The Association of Vitamin D with Uterine Fibroids in Premenopausal Patients: a Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to consolidate existing literature regarding the association between vitamin D and uterine fibroid presence and growth. DATA SOURCES: A comprehensive search across databases including MEDLINE, Embase, CINAHL, Web of Science, ClinicalTrials.gov, and grey literature was conducted from inception to February 2023, using relevant keywords. Authors were contacted for unpublished data. STUDY SELECTION: From 9931 studies screened based on title and abstract, those evaluating serum vitamin D levels or vitamin D treatment effects, using ultrasonography for diagnosis, and involving at least 25 pre-menopausal participants were included. Case reports, case series, and reviews were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a predefined form. Methodological quality was assessed through the Newcastle-Ottawa Scale and the Risk of Bias-2 tools. Evidence quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. Data from three randomized controlled trials (n = 328) and 23 observational studies (n = 5650) were meta-analyzed via random effects modeling. Patients receiving oral vitamin D supplementation had a significantly different change in fibroid size (SMD -5.7%, CI -10.63 to -0.76, P = 0.02, I2 = 99%), as measured by percentage change in diameter or volume, compared to controls, over the span of 2-6 months. Those receiving supplementation had vitamin D insufficiency; regimens varied between 50 000 IU weekly for 12 weeks, 50 000 IU weekly for 8 weeks, and 50 000 IU biweekly for 10 weeks. Patients with fibroids exhibited lower serum vitamin D concentrations (MD -5.50 ng/mL, CI 6.99 to -4.01, P < 0.001, I2 = 87%) and higher odds of vitamin D deficiency (OR 3.71, CI 1.90-7.24, P < 0.001, I2 = 80%). CONCLUSION: This review underscores the potential of vitamin D in mitigating fibroid development and growth. While promising, further research is warranted to optimize dosage and treatment duration, potentially offering a non-invasive solution for at-risk patients. Continued exploration of vitamin D's role in fibroid treatment is encouraged. OBJECTIF: Cette étude vise à consolider la littérature existante concernant l'association entre la vitamine D et la présence et la croissance des fibromes utérins. SOURCE DES DONNéES: Une recherche exhaustive a été réalisée dans les bases de données MEDLINE, Embase, CINAHL, Web of Science et ClinicalTrials.gov et dans la littérature à l'aide de mots-clés pertinents pour la période allant de leur création à février 2023. Les auteurs ont été contactés pour obtenir des données non publiées. SéLECTION DES éTUDES: Dans les 9 931 études sélectionnées d'après leurs titre et résumé, seules celles ayant évalué les taux sériques de vitamine D ou les effets d'un traitement à la vitamine D, utilisé l'échographie pour le diagnostic et comptant au moins 25 participantes non ménopausées ont été retenues. Les études de cas, les études de série de cas et les revues n'ont pas été retenues. EXTRACTION DES DONNéES ET SYNTHèSE: Les données ont été extraites au moyen d'un formulaire prédéfini. La qualité méthodologique a été évaluée au moyen de l'échelle de Newcastle-Ottawa et de l'outil d'évaluation du risque de biais RoB-2. La qualité des données a été évaluée à l'aide de la méthodologie GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Les données de trois essais cliniques randomisés (n = 328) et de 23 études observationnelles (n = 5650) ont été méta-analysées à l'aide d'une modélisation à effets aléatoires. Les patientes recevant une supplémentation orale en vitamine D ont présenté un changement significativement différent de la taille des fibromes (différence des moyennes standardisées : -5,7 %; IC : -10,63 à -0,76; P = 0,02; I2 = 99 %), tel que mesuré par le changement en pourcentage du diamètre ou du volume, par rapport aux témoins, sur une période de 2 à 6 mois. Les personnes recevant une supplémentation présentaient une insuffisance en vitamine D; les schémas posologiques étaient de 50 000 UI par semaine pendant 12 semaines, 50 000 UI par semaine pendant 8 semaines ou 50 000 UI toutes les deux semaines pendant 10 semaines. Les patientes atteintes de fibromes avaient des concentrations sériques de vitamine D plus faibles (différence moyenne : -5,50 ng/mL; IC : 6,99 à -4,01; P < 0,001; I2 = 87 %) et un risque plus élevé de carence en vitamine D (RC : 3,71; IC : 1,90-7,24; P < 0,001; I2 = 80 %). CONCLUSION: Cette étude souligne le potentiel de la vitamine D dans l'atténuation du développement et de la croissance des fibromes. Bien que ces conclusions soient prometteuses, la recherche doit se poursuivre afin d'optimiser le dosage et la durée du traitement, ce qui pourrait constituer une solution non invasive pour les patientes à risque. La poursuite de l'étude du rôle de la vitamine D dans le traitement des fibromes est encouragée.

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.

Directive clinique nº 451 Épaississement asymptomatique de l'endomètre chez les femmes ménopausées / Clinical directive No. 451 asymptomatic endometrial thickening in postmenopausal women

Formuler des stratégies d'évaluation clinique de l'épaississement de l'endomètre confirmé à l'échographie chez les femmes ménopausées n'ayant pas de saignement. Femmes ménopausées de tous âges. Réduire les interventions et examens invasifs inutiles chez les femmes présentant un épaississement asymptomatique de l'endomètre tout en évaluant de manière sélective les cas impliquant un risque de cancer de l'endomètre. L'adoption de ces recommandations devrait éviter angoisses, douleurs et risques de complications opératoires inutiles aux femmes ménopausées. Ces mesures devraient aussi réduire les coûts pour le système de santé en éliminant les interventions inutiles.

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

To provide a contemporary approach to the understanding of the impact and methods for the diagnosis of endometriosis in Canada. 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. 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. 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. 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. 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. 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). 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.

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.

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.

Guideline No. 447: diagnosis and management of endometrial polyps

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 for management of endometrial polyps include expectant, medical, and surgical management. These will depend on symptoms, risks for malignancy, and patient choice. Outcomes include resolution of symptoms, histopathological diagnosis, and complete removal of the polyp. 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. 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. 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). Gynaecologists, family physicians, registered nurses, nurse practitioners, medical students, and residents and fellows. 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.

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.

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.

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.

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.

Complications following surgeries for endometriosis: A systematic review protocol.

BACKGROUND: Endometriosis is a common gynecological condition with a wide range of symptoms, including infertility, dyspareunia, intestinal disorders, and pelvic pain. Laparoscopy and laparotomy are used widely for diagnosing and managing endometriosis. We will conduct a systematic review and meta-analysis with the aims of reporting complications rates following each type of surgeries for endometriosis and determinants of complications. METHOD: We will search Medline (via PubMed), Embase, the Cochrane Library, Web of Science, and Google Scholar for both retrospective and prospective cohorts or trials of at least 30 participants reporting perioperative and postoperative complications for endometriosis surgeries. We will restrict the studies to those conducted after 2011, to be representative of current practices, and will exclude studies of surgeries for gynecological cancer, or other concomitant benign gynecologic surgeries such as myomectomy. Two reviewers will independently screen references and select eligible studies. A standardized form will be used to collect data related to the baseline characteristics, potential determinants of complications, types of interventions, and outcomes. Cumulative incidences of complications will be pooled using DerSimonian and Laird random-effects method. The relation between potential determinants and complications will be reported with risk ratios and their 95% of confidence intervals. Subgroup analysis of surgical approach, surgical procedure, superficial and deep infiltrating endometriosis, and the indication of surgery will be conducted. Sensitivity analyses restricted to studies with low risk of bias will be performed. DISCUSSION: This systematic review will provide information on the rates of complications for different surgical approaches and procedures for the treatment of endometriosis. It will contribute to inform patients when making decisions regarding their care. Identifying potential determinants of complications will also help to improve care by identifying women being at higher risk of complications. TRIAL REGISTRATION: Systematic review registration: CRD42021293865.

Disease Burden of Dysmenorrhea: Impact on Life Course Potential.

Dysmenorrhea is the most common gynecologic condition among the female population and has a significant impact on life course potential. It has a widespread impact on a female's mental and physical well-being, with longstanding impairments on quality of life, personal relationships, and education and career attainment. Furthermore, untreated dysmenorrhea can lead to hyperalgesic priming, which predisposes to chronic pelvic pain. Primary dysmenorrhea is pain in the lower abdomen that occurs before or during menses and in the absence of pelvic pathology. One possible mechanism is endometrial inflammation and increased prostaglandin release, resulting in painful uterine contractions. Dysmenorrhea may also occur secondary to pelvic pathology, such as endometriosis, adenomyosis or due to cyclic exacerbation of non-gynecologic pain conditions. A thorough patient evaluation is essential to differentiate between potential causes and guide management. Treatment must be tailored to individual patient symptoms. Pharmacologic management with non-steroidal anti-inflammatory medications and/or combined hormonal contraceptives is most common. Heat therapy, exercise, vitamins and dietary supplements have limited evidence and can be offered for patients seeking non-pharmacologic adjunctive or alternative options. Greater awareness for both health-care providers and patients allows for early intervention to reduce impact on quality of life and life course potential.

The dysregulation of leukemia inhibitory factor and its implications for endometriosis pathophysiology.

Endometriosis is an estrogen dominant, chronic inflammatory disease characterized by the growth of endometrial-like tissue outside of the uterus. The most common symptoms experienced by patients include manifestations of chronic pelvic pain- such as pain with urination, menstruation, or defecation, and infertility. Alterations to Leukemia Inhibitory Factor (LIF), a cytokine produced by the luminal and glandular epithelium of the endometrium that is imperative for successful pregnancy, have been postulated to contribute to infertility. Conditions such as recurrent implantation failure, unexplained infertility, and infertility associated diseases such as adenomyosis and endometriosis, have demonstrated reduced LIF production in the endometrium of infertile patients compared to fertile counterparts. While this highlights the potential involvement of LIF in infertility, LIF is a multifaceted cytokine which plays additional roles in the maintenance of cell stemness and immunomodulation. Thus, we sought to explore the implications of LIF production within ectopic lesions on endometriosis pathophysiology. Through immunohistochemistry of an endometrioma tissue microarray and ELISA of tissue protein extract and peritoneal fluid samples, we identify LIF protein expression in the ectopic lesion microenvironment. Targeted RT qPCR for LIF and associated signaling transcripts, identify LIF to be significantly downregulated in the ectopic tissue compared to eutopic and control while its receptor, LIFR, is upregulated, highlighting a discordance in ectopic protein and mRNA LIF expression. In vitro treatment of endometriosis representative cell lines (12Z and hESC) with LIF increased production of immune-recruiting cytokines (MCP-1, MCP-3) and the angiogenic factor, VEGF, as well as stimulated tube formation in human umbilical vein endothelial cells (HUVECs). Finally, LIF treatment in a syngeneic mouse model of endometriosis induced both local and peripheral alterations to immune cell phenotypes, ultimately reducing immunoregulatory CD206+ small peritoneal macrophages and T regulatory cells. These findings suggest that LIF is present in the ectopic lesions of endometriosis patients and could be contributing to lesion vascularization and immunomodulation.

Endometriosis and cardiovascular disease: a population-based cohort study.

BACKGROUND: Endometriosis, a prevalent condition among females of reproductive age, may be associated with increased risk of cardiovascular disease (CVD) through chronic inflammation and early menopause. The objective of this study was to estimate the association between endometriosis and subsequent risk of CVD. METHODS: We conducted a population-based cohort study using administrative health data from Ontario residents from 1993 to 2015. We compared the incidence of CVD and cardiovascular health outcomes between females with endometriosis and 2 age-matched females without endometriosis. The primary outcome was hospital admission for CVD. Secondary outcomes included in-hospital CVD events of interest and emergency department visits for CVD. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) between endometriosis and CVD events. RESULTS: We identified 166 835 eligible patients with endometriosis and matched 333 706 patients without endometriosis. The mean age of those with endometriosis was 36.4 years. Patients with endometriosis had a higher incidence of hospital admission for CVD (195 admissions/100 000 person-years) compared with those without endometriosis (163 admissions/100 000 person-years). Similarly, the incidence of secondary CVD events was slightly higher among patients with endometriosis (292 cases/100 000 person-years) than among those without endometriosis (224 cases/100 000 person-years). Females with endometriosis had an increased risk of hospital admission (adjusted HR 1.14, 95% confidence interval [CI] 1.10-1.19) and secondary CVD events (adjusted HR 1.26, 95% CI 1.23-1.30). INTERPRETATION: In this large, population-based study, endometriosis was associated with a small increased risk of CVD events. Future studies need to investigate potential etiological mechanisms and strategies to decrease long-term CVD risk in patients with endometriosis.