery, and capsular contracture of the implant. It was not possible to perform a meta-analysis for cosmetic and quality of life outcomes due to a lack of data. One study performed an evaluation of aesthetic outcome after SSM: 77.7% of participants with immediate breast reconstruction had an overall aesthetic result of excellent or good versus 87% of participants with delayed breast reconstruction. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence from observational studies, it was not possible to draw definitive conclusions on the effectiveness and safety of SSM for breast cancer treatment. The decision for this technique of breast surgery for treatment of DCIS or invasive breast cancer must be individualized and shared between the physician and the patient while considering the potential risks and benefits of available surgical options.

Comparison between anterior and posterior vaginal approach in apical prolapse repair in relation to anatomical structures and points of fixation to the sacrospinous ligament in fresh postmenopausal female cadavers.

INTRODUCTION AND HYPOTHESIS: The high prevalence of pelvic organ prolapse (POP) in women requires attention and constant review of treatment options. Sacrospinous ligament fixation (SSLF) for apical prolapse has benefits, high efficacy, and low cost. Our objective is to compare anterior and posterior vaginal approach in SSLF in relation to anatomical structures and to correlate them with body mass index (BMI). METHODS: Sacrospinous ligament fixation was performed in fresh female cadavers via anterior and posterior vaginal approaches, using the CAPIO®SLIM device (Boston Scientific, Natick, MA, USA). The distances from the point of fixation to the pudendal artery, pudendal nerve, and inferior gluteal artery were measured. RESULTS: We evaluated 11 cadavers with a mean age of 70.1 ± 9.9 years and mean BMI 22.4 ± 4.6 kg/m2. The mean distance from the posterior SSLF to the ischial spine, pudendal artery, pudendal nerve, and inferior gluteal artery were 21.18 ± 2.22 mm, 17.9 ± 7.3 mm, 19.2 ± 6.8 mm, and 18.9 ± 6.9 mm respectively. The same measurements relative to the anterior SSLF were 19.7 ± 2.7 mm, 18.6 ± 6.7 mm, 19.2 ± 6.9 mm, and 18.3 ± 6.7 mm. Statistical analysis showed no difference between the distances in the two approaches. The distances from the fixation point to the pudendal artery and nerve were directly proportional to the BMI. CONCLUSIONS: There was no difference in the measurements obtained in the anterior and posterior vaginal approaches. A direct correlation between BMI and the distances to the pudendal artery and pudendal nerve was found.

Vitamin D and in vitro fertilization: a systematic review.

PURPOSE: Vitamin D (VD) action on calcium is well known, but its other properties, particularly in the human reproductive system, are not completely understood. This review aims at assessing the relationship between serum VD levels and IVF results. METHODS: A systematic review was carried out using MEDLINE, EMBASE, LILACS, Google scholar, the CAPES journal portal, and the Cochrane Library, as well as the descriptors "vitamin D" and "fertilization in vitro." The review was conducted by two authors following the PRISMA recommendations between September 2021 and February 2022. RESULTS: Eighteen articles were selected. Five of them showed a positive correlation between serum VD levels and IVF results, 12 lacked any association, and 1 exhibited a negative correlation. The 3 studies that assessed VD in the follicular fluid found a positive correlation between the serum and follicular levels. Non-Hispanic White patients seemed to suffer the consequence of vitamin D deficiency more than Asian patients. In one study alone in the VD-deficient group, there was a larger number of natural killer (NK) cells, B cells, a greater proportion of helper T cells/cytotoxic T cells (Th/Tc), and an association with a smaller number of mature oocytes. CONCLUSION: The association between serum VD levels and the post-IVF pregnancy rate is uncertain. However, VD levels might be more relevant in the White than in the Asian ethnicity and in the number of aspiration follicles, and they could act in the immune system having an impact both on embryo implantation and on pregnancy.

Gene Expression Profile of Uterine Leiomyoma from Women Exposed to Different Air Pollution Levels in Metropolitan Cities of Sao Paulo, Brazil.

Leiomyomas (LMs) are the most frequent uterine benign tumors, representing the leading cause of hysterectomy indications worldwide. They are highly associated with women's reproductive complications, and endocrine disruptors may influence their etiology. In this sense, air pollution represents a relevant hormonal disruptor that acts on key signaling pathways, resulting in tumor development and infertility. Our goal was to evaluate submucosal LM samples from patients living in the metropolitan and Sao Paulo city regions, focusing on genes involved in tumor development and infertility features. Twenty-four patients were selected based on their region of residence and clinical information availability. Several genes were differentially expressed between women living in metropolitan areas and Sao Paulo city. Significant associations were observed between BCL-2, DVL1, FGFR3, and WNT5b downregulation and contraceptive use in the samples from women living in Sao Paulo city. ESR1 and HHAT downregulation was associated with ethnicity. WNT5b and GREM were associated with LM treatment and related pathologies, respectively. In the samples from women living in other cities of the metropolitan region, abortion occurrence was associated with BMP4 upregulation. Although further studies may be necessary, our results showed that air pollution exposure influences the expression of genes related to LM development and female reproductive features.

The oncological safety of autologous fat grafting: a systematic review and meta-analysis.

OBJECTIVE: To present a systematic review of the literature and a meta-analysis evaluating the oncological safety of autologous fat grafting (AFG). SUMMARY BACKGROUND DATA: AFG for breast reconstruction presents difficulties during follow-up radiological exams, and the oncological potential of grafted fat is uncertain. Previous studies confirmed that the fatty tissue could be transferred under a good condition suitable would not interfere with mammographic follow-up, although the issue of oncological safety remains. METHODS: We reviewed the literature published until 01/18/2021. The outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). We included studies that evaluated women with breast cancer who undergone surgery followed by reconstruction with AFG. We synthesized data using the inverse variance method on the log-HR (log of the hazard ratio) scale for time-to-event outcomes using RevMan. We assessed heterogeneity using the Chi2 and I2 statistics. RESULTS: Fifteen studies evaluating 8541 participants were included. The hazard ratios (HR) could be extracted from four studies, and there was no difference in OS between the AFG group and control (HR 0.9, 95% CI 0.53 to 1.54, p = 0.71, I2 = 58%, moderate certainty evidence), and publication bias was not detected. The HR for DFS could be extracted from six studies, and there was no difference between the AFG group and control (HR 1.01, 95% CI 0.73 to 1.38, p = 0.96, I2 = 0%, moderate certainty evidence). The HR for LR could be extracted from ten studies, and there was no difference between the AFG group and control (HR 0.86, 95% CI 0.66 to 1.12, p = 0.43, I2 = 1%, moderate certainty evidence). CONCLUSION: According to the current evidence, AFG is a safe technique of breast reconstruction for patients that have undergone BC surgery and did not affect OS, DFS, or LR.

Hyperestrogenemia resulting from a granulosa cell tumor and causing pulmonary thromboembolism: a case report.

Estrogen modulates platelet activation and aggregation, and it increases the levels of the von Willebrand factor, factors II, VII, VIII, and X, and of fibrinogen, all of which increase the risk for thromboembolism. We report the case of a 59-year-old woman, postmenopausal for 4 years, not using hormone replacement therapy, who was admitted into the emergency room with shortness of breath and increased abdominal volume. After physical examination and imaging and biochemical tests, she was diagnosed with pulmonary thromboembolism and a large left adnexal tumor. The patient was promptly received full anticoagulation therapy for the pulmonary thromboembolism. High levels of estradiol (810.4 pg/mL), anti-Mullerian hormone (16.39 ng/mL), inhibin (11250 pg/mL), and suppressed FSH (<0.16 IU/L) led to a suspicion of granulosa-cell tumor. After clinical stabilization, she underwent to an exploratory laparotomy with total hysterectomy and bilateral adnexectomy to treat the pelvic tumor. Pathologic report confirmed a granulosa-cell tumor.

Etonogestrel-releasing contraceptive implant in a patient using thalidomide for the treatment of erythema nodosum leprosum: a case report.

INTRODUCTION: Thalidomide is an immunomodulatory drug and first choice in the treatment of erythema nodosum leprosum. Given its teratogenic potential, it is essential that an effective contraceptive method is used, especially a long-acting reversible contraceptive (LARC) method. The subdermal etonogestrel (ENG)-releasing implant is an adequate method due to the high effectiveness and long-term use. However, interaction between thalidomide and ENG has not been well documented. Concern arises because thalidomide interacts with cytochrome P450 (CYP450) enzymes that metabolize sexual steroids. AIM: We aimed to study the effectiveness and safety of the ENG-implant in a thalidomide user. METHODS: Case report of a sexually active 21-year-old patient with both Hansen's disease and leprosy reaction type 2 treated with thalidomide requiring effective contraception. Follow-up was up to 36 months after implant placement. RESULTS: Contraception with ENG-implant was effective and safe, based on clinical parameters (reduction of menstrual flow and cervical mucus thickening) and laboratory parameters (gonadotropins and sexual steroids). CONCLUSION: To the best of our knowledge, this is the first case reported which presents a patient in simultaneous use of thalidomide and ENG-implant. Although this case report preliminary supports effectiveness and safety of ENG-implant as a contraceptive option in women using thalidomide, rigorous drug-drug interaction research is needed to better characterize the interaction between thalidomide and the ENG-implant.

Effects of clinical and metabolic variables and hormones on the expression of immune protein biomarkers in the endometrium of women with polycystic ovary syndrome and normal-cycling controls.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are at an elevated risk of endometrial cancer, which may be associated with the continuous proliferative state caused by the interaction between hormones and metabolic factors. OBJECTIVE: To investigate the impact of hormones and metabolic factors in the proliferation and death of endometrium during the proliferative phase. METHODS: Cross-sectional study with 11 women with PCOS and eight normal-cycling non-PCOS controls at the Federal University of the State of Rio de Janeiro from February 2011 to June 2019. Clinical, biochemical, and hormonal data were collected to analyze their influence on the expression of biomarkers related to the endometrial tissue breakdown. Hysteroscopy and endometrial biopsies were conducted, and the endometrial samples underwent immunohistochemistry for markers of apoptosis B-cell lymphoma 2 (BCL2), cleaved caspase-3 (CASP3), fas cell surface death receptor (FAS), FAS ligand (FASLG), BCL2 associated X (BAX), marker of proliferation Ki-67 (MKI67), and cell death using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL). RESULTS: CASP3 and TUNEL expressions were lower in both stroma and endometrium gland of PCOS women than in controls. MKI67 and homeostasis indexes (BCL2/BAX; FASLG/FAS) in the endometrium of the PCOS group were significantly higher. Body mass index (BMI) values were positively correlated with the expression of MKI67 and MKI67/TUNEL ratio in the endometrial stroma compartment. Fasting insulin levels were positively correlated with the expression of BCL2, and DHEA-S levels were negatively correlated with the expression of CASP3 of women with PCOS. CONCLUSION: BMI, insulin, and DHEA-S influence the endometrial homeostasis breakdown in PCOS in the endometrium stroma.

Impacts of bariatric surgery in health outcomes and health care costs in Brazil: Interrupted time series analysis of multi-panel data.

BACKGROUND: The increasing burden of obesity generates significant socioeconomic impacts for individuals, populations, and national health systems worldwide. The literature on impacts and cost-effectiveness of obesity-related interventions for prevention and treatment of moderate to severe obesity indicate that bariatric surgery presents high costs associated with high effectiveness in improving health status referring to certain outcomes; however, there is a lack of robust evidence at an individual-level estimation of its impacts on multiple health outcomes related to obesity comorbidities. METHODS: The study encompasses a single-centre retrospective longitudinal analysis of patient-level data using micro-costing technique to estimate direct health care costs with cost-effectiveness for multiple health outcomes pre-and post-bariatric surgery. Data from 114 patients who had bariatric surgery at the Hospital of Clinics of the University of Sao Paulo during 2018 were investigated through interrupted time-series analysis with generalised estimating equations and marginal effects, including information on patients' characteristics, lifestyle, anthropometric measures, hemodynamic measures, biochemical exams, and utilisation of health care resources during screening (180 days before) and follow-up (180 days after) of bariatric surgery. RESULTS: The preliminary statistical analysis showed that health outcomes presented improvement, except cholesterol and VLDL, and overall direct health care costs increased after the intervention. However, interrupted time series analysis showed that the rise in health care costs is attributable to the high cost of bariatric surgery, followed by a statistically significant decrease in post-intervention health care costs. Changes in health outcomes were also statistically significant in general, except in cholesterol and LDL, leading to significant improvements in patients' health status after the intervention. CONCLUSIONS: Trends multiple health outcomes showed statistically significant improvements in patients' health status post-intervention compared to trends pre-intervention, resulting in reduced direct health care costs and the burden of obesity.

Pretreatment with melatonin improves ovarian tissue cryopreservation for transplantation.

BACKGROUD: Melatonin has anti-inflammatory and antioxidative actions at the mitochondrial level. This indole-containing molecule may protect ovarian grafts during the process of cryopreservation. Therefore, we aimed to determine whether melatonin pretreatment improves rat ovarian graft quality. METHODS: Twenty-six female rats were allocated to two study groups of thirteen animals each: 1) control group: ovaries cryopreserved using the standard protocol; and 2) melatonin group: ovaries cryopreserved in a medium with melatonin. Ten rats of each group were submitted to 24-h freezing, and whole ovaries autologous and avascular transplantation with retroperitoneal placement. After postoperative (PO) day 15, daily vaginal smears were obtained for estrous cycle characterization. Between PO days 30 and 35, the animals were euthanized and ovarian grafts were recovered for histological and immunohistochemical (Ki-67, cleaved caspase-3, TUNEL, von Willebrand factor, estrogen, and progesterone receptors) analyses. The ovaries of the three remaining rats from each group were studied immediately after thawing to assess the effects of cryopreservation. ANOVA and Tukey's tests were used and the rejection level of the null hypothesis was set at 0.05 or 5% (p < 0.05). RESULTS: Melatonin promoted faster restart of the estrous cycle and increased the expression of mature follicles, collagen type I, von Willebrand factor, Ki-67, and cleaved caspase-3 on corpora lutea and estrogen receptors in the ovaries as compared to control. There was a reduction in apoptosis by TUNEL on follicles, corpora lutea, and collagen type III. CONCLUSION: Based on the evaluated parameters, melatonin may promote the quality of ovarian grafts. Reproductive function enhancement should be further studied.

Uterus procurement from deceased donor for transplantation.

Women with absolute uterine factor infertility cannot get pregnant. The current experience in uterine transplantation is limited and the use of a deceased donor uterus in this area is incipient after some initial unsuccessful attempts. The birth of healthy babies through this modality in four different centers has given a new impetus to the use of this transplantation technique. We aimed to develop a technique for uterus procurement and preparation for transplantation from a brain dead donor. Fifteen uteri were retrieved from multi-organ donor patients, 10 of these were used in bench surgeries with the proposed technique. All procedures were performed after obtaining family's consent. This study allowed the clinical use of two of the 15 organs that were procured for transplantation. One of these organs resulted in the first live birth worldwide using a uterus transplanted from a deceased donor, a landmark in reproductive medicine. Another outcome was the optimization of the surgical technique involving less manipulation of the uterine vascular pedicles. The success of this novel technique suggests that the proposed model can be replicated and optimized further to facilitate the transplantation of uterus from deceased donors.

Comparison of stress urinary incontinence between urban women and women of indigenous origin in the Brazilian Amazon.

INTRODUCTION AND HYPOTHESIS: This study compared two populations in the Brazilian Amazon, one comprising urban women and the other indigenous origin women from a riparian population, to assess the prevalence of and risk factors associated with stress urinary incontinence (SUI). METHODS: Following sample calculation, 120 indigenous and 260 urban women underwent evaluations including medical history, UI-oriented physical examination, pelvic organ prolapse, and functional assessment of the pelvic floor. Women with complaints of SUI underwent a urodynamic study and completed a quality of life questionnaire (King's Health Questionnaire). Univariate ORs were calculated, and multiple logistic regression models were then built using the stepwise backward method. RESULTS: The prevalence of SUI was similar in both groups (25.8% in indigenous origin women and 20.4% in the urban group (P > 0.05). The parity and number of spontaneous deliveries and home births were higher in the indigenous origin group. Multivariate analysis showed a decreased prevalence of SUI in patients with modified Oxford Scale scores ≥ 3. Women with homebirths had a 3.45-fold higher likelihood of having SUI than women with hospital deliveries (OR 3.45 -CI 1.78-6.70). Quality of life was worse in the domains of SUI impact, hindering daily and physical activities as well as jeopardizing personal and emotional relationships in urban women. CONCLUSIONS: No significant difference in SUI was observed between the groups, despite significantly higher risk factors for SUI in the indigenous origin group.

Does obesity modify the expression of cyclin D1 and pten in endometrial polyps in postmenopausal women?

OBJECTIVE: To assess cyclin D1 and PTEN immunoexpression in benign endometrial polyps (EPs) in asymptomatic postmenopausal women and its correlation with obesity. Methods: This was a cross-sectional study based on data from a sample of 52 patients diagnosed with EP between February 2018 and January 2019. The women included in this study were amenorrheal for at least 1 year and were asymptomatic (no postmenopausal bleeding). Obesity defined by body mass index (BMI) was investigated for correlation with Cyclin-D1 and PTEN gene expression (immunohistochemistry) in glandular and stromal compartments of polyps. Results: No significant differences among groups were identified in any clinical and epidemiological parameter (age, age of menopause, time since menopause, number of gestations, polyp size, leucocyte count, fasting blood glucose and basic pathologies), except for BMI. Body mass index did not alter PTEN or Cyclin D1 immunoexpression. Conclusion: Our study shows that obesity does not appear to be a relevant factor in the immunoexpression of PTEN and Cyclin D1 in benign EP, in either the stromal or glandular compartments.

Histomorphometric and immunohistochemical changes in interstitial cells and ovarian follicles of rats with polycystic ovaries treated with clomiphene citrate.

OBJECTIVE: To evaluate the histomorphometric and immunohistochemical changes in interstitial cells and ovarian follicles of rats treated with clomiphene citrate during and after induction of permanent estrus. METHODS: Twenty four adult-female rats with regular estrous cycle were equally divided into three groups: (1) GCtrl-at estrous phase. (2) GPCOS-at permanent-estrous phase. (3) GCC-PCOS rats, which remained exposed to 60 days of continuous illumination and treated with Clomiphene Citrate. After that, the animals were euthanized, and the ovaries were removed and processed for paraffin embedding. Sections were stained with H.E. for histomorphometry or subjected to immunohistochemistry for Ki-67 and cleaved caspase-3 detections. RESULTS: The GPCOS showed lack of corpus luteum and several ovarian cysts, as well as interstitial-like cells. The presence of corpus luteum and a significant increase in primary and antral follicles were observed in GCC, which also showed a decrease in the number of ovarian cysts and in the area occupied by interstitial-like cells, as well as a decrease in nuclear volume of interstitial cells. The percentage of cell proliferation was significantly higher in granulosa cells of the GCC. On the other hand, the percentage of apoptosis was significantly higher in the granulosa cells of GPCOS than the GCC. CONCLUSION: The ovaries of rats treated with clomiphene citrate showed a decrease in the number of cysts, an increase in the number of ovarian follicles, the presence of corpus luteum along with a decrease in the nuclear volume in the area occupied by interstitial cells.