Altered Endometrial Expression of α-Inhibin Subunit and Its Co-Receptor Betaglycan in Infertile Women with Endometriosis.

BACKGROUND: Inhibins and their co-receptor betaglycan are members of the transforming growth factor ß superfamily, a group of signaling molecules that control the differentiation of human endometrium in the secretory phase of the menstrual cycle. OBJECTIVE: Since endometriosis is associated with endometrial dysfunction and infertility, this study aimed at evaluating the expression of α-inhibin and betaglycan mRNA and proteins in endometrial samples of infertile women with and without endometriosis. DESIGN: This was a cross-sectional study. Participants/Materials: Endometrial samples of women with (n = 17) and without (n = 22) endometriosis were subdivided according to the menstrual cycle phase into proliferative and secretory. SETTING: University hospital. METHODS: We used real-time RT-PCR to quantify mRNA levels and immunohistochemistry to localize the proteins. RESULTS: α-inhibin mRNA levels were significantly increased in the secretory phase (p < 0.01 vs. proliferative phase) only among women with endometriosis. Conversely, betaglycan mRNA levels were downregulated in the secretory endometrium of controls (p < 0.01 vs. proliferative) but failed to change between cycle phases of patients with endometriosis. Both proteins were present in the glandular epithelium and stroma in the endometrium of women with and without endometriosis. Immunostaining analysis showed that while α-inhibin protein expression did not vary significantly, the intensity of betaglycan immunostaining decreased in the secretory phase in the control group (p = 0.038 vs. proliferative phase) but not in the endometriosis group. LIMITATIONS: We cannot determine whether endometriosis causes the abnormal expression of α-inhibin and betaglycan in the eutopic endometrium or if this alteration already existed before the establishment of endometriotic lesions. CONCLUSION: Our findings suggest an abnormally increased expression of α-inhibin mRNA (not protein) and betaglycan (mRNA and protein) in the secretory-phase endometrium of women with endometriosis.

Impact of Surgery for Deep Infiltrative Endometriosis before In Vitro Fertilization: A Systematic Review and Meta-analysis.

OBJECTIVE: The aims of this systematic review and meta-analysis were to compare reproductive outcomes in patients who underwent surgery for deep infiltrative endometriosis (DIE) before in vitro fertilization (IVF) with those in patients who underwent IVF without a previous surgery for DIE, to analyze data according to different types of surgery (complete or incomplete) or subgroups of patients (DIE with or without bowel involvement), and to assess surgical and IVF complications and data regarding safety concerns. DATA SOURCES: A systematic literature search from January 1980 to November 2019 with no language restriction was performed in PubMed, MEDLINE, Embase, and Web of Science. The search strategy used the following Medical Subject Headings terms: "in vitro," "fertilization," "IVF," "assisted reproduction," "colorectal," "endometriosis," "deep," "infiltrating," "deep infiltrative endometriosis," "intestinal," "bowel," "rectovaginal," "uterosacral," "vaginal," and "bladder." METHODS OF STUDY SELECTION: We included studies that compared reproductive outcomes in women with infertility with DIE who received IVF with or without a previous surgery for DIE lesions. Meta-analysis was performed using Review Manager (RevMan v.5.3; Cochrane Training, London, United Kingdom). The risk of bias of the included studies was assessed using the method recommended by Cochrane Collaboration. TABULATION, INTEGRATION, AND RESULTS: The systematic search retrieved 150 articles; 98 studies were potentially eligible, and their full texts were reviewed. Of these, 12 studies met our inclusion criteria, and 5 presented data suitable for inclusion in a meta-analysis; however, 2 of the studies provided overlapping data, and only the larger study was finally included. No randomized controlled trials (RCTs) were found. The pregnancy rate per patient was 1.84 (95% confidence interval [CI], 1.28-2.64), the pregnancy rate per cycle was 1.84 (95% CI, 1.26-2.70), and the live birth rate per patient was 2.22 (95% CI, 1.42-3.46) times more likely for operated patients than for nonoperated ones. The addition of data from the incomplete surgery groups also showed a higher pregnancy rate per patient for surgery before IVF (odds ratio [OR] 1.63; 95% CI, 1.16-2.28). The results favor previous surgery in DIE with digestive involvement (OR 2.43; 95% CI, 1.13-5.22) and also in DIE without digestive involvement (OR 1.55; 95% CI, 0.61-3.95). A qualitative analysis of the complications of surgery and IVF showed a partial or complete lack of information on these issues as well as high heterogeneity in the reported data. None of these studies is an RCT; therefore, all have a high risk of selection and allocation bias, except for 1 study that statistically controlled the latter risk by using propensity scores. Funnel plots showed no asymmetry. CONCLUSION: The results were very consistent for all the studied outcomes, showing a statistically significant benefit for surgery before IVF, although they should be confirmed with RCTs. In addition to the reproductive outcomes, safety data should also be reported to obtain a complete assessment of the risks and benefits.

Laparoscopic Treatment of Ureteral Endometriosis: A Systematic Review.

OBJECTIVE: To review the literature for the preoperative clinical characteristics, surgical findings, and outcomes of patients who underwent laparoscopic surgical treatment of ureteral endometriosis (UE). DATA SOURCES: A systematic search was performed in the PubMed and Scopus databases. METHODS OF STUDY SELECTION: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies in English language that assessed UE treated surgically by laparoscopy published between 2008 and 2020 were selected. TABULATION, INTEGRATION, AND RESULTS: In an initial search, 1313 articles were identified, 193 in PubMed and 1120 in Scopus databases. A total of 1291 articles that did not meet eligibility criteria were excluded. The remaining 22 studies were included in the final qualitative analysis, with a total of 1337 patients. Data on preoperative patient's characteristics, preoperative imaging examinations, intraoperative findings, and postoperative complications were abstracted by 1 author. The descriptive nature of included studies prevented the performance of meta-analysis. Preoperative symptoms included dysmenorrhea (76.3%), pelvic pain (59.6%), dyspareunia (46.2%), lower urinary tract symptoms (21.3%), and ureteral obstructive symptoms (9.9%). Intraoperative findings showed that UE lesions were left-sided in 55% of the cases, right-sided in 28.9% of the cases, and bilateral in 8.7% of the cases. Ureterolysis alone or before another technique was performed in 69.1% of the cases, ureteral resection followed by ureteroureteral anastomosis in 6%, ureteroneocystostomy after ureteral resection in 21%, and nephrectomy in 0.45% of the patients. Double-J ureteral stent placement was reported in 33.3% of the cases. Concomitant resection of the bladder owing to endometriosis involvement was performed in 15.5% of the cases. The prevalence of ureteral injury was 3.1%. Postoperative complications included ureteral fistula (2.8%), ureteral stenosis (24.2%), persistence/recurrence of UE (3.8%), and reoperation for fistula and/or stricture treatment (3.9%). CONCLUSION: UE is associated with common endometriosis pain symptoms and a low rate of lower urinary tract symptoms. The standard surgical technique for UE treatment is not yet a consensus; however, the laparoscopic approach with previous ureterolysis, leaving ureteral resection only for refractory cases, seems to be a safe and effective treatment, with improvement of symptoms and few intraoperative and postoperative complications.

Comparison of Sensitivity and Specificity of Structured and Narrative Reports of Transvaginal Ultrasonogaphy for Adenomyosis.

STUDY OBJECTIVE: To compare the sensitivity and specificity of the transvaginal ultrasonography (TVUS) narrative report with those of the structured report for the diagnosis of adenomyosis. DESIGN: Retrospective study. SETTING: A tertiary teaching hospital. PATIENTS: One hundred ninety-two patients (45 with adenomyosis and 147 controls) who underwent hysterectomy between 2012 and 2016 and were aged 30 years to 55 years, with available preoperative TVUS images, were included. INTERVENTIONS: To compare preoperative TVUS with histologic analysis of the uterus after hysterectomy for the diagnostic of adenomyosis. MEASUREMENTS AND MAIN RESULTS: Data regarding the presence of the ultrasonographic characteristics previously described for the diagnosis of adenomyosis were obtained from the original TVUS report (narrative report) and the structured report from 2 blinded radiologists (R1 and R2). Histologic analysis is defined as the gold standard for the diagnosis of adenomyosis. The mean age (45.4 ± 5.3 years vs 44.9 ± 4.8 years; p = .496) and clinical symptoms were similar between the adenomyosis and control groups, except for dyspareunia, which was more frequently reported in the patients with adenomyosis (25.6% vs 9.4%; p = .006). Most of TVUS characteristics were more frequently observed in the structured reports than in the narrative reports. The structured report presented higher sensitivity (R1: 84.4%, R2: 69.1%; narrative report: 31.1%; p <.05) and lower specificity (R1: 28.0%, R2: 31.2%; narrative report: 90.5%; p <.05) for adenomyosis. The structured report presented higher sensitivity and lower specificity for most of sonographic characteristics evaluated. After logistic regression analysis, no sonographic characteristics presented with statistical significance for the diagnosis of adenomyosis on R1's structured report, while globular uterus (odds ratio [OR] 0.276; p = .006; 95% CI, 0.11-0.697) and poorly defined junctional zone (OR 3.6; p = .007; 95% CI, 1.4-9.2) were significantly associated with adenomyosis. In the narrative report, a myometrial cyst was associated with a higher risk of adenomyosis (odds ratio 9.486, p =.002; CI, 2.359-38.149). CONCLUSION: The narrative reports were more specific, whereas the structured reports were more sensitive for the diagnosis of adenomyosis. In addition, the sensitivity of most of sonographic feature of adenomyosis was higher and the specificity was lower in the structured report. Future prospective studies comparing both reports are needed to validate the current findings.

Surgical Principles for Disc Resection of Deep Bowel Endometriosis.

OBJECTIVE: Colorectal involvement represents 90% of bowel endometriosis. The best surgical approach must consider the patient's clinical symptoms, preoperative imaging, and correlation with surgical findings. For patients with severe pain who either have failed medical treatment or contraindications to hormonal treatment and have a single bowel lesion <3 cm that involves the inner muscularis, disc resection is the preferred approach to treat bowel endometriosis [1,2]. Therefore, here we describe the surgical principles for disc resection for deep bowel endometriosis. DESIGN: Step-by-step video illustration of our surgical technique with clarification of surgical principles. SETTING: Tertiary care center. INTERVENTION: A mechanical bowel preparation is given before surgery. A 10-mm port is placed in the umbilicus, and 3 other 5-mm auxiliary ports are placed in the right and left iliac fossa and in the suprapubic region. Dissection starts with development of both medial pararectal spaces. The retrocervical region is approached, and the bowel lesion is isolated. A suture is placed into the endometriosis bowel lesion to facilitate invagination into the stapler. A circular stapler is inserted into the rectum, and the anvil is opened at the level of the endometriosis lesion. Each end of the suture held by 2 graspers are pushed dorsally, whereas the stapling device is gently pushed ventrally, imbricating the delineated area. The stapler is closed, including the endometriosis area. After reassuring that the posterior part of the mesentery is free, the device is fired, excising only the anterior wall of the rectum. CONCLUSION: Disc resection is the technique of choice to treat a focal bowel endometriosis lesion <3 cm.

Is High-intensity Focused Ultrasound Effective for the Treatment of Adenomyosis? A Systematic Review and Meta-analysis.

STUDY OBJECTIVE: To systematically review the literature regarding the efficacy of high-intensity focused ultrasound (HIFU) in reducing adenomyotic lesions, patients' pain and bleeding symptoms, and the impact on patients' quality of life. DATA SOURCE: A search was performed through PubMed/MEDLINE and Cochrane databases. METHODS OF STUDY SELECTION: All available studies published in the English language in the last 10 years that evaluated the effects of HIFU for adenomyosis. TABULATION, INTEGRATION, AND RESULTS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis was performed on data from homogeneous studies. Pooled results from the meta-analysis showed that after HIFU treatment for adenomyosis, a large effect was observed in reducing the uterine volume at 12 months (standard mean difference [SMD] = 0.85), a significant reduction in dysmenorrhea at 3 months (SMD = 1.83) and 12 months (SMD = 2.37), and a significant improvement in quality of life at 6 months (SMD = 3.0) and 12 months (SMD = 2.75). Adverse reactions after HIFU were reported in 55.9% of patients. CONCLUSION: This review suggests a potential benefit for HIFU in the treatment of adenomyosis-related symptoms; however, findings of the meta-analysis were based on fewer, nonuniform studies, which did not equally account for each specific symptom/parameter across the board. Results showed there appears to be a potential of HIFU in the treatment of adenomyosis-related symptoms. To date, there are no comparative and randomized clinical trials comparing the HIFU technique with other conservative treatment options. As yet, there are insufficient data regarding fertility and pregnancy outcomes.

Extrapelvic Endometriosis: A Systematic Review.

OBJECTIVE: To conduct a systematic review of the literature on patients with extrapelvic deep endometriosis. DATA SOURCES: A thorough search of the PubMed/Medline, Embase, and Cochrane databases was performed. METHODS OF STUDY SELECTION: Studies in the last 20 years that reported on primary extrapelvic endometriosis were included (PROSPERO registration number CRD42019125370). TABULATION, INTEGRATION, AND RESULTS: The initial search identified 5465 articles, and 179 articles, mostly case reports and series, were included. A total of 230 parietal (PE), 43 visceral (VE), 628 thoracic (TE), 6 central nerve system, 12 extrapelvic muscle or nerve, and 1 nasal endometriosis articles were identified. Abdominal endometriosis was divided into PE and VE. PE lesions involved primary lesions of the abdominal wall, groin, and perineum. When present, symptoms included a palpable mass (99%), cyclic pain (71%) and cyclic bleeding (48%). Preoperative clinical suspicion was low, the use of tissue diagnosis was indeterminate (25%), and a few (8%) malignancies were suspected. Surgical treatment for PE included wide local excision (97%), with 5% recurrence and no complications. Patients with VE involving abdominal organs - kidneys, liver, pancreas, and biliary tract - were treated surgically (86%) with both conservative (51%) and radical resection (49%), with 15% recurrence and 2 major complications reported. In patients with TE involving the diaphragm, pleura, and lung, isolated and concomitant lesions occurred and favored the right side (80%). Patients with TE presented with the triad of catamenial pain, pneumothorax, and hemoptysis. Thoracoscopy with resection followed by pleurodesis was the most common procedure performed, with 29% recurrence. Adjuvant medical therapy with gonadotropin-releasing hormone was administered in 15% of cases. Preoperative magnetic resonance imaging was performed in all cases of nonthoracic and nonabdominal endometriosis. Common symptoms were paresthesia and cyclic pain with radiation. Surgical resection was reported in 84%, with improvement of symptoms. CONCLUSION: Extrapelvic endometriosis, traditionally thought to be rare, has been reported in a considerable number of cases. Heightened awareness and clinical suspicion of the disease and a multidisciplinary approach are recommended to achieve a prompt diagnosis and optimize patient outcomes. Currently, there are no comparative studies to provide recommendations regarding optimal diagnostic methods, treatment options, and outcomes for endometriosis involving extrapelvic sites.

Postoperative Bowel Symptoms Improve over Time after Rectosigmoidectomy for Endometriosis.

STUDY OBJECTIVE: To evaluate bowel function (changes in stool caliber, sensation of incomplete evacuation, stooling frequency, and rectal bleeding) and urinary function (dysuria and retention) after segmental resection in patients with bowel endometriosis. DESIGN: Retrospective study. SETTING: Tertiary hospital. PATIENTS: A total of 413 (mean age = 33.6 ± 5.1 years) of reproductive aged women, with bowel endometriosis that underwent segmental bowel resection of the rectosigmoid from 2005 to 2018, without history of prior bowel surgery, without existing or history of malignancy. INTERVENTIONS: Laparoscopic segmental bowel resection performed by the same team and with the same technique. MEASUREMENTS AND MAIN RESULTS: Data collected from the patients' records included length of resected segment, distance of the lesion from the anal verge, and complications. Information on intestinal and urinary function was obtained from a questionnaire applied before the surgery and at 2, 6, and 12 months after the surgery. There was a significant increase in the incidence of stool thinning and rectal bleeding 2 months after surgical procedure; these symptoms decreased significantly over time. The incidence of urinary symptoms decreased significantly over time after surgery. The length of the bowel segment resected was not associated with the postoperative symptoms, but the rectosigmoid lesion was significantly closer to the anal verge in patients with rectal bleeding and urinary symptoms. There was no association between the length of intestinal segment resected and the frequency of stooling. At 6 months, patients who had a decreased frequency of stooling underwent a resection closer to the anal verge (9.7 cm) in comparison with the ones with unchanged or increase frequency of stooling (10.1 cm and 10.7 cm, respectively; p <.05). CONCLUSION: Patient complaints on bowel and urinary alterations after segmental resection were transient with significant improvement over time up to 12 months. Bowel and urinary symptoms were not associated with the size of the bowel segment resected, whereas rectal bleeding at 2 months after surgery was significantly associated with the distance from anal verge. Segmental resection was also associated with a great improvement in constipation at 12 months postoperative.

Surgery for Endometriosis Improves Major Domains of Quality of Life: A Systematic Review and Meta-Analysis.

Because surgery for endometriosis can involve severe complications, it is important to determine if the patient's quality of life (QOL) is indeed improved after surgery. A systematic review and meta-analysis, when appropriate, was conducted and included 38 studies that assessed the QOL using validated questionnaires administered before and after surgery. Results were grouped according to the type of endometriosis reported: all types endometriosis, deep infiltrative endometriosis (DIE), and bowel endometriosis. Quantitative analysis was performed on 17 homogeneous studies. Pooled response mean differences between the 36-Item and 12-Item Short Form Survey (SF-36 and SF-12) showed significant improvement in Mental Component Score (MCS) after surgery for all types of endometriosis (.21; 95% confidence interval [CI], .04-.38); significant improvement after surgical treatment for DIE in Vitality (.67; 95% CI, .41-.94), Social Functioning (.59; 95% CI, .18-.99), Role Emotional .49; 95% CI, .02-.97), Mental Health (.39; 95% CI, .03-.74), Physical Functioning (.93; 95% CI, .49-1.38), Bodily Pain (1.23; 95% CI, .47-1.99), General Health (.57; 95% CI, .02-1.12), MCS (.55; 95% CI, .10-1.00), and Physical Component Score (PCS; .73; 95% CI, .27-1.18); and significant improvement after surgery for bowel endometriosis for all 8 domains (Vitality [1.00; 95% CI, .56-1.43], Social Functioning [.97; 95% CI, .57-1.37], Role Emotional [1.17; 95% CI, .7-1.63], Mental Health [.94; 95% CI, .5-1.38], Physical Functioning [.74; 95% CI, .3-1.18], Role Physical [1.25; 95% CI, .75-1.76], Bodily Pain [1.39; 95% CI, .79-1.98], General Health [.84; 95% CI, 1.46-1.22]), MCS (.93; 95% CI, .47-1.40), PCS (.82; 95% CI, .40-1.23), and total score (1.15; 95% CI, .48-1.83). Only 1 study assessed patients with minimal disease and showed significant improvement in PCS (p = .002) and MCS (p <.001). This systematic review reveals that surgery for endometriosis resulted in overall improvement in most health domains of health-related QOL, with the greatest improvement found in the Bodily Pain domain.

Interleukin-15 and Interleukin-7 are the Major Cytokines to Maintain Endometriosis.

OBJECTIVE: The objective of this study was to evaluate cytokines related to natural killer and T-regulatory cells in endometriotic lesions, peritoneal fluid (PF) and the peripheral blood (PB) of patients with deep infiltrative endometriosis. STUDY DESIGN: A case-control study was conducted in a tertiary referral hospital. Sixty-four consecutive patients after laparoscopy were divided into 2 groups: with endometriosis (Group A - n = 32) and without endometriosis (Group B - n = 32). MAIN OUTCOME MEASURES: Interleukin (IL)-2, IL-4, IL-7, IL-10, IL-12, IL-15, transforming growth factor ß1, and IFNγ concentration was measured using a LuminexTM multiplex suspension bead array. Tissues from endometriotic lesions of patients with endometriosis and from eutopic endometrium were evaluated, as well as PF and PB of all patients. RESULTS: Compared to the other analyzed groups, IL-15 concentration was significantly higher in the ectopic endometrium and IL-7 in the eutopic endometrium of the endometriosis group (p < 0.05). Compared to endometriosis group, IFNγ, IL-7, and IL-15 were observed to be significantly higher in the PF of the control group, and IL-10 was lower in the control group (p < 0.05). In PB, compared to endometriosis group, IL-4, IL-10, IL-12, IL-15, and IFNγ concentrations were significantly higher in the control group (p < 0.05). CONCLUSIONS: Our hypothesis is that deep endometriosis is a disease out of control. This disease's nature is of progression and invasion of adjacent structures, and proof of this disease state is the disorganized secretion of cytokine regulation and inflammation, which seem to be among the factors responsible for the maintenance of the disease.

Transvaginal Ultrasound for the Diagnosis of Adenomyosis: Systematic Review and Meta-Analysis.

Adenomyosis is characterized by the presence of ectopic foci of endometrial glandular tissue and/or stroma within the myometrium. The diagnosis of adenomyosis is traditionally made through histologic evaluation of the postsurgical specimen. More recently, imaging with transvaginal ultrasound (TVUS) has been used for the preoperative diagnosis of adenomyosis. As yet, there is no consensus regarding the best imaging feature or combination thereof for the nonsurgical diagnosis of adenomyosis. This study systematically evaluated the literature in the last 10 years to determine the accuracy of 2-dimensional (2D) TVUS, different imaging features, enhancing methods such as 3-dimensional (3D) TVUS, elastography and color Doppler in the nonsurgical diagnosis of adenomyosis. A total of 8 studies were included. Pooled sensitivity and specificity for 2D TVUS for the diagnosis of adenomyosis for all combined imaging characteristics was 83.8% and 63.9%, respectively. Pooled sensitivity for 355 total patients with use of imaging feature of heterogeneous myometrium with 2D TVUS was highest (86.0%), and pooled specificity for 283 total patients with use of globular uterus was highest (78.1%). After including the "question mark" sign with other TVUS features, higher sensitivity and specificity, of 92% and 88%, respectively, were noted. For 3D TVUS, pooled sensitivity and specificity for all combined imaging characteristics was 88.9% and 56.0%, respectively. Poor definition of junctional zone showed the highest pooled sensitivity (86%) and the highest pooled specificity (56.0%) for the diagnosis of adenomyosis with 3D TVUS. There was no improvement in overall accuracy in 3D TVUS compared with 2D TVUS. Preliminary results of TVUS with color Doppler showed a high sensitivity and specificity for the differentiation between adenomyosis and myomas (95.6% and 93.4%, respectively). Also, TVUS elastography in 1 study showed an improvement in specificity (82.9%) compared with 2D TVUS (63.9%), albeit with comparable sensitivity. Larger studies are needed to advance our understanding of the different types of adenomyosis and their clinical impact.

Bowel Preparation Improves the Accuracy of Transvaginal Ultrasound in the Diagnosis of Rectosigmoid Deep Infiltrating Endometriosis: A Prospective Study.

STUDY OBJECTIVE: To compare the accuracy of transvaginal ultrasound (TVUS) with and without bowel preparation (BP) to detect and describe intestinal nodules of deep infiltrating endometriosis (DIE) with laparoscopic findings. DESIGN: A prospective study of paired data (Canadian Task Force classification II.1). SETTING: A tertiary university hospital from November 2014 to November 2015. PATIENTS: A cohort of women awaiting surgery for endometriosis. INTERVENTIONS: The wall of the rectum and the lower sigmoid colon of the patients were evaluated by 2 TVUSs: the first ultrasound was performed without previous BP, and the second was done after a 3-day low-residue diet and two 250-mL enemas 12 hours and 3 hours before TVUS. MEASUREMENTS AND MAIN RESULTS: The presence or absence of rectosigmoid nodules visualized by TVUS with and without BP was compared with laparoscopic results. Forty patients with a mean age of 36.8 ± 5.0 years were included in the study. By comparing the surgical findings histologically confirmed (the presence or absence of bowel nodules and localization) with those of the 2 TVUSs with and without BP, the sensitivity, specificity, and Cohen kappa were 100%, 96%, and 0.95 and 73%, 88%, and 0.61, respectively. Laparoscopy showed that up to 37.5% of patients (15/40) presented bowel involvement. Variables were clearly more evaluable with than without BP. CONCLUSION: TVUS with BP has a higher accuracy than TVUS without BP. BP allows and facilitates the detection of more rectal nodules of DIE in patients with suspected endometriosis and surgical criteria.

Role of Imaging Tools for the Diagnosis of Borderline Ovarian Tumors: A Systematic Review and Meta-Analysis.

Borderline ovarian tumors (BOTs) have a low malignant potential and occur most often in young women. Its preoperative diagnosis can improve surgical strategy and reproductive approach. This study systematically reviews the literature for the accuracy of transvaginal ultrasound (TVUS), magnetic resonance (MRI), and computed tomography (CT) in the diagnostic of BOTs. We conducted a search in PubMed/Medline of articles in English from the last 5 years and included 14 studies for systematic review, 9 of them in the meta-analysis. The pooled sensibility and specificity was respectively 77.0% and 83.0% for TVUS (5 studies) and 85% and 74% for MRI (4 studies) in differentiating benign from malignant BOTs. CT and positron emission tomography (PET)-CT techniques were heterogeneous between studies, so a meta-analysis was not performed for the 4 studies on CT and PET-CT. However, these 4 studies have also shown a high accuracy in differentiating BOTs from malignant ovarian cancers.

Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease.

INTRODUCTION: Environmental toxicants can act as endocrine disrupters on the female reproductive system. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is resistant to degradation and due to its lipophilic nature, accumulates in the fat tissue and in the food chain. Human and animal exposure to TCDD affects levels of the steroid receptors and steroid-responsive gene expression and has an impact on metabolism and serum transport of steroids. Gene expression is commonly altered in endometriosis and in the eutopic endometrium of women with the disease. Aberrantly expressed genes include those associated with the regulation of transcription, proliferation, sex steroid metabolism, apoptosis, cell cycle, the immune response and cell adhesion. METHODS: In this paper, we review the evidence about TCDD's effect on eutopic and ectopic endometrium, in order to unravel the machinery behind the dysregulation of immune and hormonal homeostasis caused by this environmental toxicant. CONCLUSION: The evidence collected in this review suggests that TCDD could modulate transcription at multiple levels, including the epigenetic level, and via microRNAs, thus disturbing the physiologic processes mediated through the aryl hydrocarbon receptor pathways. Exposure to TCDD also modulates the immune response by influencing the production and action of endometrial cytokines and chemokines, destroying mucosal immunity of the reproductive tract and re-directing the tissue distribution and behavior of leukocytes. Despite this large body of evidence, current human-based epidemiological studies on the association between TCDD and endometriosis remain controversial.

Role of vascular endothelial growth factor polymorphisms (-2578C>A, -460 T>C, -1154G>A, +405G>C and +936C>T) in endometriosis: a case-control study with Brazilians.

BACKGROUND: Endometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms. METHODS: This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model. RESULTS: Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1 ± 3.9 versus 27.3 ± 5.9, P < 0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23-2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the -2578C > A, -460 T > C, +405G > C and +936C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, -460 T > C, -1154G > A and +405G > C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15-0.86), DIE (OR: 0.37 95% CI: 0.15 - 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 - 0.95). CONCLUSIONS: The present results indicate a positive association between VEGF -1154G > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

Cellular, histologic, and molecular changes associated with endometriosis and ovarian cancer.

Our understanding of the pathogenesis of endometriosis is rapidly evolving as early molecular events are increasingly identified. Endometriosis is associated with increased risk of ovarian cancer and exhibits neoplastic phenotypes including invasion of stromal tissue and lymphatic spread to distant organs. This review of the literature establishes the clinical, epidemiologic, and pathologic correlation between endometriosis and low-grade ovarian cancer. Genetic studies have demonstrated that endometriotic lesions have mutations in genes directly related to neoplasms, in particular the p53, KRAS, PTEN, and ARID1A genes, which suggests a direct transition from a subset of endometriotic lesions to invasive carcinomas. The identification of both genetic and epigenetic biomarkers including microRNAs are essential for identifying patients at risk for the transition to neoplasia.

Soluble MICA in endometriosis pathophysiology: Impairs NK cell degranulation and effector functions.

PROBLEM: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain-related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell-deficient activity in endometriosis. METHODS OF STUDY: sMICA levels (serum and peritoneal fluid-PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN-γ and IL-10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. RESULTS: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56dim CD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN-γ expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA-blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. CONCLUSIONS: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN-γ response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.

Foxp3+CD39+CD73+ regulatory T-cells are decreased in the peripheral blood of women with deep infiltrating endometriosis.

Endometriosis's pathophysiology remains incompletely understood, with evidence pointing towards a dysregulated immune response. Regulatory T (Treg) cells, pivotal in maintaining self-tolerance, may facilitate the survival of ectopic endometrial cells within the abdominal cavity, thereby contributing to endometriosis development. This study aimed to assess the prevalence of CD39+CD73+ suppressor Treg cell subsets in the peripheral blood of endometriosis patients. This research focuses on the pivotal role of regulatory T-cells (Tregs), which are essential for maintaining immune tolerance and preventing autoimmune diseases. A case-control study was conducted, including 32 women diagnosed with endometriosis and 22 control subjects. The frequency of peripheral blood CD39+CD73+ suppressor Treg cells was quantified using flow cytometry. No significant differences were observed in the frequency of CD3+CD4+CD25High cells (Median [M]: 10.1; Interquartile Range [IQR]: 6.32‒18.3 vs. M: 9.72; IQR: 6.22-19.8) or CD3+CD4+CD25HighCD39+Foxp3+ cells (M: 31.1; IQR: 19.7-44.0 vs. M: 30.55; IQR: 18.5-45.5) between controls and patients. However, a significantly lower frequency of CD3+CD4+CD25HighCD39+CD73+ cells was observed in the endometriosis group compared to controls (M: 1.98; IQR: 0.0377-3.17 vs. M: 2.25; IQR: 0.50-4.08; p = 0.0483), suggesting a reduction in systemic immune tolerance among these patients. This finding highlights the potential role of CD39 and CD73 expression on Treg cells as biomarkers for assessing disease severity and progression. Furthermore, elucidating the mechanisms driving these alterations may unveil new therapeutic strategies to restore immune equilibrium and mitigate endometriosis symptoms.

Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study.

OBJECTIVE: To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. METHOD: A retrospective cross-sectional study, was conducted in a Tertiary hospital. PATIENTS: Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. INTERVENTION: The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. RESULTS: A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. CONCLUSION: Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.