{"paper_id":"2301aed9-6eff-423b-b9b6-ae562b8c6ad4","body_text":"Abstract\nIntroduction:\nEndometriosis is a chronic gynecological disease associated with pelvic pain, infertility, and reduced quality of life. Ovarian endometrioma is its most common manifestation. Although laparoscopic cystectomy is widely used, concerns regarding ovarian reserve have led to increasing interest in conservative approaches. Ultrasound-guided ethanol sclerotherapy (EST) has emerged as a minimally invasive alternative with potential benefits for symptom control and reproductive outcomes. The ESCOMA trial aims to evaluate the impact of EST compared with expectant management on quality of life in women with ovarian endometriomas.\nMethods and analysis:\nESCOMA is a prospective, multicentre, randomised controlled trial comparing ultrasound-guided ethanol sclerotherapy with expectant management. A total of 288 women with ovarian endometriomas will be randomised in a 1:1 ratio. The primary outcome is change in quality of life at 6 months, assessed using the Endometriosis Health Profile-5 (EHP-5). Secondary outcomes include pain reduction, changes in pain-related biomarkers, ovarian reserve markers, cyst size reduction, reproductive outcomes, adverse events and complications, diagnostic accuracy, and healthcare costs. Analyses will be performed according to both intention-to-treat and per-protocol principles.\nEthics and dissemination:\nThe study was approved by the Clinical Research Ethics Committee of Hospital Universitari de Bellvitge (PR070/25). Written informed consent will be obtained from all participants.\nClinical Trial Registration:\nClinicalTrials.gov, identifier NCT06955221.\nStrengths and limitations of this study\nFirst multicentre randomised clinical trial directly comparing ethanol sclerotherapy and expectant management for ovarian endometriomas.\nPrimary outcome focused on quality of life, assessed with a validated and widely used tool (EHP-5).\nInclusion of ovarian reserve markers and reproductive outcomes (pregnancy rates and time to conception) enhances the clinical relevance of the study; however, fertility outcomes will only be evaluated in the subgroup of women who express a desire for pregnancy, which reduces the sample size for these endpoints and may limit the statistical power to detect differences between groups.\nThe additional assessment of healthcare costs provides valuable information on the health-economic impact of both treatment strategies.\nAlthough an open-label design may influence subjective outcomes such as quality of life, objective biomarkers and pregnancy outcomes are less susceptible to bias.\nAdministrative information\nProtocol version: v2.\nSponsor and roles\nSponsor: IDIBELL\nContact: Dra Amparo García-Tejedor (agarciat@bellvitgehospital.cat).\nFunder: Instituto de Salud Carlos III (FIS PI24/01014).\nResponsibilities: The sponsor is responsible for trial conduct, regulatory obligations, and insurance. The funder has no role in study design, data collection, analysis, interpretation, manuscript writing, or decision to publish.\nCommittees: Trial management is overseen by a Trial Steering Committee (investigators and biostatistician) and an independent Data Safety Monitoring Board (DSMB) every 6 months.\nIntroduction\nEndometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease that affects approximately 5%–10% of women of reproductive age (, ) and is associated with infertility in up to 40% of cases (). Ovarian endometrioma is its most frequent manifestation, occurring in 15%–45% of affected women (). In addition to infertility, chronic pelvic pain is one of the main clinical symptoms, often causing work absenteeism and a substantial impairment in quality of life (QoL) (, ).\nThe optimal management of ovarian endometriomas remains controversial, and treatment should be individualized according to symptoms, reproductive plans, ovarian reserve, and cyst characteristics (, ). When surgical treatment is indicated, laparoscopic cystectomy remains the reference surgical technique because of its effectiveness in reducing pain and recurrence. However, surgery may reduce ovarian reserve owing to the inadvertent excision of healthy ovarian tissue, which is particularly detrimental in women with an already compromised reproductive potential (, ). Furthermore, postoperative recurrence rates remain high, ranging between 15%–30% (). These limitations have stimulated increasing interest in conservative treatment strategies aimed at preserving ovarian reserve while achieving adequate symptom control, particularly in women wishing to conceive ().\nCurrent management of ovarian endometriomas has progressively shifted towards more conservative and fertility-preserving approaches, including expectant management, medical therapy, and minimally invasive interventions (, ). Treatment decisions should be individualized based on symptom severity, cyst characteristics, ovarian reserve, and the patient's reproductive goals (, ). Expectant management may be considered for selected asymptomatic women with ovarian endometriomas. However, because untreated endometriomas may be associated with a progressive decline in ovarian reserve, regular monitoring of cyst size and ovarian reserve is recommended (). For symptomatic women who are not seeking immediate pregnancy, hormonal therapy is considered the first-line conservative treatment and includes combined oral contraceptives, progestins, and gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (, ). Combined oral contraceptives are widely used as first-line medical therapy for pain and symptom control in women with endometriosis. However, evidence regarding their effect on endometrioma size and ovarian reserve remains limited (, –). Among progestins, dienogest is currently considered the first-line long-term medical treatment for endometriosis because of its effectiveness in reducing pain and improving endometriosis-related symptoms, with increasing evidence supporting its role in the management of ovarian endometriomas (, –). GnRH agonists remain an effective option for pain and symptom control in selected women with endometriosis. In women who are not seeking immediate pregnancy after surgery, postoperative treatment has been associated with lower endometrioma recurrence rates. However, their long-term use is limited by hypoestrogenic adverse effects; and add-back therapy is recommended to improve tolerability and facilitate prolonged treatment (, ). Although these conservative approaches play a key role in the management of ovarian endometriomas, each has specific indications and limitations, and none provides a definitive treatment while preserving ovarian reserve in all patients (, , ). Therefore, there remains a need for fertility-preserving alternatives that effectively control symptoms while minimizing the impact on ovarian reserve, particularly in women wishing to conceive (, ).\nIn this context, ultrasound-guided ethanol sclerotherapy has emerged as a promising minimally invasive, fertility-preserving alternative for selected women with ovarian endometriomas (, ). Its minimally invasive nature, outpatient setting, and potential to preserve ovarian reserve make ethanol sclerotherapy an attractive option for selected women with ovarian endometriomas, particularly those wishing to preserve their fertility (, –). Current evidence suggests that ethanol sclerotherapy achieves recurrence rates comparable to laparoscopic cystectomy while offering lower procedural costs and favorable reproductive outcomes, particularly in women with diminished ovarian reserve undergoing assisted reproductive treatment (, , –). However, despite these encouraging results, high-quality evidence on the long-term effects of ethanol sclerotherapy on quality of life, ovarian reserve, and reproductive outcomes remains limited (, , , ). These remaining uncertainties highlight the need for randomised clinical trials to better define the role of ethanol sclerotherapy in the management of ovarian endometriomas and provide the rationale for the present multicentre randomised clinical trial (, , ).\nBeyond reproductive outcomes, improving quality of life is a key objective in the management of endometriosis. The Endometriosis Health Profile (EHP-30 and its shorter version, the EHP-5), developed at the University of Oxford, is a validated and widely used patient-reported outcome measure for assessing the impact of endometriosis on quality of life (, ).\nAccordingly, the ESCOMA trial aims to compare ultrasound-guided ethanol sclerotherapy with expectant management in women with ovarian endometriomas, with the primary objective of comparing quality of life. Secondary objectives include assessing pain, ovarian reserve, reproductive outcomes, the need for subsequent surgery, safety, and treatment-related healthcare costs.\nObjectives\nPrimary objective\nTo compare the impact of ethanol sclerotherapy vs. expectant management on quality of life in women with ovarian endometriomas, assessed with the EHP-5 questionnaire at baseline and at 6 months.\nSecondary objectives\nTo compare pain reduction between groups, measured by the Visual Analogue Scale (VAS) at 6 months and time to improvement.\nTo assess changes in pain-associated biomarkers in serum [cortisol, C-reactive protein (CRP), interleukin-6 (IL-6)] and urine (cortisol, adrenaline, noradrenaline) between baseline and 6 months.\nTo evaluate changes in ovarian reserve markers, including serum Anti-Müllerian Hormone (AMH) and antral follicle count (AFC), between baseline and 6 months.\nTo compare the reduction in cyst size (largest diameter) between baseline and 6 months.\nTo assess reproductive outcomes among women with pregnancy desire during the 24-month follow-up, including spontaneous pregnancies, assisted reproductive technology (ART) pregnancies, number of ART cycles required, and oocyte yield.\nTo compare the number and type of adverse events and complications between groups.\nTo identify the number of misdiagnosed cysts (non-endometriomas) in the sclerotherapy group.\nTo compare treatment-related healthcare costs between groups.\nTo assess endometrioma recurrence or progression during the 24-month follow-up.\nMethods and analysis\nStudy design\nThis is a multicentre, open-label, randomised controlled clinical trial conducted across 39 hospitals in Spain. Participants will be randomised in a 1:1 ratio to undergo EST or expectant management. Given the nature of the intervention, blinding is not feasible; however, objective outcomes will mitigate bias.\nConcomitant care\nBoth groups may receive complementary medical treatment at the discretion of the treating specialist, in accordance with the clinical protocols of each participating centre. In most cases, such treatments will already have been prescribed before study entry.\nParticipants\nEligibility criteria are listed below\nInclusion Criteria\nFemale sex\nAge ≥18 and ≤45 years\nUltrasound suspicion of unilocular endometrioma or with a thin septum less than 3 mm\nSize between 30 and 100 mm, persistent for at least 3–6 months since diagnosis\nCa125 marker < 300 UI/mL and HE4 < 70 pM\nBilateral endometriomas.\nRecurrent endometriomas\nPrevious ovarian intervention, including ovarian surgery or sclerotherapy\nSigned informed consent\nExclusion Criteria\nAge <18 or >45 years\nHistory of ovarian or uterine cancer\nEndometrioma size < 30 mm or >100 mm\nIndication for surgical treatment of the endometrioma due to suspected severe extra-ovarian endometriosis or any other cause. In cases of clinical suspicion of severe extra-ovarian endometriosis, pelvic MRI will be performed to assess disease extent and confirm eligibility.\nUltrasound suspicion of dermoid cysts, anechoic cysts, or cysts with high risk of malignancy\nCa125 > 300 UI/mL\nHE4 > 70 pM\nPregnant women\nPatients who do not wish to participate in the study or who are mentally incapacitated\nAll participant centers are members of the ESCOMA team. The list of participating Hospitals is shown in the Supplementary Appendix S1.\nInterventions\nIntervention group: Ultrasound-guided ethanol sclerotherapy (EST).\nProcedure\nAnalgesic treatment is administered before the procedure, consisting of ibuprofen 1 h before and diazepam ½ hour before. On the day of the puncture, the patient must not present purulent leucorrhoea or genital bleeding.\nA single puncture is performed, preferably via the vaginal route, although an abdominal approach may be used if required by the patient's condition or by the cyst's characteristics, for example in virginal patients or when marked vascularization is observed along the puncture pathway.\nThe abdominal wall or vaginal canal is disinfected with a povidone–iodine solution.\nA sterile 17-gauge needle (BD Medical Franklin Lakes, NJ, Becton, Dickinson and Company) is used. Under ultrasound guidance, the needle is advanced into the centre of the cyst and connected, through an extension tube and a three-way stopcock, to a vacuum aspiration system.\nAspiration of the endometrioma contents may require dilution with saline solution (SS) when the fluid is thick. The aspirated fluid is measured using a syringe or an adapted measurement system.\nAfter nearly complete aspiration, several washes with Saline solution (SS) are performed until clear fluid is obtained.\nA volume of 100% ethanol equivalent to two-thirds of the aspirated volume is then instilled into the cyst, without exceeding 100 mL.\nThe ethanol is left in place for 15 min without moving the needle, which remains inside the cyst.\nSubsequently, the cyst is emptied and washed twice with SS, using the same volume as the instilled ethanol.\nThe aspirated fluid is sent to the pathology department for cytological examination to confirm the absence of atypical cells.\nThe 100% ethanol solution used at all participating centres will be identical. The product will be supplied by Farmacia Carreras, the authorized provider for hospitals throughout Spain, ensuring consistency and avoiding potential bias related to variations in preparation.\nExpectant management group\nParticipants will continue the treatment they were receiving before study inclusion, or no treatment if none was previously prescribed. During follow-up, medical treatment may be initiated or modified according to clinical circumstances, patient preference, and usual clinical practice. Recommendations are provided to investigators to promote consistency in the management of the expectant-management group across participating centres (Supplementary Appendix 3); however, treatment decisions are not mandated by the study protocol. All concomitant treatments and subsequent changes will be prospectively recorded in the study database. Analgesia and supportive care are permitted in both groups. To minimize potential imbalance in this relevant clinical factor, randomisation will be stratified according to the presence or absence of concomitant hormonal treatment at study inclusion. In addition, the potential effect of hormonal treatment received during follow-up will be accounted for in the statistical analysis, including appropriate adjusted and sensitivity analyses.\nOutcomes\nPrimary outcome: Quality of life assessed with the EHP-5 questionnaire, a validated self-administered patient-reported outcome measure, at baseline and 6 months.\nSecondary outcomes\nPain reduction (VAS score at 6 months and time to improvement)\nChanges in pain-associated biomarkers in serum (cortisol, CRP, IL-6) and urine (cortisol, adrenaline, noradrenaline)\nOvarian reserve markers (AMH and AFC)\nReduction in cyst size (largest diameter)\nReproductive outcomes (spontaneous pregnancies, ART pregnancies, number of ART cycles, oocyte yield),\nAdverse events and complications,\nNumber of misdiagnosed cysts (non-endometrioma)\nTreatment-related direct medical costs from the healthcare system perspective.\nEndometrioma recurrence or progression.\nLong-term outcomes assessed during follow-up up to 24 months will include endometrioma recurrence or progression, subsequent interventions, and reproductive outcomes among women with pregnancy desire, including spontaneous pregnancies and ART-related outcomes (number of ART cycles, number of oocytes retrieved, and pregnancies achieved through ART).\nA detailed description of all secondary outcomes, including definitions, timing and methods of aggregation, is provided in Supplementary Table S1.\nSample size\nFor the primary endpoint (quality of life), the sample size was estimated based on published data reporting an improvement in quality of life—considering patient-reported pain—of approximately 55.25% (range 53%–60%) after conservative management and 71.5% (range 63%–80%) after EST. Assuming a two-sided α of 0.05 and a statistical power greater than 0.80, 144 participants per group are required to detect a statistically significant difference between the two proportions (p1 = 0.5525 and p2 = 0.715). Considering a 5% loss to follow-up, the total sample size will be 288 participants (144 per group). Calculations were performed using the arcsine (arcsin–square-root) approximation for comparison of proportions.\nFor the fertility substudy (subgroup of women expressing a desire for pregnancy), published data indicate pregnancy rates of approximately 48% after EST (range 37%–55%) and 15% with conservative management. Assuming a two-sided α of 0.05 and a β of 0.20 (power = 0.80), 33 participants per group are required to detect this difference (p1 = 0.48, p2 = 0.15). Allowing for a 10% loss to follow-up, the final target will be 37 participants per group, yielding a total of 74 women for the fertility analysis.\nThese calculations ensure adequate statistical power to detect clinically meaningful differences in both quality of life and reproductive outcomes between treatment groups.\nRandomisation and allocation\nRandomisation will be performed by an independent statistician using computer-generated permuted blocks, stratified by prior ovarian intervention (surgery or EST), pregnancy desire, and hormonal treatment. Allocation will be centrally managed through a secure, web-based REDCap platform with concealed randomisation sequence. Site investigators will enrol eligible participants, and group allocation will be automatically assigned by the electronic system.\nBlinding\nThis is an open-label, non-blinded study. Both physician and patient will be aware of the allocated treatment arm, since blinding is not considered feasible when comparing an interventional procedure (EST) with expectant management according to standard clinical practice. The absence of blinding may influence patient-reported quality of life outcomes; however, it should not affect reproductive or biomarker outcomes, which are objective measures.\nStatistical analysis\nPrimary analysis will use mixed linear regression models with clustering by patient to compare QoL scores. Secondary analyses will include chi-square for categorical outcomes, repeated measures ANOVA, Kaplan–Meier survival curves for pregnancy rates, and Mann–Whitney U tests for oocyte counts. Analyses will be performed on both intention-to-treat and per-protocol populations. A statistical analysis plan will be finalised prior to database lock.\nSecondary outcomes will be analysed as defined in Supplementary Table S1. Continuous outcomes (e.g., VAS, AMH, AFC, cyst diameter, oocyte yield, biomarker levels) will be compared between groups using appropriate parametric or non-parametric tests depending on distribution. Categorical outcomes (e.g., pregnancy rates, adverse events, misdiagnosis) will be compared using χ2 or Fisher's exact test. Time-to-event outcomes (e.g., time to clinical improvement, time to spontaneous pregnancy) will be analysed using Kaplan–Meier curves and log-rank tests. Effect estimates will be presented with 95% confidence intervals. A detailed Statistical Analysis Plan is provided in the Supplementary Appendix S7.\nHandling of concomitant treatments\nAll concomitant medical treatments will be recorded at baseline and during follow-up. Sensitivity analyses will be performed to explore whether concomitant medication use modifies the treatment effect on primary and secondary outcomes. These analyses will be exploratory in nature.\nData management and monitoring\nData will be entered into a secure REDCap database hosted at IDIBELL. Monitoring will be performed by an independent contract research organisation (CRO) hosted in IDIBELL, including initiation, interim, and close-out visits. A Data Safety Monitoring Board (DSMB) will meet at 6, 12, and 18 months to review safety and efficacy. Details are provided in the Supplementary Appendix.\nEthics and dissemination\nThe trial complies with the Declaration of Helsinki and Good Clinical Practice. Ethics approval has been obtained from the Bellvitge University Hospital Research Ethics Committee (PR 070/25). Written informed consent will be obtained from all participants. Data will be pseudonymised and stored securely. Results will be disseminated through peer-reviewed journals, conferences, professional networks, and patient associations. Regardless of outcomes, results will be published.\nPatient and public involvement\nPatients and the public were not involved in the design or conduct of the study. Dissemination will be facilitated through patient associations, public talks, and online platforms.\nDiscussion\nThis protocol describes the first multicentre randomised controlled trial designed to compare ultrasound-guided ethanol sclerotherapy (EST) with expectant management in women with ovarian endometriomas. Although laparoscopic cystectomy remains the most widely used treatment, increasing concerns regarding its impact on ovarian reserve have led to growing interest in less invasive alternatives. EST has shown promising results in observational studies and small comparative cohorts, but high-quality randomised evidence remains limited. The ESCOMA trial aims to address this knowledge gap by providing robust data from a large multicentre population representative of routine clinical practice.\nA major strength of this study is the selection of quality of life as the primary outcome. Endometriosis is a chronic disease with a substantial physical, psychological, and social burden, and treatment success should not be evaluated solely through anatomical or reproductive outcomes. The use of the EHP-5 questionnaire, a validated disease-specific instrument, allows the assessment of outcomes that are directly meaningful to patients and aligns with current recommendations promoting patient-centred care in endometriosis research.\nAnother important aspect of this trial is the comprehensive evaluation of secondary outcomes. In addition to pain relief and cyst size reduction, the study incorporates ovarian reserve markers, reproductive outcomes, pain-related biomarkers, treatment-related complications, diagnostic accuracy, and healthcare costs. This multidimensional approach will provide a broader understanding of the potential benefits and limitations of EST and may help clinicians individualize treatment decisions according to patient priorities, particularly among women wishing to preserve fertility.\nThe inclusion of ovarian reserve assessment is particularly relevant. Surgical treatment of endometriomas has consistently been associated with reductions in serum anti-Müllerian hormone levels and potential damage to healthy ovarian tissue. As many affected women are diagnosed during their reproductive years, preserving ovarian function has become a key consideration when selecting therapeutic strategies. If EST demonstrates comparable symptom control while minimizing the impact on ovarian reserve, it may represent an attractive alternative to surgery in selected patients.\nThe economic evaluation of the ESCOMA study will compare direct medical costs between treatment groups, including healthcare resource utilization and the management of treatment-related complications. This will allow us to assess the healthcare costs associated with EST compared with expectant management.\nSome limitations should be considered when interpreting the results of this study. First, the open-label design may influence patient-reported outcomes such as quality of life and pain perception. However, blinding is not feasible when comparing an invasive procedure with expectant management, and several secondary outcomes, including biomarkers, ovarian reserve parameters, and reproductive outcomes, are objective measures less susceptible to observer bias. Second, variations in clinical practice among participating centres may introduce heterogeneity. Nevertheless, the multicentre nature of the study enhances the external validity and generalizability of the findings. Third, reproductive outcomes will be evaluated only among women who express a desire for pregnancy, reducing the effective sample size for fertility-related analyses. Finally, although the primary endpoint will be assessed at 6 months, patients will be followed for a total of 24 months, allowing longer-term assessment of endometrioma recurrence or progression, reproductive outcomes, and subsequent interventions.\nIn conclusion, the ESCOMA trial has the potential to generate high-quality evidence regarding the role of EST in the management of ovarian endometriomas. By integrating patient-reported outcomes, reproductive outcomes, biological markers, and economic analyses, this study may contribute to redefining treatment algorithms and informing future clinical guidelines for women affected by this common and challenging condition.\nData sharing\nDe-identified participant data and statistical code will be available upon reasonable request after publication, subject to ethics approval and GDPR compliance. Requests should be directed to the corresponding author.\nPost-trial care\nThe intervention is minimally invasive and part of standard practice; any harm will be managed per institutional policies. No additional post-trial care is planned.\nAuthorship and dissemination\nAuthorship will follow ICMJE criteria. Results will be submitted within 12 months after database lock and posted on the trial registry. The full protocol and SAP will be publicly accessible. Findings will also be disseminated to participants, healthcare professionals, and policy makers through open-access publication and presentations at international conferences.\nStatements\nEthics statement\nThe studies involving humans were approved by Clinical Research Ethics Committee of Hospital Universitari de Bellvitge (PR070/25). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.\nAuthor contributions\nRG: Conceptualization, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing. JM: Conceptualization, Writing – review & editing. CO: Conceptualization, Writing – review & editing. MP: Conceptualization, Writing – review & editing. CY: Data curation, Formal analysis, Software, Writing – review & editing. JPe: Data curation, Formal analysis, Investigation, Methodology, Writing – review & editing. JG: Writing – review & editing. JPo: Writing – review & editing. AG: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing.\nFunding\nThe author(s) declared that financial support was received for this work and/or its publication. This study is funded by the Instituto de Salud Carlos III (FIS PI24/01014), co-funded by the European Union. The funder has no role in study design, data collection, analysis, interpretation, manuscript preparation, or decision to publish.\nAcknowledgments\nWe would like to acknowledge the CERCA Program/Generalitat de Catalunya for institutional support.\nConflict of interest\nThe author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\nGenerative AI statement\nThe author(s) declared that generative AI was used in the creation of this manuscript. The authors used AI to assist with language editing and manuscript preparation. All content was reviewed and approved by the authors, who take full responsibility for the final version of the manuscript.\nAny alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.\nPublisher’s note\nAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.\nSupplementary material\nThe Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/frph.2026.1911200/full#supplementary-material\nReferences\n1.\nBeckerCMBokorAHeikinheimoOHorneAJansenFKieselLet al. ESHRE guideline: endometriosis. Hum Reprod Open. (2022) 2022(2):hoac009. 10.1093/hropen/hoac009\n2.\nHorneAWMissmerSA. Pathophysiology, diagnosis, and management of endometriosis. Br Med J. (2022) 379:e070750. 10.1136/bmj-2022-070750\n3.\nCocciaMERizzelloFCammilliFBraccoGLScarselliG. Endometriosis and infertility. Eur J Obstet Gynecol Reprod Biol. (2008) 138(1):54–9. 10.1016/j.ejogrb.2007.11.010\n4.\nCranneyRCondousGReidS. An update on the diagnosis, surgical management, and fertility outcomes for women with endometrioma. Acta Obstet Gynecol Scand. (2017) 96(6):633–43. 10.1111/aogs.13114\n5.\nGordtsSCampoR. Modern approaches to surgical management of endometrioma. Best Pract Res Clin Obstet Gynaecol. (2019) 59:48–55. 10.1016/j.bpobgyn.2018.12.013\n6.\nAlborziSAskaryEKeramatiPMoradi AlamdarlooSPoordastTAshrafMAet al. Assisted reproductive technique outcomes in patients with endometrioma undergoing sclerotherapy vs laparoscopic cystectomy: prospective cross-sectional study. Reprod Med Biol. (2021) 20(3):313–20. 10.1002/rmb2.12386\n7.\nMartinez-GarciaJMCandasBSuarez-SalvadorEGomezMMerinoECastellarnauMet al. Comparing the effects of alcohol sclerotherapy with those of surgery on anti-Müllerian hormone and ovarian reserve after endometrioma treatment. A prospective multicenter pilot cohort study. Eur J Obstet Gynecol Reprod Biol. (2021) 259:60–6. 10.1016/j.ejogrb.2021.01.027\n8.\nJeeBC. Efficacy of ablation and sclerotherapy for the management of ovarian endometrioma: a narrative review. Clin Exp Reprod Med. (2022) 49(2):76–86. 10.5653/cerm.2021.05183\n9.\nMuziiLGalatiGMatteiGChinèAPerniolaGDi DonatoVet al. Expectant, medical, and surgical management of ovarian endometriomas. J Clin Med. (2023) 12(5):1858. 10.3390/jcm12051858\n10.\nPiriyevESchiermeierSRömerT. Hormonal treatment of endometriosis: a narrative review. Pharmaceuticals. (2025) 18(4):588. 10.3390/ph18040588\n11.\nThielPSDondersFKobylianskiiAMaheux-LacroixSMatelskiJWalshCet al. The effect of hormonal treatment on ovarian endometriomas: a systematic review and meta-analysis. J Minim Invasive Gynecol. (2024) 31(4):273–9. 10.1016/j.jmig.2024.01.002\n12.\nAlonsoAGuntherKMaheux-LacroixSAbbottJ. Medical management of endometriosis. Curr Opin Obstet Gynecol. (2024) 36(5):353–61. 10.1097/GCO.0000000000000983\n13.\nMurjiABiberoğluKLengJMuellerMDRömerTVignaliMet al. Use of dienogest in endometriosis: a narrative literature review and expert commentary. Curr Med Res Opin. (2020) 36(5):895–907. 10.1080/03007995.2020.1744120\n14.\nLeeJParkHJYiKW. Dienogest in endometriosis treatment: a narrative literature review. Clin Exp Reprod Med. (2023) 50(4):223–9. 10.5653/cerm.2023.06128\n15.\nSurreyES. GnRH agonists in the treatment of symptomatic endometriosis: a review. F S Rep. (2023) 4(2):40–5. 10.1016/j.xfre.2022.11.009\n16.\nRonsiniCIavaroneIBracaEVastarellaMGDe FranciscisPTorellaM. The efficiency of sclerotherapy for the management of endometrioma: a systematic review and meta-analysis of clinical and fertility outcomes. Medicina (B Aires). (2023) 59(9):1643. 10.3390/medicina59091643\n17.\nIvánkováKHeřmanHDrahoňovskýJHájková HympánováL. Sclerotherapy of endometrioma and its impact on ovarian reserve—a narrative review. Ceska Gynekol. (2025) 90(2):163–6. 10.48095/cccg2025163\n18.\nGarcia-TejedorAMartinez-GarciaJMCandasBSuarezEMañalichLGomezMet al. Ethanol sclerotherapy versus laparoscopic surgery for endometrioma treatment: a prospective, multicenter, cohort pilot study. J Minim Invasive Gynecol. (2020) 27(5):1133–40. 10.1016/j.jmig.2019.08.036\n19.\nZhangYZhangSZhaoZWangCXuSWangF. Impact of cystectomy versus ablation for endometrioma on ovarian reserve: a systematic review and meta-analysis. Fertil Steril. (2022) 118(6):1172–82. 10.1016/j.fertnstert.2022.08.860\n20.\nMiquelLLiottaJPivanoAGnisciANetterACourbiereBet al. Ethanol endometrioma sclerotherapy: safety through 8 years of experience. Hum Reprod. (2024) 39(4):733–41. 10.1093/humrep/deae014\n21.\nCohenAAlmogBTulandiT. Sclerotherapy in the management of ovarian endometrioma: systematic review and meta-analysis. Fertil Steril. (2017) 108(1):117–24.e5. 10.1016/j.fertnstert.2017.05.015\n22.\nMiquelLPreaubertLGnisciAResseguierNPivanoAPerrinJet al. Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis. PLoS One. (2020) 15(9):e0239846. 10.1371/journal.pone.0239846\n23.\nGarcía-TejedorAGuevara-PeraltaRMartinez-GarciaJMCorbalánSAgüeroMGomez-RomeroMet al. Ultrasound-guided ethanol sclerotherapy versus laparoscopic surgery for endometriomas: a randomized clinical trial in a real-world setting. Arch Gynecol Obstet. (2025) 312(6):2199–210. 10.1007/s00404-025-08205-1\n24.\nBourdelNChauvetPBilloneVDouridasGFauconnierAGerbaudLet al. Systematic review of quality of life measures in patients with endometriosis. PLoS One. (2019) 14(1):e0208464. 10.1371/journal.pone.0208464\n25.\nJonesGLBuddsKTaylorFMussonDRaymerJChurchmanDet al. A systematic review to determine use of the endometriosis health profiles to measure quality of life outcomes in women with endometriosis. Hum Reprod Update. (2024) 30(2):186–214. 10.1093/humupd/dmad029\nSummary\nKeywords\nendometrioma, endometriosis, ethanol sclerotherapy, fertility, ovarian reserve, pelvic pain, quality of life, randomised controlled trial\nCitation\nGuevara-Peralta R, Martinez-Garcia JM, Ortega-Expósito C, Pla-Farnós MJ, Yeste C, Peñafiel J, Guevara-Figueras J, Ponce J and García-Tejedor A (2026) Impact of ethanol sclerotherapy on pelvic pain and quality of life in patients with endometriomas (ESCOMA study): protocol for a randomised clinical trial. Front. Reprod. Health 8:1911200. doi: 10.3389/frph.2026.1911200\nReceived\n16 June 2026\nRevised\n18 August 2026\nAccepted\n31 August 2026\nPublished\n10 September 2026\nVolume\n8 - 2026\nEdited by\nTullio Golia D'Augè, Sapienza University of Rome, Italy\nReviewed by\nMaria Grazia Porpora, Sapienza University of Rome, Italy\nQun Wang, Shanghai AM-SINO Women and Children’s Hospital, China\nUpdates\nCopyright\n© 2026 Guevara-Peralta, Martinez-Garcia, Ortega-Expósito, Pla-Farnós, Yeste, Peñafiel, Guevara-Figueras, Ponce and García-Tejedor.\nThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.\n*Correspondence: Rodrigo Guevara-Peralta rguevara.hv@gencat.cat\nDisclaimer\nAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.","source_license":"CC0","license_restricted":false}