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.

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.

Clinical diagnosis of endometriosis: a call to action.

Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4-11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide.

Assessing research gaps and unmet needs in endometriosis.

Endometriosis, a systemic disease that is often painful and chronic, affects ∼10% of reproductive-age women. The disease can have a negative impact on a patient's physical and emotional well-being, quality of life, and productivity. Endometriosis also places significant economic and social burden on patients, their families, and society as a whole. Despite its high prevalence and cost, endometriosis remains underfunded and underresearched, greatly limiting our understanding of the disease and slowing much-needed innovation in diagnostic and treatment options. Due in part to the societal normalization of women's pain and stigma around menstrual issues, there is also a lack of disease awareness among patients, health care providers, and the public. The Society for Women's Health Research convened an interdisciplinary group of expert researchers, clinicians, and patients for a roundtable meeting to review the current state of the science on endometriosis and identify areas of need to improve a woman's diagnosis, treatment, and access to quality care. Comprehensive and interdisciplinary approaches to disease management and increased education and disease awareness for patients, health care providers, and the public are needed to remove stigma, increase timely and accurate diagnosis and treatment, and allow for new advancements.

Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood.

BACKGROUND: Endometriosis symptoms often start at a young age, and the time between symptom onset and endometriosis diagnosis can be several years. It is not clear whether the symptoms that are experienced by adolescents differ from adults. Better understanding may shorten the often lengthy delay in diagnosis. OBJECTIVE: The purpose of the study was to further elucidate the symptom presentation of adolescents as compared with adults to determine whether differences existed, based on age at surgical diagnosis that could impact time to diagnosis. STUDY DESIGN: This investigation was a cross-sectional study at enrollment within a longitudinal cohort of adolescents and women with endometriosis. The population-based cohort was recruited from 2 tertiary care centers and the surrounding communities. Participants included adolescents (diagnosed at ≤18 years old; n=295) and adults (diagnosed at >18 years old; n=107) with surgically confirmed endometriosis who were enrolled into The Women's Health Study: From Adolescence to Adulthood. Participants completed an expanded version of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project standard clinical questionnaire that included items regarding menstrual history, associated symptoms, and pain. Chi-square or Fisher's exact tests were applied to categoric data; Wilcoxon rank sum tests were applied to continuous data. RESULTS: Most participants (90%) experienced moderate-severe menstrual pain. On average, 3 doctors were seen before diagnosis, regardless of age at presentation (range, 0-25 years). Time from symptoms to diagnosis averaged 2 years for adolescents and 5 years for adults (P<.001). More adolescents (50%) than adults (33%) reported pain starting at menarche (P=.002) and nausea accompanying pain (69% vs 53%; P=.01). Noncyclic, general pelvic pain was prevalent. One-half of the participants reported relief of their general pelvic pain after a bowel movement. Pain interfered with work/school, daily activities, exercise, and sleep to a moderate-extreme degree; difficulties were similar by age at diagnosis. CONCLUSIONS: Pelvic pain was severe and noncyclic and negatively impacted quality of life. At our tertiary care centers, symptoms of endometriosis did not differ between women surgically diagnosed during adolescence compared with those diagnosed as adults. Adolescents had more nausea and symptom onset at menarche. Multi-year delays in diagnosis were common. Clinicians should be aware of these alternate symptom patterns and include endometriosis in their differential diagnosis for both adolescent and young adult women who experience noncyclic pelvic pain and nausea.

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.

Endometriosis for the primary care physician.

PURPOSE OF REVIEW: This review will empower the primary care provider (PCP) to evaluate, manage, and refer as needed adolescents with dysmenorrhea and/or chronic pelvic pain (CPP) who are suspected to have endometriosis. RECENT FINDINGS: Endometriosis is a common cause of CPP in adolescents who do not respond to primary medical treatment. The presentation in adolescents is unique, causing high rates of misdiagnosis or delayed treatment. Endometriosis-related pain has a marked negative impact on social and mental health. Simple treatments that are available in the primary care setting can alleviate pain and improve quality of life for these young women if initiated in a timely fashion. SUMMARY: Adolescents usually turn to their PCP for evaluation of dysmenorrhea and CPP. By maintaining a high index of suspicion, initiating treatment, and referring when needed, the PCP can have a tremendous effect on the patient's present and future quality of life.

The use of gonadotropin releasing hormone analogues in adolescent and young patients with endometriosis.

PURPOSE OF REVIEW: Endometriosis is increasingly being recognized and diagnosed in adolescents. As a result of this earlier diagnosis, treatment with agents like gonadotropin releasing hormone agonist (GnRHa) begins earlier and may last longer. Long-term effects of GnRHa treatment for endometriosis are of concern when treating adolescents. RECENT FINDINGS: GnRHas are used for adolescents with surgically confirmed endometriosis. GnRHa treatment is effective for pain reduction, but is associated with menopausal symptoms and decreases in bone density. Different regimens of hormonal add-back therapy have been studied in adults to attempt to prevent these side-effects. SUMMARY: GnRHa therapy is a highly effective, nonsurgical treatment option for many adolescents with endometriosis, but is accompanied by side-effects of bone loss and menopausal symptoms. Side-effects may be decreased by introducing appropriate add-back therapy. Monitoring of bone density by DXA is recommended for prolonged use of GnRHa in adolescents.

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.

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.

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.

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.

Spontaneous Cervicovaginal Fistula in Obstructed Hemivagina and Ipsilateral Renal Anomaly Syndrome: A Case Report.

BACKGROUND: Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare diagnosis; patients classically present with dysmenorrhea and increasing pelvic pain. Unusual manifestations of OHVIRA syndrome might occur as a result of patient anatomy and the rupture or relief of the obstructed hemivagina. CASE: We present a 15-year-old patient with OHVIRA syndrome who developed a spontaneous cervicovaginal fistula and subsequently underwent hemihysterectomy.

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.

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.