The Dysregulated IL-23/TH17 Axis in Endometriosis Pathophysiology.

Endometriosis is a chronic inflammatory disease in which endometrial-like tissue grows ectopically, resulting in pelvic pain and infertility. IL-23 is a key contributor in the development and differentiation of TH17 cells, driving TH17 cells toward a pathogenic profile. In a variety of inflammatory and autoimmune disorders, TH17 cells secrete proinflammatory cytokines, including IL-17, contributing to disease pathophysiology. Our studies and others have implicated IL-17 and TH17 cell dysregulation in endometriosis, which is associated with disease severity. In this article, we address whether IL-23-driven TH17 cells contribute to cardinal features of lesion proliferation, vascularization, and inflammation in endometriosis using patient samples, representative cell lines, and our established mouse model of endometriosis. The results indicated dysregulated expression of key genes in the IL-23/TH17 axis in patient ectopic and eutopic endometrial samples and increased IL-23 protein in patient plasma compared with controls. In vitro studies using primary human TH cells determined that rIL-23 mixture treatment increased pathogenic TH17 cell frequency. Similarly, rIL-23 treatment of cell lines (12Z cells, EECCs, HUVECs, and hESCs) representative of the endometriotic lesion microenvironment increased cytokines and growth factors, which play a role in lesion establishment and maintenance. In a syngeneic mouse model of endometriosis, rIL-23 treatment altered numbers of myeloid and T cell subsets in peritoneal fluid and increased giant cells within the lesion. Lesions from rIL-23-treated mice did not reveal significant alterations in proliferation/vascularization, although trends of increased proliferation and vascularization were observed. Collectively, these findings provide insights into the impact of the IL-23/TH17 axis on local immune dysfunction and broadly on endometriosis pathophysiology.

Endometriosis and mental health: a population-based cohort study.

BACKGROUND: Endometriosis is a chronic gynecologic disorder that leads to considerable pain and a reduced quality of life. Although its physiological manifestations have been explored, its impact on mental health is less well defined. Existing studies of endometriosis and mental health were conducted within diverse healthcare landscapes with varying access to care and with a primary focus on surgically diagnosed endometriosis. A single-payer healthcare system offers a unique environment to investigate this association with fewer barriers to access care while considering the mode of endometriosis diagnosis. OBJECTIVE: Our objective was to assess the association between endometriosis and the risk for mental health conditions and to evaluate differences between patients diagnosed medically and those diagnosed surgically. STUDY DESIGN: A matched, population-based retrospective cohort study was conducted in Ontario and included patients aged 18 to 50 years with a first-time endometriosis diagnosis between January 1, 2010, and July 1, 2020. Endometriosis exposure was determined through either medical or surgical diagnostic criteria. A medical diagnosis was defined by the use of the corresponding International Classification of Disease diagnostic codes from outpatient and in-hospital visits, whereas a surgical diagnosis was identified through inpatient or same-day surgeries. Individuals with endometriosis were matched 1:2 on age, sex, and geography to unexposed individuals without a history of endometriosis. The primary outcome was the first occurrence of any mental health condition after an endometriosis diagnosis. Individuals with a mental health diagnosis in the 2 years before study entry were excluded. Cox regression models were used to generate hazard ratios with adjustment for hysterectomy, salpingo-oophorectomy, infertility, pregnancy history, qualifying surgery for study inclusion, immigration status, history of asthma, abnormal uterine bleeding, diabetes, fibroids, hypertension, irritable bowel disorder, migraines, and nulliparity. RESULTS: A total of 107,832 individuals were included, 35,944 with a diagnosis of endometriosis (29.5% medically diagnosed, 60.5% surgically diagnosed, and 10.0% medically diagnosed with surgical confirmation) and 71,888 unexposed individuals. Over the study period, the incidence rate was 105.3 mental health events per 1000 person-years in the endometriosis group and 66.5 mental health events per 1000 person-year among unexposed individuals. Relative to the unexposed individuals, the adjusted hazard ratio for a mental health diagnosis was 1.28 (95% confidence interval, 1.24-1.33) among patients with medically diagnosed endometriosis, 1.33 (95% confidence interval, 1.16-1.52) among surgically diagnosed patients, and 1.36 (95% confidence interval, 1.2-1.6) among those diagnosed medically with subsequent surgical confirmation. The risk for receiving a mental health diagnosis was highest in the first year after an endometriosis diagnosis and declined in subsequent years. The cumulative incidence of a severe mental health condition requiring hospital visits was 7.0% among patients with endometriosis and 4.6% among unexposed individuals (hazard ratio, 1.56; 95% confidence interval, 1.53-1.59). CONCLUSION: Endometriosis, regardless of mode of diagnosis, is associated with a marginally increased risk for mental health conditions. The elevated risk, particularly evident in the years immediately following the diagnosis, underscores the need for proactive mental health screening among those newly diagnosed with endometriosis. Future research should investigate the potential benefits of mental health interventions for people with endometriosis with the aim of enhancing their overall quality of life.

Determinants of Perioperative Complications in Day-Surgery for Endometriosis: A Retrospective Cohort.

OBJECTIVES: Endometriosis is a common gynaecologic disease for which surgery is often required. Our objective was to evaluate the potential determinants of perioperative complications in day-surgeries for endometriosis. METHODS: We conducted a retrospective cohort study of patients undergoing day-surgeries for endometriosis using Canadian administrative data from between 2015 and 2019. A multilevel logistic model with a random intercept at the centre level was created to assess the association between potential determinants, including age, site(s) of endometriosis lesion, centre-volume, surgical intervention, and a composite outcome of complications or specific complications. RESULTS: We observed a higher risk of complications associated with greater age (40-44 vs. 20-24 years, adjusted odds ratio [aOR] 1.58; 95% CI 1.26-1.98); hysterectomies (aOR 2.29; 95% CI 1.73-3.06) compared with minor conservative surgery; lesions of the bowel or urinary tract system (aOR 1.54; 95% CI 1.16-2.06), and extra-pelvic sites of endometriosis (aOR 1.24; 95% CI 1.07-1.52) compared with endometriosis of the uterus; and with comorbidities (aOR 1.59; 95% CI 1.09-2.32). Endometriosis lesions to the bowel and urinary tract system and to extra-pelvic sites (compared with no endometriosis at the site) were associated with a greater risk of accidental damages (aOR 1.84; 95% CI 1.43-2.37) and urinary system complications (aOR 1.75; 95% CI 1.24-2.48), respectively. Among patients undergoing hysterectomies compared with those undergoing minor conservative surgery, infectious complications (aOR 8.56; 95% CI 4.70-15.59) and accidental damages (aOR 2.31; 95% CI 1.70-3.14) were more frequent. CONCLUSIONS: Complications in day-surgeries for endometriosis are more frequent with older age, hysterectomy, comorbidities, and endometriosis of the bowel, urinary tract system, and extra-pelvic locations. More extensive disease is associated with more extensive surgical dissection and a higher risk of complications.

Guideline No. 451: Asymptomatic Endometrial Thickening in Postmenopausal Women.

OBJECTIVE: To formulate strategies for clinical assessments for endometrial thickening on ultrasound in a postmenopausal woman without bleeding. TARGET POPULATION: Postmenopausal women of any age. OUTCOMES: To reduce unnecessary invasive interventions and investigations in women with asymptomatic endometrial thickening while selectively investigating women at risk for endometrial cancer. BENEFITS, HARMS, AND COSTS: It is anticipated that the adoption of these recommendations would save postmenopausal women unnecessary anxiety, pain, and risk of procedural complications. It is also expected to decrease the cost to the health care system by eliminating unnecessary interventions. EVIDENCE: English language articles from Medline, Cochrane, and PubMed databases for relevant peer-reviewed articles dating from 1995 to 2022 (e.g., asymptomatic endometrial thickness, endometrial cancer, postmenopausal bleeding, transvaginal ultrasound, endometrial biopsy, cervical stenosis, hormone therapies and the endometrium, tamoxifen, tibolone, aromatase inhibitors). Results were restricted to systematic reviews and meta-analyses, randomized controlled trials/controlled clinical trials, and observational studies. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Physicians, including gynaecologists, obstetricians, family physicians, radiologists, pathologists, and internists; nurse practitioners and nurses; medical trainees, including medical students, residents, and fellows; and other providers of health care of the postmenopausal population. SOCIAL MEDIA ABSTRACT: Postmenopausal women often have a thickening of the lining of the uterus found during ultrasound. Without bleeding, an endometrium <11 mm is rarely a serious problem but should be evaluated by a health care provider. SUMMARY STATEMENTS: RECOMMENDATIONS.

Endometriosis, Severe Maternal Morbidity, and the Effect of Infertility: Population-Based Cohort Study.

This population-based cohort evaluated the association between endometriosis and severe maternal morbidity (SMM), and the mediating effect of infertility and fertility treatment. Included were all singleton deliveries in Ontario between 2006 and 2014. Modified Poisson regression generated adjusted relative risks. Mediation analysis estimated the direct effect of endometriosis and indirect effect through infertility and mode of conception. 787 449 deliveries were included (19 099, 2.4% with endometriosis). SMM occurred in 29.0 per 1000 deliveries among women with endometriosis, in contrast to 18.2 per 1000 deliveries among those without endometriosis-corresponding to an adjusted relative risk of SMM of 1.43 (95% CI 1.31-1.56). Mediation analysis demonstrated that the effect of endometriosis on SMM was independent of infertility or fertility treatment. We conclude that SMM in women with endometriosis appears to be due to the disease itself and not to infertility or related treatments.

Guideline No. 447: Diagnosis and Management of Endometrial Polyps.

OBJECTIVE: The primary objective of this clinical practice guideline is to provide gynaecologists with an algorithm and evidence to guide the diagnosis and management of endometrial polyps. TARGET POPULATION: All patients with symptomatic or asymptomatic endometrial polyps. OPTIONS: Options for management of endometrial polyps include expectant, medical, and surgical management. These will depend on symptoms, risks for malignancy, and patient choice. OUTCOMES: Outcomes include resolution of symptoms, histopathological diagnosis, and complete removal of the polyp. BENEFITS, HARMS, AND COSTS: The implementation of this guideline aims to benefit patients with symptomatic or asymptomatic endometrial polyps and provide physicians with an evidence-based approach toward diagnosis and management (including expectant, medical, and surgical management) of polyps. EVIDENCE: The following search terms were entered into PubMed/Medline and Cochrane: endometrial polyps, polyps, endometrial thickening, abnormal uterine bleeding, postmenopausal bleeding, endometrial hyperplasia, endometrial cancer, hormonal therapy, female infertility. All articles were included in the literature search up to 2021 and the following study types were included: randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Additional publications were identified from the bibliographies of these articles. Only English-language articles were reviewed. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: Gynaecologists, family physicians, registered nurses, nurse practitioners, medical students, and residents and fellows. TWEETABLE ABSTRACT: Uterine polyps are common and can cause abnormal bleeding, infertility, or bleeding after menopause. If patients don't experience symptoms, treatment is often not necessary. Polyps can be treated with medication but often a surgery will be necessary. SUMMARY STATEMENTS: RECOMMENDATIONS.

Guideline No. 449: Diagnosis and Impact of Endometriosis - A Canadian Guideline.

OBJECTIVE: To provide a contemporary approach to the understanding of the impact and methods for the diagnosis of endometriosis in Canada. TARGET POPULATION: Individuals, families, communities, health care providers, and health care administrators who are affected by, care for patients with, or manage delivery of services for endometriosis. OPTIONS: The diagnosis of endometriosis is facilitated by a detailed history, examination, and imaging tests with providers who are experienced in endometriosis care. Surgical evaluation with pathology confirms a diagnosis of endometriosis; however, it is not required for those whose diagnosis was confirmed with imaging. OUTCOMES: There is a need to address earlier recognition of endometriosis to facilitate timely access to care and support. Education directed at the public, affected individuals and families, health care providers, and health care administrators are essential to reduce delays in diagnosis and treatment. BENEFITS, HARMS, AND COSTS: Increased awareness and education about the impact and approach to diagnosis may support timely access to care for patients and families affected by endometriosis. Earlier and appropriate care may support a reduced health care system burden; however, improved clinical evaluation may require initial investments. EVIDENCE: Each section was reviewed with a unique search strategy representative of the evidence available in the literature related to the area of focus. The literature searches for each section of this guideline are listed in Appendix A and include information from published systematic reviews described in the text. VALIDATION METHODS: The recommendations were developed following two rounds of review by a national expert panel through an iterative 2-year consensus process. Further details on the process are shared in Appendix B. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix C (Table C1 for definitions and Table C2 for interpretations of strong and conditional recommendations). INTENDED AUDIENCE: This guideline is intended to support health care providers and policymakers involved in the care of those impacted by endometriosis and the systems required to support them. TWEETABLE ABSTRACT: Endometriosis impact and diagnosis updated guidelines for Canadian health care providers and policymakers. SUMMARY STATEMENTS: RECOMMENDATIONS.

Validation of the Canadian Institute for Health Information Diagnostic Codes for Benign Gynaecologic Surgery.

We investigated the validity of the 10th Revision Canadian modification of International Statistical Classification of Disease and Related Health Problems (ICD-10-CA) diagnostic codes for surgery for benign gynaecologic conditions in the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD), the main source of routinely collected data in Canada. Reabstracted data from patient charts was compared to ICD-10-CA codes and measures of validity were calculated with 95% confidence intervals. A total of 1068 procedures were identified. More objective, structural diagnoses (fibroids, prolapse) had higher sensitivity and near-perfect Kappa coefficients, while more subjective, symptomatic diagnoses (abnormal uterine bleeding, pelvic pain) had lower sensitivity and moderate-substantial Kappa coefficients. Specificity, positive predictive values, and negative predictive values were generally high for all diagnoses. These findings support the use of CIHI-DAD data for gynaecologic research.

Day surgery for endometriosis in Canada: A retrospective cohort of trend and regional variation in types of surgeries and their complications.

BACKGROUND: A significant proportion of patients with endometriosis require surgery for management of the disease. AIMS: We aimed to assess the trend and regional variation in day surgeries for endometriosis across Canada and to identify perioperative complications associated with types of surgeries and their temporal trend and regional variation. MATERIALS AND METHODS: We conducted a retrospective cohort study of women undergoing day surgeries for endometriosis between 2015 and 2019 using Canadian administrative data from the National Ambulatory Care Reporting System, which includes data from four provinces (Ontario (ON), Alberta (AB), Nova Scotia (NS) and Prince Edward Island (PEI)). Multivariate logistic regression models were used to compare perioperative complication rates, while adjusting for site(s) of endometriosis lesion, age, type of surgical intervention, and comorbidities. RESULTS: During the study period, the rate of day surgeries for endometriosis remained nearly constant at 80-90 cases per 100 000 women of reproductive age (P = 0.12). The rate of day surgeries was significantly different between provinces (AB = 94, NS = 93 vs ON = 85 per 100 000 women of reproductive age: P < 0.02). The odds of complications decreased with time (2019 vs 2015; adjusted odds ratio (aOR): 0.84; 95% CI: 0.73-0.98). There was a significant regional variation in the frequency of perioperative complications (PEI vs ON aOR: 4.13, 95% CI: 2.58-6.62; and NS vs ON aOR: 1.47, 95% CI: 1.11-1.95). CONCLUSION: The rates of day surgery for endometriosis remained stable and the risks of perioperative complications decreased during the five-year study period. However, there were significant regional variations in the risk of perioperative complications.

Individualized Assessment of Risk of Complications after Benign Hysterectomy.

STUDY OBJECTIVES: The primary objective of this study is to identify patient characteristics associated with postoperative complications or readmissions after hysterectomy for a benign indication. DESIGN: Retrospective cohort. SETTING: The Surgical Gynecologic Scorecard Database includes performance metrics and patient outcomes for hysterectomies across 7 sites in Ontario, Canada. PARTICIPANTS: Individuals who underwent hysterectomy for benign gynecologic indication and were recorded in the Surgical Gynecologic Scorecard Database between July 2016 and June 2019 were included in this study. MEASUREMENTS AND MAIN RESULTS: Two outcomes of interest were considered: (1) complications grade II or greater on the Clavien-Dindo classification scale and (2) emergency room visits or hospital readmissions within 6 weeks after operation. Logistic models were generated to determine the associations between outcome of interest and potential predictors using a mixed-step AIC selection algorithm. A total of 2792 patients underwent hysterectomy for a benign indication during the study period, with a mean age of 52.6 ± 11.7 years and mean body mass index of 29.0 ± 0.7 kg/m2. The most common indications for surgery were abnormal uterine bleeding (33.3%) and myomas (33.6%). Previous cesarean delivery (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.04-1.42), American Society of Anesthesiologists class ≥3 (aOR, 2.31; 95% CI, 1.42-3.99), preoperative anemia (aOR, 1.51; 95% CI, 1.12-2.02), and laparotomic approach (aOR, 1.73; 95% CI, 1.30-2.29) were associated with increased odds of complication. Perioperative complications (aOR, 2.95; 95% CI, 2.12-4.08), preoperative anemia (aOR, 1.43; 95% CI, 1.03-1.98), and vaginal (aOR, 1.94; 95% CI, 1.26-2.96) or laparotomic (aOR, 1.64; 95% CI, 1.10-2.43) approach were associated with increased odds of emergency room visit or readmission to hospital. CONCLUSION: This study identified several important risk factors for complications after hysterectomy. The utility of these data is important to help improve counseling for patients undergoing a hysterectomy and potentially optimize modifiable risk factors when identified preoperatively.

Evaluation of Opioid Prescribing Patterns and Use Following Hysterectomy for Benign Indication: A Prospective Cohort Study.

OBJECTIVES: To evaluate surgeon opioid prescribing patterns for patients undergoing hysterectomy for benign indication, as well as patient use of postoperative medications and satisfaction with postoperative pain management. METHODS: Patients undergoing hysterectomy for benign indications at Kingston Health Sciences Centre were invited to participate in a telephone survey 2 weeks post-surgery to review their analgesia use and pain management. Patient demographics, medical history, intraoperative surgical details, and postoperative prescriptions were gathered through patient record review. Opioid prescribing and utilization patterns were assessed, as was satisfaction with postoperative pain management. RESULTS: Of 124 eligible patients 110 (89%) completed the telephone survey, a mean 15.9 ± 2.3 days after surgery. The mean age of participants was 51.6 ± 11.9 years. Most surgeries (84.5%) were minimally invasive, and 45.5% of patients were discharged within 24 hours of surgery. An opioid prescription was given to 71.8% of participants, and 52.7% used at least 1 dose of opioid medication after discharge. Most participants described very good or adequate postoperative pain management (88.2%). Satisfaction with postoperative pain control was not associated with receipt of an opioid prescription (P = 0.89). A greater proportion of those who used 1 or more doses of opioids versus none indicated poor or inadequate pain management (19.0% vs. 4.1%; P = 0.035). CONCLUSION: Many patients do not use postoperative opioid analgesia following hospital discharge after hysterectomy, without experiencing poor pain management. Surgeons should assess each individual and tailor the analgesia plan as necessary, optimizing non-opioid options.

Long-term follow-up of endometriosis surgery in Ontario: a population-based cohort study.

BACKGROUND: Endometriosis is a chronic gynecological disease affecting approximately 10% of reproductive aged females and leads to decreased quality of life and productivity. Despite effective medical options, many women do require surgery for endometriosis. There is limited literature examining long term outcomes of endometriosis surgery. OBJECTIVE: This study aimed to characterize the long-term outcomes, including recurrence of symptoms, fertility outcomes, and need for reoperation, of patients who underwent surgical management for endometriosis. STUDY DESIGN: This was a population-based cohort study in which the universal coverage health database for the province of Ontario, Canada, was used to identify women aged 18 to 50 years who underwent surgery for endometriosis from April 1, 2002, through March 31, 2018. Surgery was classified as diagnostic laparoscopy, conservative or uterine preserving (minor or major, with and without ovarian preservation), or hysterectomy (with and without ovarian preservation). The outcomes were evaluated from 30 days after the index surgery to the end of the study period or at censoring. Cox proportional hazard regression models were used to estimate the hazard ratios between exposures and outcomes following adjustment for confounders. RESULTS: A total of 84,885 women 2,718 (3.2%) diagnostic laparoscopy, 21,594 (25.4%) minor conservative surgery, 28,484 (33.6%); major conservative with ovarian preservation, 2,102 (2.5%) major conservative without ovarian preservation, 21,609 (25.5%) hysterectomy with ovarian preservation, and 8,378 (9.9%) hysterectomy without ovarian preservation) were included in the cohort and followed for a median of 10 years (interquartile range, 6-13 years). In the first postoperative year, women who underwent diagnostic laparoscopy were significantly more likely to require repeat surgery (adjusted hazard ratio, 1.68; 95% confidence interval, 1.51-1.87), whereas those who underwent major conservative surgery were significantly less likely to require repeat surgery (with ovarian preservation: adjusted hazard ratio, 0.44; 95% confidence interval, 0.41-0.48; without ovarian preservation: adjusted hazard ratio, 0.05; 95% confidence interval, 0.03-0.09). Among women who did not receive repeat surgery in the first year, those who underwent a diagnostic laparoscopy (adjusted hazard ratio, 0.85; 95% confidence interval, 0.76-0.95) and major conservative surgery without ovarian preservation were less likely to undergo repeat surgery (adjusted hazard ratio, 0.12; 95% confidence interval, 0.09-0.18) than those who initially had minor surgery. Compared with those who initially underwent minor surgery, patients who underwent other treatment modalities were less likely to undergo a hysterectomy (diagnostic laparoscopy: adjusted hazard ratio, 0.85; 95% confidence interval, 0.75-0.96; major surgery with ovarian preservation: adjusted hazard ratio, 0.60; 95% confidence interval, 0.57-0.64; major surgery without ovarian preservation: adjusted hazard ratio, 0.05; 95% confidence interval, 0.03-0.08). Following minor and major conservative with ovarian preservation surgery, 8,331 (38.6%) and 9,498 (33.3%) of patients sought an infertility consult within 1 year, respectively. By 5 years after the index surgery, 5,290 (29.4%) of patients who had minor conservative surgery and 4,528 (20.7%) of those who had major conservative with ovarian preservation surgery had given birth at least once. CONCLUSION: Our study suggests that only a few endometriosis patients who undergo hysterectomy surgery require repeat surgery; however, up to 1 in 4 who undergo minor surgery and 1 in 5 who undergo major conservative surgery with ovarian preservation require additional endometriosis surgery. Up to 1 in 3 patients who had uterine sparing endometriosis surgery subsequently sought an infertility assessment. These findings may inform preoperative counseling in terms of recurrence of symptoms, fertility outcomes, and need for reoperation of women seeking surgical management for endometriosis. Future studies should consider the outcomes of patient satisfaction and quality of life based on the current practices for management of endometriosis.

Short-term outcomes of endometriosis surgery in Ontario: A population-based cohort study.

INTRODUCTION: Our objective was to compare the short-term outcomes by type of surgical management of endometriosis in Ontario, Canada and to characterize the population of women undergoing surgical management of endometriosis. MATERIAL AND METHODS: We conducted a population-based cohort study including women aged 18-50 years undergoing same-day or inpatient surgery for endometriosis from 1 April 2002 through 31 March 2018. Surgery was classified as minimally invasive hysterectomy (MIH), total abdominal hysterectomy (TAH) or minor or major conservative (uterus-preserving) surgery. Outcomes examined included length of stay, intraoperative complications, postoperative complications, emergency department visits, ambulatory care visits, and readmission. We estimated the relative risk of these outcomes in minor, major conservative surgery and TAH vs MIH adjusted for age, income quintile, parity, and comorbidities. RESULTS: A total of 85 605 patients underwent surgery, 12.9% MIH, 22.1% TAH, 36.3% major conservative, and 28.6% minor conservative. The mean age at index surgery was 37.6 ± 7.7 years. Before surgery, 70.6% of patients had visited a physician for pain at least once (64.7% MIH, 69.5% TAH, 71.1% major conservative and 73.4% minor conservative) and 23.5% of patients had sought infertility consultation (5.7% MIH, 6.6% TAH, 29.3% major conservative and 37.1% minor conservative). The overall risk of intraoperative and postoperative complications was 1.5% and 4.7%, respectively. In adjusted models, compared with those undergoing minor conservative surgery, those having major conservative surgery were 1.77 (95% CI 1.49-2.11) times as likely to experience an intraoperative complication, those having MIH and TAH were 2.55 (95% CI 2.08-3.13) and 2.34 (95% CI 1.93-2.82) times as likely to do so, respectively. Similarly, compared with those undergoing minor conservative surgery, those having major conservative surgery were 2.60 (95% CI 2.30, 2.93) times as likely to experience any postoperative complication, and those having MIH and TAH were 4.69 (95% CI 4.11-5.36) and 5.38 (95% CI 4.76-6.09) times as likely to do so, respectively. CONCLUSIONS: Approximately one-third of patients undergoing surgical management for endometriosis in Ontario between 2002 and 2018 had a hysterectomy. Overall, complications following surgery were low, and dependent on extent of surgery. These results should help to inform preoperative counseling for patients and health policy development for providers.

Technicity in Canada: A Nationwide Whole-Population Analysis of Temporal Trends and Variation in Minimally Invasive Hysterectomies.

STUDY OBJECTIVE: The objective of our study was to provide a contemporary description of hysterectomy practice and temporal trends in Canada. DESIGN: A national whole-population retrospective analysis of data from the Canadian Institute for Health Information. SETTING: Canada. PATIENTS: All women who underwent hysterectomy for benign indication from April 1, 2007, to March 31, 2017, in Canada. INTERVENTIONS: Hysterectomy. MEASUREMENTS AND MAIN RESULTS: A total of 369 520 hysterectomies were performed in Canada during the 10-year period, during which the hysterectomy rate decreased from 313 to 243 per 100 000 women. The proportion of abdominal hysterectomies decreased (59.5% to 36.9%), laparoscopic hysterectomies increased (10.8% to 38.6%), and vaginal hysterectomies decreased (29.7% to 24.5%), whereas the national technicity index increased from 40.5% to 63.1% (p <.001, all trends). The median length of stay decreased from 3 (interquartile range 2-4) days to 2 (interquartile range 1-3), and the proportion of patients discharged within 24 hours increased from 2.1% to 7.2%. In year 2016-17, women aged 40 to 49 years had significantly increased risk of abdominal hysterectomy compared with women undergoing hysterectomy in other age categories (p <.001). Comparing women with menstrual bleeding disorders, women undergoing hysterectomy for endometriosis (adjusted relative risk [aRR] 1.36; 95% confidence interval [CI], 1.28-1.44) and myomas (aRR 2.01; 95% CI, 1.94-2.08) were at increased risk of abdominal hysterectomy, whereas women undergoing hysterectomy for pelvic organ prolapse and pelvic pain (aRR 1.47; 95% CI, 1.41-1.53) were at decreased risk. Using Ontario as the comparator, Nova Scotia (aRR 1.35; 95% CI, 1.27-1.43), New Brunswick (aRR 1.25; 95% CI, 1.18-1.32]), Manitoba (aRR 1.35; 95% CI, 1.28-1.43), and Newfoundland and Labrador (aRR 1.18; 95% CI, 1.10-1.27) had significantly higher risks of abdominal hysterectomy. In contrast, Saskatchewan (aRR 0.75; 95% CI, 0.74-0.77) and British Columbia (aRR 0.86; 95% CI, 0.85-0.88) had significantly lower risks, whereas Prince Edward Island, Quebec, and Alberta were not significantly different. CONCLUSION: The proportion of minimally invasive hysterectomies for benign indication has increased significantly in Canada. The declining use of vaginal approaches and the variation among provinces are of concern and necessitate further study.

Preoperative Factors of Endometrial Carcinoma in Patients Undergoing Hysterectomy for Atypical Endometrial Hyperplasia.

OBJECTIVE: To identify clinicopathological preoperative factors associated with concurrent endometrial carcinoma in patients undergoing surgical management of atypical endometrial hyperplasia. METHODS: The records of all patients who underwent hysterectomy for preoperatively diagnosed atypical endometrial hyperplasia at a tertiary care hospital from April 2017 to April 2020 were retrospectively reviewed. Clinicopathological characteristics of patients were extracted. Patients who did not undergo hysterectomy or who had evidence of simple hyperplasia or carcinoma on initial biopsy were excluded. Univariate analysis was performed. A multivariate regression model for progression to endometrial carcinoma was developed. RESULTS: A total of 126 patients were included. Of these patients, 19 (15.1%) had a final diagnosis of endometrial carcinoma, whereas 86 (68.2%) retained the diagnosis of atypical endometrial hyperplasia and 21 (16.7%) were found to have no residual atypical endometrial hyperplasia. The odds of a patient being diagnosed with endometrial carcinoma were 6.1 times higher (95% CI 1.32-27.68) if they had an endometrial stripe thickness >1.1 cm and 13.5 times higher (95% CI 3.56-51.1) if there was histological suspicion of carcinoma. The odds of a patient being diagnosed with endometrial carcinoma were significantly lower if the patient had an initial diagnosis of atypical endometrial hyperplasia in a polyp (OR 0.07; 95% CI 0.02-0.34). CONCLUSION: Our results suggest that an endometrial stripe thickness >1.1 cm, a histological suspicion of carcinoma on preoperative pathology, and the absence of polyp involvement on initial diagnosis are the strongest predictors of endometrial carcinoma at the time of hysterectomy in patients with atypical endometrial hyperplasia.

Impact of Minimally Invasive Gynaecology Fellowship Training on Quality Performance Metrics for Hysterectomy.

OBJECTIVE: To evaluate differences in quality metrics between hysterectomies performed by fellowship-trained surgeons and those performed by generalists. METHODS: Retrospective review of 2845 consecutive hysterectomies by 75 surgeons (23 fellowship-trained, 52 generalists) at 7 hospitals in Ontario, Canada. The primary outcome was a composite of any complication or return to the emergency department (ED) within 30 days of hysterectomy. Secondary outcomes were 2 quality outcome measures (grade of complication and return to ED within 30 days) and 4 quality process measures (minimally invasive hysterectomy rate, rate of preoperative anemia, same-day discharge for laparoscopic hysterectomy [LH], and performing cystoscopy at LH). RESULTS: Fellowship-trained surgeons were more likely to perform concurrent resection of endometriosis, bilateral ureterolysis, lysis of adhesions, uterine/internal iliac artery ligation, and morcellation (all P < 0.001). Generalists performed more vaginal procedures, including vaginal repair, vault suspension, and insertion of mid-urethral sling (all P < 0.001). After controlling for patient and surgical factors, there was no difference in the primary outcome (adjusted odds ratio [aOR] 1.07; 95% CI 0.79-1.45, P = 0.667). Fellowship-trained surgeons were more likely to perform minimally invasive hysterectomy (aOR 2.38; 95% CI 1.15-4.93, P = 0.020), had higher rates of same-day discharge for LH (aOR 2.23; 95% CI 1.31-3.81, P = 0.003), and were more likely to perform cystoscopy (unadjusted OR 2.94; 95% CI 2.30-3.85, P < 0.001). There were no differences in the rates of preoperative anemia, surgical complications, and ED visits. CONCLUSION: Differences exist between fellowship-trained surgeons and generalists regarding case mix and process quality metrics. Postoperative complications and readmissions were comparable for both groups of surgeons.

Venous Thromboembolism After Blood Transfusions in Women Undergoing Hysterectomy for Non-Malignant Indications: A Retrospective Cohort Study.

OBJECTIVE: To quantify the effect of blood transfusion on the risk of venous thromboembolism (VTE) among women undergoing hysterectomy for non-malignant indications. METHODS: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was conducted. Women who underwent hysterectomy for non-malignant indications between 2011 and 2016 were identified using the Current Procedural Terminology and Internationally Classification of Diseases codes. The primary outcome was development of VTE. Data on patient demographics and perioperative variables were obtained. Pair-wise comparison using χ2 tests were performed to compare women with and without VTE. Multivariable logistic regression was performed to adjust for potential confounders and identify independent predictors of VTE. RESULTS: Between 2011 and 2016, 169 593 women underwent hysterectomy for non-malignant indications. The overall incidence of VTE was 0.32%. Patient characteristics associated with VTE included obesity and higher American Society of Anesthesiologists (ASA) status. Associated operative factors included abdominal surgery, blood transfusion, and prolonged operative time (P < 0.05 for all). Following adjustment for potential confounders, abdominal hysterectomy was associated with greater odds of VTE than laparoscopic or vaginal approaches (adjusted odds ratio [aOR] 1.81; 95% CI 1.48-2.21 and aOR 2.31; 95% CI 1.62-3.28, respectively). Greater odds of VTE were also observed with OR time >150 minutes (aOR 1.88; 95% CI 1.46-2.42), ASA class ≥III (aOR 1.53; 95% CI 1.05-2.26), and intra- and postoperative transfusion (aOR 2.65; 95% CI 1.78-3.95 and aOR 2.98; 95% CI 1.95-4.55, respectively). CONCLUSION: The risk of VTE is low in women undergoing hysterectomy for non-malignant indications. Blood transfusion was associated with the highest risk of VTE.

A Practical Guide to the Clinical Evaluation of Endometriosis-Associated Pelvic Pain.

Endometriosis-associated pain (EAP) has a significant impact on the quality of life of those affected and their families. Recognizing that endometriosis is a chronic condition associated with an impairment in function and negative social impact, there is a shift toward reducing diagnostic delays and initiating timely management. This article provides a comprehensive and practical approach to the clinical diagnosis of EAP, which can subsequently facilitate prompt and directed treatment. The key components of the history, physical examination, and high-quality imaging to evaluate suspected EAP and related pain conditions are presented. Currently, biomarkers have limited utility in the diagnosis of endometriosis, but research in this area continues; development of a reliable noninvasive test for endometriosis may further improve early identification of this condition.

Dienogest and the Risk of Endometriosis Recurrence Following Surgery: A Systematic Review and Meta-analysis.

STUDY OBJECTIVE: To determine whether dienogest therapy after endometriosis surgery reduces the risk of endometriosis recurrence compared with expectant management. DATA SOURCES: Ovid MEDLINE, Ovid EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, clinicaltrials.gov, and International Standard Randomized Controlled Trial Number Registry were searched from inception to March 2019 for observational and randomized controlled trials. METHODS OF STUDY SELECTION: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Medical Subject Heading terms and keywords such as "dienogest," "endometriosis," and "recurrence" were used to identify relevant studies. TABULATION, INTEGRATION, AND RESULTS: The search yielded 328 studies, 10 of which were eligible for inclusion, representing 1184 patients treated with dienogest and 846 expectantly managed controls. Among these studies, 9 looked exclusively at endometrioma recurrence, whereas 1 used reappearance of symptoms as evidence of disease recurrence. Data on both incidence of and time to recurrence of endometriosis were extracted. The incidence rate of endometriosis recurrence in patients treated with dienogest was 2 per 100 women over a mean follow-up of 29 months (95% confidence interval [CI], 1.43-3.11) versus 29 per 100 women managed expectantly over a mean follow-up of 36 months (95% CI, 25.66-31.74). The likelihood of recurrence was significantly reduced with postoperative dienogest (log odds -1.96, CI, -2.53 to -1.38, p <.001). CONCLUSION: Patients receiving dienogest after conservative surgery for endometriosis had significantly lower risk of postoperative disease recurrence than those who were expectantly managed.

Retrospective Comparison of PGE2 Vaginal Insert and Foley Catheter for Outpatient Cervical Ripening.

OBJECTIVE: To compare the efficacy of two methods of outpatient cervical ripening (CR): an intracervical Foley catheter and a prostaglandin E2 (PGE)2 slow-release vaginal insert. METHODS: All records of women receiving outpatient CR at a tertiary care hospital from January 2017 to June 2018 were retrospectively reviewed. We compared time from insertion of first CR agent until delivery between groups using a Cox proportional hazards (CPH) model. Exclusion criteria included age <18 years, multiple gestation, or contraindication to either CR method. Secondary outcomes included time from removal of agent and time from admission until delivery, additional CR used, uterine tachysystole, labour and delivery complications, type of delivery, and adverse neonatal outcomes. RESULTS: A total of 153 patients were included (82 Foley; 71 PGE2). Baseline characteristics were comparable except for lower dilation in the PGE2 group (16% vs. 38% <1cm dilated; P < 0.05). In the CPH model, time from insertion to delivery was not different between PGE2 and Foley catheter groups (median 27 vs. 33 h), controlling for parity, gestational age, initial dilation, and use of oxytocin (HR 1.13, 95% confidence interval 0.77-1.68). Patients in the PGE2 group were more likely to experience uterine tachysystole (9% vs. 0%; P < 0.01) and require another method of CR (34% vs. 1%; P < 0.001). There were no differences in neonatal or maternal adverse outcomes between groups. CONCLUSION: Our results suggest that outpatient Foley catheter and PGE2 CR are comparable in time from insertion to delivery; however, PGE2 inserts are associated with higher rates of tachysystole and the need for second CR method. A prospective study is warranted to further investigate these findings.