Nerve Bundle Density and Expression of NGF and IL-1ß Are Intra-Individually Heterogenous in Subtypes of Endometriosis.

Endometriosis is a gynecological disorder associated with local inflammation and neuroproliferation. Increased nerve bundle density has been attributed to increased expression of nerve growth factor (NGF) and interleukin-1ß (IL-1ß). Immunohistochemical analysis was carried out on 12 patients presenting with all three anatomic subtypes of endometriosis (deep, superficial peritoneal, endometrioma) at surgery, with at least two surgically excised subtypes available for analysis. Immunolocalization for nerve bundle density around endometriosis using protein gene product 9.5 (PGP9.5), as well as NGF and IL-1ß histoscores in endometriosis epithelium/stroma, was performed to evaluate differences in scores between lesions and anatomic subtypes per patient. Intra-individual heterogeneity in scores across lesions was assessed using the coefficient of variation (CV). The degree of score variability between subtypes was evaluated using the percentage difference between mean scores from one subtype to another subtype for each marker. PGP9.5 nerve bundle density was heterogenous across multiple subtypes of endometriosis, ranging from 50.0% to 173.2%, where most patients (8/12) showed CV ≥ 100%. The percentage difference in scores showed that PGP9.5 nerve bundle density and NGF and IL-1ß expression were heterogenous between anatomic subtypes within the same patient. Based on these observations of intra-individual heterogeneity, we conclude that markers of neuroproliferation in endometriosis should be stratified by anatomic subtype in future studies of clinical correlation.

Outcomes After Surgery at an Interdisciplinary Centre of Expertise for Endometriosis and Pelvic Pain in Canada: A Prospective Cohort Study.

OBJECTIVES: To prospectively evaluate pain-related quality-of-life (Endometriosis Health Profile-30 [EHP-30] pain subscale) after surgery at an interdisciplinary centre of expertise for endometriosis and pelvic pain. METHODS: A prospective cohort study was completed of persons undergoing surgical management for pelvic pain between December 2013 and July 2016 at an interdisciplinary tertiary referral centre for pelvic pain and endometriosis. We compared the change in EHP-30 scores for the following scenarios: (1) type of surgery (conservative surgery vs. hysterectomy), (2) stage of endometriosis (stage I/II vs. III/IV), and (3) age (age <40 vs. age ≥40 years). We used mixed-effects models to evaluate changes in pain during follow-up after surgery. RESULTS: Overall, 595 individuals met our inclusion criteria; the follow-up rate was 65.9% (392/595). In total, 436 (73.3%) underwent conservative surgery, while 159 (26.7%) underwent hysterectomy. Improvements in pain-related quality-of-life were seen for both conservative surgery and hysterectomy but greater improvements were seen with hysterectomy (P < 0.001). For conservative surgery, similar improvements in quality-of-life were observed regardless of endometriosis stage (I/II vs. III/IV) (P = 0.84) or age (<40 or ≥40 years old) (P = 0.87). We also observed similar improvements in quality-of-life regardless of stage (P = 0.24) or age (P = 0.71) after hysterectomy. CONCLUSIONS: At an interdisciplinary centre of expertise, there were significant improvements in quality-of-life after endometriosis surgery. These improvements were seen for both conservative surgery and hysterectomy (although greater improvement with the latter), for early and advanced stage disease, and younger and older patients.

Patient-Centered Approaches for Designing Destigmatizing Sexual Pain-Related Web-Based Platforms: Qualitative Study.

BACKGROUND: Sexual pain is a common but neglected disorder that affects approximately 3% to 18% of women and an unmeasured number of gender-diverse people worldwide. Despite its wide prevalence, many people feel reluctant to visit conventional health care services or disclose their symptoms due to the fear of stigmatization. To alleviate this stigma, various web-based interventions have been developed to complement and, in some cases, replace conventional sexual health interventions. However, the way these web-based interventions are developed could inadvertently reproduce, perpetuate, or exacerbate stigma among end user patients. OBJECTIVE: The purpose of this study was to understand patients' perspectives on how sexual pain-related web platforms can be designed to alleviate stigma or prevent the unintended effects of stigma among patients who use web-based interventions. METHODS: Individual semistructured interviews were conducted among 16 participants with lived experiences of painful sex in a large urban city in Western Canada. Participants were recruited via social media platforms, newsletters, and a provincial health volunteer website. Using a sample sexual pain website to provide context, participants were interviewed about their experiences of stigma and how they think web platforms could be designed to address stigma. The interviews were conducted via Zoom (Zoom Technologies Inc) and analyzed using thematic analysis. RESULTS: The findings revealed 4 overarching themes that represented participants' perspectives on designing web platforms that may alleviate or prevent the unintended effects of stigma. These findings suggested the design of inclusive web platforms, having a nonprovocative and calming user interface, having features that facilitate connections among users and between users and providers, and displaying personal testimonials and experiences of sexual pain. CONCLUSIONS: This study highlighted patient-centered design approaches that could serve as a reference guide in developing web platforms that alleviate or prevent the unintended effects of stigma, particularly among nonheterosexual and gender-diverse people. While this study was conducted in the context of sexual pain, the results might also apply to web platforms on other potentially stigmatizing health-related disorders or conditions.

Women's Self-Management of Dyspareunia Associated With Endometriosis: A Qualitative Study.

Given the limitations of medical treatment for endometriosis, self-management is a critical component of symptom management, and providing patients with information and education is a necessary complement to medical interventions. Though 50 to 70% of people with endometriosis experience dyspareunia (painful sex), there is limited knowledge of self-management specific to painful sex. A comprehensive understanding of the self-management strategies used is foundational to developing supportive care interventions that help ease pain and related psychosocial sequelae. The objective was to describe people's experiences of navigating endometriosis-associated painful sex and developing self-management strategies. We analyzed interview data from 20 women using constant comparative and thematic analysis techniques, guided by qualitative interpretive description methodology. Participants (age range 18-44 years) all identified as women and were predominately Caucasian (90%) and heterosexual (80%). Throughout their lives, the women appeared to gradually develop self-management strategies while navigating painful sexual experiences. This complex journey encompassed four phases: 1) viewing painful sex as normal, 2) experiencing evolving thoughts and emotions, 3) coming to understand painful sex and seeking help, and 4) learning strategies to navigate painful sex, these include preparing mentally and physically for sex and communicating with intimate partner(s). Women in this study developed self-management strategies over time through engagement with others who understood their challenges. Future research is warranted regarding initiatives to counter the normalization of painful sex, develop and disseminate patient-facing information, provide education specific to dyspareunia, improve access to multidisciplinary care, facilitate social connections and support, and enhance communication with intimate partners. PERSPECTIVE: In this paper, we report on the experiences of women with endometriosis-associated painful sex and their self-management strategies. Clinicians may be interested in a qualitative exploration of endometriosis-associated painful sex as they seek to further understand their patient's experiences and what strategies can be implemented to alleviate dyspareunia. DATA AVAILABILITY: The data sets generated during and/or analyzed during the current study are not publicly available as participants did not consent to making their data publicly available but are available from the corresponding author on reasonable request.

The quality, suitability, and readability of web-based resources on endometriosis-associated dyspareunia: A systematic review.

People commonly and increasingly rely on the internet to search for health information, including those related to endometriosis-associated dyspareunia. Yet the content of such websites may be of variable accuracy and quality. This review aims to evaluate the quality, readability, and suitability of web-based resources on endometriosis-associated dyspareunia for patients. We searched 3 databases - Google, Bing, and Yahoo - to identify websites related to endometriosis-associated dyspareunia. Two independent reviewers screened the search results against inclusion and exclusion criteria. Another set of two reviewers evaluated the selected websites using validated measurement instruments. Out of 450 websites, 21 met the inclusion criteria and were evaluated. More than half of the websites had information on content updates, reported on authorship, or disclosed sponsorship information. The mean quality and suitability scores were 47.5 (SD = 13.3) and 65.2 (SD = 13.6) respectively, thus suggesting generally adequate quality and suitability levels. However, the mean readability scores exceeded the recommended level for health-related websites. The poor readability of the websites might limit accessibility for a significant proportion of patients with low educational levels. The findings of this review have implications for designing high-quality, readable and up-to-date web interventions for people who rely on web platforms as an alternative or complementary source of health information on dyspareunia.

Mental Health Outcomes of Endometriosis Patients during the COVID-19 Pandemic: Impact of Pre-pandemic Central Nervous System Sensitization.

To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0-100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. PERSPECTIVE: This article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors.

Standardized protocol for quantification of nerve bundle density as a biomarker for endometriosis.

Introduction: We propose a standardized protocol for measurement of nerve bundle density in endometriosis as a potential biomarker, including in deep endometriosis (DE), ovarian endometriomas (OMA) and superficial peritoneal endometriosis (SUP). Methods: This was a prospective cohort of surgically excised endometriosis samples from Dec 1st 2013 and Dec 31st 2017 at a tertiary referral center for endometriosis in Vancouver, BC, Canada. Surgical data were available from linked patient registry. Protein gene product 9.5 (PGP9.5) was used to identify nerve bundles on immunohistochemistry. PGP9.5 nerve bundles were counted visually. To calculate nerve bundle density, PGP9.5 nerve bundle count was divided by the tissue surface area (total on the slide). All samples were assessed using NHS Elements software for semi-automated measurement of the tissue surface area. For a subset of samples, high power fields (HPFs) were also counted as manual measurement of the tissue surface area. Intraclass correlation was used to assess intra observer and inter observer reliability. Generalized linear mixed model (GLMM) with random intercepts only was conducted to assess differences in PGP9.5 nerve bundle density by endometriosis type (DE, OMA, SUP). Results: In total, 236 tissue samples out of 121 participants were available for analysis in the current study. Semi-automated surface area measurement could be performed in 94.5% of the samples and showed good correlation with manually counted HPFs (Spearman's rho = 0.781, p < 0.001). To assess intra observer reliability, 11 samples were assessed twice by the same observer; to assess inter observer reliability, 11 random samples were blindly assessed by two observers. Intra observer reliability and inter observer reliability for nerve bundle density were excellent: 0.979 and 0.985, respectively. PGP9.5 nerve bundle density varied among samples and no nerve bundles could be found in 24.6% of the samples. GLMM showed a significant difference in PGP9.5 nerve bundle density between the different endometriosis types (X2 = 87.6, P < 0.001 after adjusting for hormonal therapy, with higher density in DE and SUP in comparison to OMA). Conclusion: A standardized protocol is presented to measure PGP9.5 nerve bundle density in endometriosis, which may serve as a biomarker reflecting local neurogenesis in the endometriosis microenvironment.

Acceptability, reliability, and validity of a vaginal insert for the self-assessment of endometriosis-associated deep dyspareunia: a cross-sectional study.

BACKGROUND: Approximately half of people with endometriosis experience deep dyspareunia; however, there is no means of objective self-testing of endometriosis-associated deep dyspareunia. AIM: The aim of this study was to assess the acceptability, test-retest reliability, and validity of a vaginal insert for a self-assessment of endometriosis-associated deep dyspareunia. METHODS: Participants were recruited from a tertiary endometriosis center. Inclusion criteria were: 19 to 49 years of age, self-reported deep dyspareunia of ≥4 of 10, and surgically confirmed endometriosis. Participants completed 2 self-assessments using the vaginal insert to self-assess tenderness at the right and left pelvic floor, bladder, cervix-uterus, and posterior cul-de-sac (vaginal fornix). The participants recorded tenderness at each pelvic site and completed a questionnaire regarding the acceptability of the vaginal insert to assess deep dyspareunia. Test-retest reliability was assessed by correlating the tenderness scores between the 2 assessment dates. Over a 4-week period, the participants also recorded deep dyspareunia severity at each penetrative vaginal sex encounter. Validity was assessed by correlating vaginal insert tenderness to deep dyspareunia severity, and also to tenderness reported on a prior gynecologic pelvic examination. OUTCOMES: The main outcome measures were the acceptability index score, tenderness (0-10) at each pelvic site, and prospective deep dyspareunia scores (0-10) over 4 weeks. RESULTS: There were 19 participants (mean age 34 ± 7 years) who completed the study. The majority identified as female (94.7%), heterosexual (89.5%), and white (89.5%). The median acceptability index score was 0.72 (interquartile range, 0.66-0.81). For test-retest reliability, the intraclass correlation coefficients were 0.79 (P = .001) for the left pelvic floor, 0.82 (P < .001) for the right pelvic floor, 0.54 (P = .07) for the bladder, 0.89 (P < .001) for the cervix-uterus, and 0.77 (P = .003) for the cul-de-sac. The correlation between the highest self-assessed mean tenderness in each participant and self-reported deep dyspareunia over 4 weeks was r = 0.32, but correlations for each pelvic site varied significantly. Tenderness at each site on prior gynecologist pelvic exam was associated with higher self-assessed mean tenderness with the vaginal insert in each participant (effect sizes = 0.42-0.88). CLINICAL IMPLICATIONS: The vaginal insert is acceptable and reliable for the objective self-assessment of endometriosis-associated deep dyspareunia, with initial evidence of validity. STRENGTHS AND LIMITATIONS: A strength was the inclusion of participants who were avoiding sexual activity and a limitation was the small sample size. CONCLUSION: Future studies with larger sample sizes are required to further establish the validity of the vaginal insert for the self-assessment of endometriosis-associated deep dyspareunia.

Pelvic pain comorbidities associated with quality of life after endometriosis surgery.

BACKGROUND: After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. OBJECTIVE: This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. STUDY DESIGN: This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. RESULTS: The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (ß=3.19), pelvic floor myalgia (ß=2.44), and Patient Health Questionnaire 9 depression score (ß=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. CONCLUSION: Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.

KRAS mutations and endometriosis burden of disease.

The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p = 0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p = 0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR] = 1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR = 0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR = 1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis.

Ohnut Versus a Waitlist Control for the Self-management of Endometriosis-Associated Deep Dyspareunia: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Endometriosis-associated deep dyspareunia is associated with reduced sexual quality of life, lower self-esteem, and impaired sexual function. OBJECTIVE: The primary objective is to assess the acceptability of a phallus length reducer (brand name: Ohnut [OhnutCo]), which is a buffer worn over the penis or a penetrating object to reduce endometriosis-associated deep dyspareunia, and the feasibility of a definitive randomized controlled trial (RCT). The secondary objective is to obtain estimates of the effectiveness of the buffer. An embedded substudy will explore the acceptability and the preliminary validity and reliability of a vaginal insert for the self-assessment of deep dyspareunia. METHODS: Ours is an investigator-initiated, 2-arm RCT. We will recruit 40 patient participants with diagnosed endometriosis between the ages of 19 and 49 years, as well as their sexual partners. The participating couples will be randomized in a 1:1 ratio into the experimental arm or the waitlist control arm. The length of the study period will be 10 weeks, during which time all participants will record deep dyspareunia severity following each episode of sexual intercourse. In weeks 1 to 4, all patient participants will record deep dyspareunia severity at each sexual encounter. In weeks 5 to 10, participants in the experimental arm will use the buffer during vaginal penetration; participants in the waitlist control arm will continue engaging in vaginal penetration as usual. Participants will complete questionnaires for assessing measures of anxiety, depression, and sexual function at baseline, at 4 weeks, and at 10 weeks. In the substudy, patient participants will self-assess dyspareunia by using a vaginal insert on 2 occasions, at least 1 week apart. The primary outcomes-the acceptability and feasibility of the buffer-will be assessed with descriptive statistics, and the secondary outcome-phallus length reducer effectiveness-will be assessed by using an analysis of covariance-based approach. For the vaginal insert, we will assess acceptability, test-retest reliability, and convergent validity via correlation analyses comparing the use of the insert to clinical examination in terms of dyspareunia assessment outcomes. RESULTS: Our pilot will provide initial data on the acceptability and effectiveness of the buffer and the feasibility of the study methodology. The results from our study are expected to be submitted for publication by the spring of 2023. As of September 2021, we have consented 31 couples into the study. CONCLUSIONS: Our study will provide preliminary evidence for the self-assessment and management of endometriosis-associated deep dyspareunia. The findings will inform the decision to proceed to a definitive RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04370444; https://clinicaltrials.gov/ct2/show/NCT04370444. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39834.

Web-Based Digital Storytelling for Endometriosis and Pain: Qualitative Pilot Study.

BACKGROUND: Endometriosis is a complex chronic disease characterized by pain, including painful sex, that can contribute to considerable sexual function, self-esteem, and relationship challenges. Digital storytelling is an arts-based, participatory methodology wherein individuals create and share their illness experiences in detailing their lived experiences. OBJECTIVE: The study objective was to pilot-test a web-based digital storytelling workshop focused on endometriosis to understand storytellers' experiences of workshop participation. We assessed the feasibility of story cocreation and sharing, including the emotional impact of workshop participation, the acceptability of the workshop for the subject matter, and the storytellers' willingness to share their stories with broader audiences as a method for knowledge translation. METHODS: This study used a community-based participatory methodology supplemented with patient-oriented research and integrated knowledge translation. Study participants, referred to as storytellers, cocreated 3- to 5-minute individual digital stories about their lived experiences of endometriosis during a web-based workshop (comprising five 2-hour sessions over 6 weeks) facilitated by The Center for Digital Storytelling. Data were collected through participant observations at the workshop, storyteller weekly reflective journals, and an end-of-workshop focus group interview with storytellers. These data were analyzed using a qualitative interpretive description approach. RESULTS: A total of 5 women and 1 nonbinary storyteller aged 19 to 39 years who had experienced endometriosis for 4 to 22 years participated in the study. We characterized storytelling workshop participation and the acceptability of story cocreation by describing participants' experiences of opportunity, commitment, and connection; complex emotions that were healing; and a desire to share. Feasibility was demonstrated through 100% engagement in the workshops. All 6 storytellers reported feeling empowered by publicly sharing their cocreated digital stories through social media and the Sex, Pain & Endometriosis website. CONCLUSIONS: Despite the complexities of the story-building process, the workshop and the cocreation and sharing of digital stories were feasible. The storytellers found that this process allowed for emotional healing and personal empowerment by offering a unique way to talk about painful sex, which also facilitated a connection among those in the workshop. The use of digital storytelling as a knowledge translation tool shows promise, and this approach also has potential as a therapeutic intervention.

Association of Central Sensitization Inventory Scores With Pain Outcomes After Endometriosis Surgery.

Importance: A subset of people who undergo surgery for endometriosis have persistent pain, suggesting that other factors besides the endometriosis, such as central sensitization, may play a role in this pain. The Central Sensitization Inventory, a validated self-reported questionnaire of central sensitization symptoms, may identify individuals with endometriosis who have more pain after surgery due to pain sensitization. Objective: To examine whether greater baseline Central Sensitization Inventory scores are associated with postsurgical pain outcomes. Design, Setting, and Participants: This prospective, longitudinal cohort study performed at a tertiary center for endometriosis and pelvic pain in British Columbia, Canada, included all patients aged 18 to 50 years with diagnosed or suspected endometriosis and a baseline visit between January 1, 2018, and December 31, 2019, who underwent surgery after the baseline visit. Individuals who were menopausal, had a prior hysterectomy, or were missing data for outcomes or measures were excluded. Data analysis was performed from July 2021 to June 2022. Main Outcomes and Measures: The primary outcome was chronic pelvic pain at follow-up measured on a scale of 0 to 10, with 0 to 3 indicating no pain or mild pain, 4 to 6 indicating moderate pain, and 7 to 10 indicating severe pain. Secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain at follow-up. The main variable of interest was baseline Central Sensitization Inventory score (measured from 0 to 100, consisting of 25 self-reported questions rated from 0 to 4 [never, rarely, sometimes, often, and always, respectively]). Results: A total of 239 patients (mean [SD] age, 34 [7] years; 189 [79.1%] White [11 (5.8%) identified as White mixed with another ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed race or ethnicity) with follow-up data at more than 4 months after surgery were included in this study (71.0% follow-up rate). The mean (SD) baseline Central Sensitization Inventory score was 43.8 (18.2), and the mean (SD) follow-up was 16.1 (6.1) months. Higher baseline Central Sensitization Inventory scores were significantly associated with higher chronic pelvic pain (odds ratio [OR], 1.02; 95% CI, 1.00-1.03; P = .02), deep dyspareunia (OR, 1.03; 95% CI, 1.01-1.04; P = .004), dyschezia (OR, 1.03; 95% CI, 1.01-1.04; P < .001), and back pain (OR, 1.02; 95% CI, 1.00-1.03; P = .02) at follow-up, when controlling for baseline pain scores. The Central Sensitization Inventory scores themselves decreased slightly from baseline to follow-up (mean [SD] score, 43.8 [18.2] vs 41.7 [18.9]; P = .05); however, individuals with high baseline Central Sensitization Inventory scores still had high scores at follow-up. Conclusions and Relevance: In this cohort study of 239 patients with endometriosis, higher Central Sensitization Inventory scores at baseline were associated with worse pain outcomes after endometriosis surgery, when controlling for baseline pain scores. The Central Sensitization Inventory could be used to counsel patients with endometriosis on their expected outcomes after surgery.

Developing an Educational Website for Women With Endometriosis-Associated Dyspareunia: Usability and Stigma Analysis.

BACKGROUND: Endometriosis is a chronic condition that affects approximately 10% of women worldwide. Despite its wide prevalence, knowledge of endometriosis symptoms, such as pelvic pain, and treatments remains relatively low. This not only leads to a trivialization of symptoms and delayed diagnosis but also fuels myths and misconceptions about pain symptoms. At the same time, the use of web-based platforms for information seeking is particularly common among people with conditions that are perceived as stigmatizing and difficult to discuss. The Sex, Pain, and Endometriosis website is an educational resource designed to provide evidence-based information on endometriosis and sexual pain to help people understand the condition, feel empowered, dispel myths, and destigmatize endometriosis-associated sexual pain. OBJECTIVE: The study objective is to evaluate the usability of the website and assess for destigmatizing properties of sexual health-related web-based resources. METHODS: We conducted a usability analysis by using a think-aloud observation, a postsystem usability questionnaire, and follow-up interviews with 12 women with endometriosis. The think-aloud data were analyzed using the framework by Kushniruk and Patel for analyzing usability video data, the questionnaire data were analyzed using descriptive statistics, and the follow-up interviews were analyzed using simple content analysis. We conducted a usability assessment by deductively analyzing the interview data via a trauma-informed care framework and a content analysis approach. RESULTS: Through usability analysis, we found the website to be simple, uncluttered, satisfying, and easy to use. However, 30 minor usability problems related to navigation; website response; the comprehension of graphics, icons, and tabs; the understanding of content; and mismatch between the website and users' expectations were reported. In our stigma analysis, we found the web content to be nonstigmatizing. The participants suggested ways in which websites could be designed to address stigma, including ensuring privacy, anonymity, inclusiveness, and factual and nonjudgmental content, as well as providing opportunities for web-based engagement. CONCLUSIONS: Overall, the participants found the website to be useful, easy to use, and satisfying. The usability problems identified were largely minor and informed the website redesign process. In the context of the limited literature on stigma and website design, this paper offers useful strategies on how sexual health-related websites can be designed to be acceptable and less stigmatizing to individuals with sensitive health issues.

Central sensitization inventory in endometriosis.

ABSTRACT: A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization.

Application of Anti-Stigma Design Heuristics for Usability Inspection.

User interface evaluation has become important in developing usable health care technologies. Although usability engineering methods have been applied in the design and evaluation of health care software, available heuristics focus on task-work aspects and do not address stigma associated with many health conditions. We used a previous set of heuristics and propose a new set of anti-stigma heuristics to evaluate stigmatization in health care websites. The extended set of heuristics were concurrently applied in a heuristic evaluation and a cognitive walkthrough to evaluate an endometriosis and sexual pain website. The walkthrough involved 5 tasks that required 21 actions to execute. Twenty-six usability problems were identified and recommendations for re-design were made to the design team before end-user testing. The anti-stigma heuristics received worse ratings than the traditional heuristics, resulting in several design changes that might otherwise have been missed. Thus, the new anti-stigma heuristics were a valuable contribution.

Negative Sliding Sign during Dynamic Ultrasonography Predicts Low Endometriosis Fertility Index at Laparoscopy.

STUDY OBJECTIVE: Endometriosis fertility index (EFI) is a robust tool to predict the pregnancy rate in patients with endometriosis who are attempting non-in vitro fertilization conception. However, EFI calculation requires laparoscopy. Newly established imaging techniques such as sliding sign, which is used to diagnose pouch of Douglas obliteration, could provide a promising alternative. The objective of this study was to investigate the practicality of using ultrasound data to predict a low EFI (score ≤6). DESIGN: Observational study from a prospective registry (Endometriosis Pelvic Pain Interdisciplinary Cohort, clinicaltrials.gov #NCT02911090). Analyzed data were captured from December 2013 to June 2017. SETTING: Tertiary referral center at British Columbia Women's Hospital. PATIENTS: We analyzed data for 2583 participants from the Endometriosis Pelvic Pain Interdisciplinary Cohort. In this cross-sectional study, we included 86 women aged <40 years. INTERVENTIONS: Dynamic ultrasonography for the sliding sign testing and EFI calculation during laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to obtain receiver operating characteristic area under the curve (AUC) for the prediction models. Significance was p <.05. Patients with a negative sliding sign were older and had severe endometriosis and longer duration of infertility. Patients with a negative sliding sign had significantly lower total EFI scores and lower surgical factors scores than patients with a positive sliding sign. Logistic regression showed that a negative sliding sign and EFI historic factors score can predict an EFI score ≤6 (sensitivity = 87.9%, specificity = 81.1%, AUC = 0.93 [95% confidence interval, 0.88-0.98]). Adding the diagnosis of endometrioma to the previous prediction model resulted in AUC = 0.95 (95% confidence interval, 0.90-0.995), sensitivity = 84.8%, and specificity = 92.5%. CONCLUSION: The sliding sign could be a potential alternative to the EFI surgical factors, and it could be used in combination with EFI historic factors and the diagnosis of endometrioma to predict an EFI score ≤6 for patients who are not scheduled for immediate surgery.

A Quantitative Analysis of Sleep Quality in Women with Endometriosis.

Background: Endometriosis is a complex condition that can negatively affect a woman's quality of life, including her sleep. This study aims to assess the multifactorial variables associated with poorer quality of sleep in women with endometriosis. Materials and Methods: Data from the Endometriosis Pelvic Pain Interdisciplinary Cohort (EPPIC) data registry were analyzed for women who underwent surgery at the BC Women's Center for Pelvic Pain and Endometriosis with histopathological confirmation of endometriosis (June 2015 to June 2017). The primary outcome was quality of sleep preoperatively, from the Chronic Pain Sleep Inventory (0-100 VAS). Bivariate analysis and multivariable linear regression were done to determine any significant associations between preoperative patient variables and overall quality of sleep, based on p-value of 0.05. Results: Two hundred and seventy-five women met the study criteria. Poorer overall quality of sleep was independently associated with poorer functional quality of life (EHP-30) (b = -0.18, p = 0.0026), more depressive symptoms (PHQ-9) (b = -1.62, p < 0.001), and painful bladder syndrome (PBS) (b = -5.82, p = 0.035). This indicates that a 1 point increase in the EHP-30 (worsening quality of life), a 1 point increase in the PHQ-9 (worsening depression), and the presence of PBS increased the primary outcome (i.e., toward poorer quality of sleep) by 0.18, 1.62, and 5.82 points. Conclusions: Poorer quality of sleep in women with endometriosis is associated with poorer quality of life, more depressive symptoms, and bladder pain. Research into interventions that improve sleep is warranted as part of the management of some women with endometriosis.

CHC for pelvic pain in women with endometriosis: ineffectiveness or discontinuation due to side-effects.

STUDY QUESTION: What are the use patterns and factors associated with combined hormonal contraception (CHC) ineffectiveness or discontinuation due to side-effects in patients with endometriosis and pelvic pain? SUMMARY ANSWER: Worse chronic pelvic pain (CPP) severity and pelvic floor myalgia were associated with continuous CHC ineffectiveness, while poorer quality-of-life was associated with continuous CHC discontinuation due to side-effects. WHAT IS KNOWN ALREADY: CHC is a first line of therapy for endometriosis-associated pelvic pain in women. However, some patients state that CHC is ineffective for their pain, while others have to discontinue CHC due to side-effects. STUDY DESIGN SIZE DURATION: Analysis of a prospective patient database from a tertiary care referral center for patients with endometriosis and pelvic pain between December 2013 and April 2015 was carried out. PARTICIPANTS/MATERIALS SETTING AND METHODS: A total of 373 patients of reproductive age with endometriosis from the database were included in the study. Data included patient self-reported questionnaires, physical examination findings and validated instruments. There were four variables of interest: history of cyclical CHC ineffectiveness (yes/no), history of cyclical CHC discontinuation due to side-effects (yes/no), history of continuous CHC ineffectiveness (yes/no) and history of continuous CHC discontinuation due to side-effects (yes/no). The primary outcome was CPP severity for the past 3 months (score of 0-10), and secondary outcomes were other pelvic pain scores, quality-of-life on the Endometriosis Health Profile 30 (EHP-30) and underlying conditions including irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia and depression, anxiety and pain catastrophizing. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 373 cases in the dataset, prior cyclical CHC use was reported by 228 (61.1%) women, of which 103 (27.6%) stated it was ineffective for their pain and 94 (25.2%) stated they discontinued CHC due to side-effects. Previous continuous CHC use was reported by 175 (46.9%) women, of which 67 (18.0%) stated it was ineffective and 59 (15.8%) stated they discontinued due to side-effects. Worse CPP severity in the last 3 months was associated with a history of continuous CHC ineffectiveness (P < 0.001). Poorer quality-of-life was present in women who reported a history of continuous CHC discontinuation due to side-effects (P = 0.005). Among the underlying conditions, pelvic floor tenderness (as a marker of pelvic floor myalgia) was associated with CHC ineffectiveness. LIMITATIONS AND REASONS FOR CAUTION: This study involved patient recall and no longitudinal follow-up. Also, we do not have data on the type of side-effect that led to discontinuation. Medication ineffectiveness was reported subjectively by the patient rather than using standardized criteria. Finally, the diagnosis of endometriosis was based on previous surgery or a current nodule or endometrioma on examination/ultrasound; without prospective surgical data on all the patients, it was not possible to do a sub-analysis by current surgical features (e.g. stage). WIDER IMPLICATIONS OF THE FINDINGS: In women with endometriosis, CHC ineffectiveness was associated with worse CPP and pelvic floor myalgia, which suggests myofascial or nervous system contributors to CPP that does not respond to hormonal suppression. A tender pelvic floor, as a sign of pelvic floor myalgia, may be a clinical marker of patients with endometriosis who are less likely to have an optimal response to hormonal suppression. For women who discontinue CHC due to side-effects, research is needed to help alleviate these side-effects as these patients report worse quality-of-life. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a Canadian Institutes of Health Research (CIHR) Transitional Open Operating Grant (MOP-142273) as well as BC Women's Hospital and the Women's Health Research Institute. PY is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB/CA has financial affiliations with Abbvie and Allergan; the other authors have no conflicts of interest.