Plasma proteins and persistent postsurgical pelvic pain among adolescents and young adults with endometriosis.

BACKGROUND: Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression. OBJECTIVE: To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. STUDY DESIGN: We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. RESULTS: The median age at blood draw was 17 years (interquartile range, 15-19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal P<.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44-6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28-5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36-0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04-14.33]). CONCLUSION: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

Surgical Considerations in the Management of Adolescent Endometriosis-An Expert Commentary.

Given the complexities and controversies that exist in diagnosing adult endometriosis, as well as optimizing medical and surgical management, it is not surprising that there is even more ambiguity and inconsistency in the optimal surgical care of endometriosis in the adolescent. This collaborative commentary aimed to provide evidence-based recommendations optimizing the role of surgical interventions for endometriosis in the adolescent patient with input from experts in minimally invasive gynecologic surgery, pediatric and adolescent gynecology, and infertility/reproductive medicine.

Case Series of Reproductive Outcomes after Surgical Correction of Obstructed Hemivagina in OHVIRA.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) is a rare congenital developmental syndrome manifested by uterine duplication, lower genital tract obstruction, and unilateral renal anomaly. Literature on reproductive outcomes in this patient population is limited. The aim of this study is to describe obstetric outcomes after surgical correction of obstructed hemivagina in a longitudinal cohort of patients with a diagnosis of OHVIRA. All cases of OHVIRA presenting to a single tertiary care children's hospital from 1990 to 2021 were retrospectively reviewed. Three cases demonstrating a variety of clinically important reproductive outcomes are described in detail including risks such as retained products, endometritis, preterm labor, and malpresentation. Understanding the reproductive outcomes associated with this diagnosis is important for practitioners seeking to counsel and care for patients with this diagnosis. This case series demonstrates a wide array of potential gynecologic and obstetric risks, though ultimately with successful term and near-term pregnancies.

Evaluation and Management of Endometriosis in the Adolescent.

Endometriosis is a chronic condition, with debilitating symptoms affecting all ages. Dysmenorrhea and pelvic pain often begin in adolescence, affecting school, daily activities, and relationships. Despite the profound burden of endometriosis, many adolescents experience suboptimal management and significant delay in diagnosis. The symptomatology and laparoscopic findings of endometriosis in adolescents are often different than in adults, and the medical and surgical treatments for adolescents may differ from those for adults as well. This Narrative Review summarizes the diagnosis, evaluation, and management of endometriosis in adolescents. Given the unique challenges and complexities associated with diagnosing endometriosis in this age group, it is crucial to maintain a heightened level of suspicion and to remain vigilant for signs and symptoms. By maintaining this lower threshold for consideration, we can ensure timely and accurate diagnosis, enabling early intervention and improved management in our adolescent patients.

Treatment of Adolescent Endometriosis Before, During, and After Use of Gonadotropin-Releasing Hormone Agonists: A Retrospective Cohort Study.

OBJECTIVE: To explore the use duration of a gonadotropin-releasing hormone agonists (GnRHa) plus add-back in adolescents with laparoscopically confirmed endometriosis and the treatment course before and after GnRHa therapy. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We identified 51 subjects with laparoscopically confirmed endometriosis who had participated in a randomized trial of a GnRHa plus add-back as adolescents between 2008 and 2012. Electronic medical records were reviewed to obtain demographic data, clinical characteristics, and treatment outcomes after trial completion. The study was deemed IRB exempt. RESULTS: The average age of participants during trial enrollment was 17.9 ± 1.7 years. Thirty-three participants had stage I endometriosis (65%). The most common treatments trialed before GnRHa therapy were combined oral contraceptives (n = 47, 92%) and progestin-only pills (n = 23, 45%). The average duration of GnRHa use during the trial was 9.5 ± 3.5 months; 34 subjects (67%) completed the 1-year trial. After trial completion, 23 subjects (45%) continued to use a GnRHa with add-back therapy. The mean duration of additional GnRHa use was 31.7 ± 28.6 months, and the longest identified duration was an additional 96 months. Twenty-four subjects switched to other hormonal treatments after trial participation, most commonly oral progestins (n = 15) or combined oral contraceptives (n = 6). Thirteen participants (25%) returned to a therapy that had been trialed before GnRHa use. CONCLUSION: Almost half the participants in this cohort continued to use a GnRHa with add-back for treatment of endometriosis beyond the 12-month recommended duration. Treatment varied widely after discontinuation of GnRHa, with many participants returning to previously trialed medical therapies.

Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis.

ABSTRACT: We described trends in pelvic pain characteristics over 2 years of follow-up among adolescents and adults with and without endometriosis participating in the longitudinal observational cohort of the Women's Health Study: From Adolescence to Adulthood, using data reported at baseline and at years 1 and 2 of follow-up. Participants completed a questionnaire at baseline (between November 2012 and May 2019) and annually thereafter that included validated measures of severity, frequency, and life interference of dysmenorrhea, acyclic pelvic pain, and dyspareunia. Our study population included 620 participants with surgically confirmed endometriosis (rASRM stage I/II = 95%) and 671 community-based and hospital-based controls, with median age = 19 and 24 years, respectively. The proportion reporting hormone use varied across the 3 years ranging from 88% to 92% for cases and 56% to 58% for controls. At baseline, endometriosis cases were more likely to report severe, frequent, and life-interfering dysmenorrhea, acyclic pelvic pain, and dyspareunia compared with controls. Among cases, frequency and severity of dysmenorrhea and dyspareunia were relatively static across 2 years. However, acyclic pelvic pain improved. Severe acyclic pain decreased from 69% at baseline to 46% at year 2. Daily pain decreased from 28% to 14%, and life interference from 68% to 38%. Trends among controls remained fairly stable across 2 years. Among endometriosis cases who completed the questionnaire at all 3 time points, 18% reported persistent, severe acyclic pelvic pain at all 3 time points. Over time, different trends were observed by pelvic pain type among endometriosis cases and controls, supporting the importance of assessing multidimensional features of pelvic pain.

Cohort profile: The Endometriosis pain QUality aftEr Surgical Treatment (EndoQUEST) Study.

Endometriosis affects reproductive-aged females and varies considerably in terms of symptom presentation, morphologic features, and treatment response. Most studies investigating symptom recurrence after an endometriosis-related surgery have been conducted among adults. The Endometriosis pain QUality aftEr Surgical Treatment (EndoQUEST) Study was established to assess characteristics and biomarkers that are associated with pain remediation and improved quality of life after an endometriosis-related surgery among adolescents and young adults. This paper describes the EndoQUEST methodology, summarizes baseline descriptive factors, and compares characteristics by participant retention status. We enrolled 100 surgically-confirmed endometriosis participants aged 12-23 years who provided questionnaire data on reproductive and behavioral factors, pain characteristics and quality of life at three time points; before surgery, 6 weeks to 26 weeks after surgery, and 1 year after surgery. Among these 100 participants, 88 provided blood and/or saliva at all three time points, while 12 provided blood and/or saliva samples only before surgery and 6 to 26 weeks after surgery. There was little evidence of lost to follow-up at 1 year after surgery due to pain symptoms, as pain and quality of life characteristics were similar between participants who completed the questionnaire 1 year after surgery and those who did not. Analyses utilizing these longitudinal data will advance personalized treatment decision making for adolescents and young adults with endometriosis.

Presurgical blood metabolites and risk of postsurgical pelvic pain in young patients with endometriosis.

OBJECTIVE: To identify metabolites in presurgical blood associated with risk of persistent postsurgical pelvic pain 1 year after endometriosis surgery in adolescent and young adult patients. DESIGN: Prospective observational study within the Women's Health Study: From Adolescence to Adulthood, a US-based longitudinal cohort of adolescents and women enrolled from 2012-2018. SETTING: Two tertiary care hospitals. PATIENT(S): Laparoscopically confirmed endometriosis patients (n = 180) with blood collected before their endometriosis surgery. Of these, 77 patients additionally provided blood samples 5 weeks to 6 months after their surgery. We measured plasma metabolites using liquid chromatography tandem mass spectrometry, and a total of 390 known metabolites were included in our analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Persistent postsurgical pelvic pain, defined as severe, life-impacting pelvic pain 1 year after endometriosis surgery. RESULT(S): Most patients (>95%) were at stage I/II of the revised American Society for Reproductive Medicine classification. Their average age at diagnosis was 18.7 years, with 36% reporting persistent postsurgical pelvic pain. Of the 21 metabolites in presurgical blood that were associated with risk of persistent postsurgical pelvic pain, 19 metabolites, which were mainly lipid metabolites, were associated with increased risk. Only 2 metabolites-pregnenolone sulfate (odds ratio = 0.64, 95% confidence interval = 0.44-0.92) and fucose (odds ratio = 0.69, 95% confidence interval = 0.47-0.97)-were associated with decreased risk. Metabolite set enrichment analysis revealed that higher levels of lysophosphatidylethanolamines (false discovery rate = 0.01) and lysophosphatidylcholines (false discovery rate = 0.01) in presurgical blood were associated with increased risk of persistent postsurgical pelvic pain. CONCLUSION(S): Our results suggest that dysregulation of multiple groups of lipid metabolites may play a role in the persistence of pelvic pain postsurgery among young endometriosis patients.

Informed Care for the Gynecologic Day Surgical Patient with a History of Sexual Trauma.

The field of Obstetrics and Gynecology is one that provides intersections between one's most private and intimate moments with scenarios that could potentially trigger significant emotional trauma. As providers, one must balance providing appropriate care with the respect and autonomy of the patient. The perioperative and operative space presents many ethical dilemmas in navigating these boundaries, particularly among individuals with a history of sexual trauma. In our commentary, we present one case of an adolescent patient, with a history of sexual trauma and pelvic pain, who underwent laparoscopic surgery. We explore the interplay of delegating autonomy during amnesia, chronic pelvic pain, post-traumatic stress disorder, and hyperarousal within this period. There is knowledge to be gained amongst Obstetrics and Gynecology providers in navigating perioperative services in individuals with complex history of social stress and trauma so that we can better understand the landscape of providing competent care.

The Use of Telemedicine in Pediatric and Adolescent Gynecology.

STUDY OBJECTIVE: To study the feasibility of virtual visits for ambulatory encounters in pediatric and adolescent gynecology DESIGN: A retrospective review SETTING: Boston Children's Hospital PARTICIPANTS: Patients who were seen virtually through the Division of Gynecology between January 1, 2020 and June 1, 2020 MAIN OUTCOME MEASURE(S): Patient demographics, visit diagnoses, and operational characteristics of the completed visits RESULTS: There were a total of 654 virtual visits for 614 patients. Ninety-one percent (n=558) of patients were in-state, and the median age of patients was 17 years (range 0 - 37 years). The majority were return visits (n=502, 76.8%), 115 (17.6%) were new patient visits, and 32 (4.89%) were post-operative visits. The median virtual visit duration was 12 minutes and 39 seconds (range 5 minutes to over 1 hour). The most common gynecologic diagnoses were dysmenorrhea/endometriosis (n=485, 74.2%), abnormal uterine bleeding (n=225, 34.4%), and pelvic pain (n=82, 12.5%). The percentage of virtual visits which required an in-person follow-up visit within 90 days was low (n=14, 2.1%). Five of these were within 30 days from the initial virtual visit, 6 were within 60 days, and 3 were within 90 days. CONCLUSION: Telemedicine is a feasible method for expanding access to, and healthcare delivery for, pediatric and adolescent gynecology, with low rates of short interval in-person follow-up required. Virtual visits can be conducted for a range of patients with a variety of gynecologic conditions, upon initial presentation and follow-up.

Interdisciplinary Management of Malignant Ovarian Tumors in the Pediatric and Adolescent Age Group.

Malignant ovarian neoplasms are uncommon in the pediatric and adolescent population. Imaging and tumor markers help to guide the preoperative risk/benefit analysis for planned surgical management, which is the mainstay of therapy. An interdisciplinary approach should be taken in the management of this vulnerable population from diagnosis through post-treatment surveillance. In this review, the initial evaluation, risk stratification, and management of various types of malignant ovarian masses will be addressed, with a special focus on how to optimize an interdisciplinary approach to ovarian masses.

Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate.

OBJECTIVE: To estimate the efficacy and safety of a novel nonhormonal therapeutic agent, cabergoline, compared with that of the standard clinical therapy, norethindrone acetate (NETA), for the treatment of endometriosis-associated pain in young women with endometriosis. DESIGN: Randomized, double-blind, placebo-controlled pilot study. SETTING: Tertiary care center. PATIENTS: Women (n = 9) with surgically confirmed endometriosis. INTERVENTIONS: A random, double-blind assignment to either NETA (5 mg/day) + placebo twice weekly or cabergoline (0.5 mg) twice weekly + placebo daily for 6 months. MAIN OUTCOME MEASURES: We collected the measures of pelvic pain and laboratory parameters every 3 months. RESULTS: We observed a decrease in pain scores and increase in pain relief in women randomized to receive cabergoline, who appeared to show similar or more improvements than women treated with NETA. The serum measures of vascular endothelial growth factor receptor 1 declined over 6 months in those who received cabergoline. Cabergoline was well tolerated, and no serious adverse events occurred. CONCLUSIONS: Safe, effective adjunct treatments are lacking for patients with endometriosis who do not respond to standard care. Because the growth of endometriosis requires angiogenesis, blood vessel growth is an attractive therapeutic target. This pilot study suggests that cabergoline, a vascular endothelial growth factor pathway inhibitor, is an effective therapeutic option for women with chronic pain due to endometriosis. Building upon this investigation, we will conduct larger, randomized trials of cabergoline, advancing research on the best treatments for endometriosis-particularly disease resistant to hormonal therapies. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov; registration number NCT02542410.

Juvenile Granulosa Cell Tumor as the Presenting Feature of McCune-Albright Syndrome.

INTRODUCTION: GNAS mutations have been reported in both McCune-Albright syndrome (MAS) and juvenile granulosa cell tumors (JGCT) but have never been reported simultaneously in the same patient. CASE PRESENTATION: A 15-year-old girl developed secondary oligomenorrhea. Laboratory studies revealed suppressed gonadotropin levels with markedly elevated estradiol and inhibin B levels. Pelvic ultrasound showed a 12-cm heterogeneous right adnexal mass; pelvic magnetic resonance imaging to further characterize the mass displayed heterogeneous bilateral femoral bone lesions initially concerning for metastatic disease. Positron emission tomography/computed tomography showed minimal 18F-fluorodeoxyglucose (FDG) uptake in the pelvic mass but unexpectedly revealed FDG uptake throughout the skeleton, concerning for polyostotic fibrous dysplasia in the context of MAS. The adnexal mass was excised and pathology confirmed a JGCT. The patient's affected bone and JGCT tissue revealed the same pathogenic GNAS p.R201C mutation, while her peripheral blood contained wild-type arginine at codon 201. CONCLUSION: This mutation has been previously reported in cases of MAS and JGCT but never simultaneously in the same patient. This demonstration of a GNAS mutation underlying both JGCT and MAS in the same patient raises questions about appropriate surveillance for patients with these conditions.

Development of a visual, patient-reported tool for assessing the multi-dimensional burden of endometriosis.

OBJECTIVE: Inadequate communication about endometriosis symptom burden between women and healthcare providers is a barrier for optimal treatment. This study describes the development of the EndoWheel, a patient-reported assessment tool that visualizes the multi-dimensional burden of endometriosis to facilitate patient-provider communication. METHODS: Assessment questions for the tool were developed using an iterative Delphi consensus process. A consensus phase included additional practitioners and specialists to broaden perspectives and select revised statements. Semi-structured qualitative interviews were conducted with 13 women with endometriosis to assess the scoring and content of the measures. RESULTS: Symptoms included in the tool were pelvic pain, vaginal bleeding, bowel/bladder symptoms, energy levels, fertility, impact on activities, emotional and sexual well-being, and self-perceived global health. Additional life impact areas included relationships, social and occupational activity, and self-perception. The 13 interviewees completed the tool in approximately 5-6 min (range 4.0-7.5 min). Most participants (92%) perceived that the tool would enable better patient-provider communication, including addressing symptoms and areas of impact not normally discussed during office visits. CONCLUSION: Similar to visual circular tools used in burden assessment of other chronic diseases, the tool may facilitate improved patient dialogue with providers around endometriosis treatment goals and options.

Safety of Surgical Fertility Preservation Procedures in Children Prior to Hematopoietic Stem Cell Transplant.

Long-term survival following hematopoietic stem cell transplant (HSCT) in childhood continues to improve, and patients are thus increasingly faced with the late effects of treatment. Infertility is very common for both males and females following HSCT and is one of the most distressing sequelae. Adoption and surrogate egg or sperm donation are possibilities for some patients, but post-HSCT reversal of gonadal failure is not possible. We have recently initiated an oncofertility program with a dedicated practitioner with specific expertise in this area. Our practice is for her to meet with all families and age-appropriate patients during the pre-HSCT evaluation period. This allows patients and families to be accurately informed about the expected treatment-related infertility risk and the available options for fertility preservation. Sperm banking and egg or embryo cryopreservation are established approaches but are not achievable for many children and adolescents. Recently, the harvesting and cryopreservation of ovarian and testicular tissue represents a novel surgical option that allows for the possibility of fertility preservation to be extended to children of all ages. The purpose of this investigation is to evaluate the safety of these procedures proximal to conditioning therapy and HSCT. This is a retrospective report on a consecutive cohort of all patients aged 0 to 25 years who, after discussion with our oncofertility specialist, chose to undergo surgical fertility preservation (laparoscopic unilateral oophorectomy or testicular biopsy) at our institution between March 2018 and April 2020. These procedures occurred under general anesthesia at the time of central line placement prior to the initiation of HSCT conditioning. We assess the safety of the procedures in terms of postoperative complications and impact on HSCT course. Twenty-two patients underwent fertility preservation surgical procedures. Thirteen patients (59%) were female, median age 13 years (1 to 22 years), and 9 (41%) were male, median age 8 years (5 to 12 years). Fourteen (63%) were prepubertal and 8 (36%) pubertal. HSCT indications were hematologic malignancies/solid tumor (40%) and nonmalignant diseases (60%). Most received an allogenic graft (68%) and 81% had myeloablative conditioning. All patients became neutropenic at a median of 10 days (0 to 51 days) from the surgical procedure; 1 was neutropenic at the time of testicular tissue cryopreservation (TTC). The mean duration for the procedures performed, including ovarian tissue cryopreservation (OTC) or TTC, was 98 minutes (49 to 260 minutes) and 97 minutes (56 to 178 minutes), respectively. Estimated blood loss was minimal and no postoperative site infections occurred. One postprocedure, blood culture-negative fever was reported without an identifiable source; the patient completed 48 hours of antibiotics with resolution of fever. Sixty-two percent of females and 56% of males started conditioning within 24 hours of OTC/TTC (15 hours to 113 days; median, 1 day). The median time to engraftment was 22 days (9 to 33 days) in females and 17 days (11 to 67 days) in males, consistent with our institutional benchmarks. One patient with aplastic anemia had primary graft failure, attributed to low cell dose. This patient engrafted after a second transplant from an alternative donor but ultimately died of multiorgan failure. He was neutropenic for over 60 days and never experienced surgical site infection. There were no procedure-related delays to start of conditioning or to discharge. Children of all ages can now be offered the possibility of fertility preservation following HSCT for benign and malignant conditions. Our review suggests that these procedure for both females and males can be performed close to the start of conditioning, which allows for coupling with central access placement. These procedures appear to be safe and do not add to transplant-related morbidity.

Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women.

PROBLEM: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune-mediated conditions and endometriosis among young women. METHOD OF STUDY: This cross-sectional analysis in the Women's Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders. RESULTS: Participants with any autoimmune and/or inflammatory condition had an increased odds of co-occurring endometriosis (OR: 1.87; CI: 0.92-3.80), as did participants with allergies (OR: 1.76; CI: 1.32-2.36), asthma (OR: 1.35; CI: 0.97-1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89-17.9), or previous mononucleosis (OR: 1.75; CI: 1.14-2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44-1.04). We observed a positive trend between the number of immune-mediated conditions and the odds of endometriosis (p-trend=0.0002). Endocrine disorders were not associated with endometriosis. CONCLUSIONS: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune-mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity.

Impact of Endometriosis on Life-Course Potential: A Narrative Review.

Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one's life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.

A Clinical and Pathologic Exploration of Suspected Peritoneal Endometriotic Lesions.

Endometriosis is generally histopathologically defined as the presence of at least 2 of the following: endometrial stroma, Müllerian epithelium, and/or hemosiderin-laden macrophages (HLM). Despite clinically evident endometriotic lesions, biopsies are frequently nondiagnostic. In this study, we conducted a large-scale review of biopsies of lesions clinically thought to represent endometriosis and correlate the histologic findings with clinical appearance to expand sensitivity of the pathologic definition of endometriosis, particularly in patients on hormonal therapy. In all, 112 biopsies from 78 patients (mean age=25, range 18-39 yr) were reviewed for histopathologic features suggestive of or diagnostic for endometriosis including the presence of endometrial stroma, Müllerian epithelium, dystrophic calcifications, HLM, chronic inflammation, adhesions, and vascular proliferation. Endometriosis was confirmed by pathologic criteria in 37 of 78 patients (47%). Biopsies from patients on hormonal therapy (n=62, 80%) were significantly less likely to meet pathologic criteria for endometriosis (P=0.01). Nondiagnostic biopsies (70/112; 63%) frequently displayed HLM (20%), chronic inflammation (29%), dystrophic calcifications (26%), vascular proliferation (20%), or adhesions (20%) and were significantly more likely to have a vascular clinical appearance (P=0.01). Diagnostic biopsies (42/112; 38%) were more likely to have a blue/black clinical appearance (P=0.03), demonstrate HLM (P=0.004), and display pseudodecidualization (P=0.05). Patients with a high clinical suspicion of endometriosis have a range of histologic findings, with less than half meeting the current histopathologic criteria for diagnosing endometriosis. Given the heterogeneous histopathologic appearance, revision of the histologic criteria may be warranted with further exploration, particularly for lesions with predominantly vascular features.

Comparison of cytokines in the peritoneal fluid and conditioned medium of adolescents and adults with and without endometriosis.

PROBLEM: To compare inflammatory- and immune-associated peritoneal cytokines of adolescents and adults with and without endometriosis. METHODS OF STUDY: In a nested case-control study in multiple university-affiliated scientific centers, ten adolescents and thirteen adults with visually and histologically confirmed endometriosis (cases), thirteen adolescents with visually suspected endometriosis but indeterminate (seven patients) or negative (six patients) histology, and fifteen adults undergoing surgery for non-malignant gynecologic disease without endometriosis (controls) underwent laparoscopic aspiration of peritoneal fluid (PF), from which PF and conditioned medium (CM) cytokine levels were assayed. RESULTS: Compared to adults with endometriosis, MCP-3, IL-12p40, MIP-1ß, and IL-15 were significantly higher among adolescents with endometriosis, while TNF-ß and CTACK were lower among adolescents. These differences were similar comparing adolescents with endometriosis to adult controls except for MIP-1ß, which was not statistically different. MIP-1ß was, however, the only cytokine observed to differ between adult cases and controls. There were no significant differences in CM cytokines among the three groups. Results were similar when analyses were restricted to samples collected (a) during menstrual cycle days 1-10, (b) from patients unexposed to exogenous hormones, or (c) from all adolescents despite presence or absence of histologic endometriosis. CONCLUSION: Biologically relevant and statistically significant differences in six PF cytokines were observed and suggest a more pro-invasion cytokine profile among adolescents with endometriosis. Adolescents with endometriosis have unique peritoneal cytokine profiles and molecular behavior when compared to adults with and without endometriosis.