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Evidence suggests that immune system dysfunction and macrophages are involved in the disease establishment and progression of endometriosis. Among the factors involved in this alteration in macrophage activity, Small Extracellular Vesicles (sEVs) have been described to play a role favoring the switch to a specific phenotype with controversial results. This study aims to investigate the potential effect of circulating sEVs in the plasma of well-characterized patients with endometriosis on the polarization of macrophages. sEVs were isolated from the plasma of patients diagnosed with endometriosis confirmed by histopathological analysis. Two groups of patients were recruited: the endometriosis group consisted of patients diagnosed with endometriosis by imaging testing (gynecological ultrasonography and/or magnetic resonance imaging), confirmed by histopathologic study (n = 12), and the control group included patients who underwent laparoscopy for tubal sterilization without presurgical suspicion of endometriosis and without endometriosis or signs of any inflammatory pelvic condition during surgery (n = 12). Human THP1 monocytic cells were differentiated into macrophages, and the effect of sEVs on cell uptake and macrophage polarization was evaluated by fluorescent labeling and measurement of the IL1B , TNF , ARG1 , and MRC1 expression, respectively. Although no changes in cell uptake were detected, sEVs from endometriosis induced a polarization of macrophages toward an M2 phenotype, characterized by lower IL1B and TNF expression and a tendency to increase MRC1 and ARG1 levels. When macrophages were stimulated with lipopolysaccharides, less activation was also detected after treatment with endometriosis sEVs. Finally, endometriosis sEVs also induced the expression of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARG); however, treatment with rosiglitazone, a PPARG agonist, had no effect on the change in macrophage phenotype. We conclude that circulating sEVs in women with endometriosis have a certain capacity to shift the activation state of macrophages toward an M2 phenotype, but this does not modify the uptake level or the response to PPARG ligands., Competing Interests: The authors declare that no competing interests exist.

Deep endometriosis (DE) can be more aggressive than other types of endometriosis, and may even lead to irreversible severe complications such as complete unilateral loss of renal function. We aimed to describe the clinical and radiologic characteristics of DE patients diagnosed with irreversible unilateral loss of renal function due to unilateral ureteral stenosis and evaluate risk factors for developing this loss. This retrospective cohort study included 436 patients who underwent laparoscopic DE surgery. We evaluated two groups of patients according to preserved (Non-Renal Loss Group; n = 421) or irreversible unilateral damaged renal function (Renal Loss Group; n = 15). Preoperative epidemiologic variables, clinical characteristics, radiologic findings and surgical treatments of all the patients were collected. The Renal Loss Group had a higher infertility rate and a higher proportion of asymptomatic patients. The following radiological variables showed statistically significant differences between the two groups: mean endometrioma diameter, the presence of intestinal DE and negative sliding sign. Multivariate analysis showed that infertility, being asymptomatic, having intestinal DE or torus uterinus/uterosacral ligament DE and a negative sliding sign significantly increased the risk of loss of renal function. Therefore, among patients with these clinical and/or radiological variables, severe urinary tract obstruction should be specifically ruled out., (© 2023. The Author(s).)

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.

Study Objective: To compare the accuracy of preoperative ultrasound (US) in predicting the laparoscopically defined 2021 American Association of Gynecologic Laparoscopists (AAGL) Endometriosis Staging., Design: Retrospective multicenter study of patients treated at 3 specialized endometriosis centers., Setting: Three specialized endometriosis surgical centers in São Paulo (Brazil), Barcelona (Spain), and Avellino (Italy) participated., Patients: A total of 878 patients aged 15 to 45 years with no history of pelvic malignancy underwent laparoscopic (LPS) treatment for suspected endometriosis., Interventions: Retrospective review of preoperative transvaginal and transabdominal US (index test) assessed for endometriosis at all sites used in the 2021 AAGL Endometriosis Classification and classified patients into AAGL-US stages 1 to 4. Results were compared with reference-standard LPS (AAGL-LPS) staging., Measurements and Main Results: The AAGL-US and AAGL-LPS stage were concordant in 586 cases (66.7%) (weighted kappa [WK] 0.759; intraclass correlation = 0.906), with the highest agreement observed in patients with no endometriosis (n = 70, 75.3% concordance), AAGL-LPS stage 1 (104, 50.7%) and stage 4 disease (358, 88.2%). Endometriosis was most accurately diagnosed in the rectum/sigmoid colon (WK 0.862), bladder (WK 0.911), and ovaries (WK 0.835/0.795 for right/left, respectively) and least accurately diagnosed at superficial peritoneal (WK 0.442), tubal (WK 0.391/0.363 for right/left, respectively), and retrocervical/uterosacral ligament (WK 0.656) sites., Conclusion: Sonographic estimation of the 2021 AAGL Endometriosis Staging is greatest in AAGL-LPS stages 1 and 4 and among patients with no endometriosis. US best identifies endometriosis of the ovaries, bladder, and bowel but is more limited for the tubes and superficial peritoneum., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Endometriosis can be classified into three phenotypes: superficial, ovarian, and deep. Deep endometriosis (DE) has been associated with more severe pain symptoms, although no large-scale studies have evaluated the association between pain intensity and infertility and the different compartments of the pelvis affected by superficial and DE. This retrospective study included 1116 women who underwent laparoscopy for endometriosis treatment at two referral centers between 2009 and 2019. For the evaluation of each symptom, patients were divided according to their visual analog scale score (< 7 and ≥ 7) and fertility status. On multiple logistic regression, severe dysmenorrhea and dyschezia were correlated with DE of the posterior compartment alone (odds ratio (OR) = 1.6, confidence interval (CI) 1.09-2.34, and p = 0.02 and OR = 2.09, CI 1.36-3.23, and p < 0.01, respectively) and in combination with other compartments. DE of the posterior and lateral compartments had the most consistent statistical power (OR = 3.55 for dysmenorrhea and OR = 4.4 for dyschezia). Infertility was associated with DE of the posterior compartment alone (OR = 1.6, CI 1.06-2.54, p = 0.04) and in combination with the anterior compartment (OR = 2.62, CI 1.29-5.29, p < 0.01), with the combination of posterior and anterior compartment having the highest OR value. Severe dyschezia and infertility were also correlated with the presence of multiple localizations of DE (p = 0.04 and p < 0.01). This study confirms the association between DE and severe pain symptoms as well as the influence of the number of DE compartments on the severity of symptoms and the chance of infertility., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: Several studies have reported a high prevalence of autoimmune diseases such as systemic lupus erythematosus (SLE) in endometriosis patients. The aim of this study was to evaluate the SLE autoimmune antibody profile in patients with deep (DE) and non-deep endometriosis (Non-DE)., Materials and Methods: Four groups of premenopausal patients were evaluated: patients with DE (n = 50); patients with ovarian endometriomas (Non-DE; n = 50); healthy patients without endometriosis (C group; n = 45); and SLE patients without endometriosis (SLE group; N = 46). Blood samples were obtained and the standard SLE autoimmune profile was evaluated in all patients. Pain symptoms related to endometriosis and clinical SLE manifestations were also recorded., Results: The DE group presented a statistically significant higher proportion of patients with antinuclear antibodies (ANA) (20%) compared to the Non-DE group (4%) and C group (2.2%). Levels of complement were more frequently lower among DE and Non-DE patients although differences did not reach statistical significance. Similarly, anti-dsDNA antibodies and anticoagulant lupus were positive in more patients of the DE group but did not reach statistical significance. The DE group complained of more arthralgia and asthenia compared to the Non-DE and C groups., Conclusions: The results of this study showed higher positivity of ANA and greater arthralgia and asthenia in patients with DE compared with Non-DE patients and healthy controls, suggesting that they may have a higher susceptibility to autoimmune diseases and present more generalized pain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 μg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed., (© 2023. The Author(s).)

Background: Vaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis., Objectives: We aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes., Design: A total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group)., Methods: Data regarding demographics, clinical characteristics, hormonal treatment, and menstrual-associated symptoms in the first and second cycle after vaccination were collected through an online survey., Results: A similar percentage of patients in both the endometriosis and the non-endometriosis group self-reported menstrual-associated changes the first (52.6% versus 48.8%, respectively) and second cycle after vaccination (29.0% versus 28.1%, respectively). Although the total symptoms recorded were not different between the two groups, several specific symptoms were statistically more frequent in the endometriosis group. These were pain disorders and fatigue in the first cycle after vaccination and pain disorders, menstrual headache and fatigue in the second cycle after vaccination. Bleeding frequency/regularity disorders were found to be more frequent in the non-endometriosis group in the first cycle after vaccination. Patients under hormonal treatment reported fewer changes in menstrual symptoms in the first and second cycle after vaccination compared with those not receiving this treatment. Similarly, patients in the endometriosis group receiving hormonal treatment reported fewer changes in menstrual-associated symptoms compared with those not following any hormonal treatment in the first and second menstrual cycle after the last vaccination., Conclusion: Women with endometriosis immunized with mRNA-based SARS-CoV-2 vaccines did not perceive greater worsening or new menstrual-associated symptoms after complete COVID-19 vaccination compared with healthy controls. Hormonal treatment may have a protective effect against worsened or new menstrual symptoms induced by COVID-19 vaccination.

Deep endometriosis (DE) occurs in 15-30% of patients with endometriosis and is associated with concomitant adenomyosis in around 25-49% of cases. There are no data about the effect of the presence of adenomyosis in terms of surgical outcomes and complications. Thus, the aim of the present study was to evaluate the impact of adenomyosis on surgical complications in women with deep endometriosis undergoing laparoscopic surgery. A retrospective cohort study including women referred to the endometriosis unit of a referral teaching hospital. Two expert sonographers preoperatively diagnosed DE and adenomyosis. DE was defined according to the criteria of the International Deep Endometriosis Analysis group. Adenomyosis was considered when 3 or more ultrasound criteria of the Morphological Uterus Sonographic Assessment group were present. Demographical variables, current medical treatment, symptoms, DE location, surgical time, hospital stay and difference in pre and post hemoglobin levels were collected. The Clavien-Dindo classification was used to assess surgical complications, and multivariate analysis was performed to compare patients with and without adenomyosis. 157 DE patients were included into the study; 77 (49.05%) had adenomyosis according to transvaginal ultrasound (TVS) and were classified in the A group, and 80 (50.95%) had no adenomyosis and were classified in the noA group. Adenomyosis was associated with a higher rate of surgical complications: 33.76% (A group) vs. 12.50% (noA group) (p < 0.001). Multivariate analysis showed a 4.56-fold increased risk of presenting complications in women with adenomyosis (CI 1.90-11.30; p = 0.001) independently of undergoing hysterectomy. There was a statistically significant association between the number of criteria of adenomyosis present in each patient and the proportion of patients presenting surgical complications (p < 0.001). Adenomyosis is an independent preoperative risk factor for surgical complications in DE surgery after adjustment for known demographic, clinical and surgical risk factors., (© 2022. The Author(s).)

Background: Endometriosis is a debilitating chronic inflammatory disease. The current SARS-COV2 pandemic has had an impact on the management of these patients. Tele-health care has been a relevant tool. The aim of this study was to analyze the impact of the SARS-COV2 pandemic on the perceived clinical health status and the type of care received in patients with endometriosis. Materials and Methods: We evaluated 945 premenopausal women treated at the Hospital Clinic of Barcelona between October 1 and December 31, 2020. Five hundred forty-nine women had endometriosis, and 396 had other benign gynecological diseases. An online health survey was sent to these patients. Clinicopathological features data were recorded. Results: Compared to patients with other benign gynecological diseases, a higher proportion of patients with endometriosis reported worsening of their symptoms (148/549, 27% vs. 85/396, 21.5%) and concern about their disease (515/549, 93.8% vs. 342/396, 86.4%), and more frequently received tele-health care (73.8% vs. 54.0%) during the pandemic. Patients with endometriosis and "significant" pelvic pain reported more concern and worsening than patients without "significant" pelvic pain, and evaluated the assistance received poorly. Multivariate analysis showed pelvic pain, limitation in usual activity, and sadness as risk factors of perception of disease worsening. Awaiting surgery and the feeling of sadness were risk factors of concern. Conclusions: Patients with endometriosis, and especially patients with "significant" pelvic pain, reported greater concern and the perception of worsening during the SARS-COV2 pandemic. Tele-health is a useful tool in patients with endometriosis, and face-to-face visit should be considered in those reporting "significant" pelvic pain. Clinical Trial Registration Number: HCB 1202011497.

Background: The quality of life of women with deep infiltrating endometriosis (DIE) is impaired and may improve with combined oral contraceptives (COCs)., Aim: To compare the overall and sexual quality of life of patients diagnosed with DIE with or without associated adenomyosis (AD) with that of healthy controls and determine the influence of a COC containing 2 mg dienogest/30 μg ethinyl estradiol on these aspects., Methods: We enrolled 42 women diagnosed with DIE; 31 diagnosed with DIE + AD by transvaginal ultrasound, and 39 non-AD/DIE controls. All patients were interviewed regarding pain symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), heavy menstrual bleeding using the Pictorial Blood Loss Assessment Chart, quality of life using the Short Form-36 questionnaire (SF-36), and sexual quality of life using the Sexual Quality of Life-Female questionnaire (SQOL-F) and the Brief Profile of Female Sexual Function (B-PFSF) before starting COCs and after 12 months of treatment., Outcomes: There was significant improvement in overall and sexual quality of life after treatment in DIE and DIE + AD patients., Results: Non-AD/DIE controls showed significantly higher scores in the B-PFSF, the SQOL-F and the SF-36 questionnaires (P < .05) at baseline versus the other groups. DIE + AD patients showed poorer quality of sexual life and greater intensity in pain symptoms compared with DIE patients. After 12 months of treatment, there was a significant improvement in overall and sexual quality of life in the DIE and DIE + AD groups, with improvement in sexual quality of life being slightly greater in DIE + AD patients compared with DIE patients. Pain symptoms also decreased in both groups., Clinical Implications: Patients with DIE + AD showed greater impairment in overall and sexual quality of life compared with patients with isolated DIE which seems to improve with a COC containing 2 mg dienogest/30 μg ethinyl estradiol., Strengths & Limitations: Strengths include the long-term follow up, assessment of the impact of two associated conditions, and administration of the same COC in all patients. Limitations include the relatively small sample size, and the fact that we did not assess the effectiveness of a flexible extended COC regimen containing 2 mg dienogest/30 μg ethinyl estradiol since the groups were different at baseline., Conclusion: Patients diagnosed with DIE with or without AD have a decreased quality of life which may improve with a COC containing 2 mg dienogest/30 μg ethinyl estradiol. Further research is needed to confirm our results. Alcalde AM, Martínez-Zamora MÁ, Gracia M, et al. Assessment of Quality of Life, Sexual Quality of Life, and Pain Symptoms in Deep Infiltrating Endometriosis Patients With or Without Associated Adenomyosis and the Influence of a Flexible Extended Combined Oral Contraceptive Regimen: Results of a Prospective, Observational Study. J Sex Med 2022;19:311-318., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Endometriosis greatly impacts women's health and quality of life. However, research on the prevalence and incidence of endometriosis remains inconclusive. This study assesses time trends in the prevalence and incidence of endometriosis diagnoses in Catalonia (Spain) from 2009 to 2018, considering differences by age and socioeconomic status., Methods: Population-based cohort study using data from the Information System for Research in Primary Care (SIDIAP) database. Data were included from over 2.4 million women aged 15-55 years between 1 January 2006 and 31 December 2018., Results: A total of 2,337,717 women were selected as the incident population; 0.7% had an endometriosis diagnosis. Median (interquartile range) age at diagnosis was 37 (32-43) years. Most women were European (92.3%) and lived in urban areas (73.6%). Overall prevalence of endometriosis consistently increased during the 2009-2018 period, and it was 1.24% in 2018. Trends were the highest for women with less socioeconomic deprivation and for the 35-44 years age group. Median incidence rates were 94.9 (92.6-102.9) per 100,000 women-years, being the highest in women aged 35-44 years throughout the whole study period. Overall, incidence increased between 2015 and 2017, and plateaued or decreased in 2018. Incidence rates in women from the most deprived and rural areas were lower, although incidence time trends by socioeconomic status were unclear., Conclusion: Healthcare services and public health strategies need to be strengthened to ensure timely endometriosis diagnosis and treatment. Special attention should be given to the most affected populations and the social inequities of health.

Adenomyosis and endometriosis are similar gynecological diseases that decrease sexual quality of life and, in the case of endometriosis, satisfaction in couple relationships. This study aimed to assess sexual quality of life and couple satisfaction in women diagnosed with adenomyosis (AD) or deep infiltrating endometriosis (DIE). The study population included three groups of couples: one composed of 58 couples in which the woman was diagnosed with AD by transvaginal ultrasound (AD group), a second group comprising 55 couples in which the woman was diagnosed with isolated DIE by transvaginal ultrasound (DIE group), and a third group composed of 60 couples in which the women did not have AD or endometriosis (non-AD/DIE group). All women completed the Sexual Quality of Life-Female (SQOL-F) questionnaire, and all the couples completed the Dyadic Adjustment Scale (DAS). Sexual quality of life was significantly worse in women with AD or DIE compared with non-AD/DIE controls. Dyadic adjustment was significantly worse in the AD and DIE groups compared with the non-AD/DIE group. AD and DIE may impair quality of sexual life and couple relationships. Clinicians should be aware of this issue when treating women with AD or DIE.

Objective: To evaluate the accuracy of transvaginal ultrasound (TVS) in diagnosing deep endometriosis (DE) involving the uterosacral ligaments (USLs), torus uterinus (TU) or posterior vaginal fornix (PVF) in women with suspected endometriosis scheduled for laparoscopic surgery., Methods: In this prospective study, consecutive women with clinically suspected pelvic endometriosis who were scheduled for laparoscopic surgery were invited to participate. TVS was performed before surgery. TVS findings were compared with those obtained at laparoscopy and confirmed histologically. The accuracy of TVS for diagnosing DE involving the USLs, TU or PVF was assessed. Additionally, the association of DE involving the USLs, TU or PVF on TVS with symptoms and with DE affecting other pelvic locations was assessed., Results: In total, 172 patients were included. The global sensitivity and specificity of TVS in diagnosing DE affecting the USLs, TU and/or PVF were 92% and 87%, respectively. For DE involving the USLs, the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio and negative likelihood ratio of TVS were 89.5%, 96.6%, 82.1%, 85.0%, 95.8%, 5.41 and 0.04, respectively; the respective values for DE involving the TU were 86.6%, 83.9%, 89.4%, 89.0%, 84.4%, 7.92 and 0.18, and the respective values for DE involving the PVF were 93.6%, 87.0%, 94.6%, 71.4%, 97.9%, 16.20 and 0.14. Logistic regression analysis showed a significant association between DE affecting the USLs, TU and/or PVF and DE affecting the rectosigmoid (odds ratio, 5.43; P < 0.001). Dyschezia was associated strongly with DE involving the USLs, TU and PVF, while dysmenorrhea was associated significantly with DE involving the TU., Conclusion: TVS has high accuracy, sensitivity, specificity, PPV and NPV for the detection of DE involving the USLs, TU and PVF in women with suspected endometriosis scheduled for laparoscopic surgery. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Study Objective: To develop a new endometriosis classification system for scoring intraoperative surgical complexity and to examine its correlation with patient-reported pain and infertility., Design: Multicenter study of patients treated at 3 recognized endometriosis centers., Setting: Three specialized endometriosis surgical centers in São Paulo, Brazil and Barcelona, Spain., Patients: Patients aged 15 to 45 years with histologically proven endometriosis and no history of pelvic malignancy underwent laparoscopic treatment of endometriosis., Interventions: Demographic data and clinical history, including dysmenorrhea, noncyclic pelvic pain, dyspareunia, dysuria and dyschezia, were prospectively recorded. All patients were staged surgically according to the new 2021 American Association of Gynecologic Laparoscopists (AAGL) and revised American Society of Reproductive Medicine (ASRM) classification systems. The staging for each system was compared against a 4-level surgical complexity scale defined by the most complex procedure performed., Measurements and Main Results: A total of 1224 patients undergoing surgery met inclusion criteria. The AAGL score discriminated between 4 stages of surgical complexity with high reproducibility (κ = 0.621), whereas the ASRM score discriminated between the complexity stages with poor reproducibility (κ = 0.317). The AAGL staging system correlated with dysmenorrhea, dyspareunia, dyschezia, total pain score, and infertility comparably with the ASRM staging system., Conclusion: The AAGL 2021 Endometriosis Classification allows for identifying objective intraoperative findings that reliably discriminate surgical complexity levels better than the ASRM staging system. The AAGL severity stage correlates comparably with pain and infertility symptoms with the ASRM stage., (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: We performed a long-term follow-up to quantify the impairment of sexual quality of life (SQL) and health-related QL (HRQL) in sexually active women after laparoscopic excision of deep infiltrating endometriosis (DIE)., Design: Prospective case-control study., Setting: Hospital Clinic of Barcelona., Patients: A total of 193 patients (after dropout and exclusions) were divided into 2 groups: one hundred twenty-nine premenopausal women with DIE (DIE group) and 64 healthy women who underwent tubal ligation (C group)., Interventions: All patients underwent laparoscopic surgery: laparoscopic endometriosis surgery in the DIE group and laparoscopic tubal ligation in the C group. All women were followed for at least 36 months, and they completed the Medical Outcomes Study 36-item short form questionnaire to assess their HRQL and 3 self-administered questionnaires that evaluate different aspects of SQL: the generic Sexual Quality of Life-Female questionnaire, the Female Sexual Distress Scale to evaluate "sexually related distress," and the Brief Profile of Female Sexual Function to screen hypoactive sexual desire disorder. The patients with DIE as well as the controls completed the 4 questionnaires before surgery, and the patients with DIE also completed the questionnaires at 6 and 36 months after surgery., Measurements and Main Results: A comparison of the patients and controls before surgery showed a statistically significant impairment in SQL and HRQL among the patients with DIE. A statistically significant improvement in SQL and HRQL was observed in the DIE group 6 months after surgery, with scores being similar to those of the C group. An evaluation 36 months after surgery showed that SQL and HRQL were better than presurgical SQL and HRQL in the DIE group, with a slight reduction compared with the 6-month evaluation., Conclusion: SQL and HRQL improved in patients with DIE undergoing complete laparoscopic endometriosis resection and were comparable to those of healthy women at 6 months after surgery, showing a slight reduction at 36 months of follow-up., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To analyze the utility of carbohydrate antigen (CA)125 and human epididymis protein 4 (HE4) to detect malignancy in women with ovarian endometriosis, when ovarian cancer is suspected and ultrasonography results are inconclusive., Methods: Women who underwent surgery between 2015 and 2019 for ovarian endometriosis or for adnexal masses, with a final diagnosis of ovarian carcinoma (clear cell and endometrioid) were included in this retrospective study. The women were divided into three groups: ovarian endometriosis (OE), ovarian carcinoma without endometriosis (OC), and ovarian carcinoma with endometriosis (OC + E). Adnexal masses were assessed preoperatively by transvaginal ultrasonography according to the International Ovarian Tumor Analysis (IOTA) simple rules, and CA125 and HE4 blood levels were obtained., Results: Of 208 women, 45 had malignancy, 16 in the OC + E group and 29 in the OC group. According to transvaginal ultrasonography, 13 were classified as undetermined risk of malignancy: OC group: 3, OE group: 3, and OC + E group: 7. When we compared the tumor biomarkers, significant differences in HE4 but not in CA125 levels were found between the groups., Conclusions: When ovarian malignancy is suspected in patients with ovarian endometriosis, HE4 is a more useful tumor biomarker to diagnose OC when ultrasonography results are inconclusive.

Objectives: To evaluate the accuracy of transvaginal ultrasound (TVUS) in predicting detrusor infiltration and ureteral meatus involvement in patients with bladder endometriosis (BE) to select which cystoscopic procedures could be avoided and, secondarily, to assess the relationship between symptoms and the characteristics of nodules and the association of BE with other forms of endometriosis., Methods: Patients with BE diagnosed by TVUS were classified according to detrusor infiltration: BE with partial involvement of the muscular layer (group 1) and total muscular layer involvement with bladder protrusion (group 2). We analyzed the accuracy of TVUS compared with subsequently performed cystoscopy, the correlation with symptoms, and the association with other forms of endometriosis., Results: Among the 22 patients included, TVUS showed 9 patients with BE nodules partially affecting the detrusor (group 1) with normal cystoscopic findings (TVUS negative predictive value, 100%). Transvaginal ultrasound detected 13 nodules with total involvement, all visible by cystoscopy (TVUS positive predictive value, 100%). Transvaginal ultrasound also identified ureteral orifices that were free of involvement at greater than 10 mm from the BE nodule in 21 of 22 women (TVUS sensitivity, 95%). Ultrasound criteria for adenomyosis and endometriosis in other locations were present in 20 of 22 patients., Conclusions: Transvaginal ultrasound can identify the infiltration of BE nodules in the bladder wall and predict cystoscopic findings with great accuracy. Nodules that partially affect the muscular layer have normal cystoscopic findings, thereby obviating the need for this procedure. Bladder endometriosis nodules are commonly associated with other forms of endometriosis and do not usually affect the ureteral meatus., (© 2020 American Institute of Ultrasound in Medicine.)

This study aimed to assess the impact of adenomyosis (AD) on different domains of sexual life. The study population included three groups: one composed of 68 women diagnosed with AD by transvaginal ultrasound, a second group comprised by 65 women diagnosed with isolated deep infiltrating endometriosis by transvaginal ultrasound and a third group including 70 women without AD or/and endometriosis. All participants completed the Brief Profile of Female Sexual Function (B-PFSF), the Female Sexual Distress Scale (FSDS), and the Sexual Quality of Life-Female (SQOL-F) questionnaire. Compared with non-AD/DIE controls, women with AD present significantly lower scores of the B-PFSF and the SQOL-F questionnaires and higher FSDS questionnaire scores ( p < .0001). There were no differences between the groups of AD and deep infiltrating endometriosis. Clinicians should be aware that the quality of sexual life may be affected in patients with AD. Early diagnosis and multidisciplinary management would contribute to preventing impairment of sexual quality of life in these patients.

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., (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objectives: To analyze the effect of bowel preparation prior to transvaginal ultrasound (TVS) examination on the detection of bowel involvement and the description of rectosigmoid nodules of deep infiltrating endometriosis (DIE), and to evaluate patient tolerance of bowel preparation., Methods: This was a prospective study of paired data obtained between September 2015 and March 2016 from a cohort of women referred, on suspicion of DIE but without surgical criteria, to the endometriosis unit of a tertiary university hospital. In all patients, the wall of the rectum and lower sigmoid colon was evaluated by two TVS examinations: the first was performed without bowel preparation and the second was done after the patient had followed a 3-day low-residue diet and received two 250-mL enemas, one the night before TVS and the second 1-3 h before the examination. The presence of adhesions, number and size of rectosigmoid nodules, deepest layer of the rectum affected, percentage of the circumference of the bowel affected and distance from the most caudal part of the bowel nodule to the anal verge were determined. Patient tolerance to bowel preparation was assessed using a 5-point Likert scale, in which 1 represented 'very well tolerated' and 5 represented 'very poorly tolerated'., Results: The mean ± SD age of the 110 patients included in the study was 36.8 ± 5.07 years. As many as 55% of those identified during the first examination (TVS alone) as having adhesions were identified at the second examination (TVS with prior bowel preparation) as having rectosigmoid nodules, and 22 additional nodules were observed on TVS following bowel preparation. These newly detected rectosigmoid nodules, initially assessed mainly as adhesions, were smaller and more superficial compared with the nodules detected on TVS alone, or located in the anterior sigmoid wall. Patient tolerance overall to bowel preparation scored a mean of 1.81 on the 5-point Likert scale., Conclusions: Bowel preparation is well tolerated by patients. When bowel preparation is performed before TVS, the detection of small and superficial nodules and those in the anterior sigmoid wall is improved, allowing more detailed description of these nodules in patients with suspected endometriosis. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess ovarian reserve through antral follicle count (AFC) and ovarian volume (OV) determination after decapsulation (stripping technique) or CO 2 laser vaporization in the surgical treatment of patients with bilateral ovarian endometriomas., Methods: This prospective, randomized, blinded, self-controlled pilot study was set in a tertiary university hospital between January 2017 and December 2017, and included consecutive patients with bilateral ovarian endometriomas ≥3 cm. The study was registered with ClinicalTrials.gov under the title 'Impact on ovarian reserve according to the type of ovarian endometrioma excision: laser versus conventional cystectomy'; NCT03826355. For each patient, the endometrioma on one side was randomly selected to undergo CO 2 laser vaporization and the contralateral endometrioma to undergo laparoscopic decapsulation., Results: A total of 16 patients were included. There were no statistically significant between-group differences in OV and AFC levels at baseline. At the 6-month follow-up, OV and AFC levels were significantly higher in the laser-treated group versus the stripping technique., Conclusion: Lower OV and AFC levels following excisional surgery for endometrioma versus CO 2 laser vaporization suggest a higher impact on ovarian reserve after the stripping procedure.

Extrapelvic endometriosis is a rare and usually misdiagnosed entity. Some extrapelvic endometriotic lesions are small and nonpalpable, which makes them difficult to locate and remove. Here, we report the use of radioactive seed localization to locate and guide the excision of a small, nonpalpable endometriotic lesion. A 32-year-old woman presented with disabling pain in the right inguinal area. Magnetic resonance imaging and abdominal ultrasound results showed an 11-mm nodule in the abdominal wall, in the vicinity of the groin, consistent with an endometriotic lesion. The radioactive seed was placed within the lesion with the help of ultrasonography, and excision was guided with a portable gamma camera. Complete excision of the endometriotic nodule was achieved. We propose radioactive seed localization as an accurate and feasible technique for the treatment of nonpalpable endometriotic lesions., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence of fibromyalgia among women with endometriosis and analyze the effect of fibromyalgia on health-related quality of life (HRQoL)., Methods: An observational case-control study conducted at a tertiary hospital in Barcelona between April 2015 and March 2017 among women with deep infiltrating endometriosis (DIE; n=80), women with superficial endometriosis or ovarian endometrioma (non-DIE; n=76), and control women without endometriosis (n=73). Fibromyalgia was assessed via the London Fibromyalgia Epidemiological Study Screening Questionnaire (LFESSQ). HRQoL was evaluated with the 36-Item Short Form (SF-36) questionnaire. The impact of fibromyalgia and other clinical characteristics was assessed by multivariate regression analysis., Results: More women fulfilled the criteria for fibromyalgia in the DIE group than in the non-DIE and control groups by LFESSQ-4 (31 [39%], 12 [16%], and 6 [8%], respectively; P=0.009) and LFESSQ-6 (22 [28%], 8 [11%], and 4 [5%], respectively; P=0.008). The DIE group reported significantly poorer HRQoL for all SF-36 dimensions. Women with DIE who fulfilled the criteria for fibromyalgia had lower physical component scores (-31.6; 95% confidence interval, -50.8 to -12.3; P=0.003)., Conclusion: The estimated prevalence of fibromyalgia was higher among women with DIE. Women with DIE and positive fibromyalgia screening had lower HRQoL., (© 2019 International Federation of Gynecology and Obstetrics.)

Study Objective: To evaluate serial generation of microparticles (MPs) after laparoscopic stripping or CO 2 laser vaporization in the surgical treatment of patients with ovarian endometrioma (OE)., Design: A prospective, randomized, blinded, pilot study (Canadian Task Force classification I)., Setting: Tertiary care university hospital from December 2014 to July 2016., Patients: Thirty women with unilateral OE undergoing laparoscopic surgery., Intervention: Patients were randomly selected to undergo either CO 2 laser vaporization (L group) or laparoscopic stripping (S group) of OE., Measurements and Main Results: Blood samples were collected before surgery and at 2 hours, 24 hours, 1 month, and 3 months after surgery. An MP generation curve after OE surgery was created. MP generation was greater in the S group than in the L group at all time points evaluated. The MP generation curve showed a significantly higher area under the curve after excisional surgery (p <.05)., Conclusion: The higher MP levels in the S group suggest an increased inflammation and procoagulant response after this procedure., (Copyright © 2018. Published by Elsevier Inc.)

Neutrophil extracellular traps (NETs) have been described to be related to the pathogenesis of inflammatory and autoimmune conditions. Endometriosis is currently considered a chronic inflammatory condition. Therefore, we performed a preliminary case-control study to compare the circulating plasma NET levels in patients with surgically confirmed endometriosis (E group, n = 82) and those of patients without surgical findings of endometriosis (C group, n = 35). Venous blood samples were obtained at the time of surgery. Circulating plasma NET levels were assessed as histone-DNA complexes (ie, nucleosomes) by a quantitative sandwich enzyme-linked immunosorbent assay. The results were expressed in arbitrary units. Circulating plasma NET levels were significantly higher in the E group compared with the C group (median [25th; 75th percentiles]): E group: 0.734 [0.484; 1.363]; C group: 0.541 [0.411; 0.653]; P = .005). The subanalysis of E group patients with deep infiltrating endometriosis (DIE group) or without DIE (non-DIE group) showed that plasma NET levels were higher in the DIE group ( P = .02). No differences were observed in NET levels among patients with and without severe pelvic pain or in patients with and without infertility, regardless of the presence of endometriotic lesions. Therefore, our study shows significantly higher NET levels in patients with endometriosis, which seem to be attributed to increased levels in the subgroup of patients with DIE, suggesting that the presence of elevated circulating plasma NET levels may reflect an inflammatory status in this gynecological condition. Further research is warranted to confirm our findings and to assess the exact role of NETs in the pathophysiological mechanisms of endometriosis.

Objective: To assess the impact of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain on endometriosis-associated pelvic pain., Study Design: Multicenter, open-label, non-comparative clinical trial in a representative sample of women with endometriosis-associated pelvic pain., Results: In total, 398 patients with a mean age of 34.6 ± 7.2 years were treated with a combination of N-acetyl cysteine, alpha lipoic acid and bromelain for 6 months. At baseline, 92.7% of the patients had pain intensity > 4 on the visual analogue scale (VAS); at 3 months of treatment, this percentage decreased to 87.2% (p = 0.074) and at 6 months the percentage was 82.7% (p < 0.05)., Conclusions: Women with endometriosis who wish to become pregnant and are treated with a preparation containing N-acetyl cysteine, alpha lipoic acid and bromelain experienced a significant improvement in endometriosis-associated pelvic pain and required lower intake of rescue analgesics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.)

Study Question: Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis?, Summary Answer: Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a consequent increase in fibrosis in patients with endometriosis., What Is Known Already: It is nowadays accepted that oxidative stress plays an important role in the onset and progression of endometriosis. Oxidative stress is able to induce the synthesis of some members of the 'ADAM' family, such as ADAM17. ADAM17/Notch signalling is dysregulated in other profibrotic and inflammatory diseases., Study Design, Size, Duration: This was a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n = 202) during surgery for a benign gynaecological condition., Participants/materials, Setting, Methods: After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free control women were enrolled. Peritoneal fluid (PF) samples were obtained from all the study participants during surgery in order to detect advanced oxidation protein products (AOPPs) and metalloproteinase activity of ADAM17. Stromal cells from endometrial specimens (n = 8) were obtained from endometrium of control patients (Cs), and from eutopic (Es) and ectopic (Ps) endometrium of patients with deep infiltrating endometriosis (DIE) (n = 8). ADAM17, Notch and the fibrosis markers α-smooth muscle actin (α-SMA) and type-I collagen were assessed using immunoblotting in all the endometrial samples obtained. Additionally, fibrosis was assessed after using Notch cleavage inhibitors (DAPT and FLI-06). Notch and fibrosis were also evaluated after stimulation of stromal endometrial cells with ADAM17 purified protein, increasing concentrations of H2O2 and primary cell culture supernatants., Main Results and the Role of Chance: Patients with DIE presented higher PF AOPP and ADAM17 protein levels than controls (P < 0.01 and P < 0.05, respectively). In addition, these two markers were positively correlated (r = 0.614; P < 0.001). At the cellular level, ADAM17 activity was increased in Es and Ps compared to Cs (P < 0.001 and P < 0.01, respectively). Furthermore, Ps presented hyperactivation of Notch signalling (P < 0.05) and augmentation of fibrosis markers (P = 0.009 for α-SMA and P = 0.015 for type-I collagen) compared to controls. The use of DAPT and FLI-06 reduced both fibrosis markers in Ps but not in Cs. Stimulation with ADAM17, H2O2 and Ps supernatant culture significantly increased Notch and fibrosis in both Ps and Cs., Large Scale Data: N/A., Limitations Reasons for Caution: The control group consisted of women who underwent surgery for benign gynaecological conditions, which could lead to biases because some of these conditions may cause alterations in oxidative stress and the ADAM17/Notch pathways. The small sample size of endometrial biopsies used for each group of patients (n = 8) is a limitation of the study, and results should be interpreted with caution., Wider Implications of the Findings: We propose a novel pathway in endometriosis pathogenesis that correlates oxidative stress, hyperactivation of ADAM17/Notch signalling and a consequent increase in fibrosis. This study suggests that Notch signalling plays a key role in the fibrotic processes that take place in ectopic lesions of patients with DIE, as already observed in other pro-fibrotic diseases., Study Funding and Competing Interest(s): This work was supported by grants from University Paris Descartes, INSERM and Fundación Alfonso Martín Escudero. The authors have no competing interests to declare., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Introduction: Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model., Study Design: Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured., Results: Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment., Conclusion: Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

Objective: The purpose of the study was to develop an easily applicable predictive model to predict deep infiltrating endometriosis in patients with ovarian endometrioma., Study Design: We performed a retrospective analysis of 178 consecutive women with ovarian endometrioma who underwent surgery, with histological confirmation and complete removal of endometriosis in the Hospital Clinic of Barcelona. Several markers were prospectively obtained and compared between the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma and women with only ovarian endometrioma. Multiple logistic regression analysis was performed to create a model to predict the presence of deep infiltrating endometriosis and internal validation was later performed., Results: Of the 178 patients studied, 80 (45%) were classified in the ovarian endometrioma group and 98 (55%) in the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma. The independent variables to predict deep infiltrating endometriosis were: at least one previous pregnancy, a past history of surgery for endometriosis and the mean endometriosis-associated pelvic pain score. The area under the ROC curve was 0.91 (95% confidence interval: 0.86-0.94), with an optimal cut-off of the predicted probability of 0.54. The sensitivity of the model was 80% and the specificity 84%., Conclusions: This model predicts the development of deep infiltrating endometriosis in patients with ovarian endometriomas allowing prioritization of women for referral to specialized centers., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Study Question: Are the levels of total circulating cell-derived microparticles (cMPs) and circulating tissue factor-containing microparticles (cMP-TF) increased in patients with endometriosis?, Summary Answer: The levels of total cMP, but not cMP-TF, were higher in patients with endometriosis, and these were attributed to higher levels in patients with deep infiltrating endometriosis (DIE)., What Is Known Already: Previous studies have reported elevated levels of total cMP in inflammatory conditions as well as higher levels of other inflammatory biomarkers in endometriosis. Increased expression of tissue factor (a transmembrane receptor for Factor VII/VIIa) in eutopic and ectopic endometrium from patients with endometriosis has been described. There is no previous data regarding total cMP and cMP-TF levels in patients with endometriosis., Study Design, Size, Duration: A prospective case-control study including two groups of patients was carried out. The E group included 65 patients with surgically confirmed endometriosis (37 with DIE lesions) and the C group comprises 33 women without surgical findings of any form of endometriosis. Patients and controls were recruited during the same 10-month period. Controls were the next patient without endometriosis undergoing surgery, after including two patients with endometriosis., Participants/materials, Setting, Methods: Venous blood samples for total cMP and cMP-TF determinations were obtained at the time of surgery, before anesthesia at a tertiary care center. To assess total cMP, an ELISA functional assay was used and cMP-TF activity in plasma was measured using an ELISA kit., Main Results and the Role of Chance: Total cMP levels in plasma were higher in the E group compared with the C group (P < 0.0001). The subanalysis of endometriosis patients with DIE or with ovarian endometriomas without DIE showed that total cMP levels were higher in the DIE group (P = 0.001). There were no statistically significant differences in cMP-TF levels among the groups analyzed., Limitations, Reasons for Caution: This is a preliminary study in which the sample size was arbitrarily decided, albeit in keeping with previous studies analyzing cMP in other inflammatory diseases and other biomarkers in endometriosis. The control group included patients with other pathologies as well as healthy controls, and blood samples were taken at different phases of the cycle., Wider Implications of the Findings: Elevated total cMP levels in DIE patients may reflect an inflammatory and/or procoagulant systemic status in these patients. Further studies are warranted to confirm our findings and to assess the role of cMP levels in the pathophysiology of DIE., Study Funding/competing Interests: This study was supported in part by a grant from FIS-PI11/01560 and FIS-PI11/00977 within the 'Plan Nacional de I + D + I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and 'Fondo Europeo de Desarrollo Regional (FEDER)' and by the grant 'Premi Fi de Residència Emili Letang 2015' from the Hospital Clínic of Barcelona. The authors have no competing interests to disclose., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The identification of presurgical clinical markers may be helpful to allow the staging of endometriosis severity. It has been suggested that pain characteristics orientate the gynecologist about the anatomical involvement of endometriosis. The study was performed to analyze the correlation between pain symptoms and the anatomical location of endometriosis., Methods: One hundred fifty-five consecutive patients with a complete removal of deep infiltrating endometriosis (DIE) were included. Prior to surgery, data on patient and disease characteristics were obtained. The intensity of the pain symptoms was registered using a Visual Analogue Scale. The endometriotic lesions were categorized according to the Enzian morphological classification. Correlation and multivariate analysis were performed to assess the potential associations between pain characteristics (dysmenorrhea, pelvic pain, dyschezia, dyspareunia or dysuria) and the location of endometriosis or other disease-related characteristics (hematuria, rectal bleeding or adenomyosis)., Results: Pelvic pain was significantly associated with the presence of adenomyosis. Dyschezia was correlated with rectal bleeding and dysuria with the presence of hematuria. No relationship was found between other kinds of pain and the morphological location of endometriosis or other disease-related characteristics., Conclusion: Our data suggest that pelvic pain is correlated with the presence of adenomyosis in women with DIE. Further studies are required., (© 2016 S. Karger AG, Basel.)

Study Question: Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)?, Summary Answer: A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE., What Is Known Already: Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE., Study Design, Size, Duration: International expert consensus based on a systematic review of literature., Participants/materials, Setting, Methods: Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings., Main Results and the Role of Chance: We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE., Limitations, Reasons for Caution: The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here., Wider Implications of the Findings: This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population., Study Funding/competing Interests: None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD., Trial Registration Number: N/A., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Our objective was to compare the feasibility and safety of surgical procedures to treat gynecological pathologies with intestinal involvement performed by skilled gynecological surgeons and by a multidisciplinary team of gynecologists plus colorectal surgeons., Material and Methods: We performed a comparative, observational, prospective study at a tertiary referral center. The population included all women undergoing bowel surgery for gynecological pathologies over a 3-year period. Cases were analyzed by the specialty of the main surgeon performing the intestinal procedure. The main outcome measures were surgical procedure characteristics and postoperative outcomes and complications., Results: A total of 65 women were included. Surgery was exclusively performed by a subspecialized gynecologist in 30.8% of the women, and undertaken by a multidisciplinary team (colorectal surgeons and gynecologists) in 69.2%. The main demographic and clinical characteristics were comparable in both groups. Main indications for bowel resection in gynecological surgery were advanced ovarian cancer and deep infiltrating endometriosis. In addition to the standard gynecological surgical procedures, a total of 135 intestinal segments were resected, with sigmoid colon the most frequent intestinal segment resected in both groups (53% in the gynecologist group and in 60% in the multidisciplinary group). No significant differences were observed between the two groups in the distribution and frequency of surgical techniques used, rate of complications, mean hospitalization time or frequency of re-intervention., Conclusion: Skilled gynecological surgeons appear to be equally good at handling common intestinal problems as a team of gynecologist and colorectal surgeons., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Study Question: Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control group without endometriosis?, Summary Answer: DIE patients have higher levels of dioxins and polychlorinated biphenyls (PCBs) in adipose tissue compared with controls without endometriosis., What Is Known Already: Some studies have investigated the levels of dioxin-like substances, in serum samples, in patients with endometriosis, with inconsistent results., Study Design, Size, Duration: Case-control study including two groups of patients. The study group (DIE group) consisted of 30 patients undergoing laparoscopic surgery because of DIE. In all patients, an extensive preoperative work-up was performed including clinical exploration, magnetic resonance imaging (MRI) and transvaginal sonography. All patients with DIE underwent a confirmatory histological study for DIE after surgery. The non-endometriosis control group (control group), included the next consecutive patient undergoing laparoscopic surgery in our center due to adnexal benign gynecological disease (ovarian or tubal procedures other than endometriosis) after each DIE patient, and who did not present any type of endometriosis., Participants/materials, Setting, Methods: During the surgical procedure 1-2 g of adipose tissue from the omentum were obtained. Dioxin-like substances were analyzed in adipose tissue in DIE patients and controls without endometriosis., Main Results and the Role of Chance: The total toxic equivalence and concentrations of both dioxins and PCBs were significantly higher in patients with DIE in comparison with the control group (P < 0.05), mainly due to the significantly higher values of the two most toxic dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin [2,3,7,8-TCDD] and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]) (P < 0.01 for each compound). The levels of furan 2,3,4,7,8-PeCDF were statistically higher in the DIE group compared with controls. Only four congeners of PCBs had toxic equivalence values and concentrations that were statistically higher in patients with DIE, but these included the most toxic and carcinogenic PCB-126 (PCB-114 P < 0.05; PCB-156 P < 0.05; PCB-189 P = 0.04; PCB-126 P < 0.01)., Limitations, Reasons for Caution: Since few patients were recruited, the study is only exploratory. Our results need to be confirmed in larger and more heterogeneous population studies since environmental and even genetic factors involved in determining dioxins and PCBs widely vary in different countries. Furthermore, the strict eligibility criteria used may preclude generalization of the results to other populations and the surgery-based sampling frame may induce a selection bias. Finally, adipose tissue was obtained only from the omentum, and not from other adipose tissue of the body., Wider Implications of the Findings: Our results suggest a potential role of dioxin-like substances in the pathogenesis of DIE. Further studies are warranted to confirm our findings., Study Funding/competing Interests: None., Trial Registration Number: Not applicable., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Endometriosis is a benign gynaecological disease. Abundant bulk of evidence suggests that patients with endometriosis have an immunity dysfunction that enables ectopic endometrial cells to implant and proliferate. Previous studies show that natural killer cells have a pivotal role in the immune control of endometriosis., Methods and Findings: This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n= 202) during surgery for benign gynaecological conditions. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free controls women were enrolled. Patients with endometriosis were classified according to a surgical classification in three different types of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE). Peritoneal fluid samples were obtained from all study participants during the surgery in order to detect soluble NKG2D ligands (MICA, MICB and ULBP-2). When samples with undetectable peritoneal fluid levels of MICA, MICB and ULBP-2 were excluded, MICA ratio levels were significantly higher in endometriosis patients than in controls (median, 1.1 pg/mg; range, 0.1-143.5 versus median, 0.6 pg/mg; range, 0.1-3.5; p=0.003). In a similar manner peritoneal fluid MICB levels were also increased in endometriosis-affected patients compared with disease-free women (median, 4.6 pg/mg; range, 1.2-4702 versus median, 3.4 pg/mg; range, 0.7-20.1; p=0.001). According to the surgical classification, peritoneal fluid soluble MICA, MICB and ULBP-2 ratio levels were significantly increased in DIE as compared to controls (p=0.015, p=0.003 and p=0.045 respectively). MICA ratio levels also correlated with dysmenorrhea (r=0.232; p=0.029), total rAFS score (r=0.221; p=0.031) and adhesions rAFS score (r=0.221; p=0.031)., Conclusions: We demonstrate a significant increase of peritoneal fluid NKG2D ligands in women with endometriosis especially in those cases presenting DIE. This study suggests that NKG2D ligands shedding is a novel pathway in endometriosis complex pathogenesis that impairs NK cell function.

Cytokines, and specifically interleukin 6 (IL-6) and interleukin 8 (IL-8), have been associated with the pathogenesis of endometriosis. We studied serum concentrations of IL-6 and IL-8 in patients with deep infiltrating endometriosis (DIE) or ovarian endometriomas (OE), but no other forms of associated endometriosis disease type. We carried out a case-control study including 19 patients with OE alone (OE group), 14 patients with DIE alone (DIE group) and 24 healthy patients without endometriosis (C group). Serum concentrations of IL-6 and IL-8 were measured in the three groups of patients. Serum levels of both IL-6 and IL-8 were significantly higher in the OE group. A high positive correlation was found between serum IL-6 and IL-8 levels in the OE group but not in the DIE and C groups. Serum IL-8 alone achieved the highest predictive value of the presence of OE (adjusted OR: 1.44; sensitivity: 78.2%; specificity: 76.2%). The combination of IL-6 and IL-8 levels did not significantly improve the discrimination between subjects with OE and those with DIE over that of IL-8. OE but not DIE are associated with increased serum levels of IL-6 and IL-8, and thus these may become useful tools for discriminating OE alone from DIE., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: To study endometrial receptivity in terms of osteopontin (OPN) and αvβ3 integrin expression and co-expression in infertile women with early stages of endometriosis., Methods: We investigated the immunohistochemical expression and co-expression of OPN and αvβ3 integrin in the endometrium of 20 infertile patients with Stage I or II endometriosis as the only detectable cause of infertility, 20 infertile patients with unexplained infertility and 20 fertile women undergoing tubal sterilization. Two endometrial biopsies were performed during a single menstrual cycle (postovulatory Day +7 to +8 and 4 days later) in each subject., Results: No statistically significant differences regarding OPN and αvβ3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvβ3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied., Conclusions: Endometrial OPN and αvβ3 integrin expression or co-expression is not impaired during the window of implantation in patients with Stage I-II endometriosis. Further studies are needed to determine whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with these markers of implantation.

Objective: To investigate the effect of two laparoscopic techniques for treatment of ovarian endometriomas on recurrence rate., Design: Prospective randomized clinical trial., Setting: University teaching hospital., Patient(s): Ninety women with ovarian endometriomas., Intervention(s): Patients were randomly selected to undergo either laparoscopic cystectomy (group 1) or laser vaporization (group 2) of ovarian endometrioma., Main Outcome Measure(s): Recurrence, evaluated by ultrasound scan examination, was assessed at 12 and 60 months of follow-up., Result(s): Endometrioma recurrence rate was higher, though not significantly different, in group 2 at 60 months of follow-up. Nevertheless, at 12 months of follow-up recurrences were statistically higher in group 2., Conclusion(s): The comparison between laparoscopic laser ablation and laparoscopic cystectomy for ovarian endometriomas after long-term follow-up showed earlier recurrences and a higher recurrence rate in the laser group, although at 5 years of follow-up there were no statistically significant differences., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the effect of surgeon's increasing experience in conservative laparoscopic surgery of women with rectovaginal endometriosis on the surgical outcome of these patients recurrence rate., Design: Prospective cohort study., Setting: University teaching hospital., Patient(s): The first 60 consecutive patients undergoing laparoscopic conservative surgery for symptomatic rectovaginal endometriosis at our institution during a 4- year period., Intervention(s): Cases were classified into two groups according to the date of the patient's operation: the first 30 cases were defined as the early cases and the subsequent 30 cases as the late cases., Main Outcome Measure(s): Operating time, perioperative complications, and surgical outcome. Univariate and multivariate analyses for risk factors with recurrence of disease., Result(s): The two groups were similar in patient characteristics. There was a reduction in the rate of laparoconversion, operating time, estimated amount of blood loss, cases with incomplete removal, and recurrence rate with increasing surgeon's experience. Surgical completeness was significantly associated with recurrence of disease., Conclusion(s): A learning curve is demonstrated in the conservative laparoscopic management of patients with rectovaginal endometriosis. After gaining experience in performing 30 cases, the recurrence rate is significantly reduced.

Background: Surgical treatment has modest efficacy for the treatment of infertility associated with early-stage endometriosis. Immunomodulation with pentoxifylline is considered as a new strategy potentially useful in treating endometriosis. Thus, this study investigated the usefulness of combined laparoscopic surgery and pentoxifylline therapy in the treatment of infertility associated with minimal to mild endometriosis., Methods: A prospective, randomized, controlled blind trial was conducted. Patients entered the study immediately after laparoscopic surgery and were randomly assigned to the treatment with either oral pentoxifylline (800 mg/day) (pentoxifylline group, n = 51) or an oral placebo (placebo group, n = 53). Patients were then observed for pregnancy for 6 months., Results: Among 98 patients finally considered in the evaluation of the results, the 6 month overall pregnancy rates were 28 and 14% in the pentoxifylline and placebo groups, respectively. Thus, an absolute difference of 14% (95% CI -2 to 30) (Chi-squared test, P = 0.1) in the cumulative probability of pregnancy in 6 months after laparoscopic surgery in patients receiving pentoxifylline versus placebo post-operatively was observed., Conclusion: Our findings provide preliminary clinical evidence to suggest the new experimental treatment approaches, toward endometriosis, that are based on immunomodulation deserve further attention. Well-designed multicenter trials are warranted to confirm or refute our results.

Problem: Hyperactivated macrophages are implicated in the pathophysiology of endometriosis-associated infertility. This study investigates transferrin receptor expression (CD71) as a marker of hyperactivity in peritoneal macrophages of infertile patients with minimal to mild endometriosis (group 1, n = 25)., Method of Study: Expression of the activation antigen CD71 on peritoneal fluid macrophages was determined by a specific monoclonal anti-CD71 antibody using indirect immunofluorescence technique and was analyzed by flow cytometry. Three different control groups of women were used: women with unexplained infertility (group 2, n = 25), fertile women with endometriosis (group 3, n = 10), and fertile women without endometriosis (group 4, n = 25)., Results: The percentage of CD71 positive cells was significantly increased in infertile women with endometriosis as compared with the three control groups. There were no differences among groups 2, 3, and 4 with respect to the percentage of CD71 positive macrophages., Conclusions: Our results favor the concept that hyperactivated macrophages play a role in the pathophysiology of endometriosis-associated subfertility, a feature which is lacking in patients with unexplained infertility.

The present study is the first prospective randomized controlled trial of the effect of pentoxifylline on future fertility in infertile women with asymptomatic minimal or mild endometriosis. After completion of a basic infertility workup and laparoscopy, patients were entered into the study and randomly allocated to receive either a 12 month course of oral pentoxifylline (800 mg/day) (n = 30) or an oral placebo (n = 30). Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be non-contributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12 month period that started immediately after laparoscopy. The 12 month actuarial overall pregnancy rates were 31 and 18.5% in the pentoxifylline and placebo groups respectively. However, this difference was not statistically significant by the chi(2)-test. Similarly, the Cox regression method showed no differences between the hazard of pregnancy in the two groups studied (odds ratio, 0.56; 95% confidence interval, 0.18-1.67). Therefore, there is no evidence from this study that immunomodulation with pentoxifylline aids fertility in those women with minimal or mild endometriosis. Further studies including more infertile patients with endometriosis are desirable in order to confirm our results.

Immunopathophysiological mechanisms in endometriosis-associated reproductive failure were studied in appropriate populations: infertile and fertile women with and without endometriosis. The incidence of sera positive for any of the autoantibodies tested among infertile women with endometriosis (n = 25) was similar to that observed in the three control groups [unexplained infertility patients (n = 25) and fertile women with (n = 10) and without (n = 25) endometriosis]. The mean volume of peritoneal fluid was significantly elevated in women with endometriosis (both fertile and infertile) as compared with patients without endometriosis (fertile or infertile). The concentration of peritoneal fluid leukocytes and the percentage of cells positive for macrophage markers were significantly increased and the percentage of T lymphocytes significantly decreased in infertile women with endometriosis but not in patients with unexplained infertility and fertile women with endometriosis, as compared with fertile controls without endometriosis. Macrophages from infertile patients with endometriosis had higher sperm phagocytosis than did those from infertile women without endometriosis or fertile subjects with or without endometriosis. Incidences of serum and peritoneal fluid samples embryotoxic to the in-vitro development of 2-cell mouse embryos were significantly higher in infertile patients with endometriosis than in unexplained infertility patients and fertile women with or without endometriosis. It is concluded that immunological mechanisms of endometriosis-associated infertility exist but that these peritoneal immunological factors in infertile women with endometriosis are related to their subfertility rather than to the presence of ectopic endometrial implants. This is supported by the lack of immunological abnormalities observed among fertile women with endometriosis. These immunological abnormalities are lacking in patients with unexplained infertility.

In 100 consecutive patients who were undergoing laparoscopy for infertility (group 1, n = 52), chronic pelvic pain (group 2, n = 18) or tubal sterilization (group 3, n = 30, asymptomatic fertile women), peritoneal biopsies were taken from areas of visually normal peritoneum of uterosacral ligaments. Twenty-six patients in group 1 (50%), eight patients in group 2 (44.4%) and 13 patients in group 3 (43.3%), were found to have laparoscopic evidence of endometriosis elsewhere in the pelvis. The majority of women (80.7% in group 1, 87.5% in group 2, and 100% in group 3) had stage I disease. The incidence of the distinctive appearances of the lesions was similar in the three groups of patients and 7% of all women or 15% (7/47) of those patients having endometriosis at laparoscopy had only subtle (non-¿typical') endometriotic peritoneal lesions. Uterosacral biopsies showed the presence of endometriotic tissue in three cases (5.7%), two cases (11%) and three cases (10%) in groups 1, 2, and 3 respectively. One of the two patients in group 2 and two of the three patients in group 3 had no evidence of endometriosis at laparoscopy; thus histological study revealed the presence of endometriosis in normal peritoneum in 11% (5/47) of patients having macroscopic endometriosis and in 6% (3/53) of patients without endometriosis at laparoscopy. Previous oral contraceptive users were significantly higher among women having macroscopic and/or microscopic endometriosis than among women without the condition. In conclusion, our prospective study shows a high prevalence (45-50%) of endometriosis (including microscopic forms) in both patients with chronic pelvic pain and asymptomatic women (fertile and infertile), thus supporting the modern concept that in many women endometriosis may be a paraphysiological condition while probably only in some patients small amounts of endometriosis are an ¿annoyance' with implications to their reproductive health and may produce symptoms (e.g. pelvic pain) and therefore should be defined as a ¿dis-ease'. Previous use of oral contraceptives may increase the risk of developing endometriosis.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), the European Society of Human Reproduction and Embryology (ESHRE), the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence‐based and clinically relevant statements on the use of imaging techniques for non‐invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counseling and planning of surgical treatment strategies. © 2024 The Authors. Published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology, by Universa Press, by The International Society for Gynecologic Endoscopy, by Oxford University Press on behalf of European Society of Human Reproduction and Embryology, by Elsevier Inc. on behalf of American Association of Gynecologic Laparoscopists and by Elsevier B.V. [ABSTRACT FROM AUTHOR]