{"paper_id":"5cf48c88-56dc-4aac-b394-cea0925ad88a","body_text":"INTRODUCTION \nReview question / Objective 1. What are \nthe benefits of medical treatment in \nsuppressing ovarian steroid production?\n2. What are the benefits of surgery in restoring \nspontaneous fertility?\n3. What is the effect of medical treatment prior to \nIVF?\n4. What is the effect of surgical treatment prior to \nIVF?\n5. Are there standardized recommendations to \nguide the choice between medical and surgical \nstrategies to:\no Restore natural fertility?\no Stabilize or delay disease progression?\no Improve IVF success?\n6. How do surgical complications in fluence \ntreatment decisions?\nRationale To evaluate the evidence of the efficacy \nof medical versus surgical treatment in the finality \nof fertility resporation both sponstaneous and with \nIVF . \nCondition being studied Endometriosis is a \nchronic inflammatory condition a ffecting \nreproductive-aged women, often associated with \ninfertility. Medical and surgical treatments are \nwidely used, but their relative e ffectiveness in \nrestoring fertility remains debated. \nMETHODS \nSearch strategy S e a r c h S t r a t e g y. A \ncomprehensive literature search was performed \nusing the databases PubMed, Embase, Scopus, \nand the Cochrane Library. The time frame was \nlimited to January 2000 through June 2025. The \nsearch terms included: “Endometriosis AND \nInfertility”- “Medical treatment vs controls”- \n“Surgical treatment vs controls”- “Medical vs \nsurgical treatment”-“Surgical complications”\nSearch strategies were adapted for each database \nusing standardized Medical Subject Headings \n(MeSH) and free-text terms, and Boolean \noperators were applied. All articles identified were \nINPLASY 1\nInternational Platform of Registered Systematic Review and Meta-analysis Protocols\nINPLASYEndometriosis and Infertility: Medical versus Surgical \nApproaches – A Systematic Review and Meta-Analysis\nBulletti, FM; Coccia, ME; Guido, M; Giacomucci, E; Palagiano, A; \nBulletti, C.\nADMINISTRATIVE INFORMATION  \nSupport -  None. \nReview Stage at time of this submission - Completed but not \npublished. \nConflicts of interest - None declared. \nINPLASY registration number: INPLASY202560103 \nAmendments - This protocol was registered with the International \nPlatform of Registered Systematic Review and Meta-Analysis Protocols \n(INPLASY) on 25 June 2025 and was last updated on 25 June 2025.\nCorresponding author: \nCarlo Bulletti\ncarlobulletti@gmail.com\nAuthor Affiliation:                   \nsingle institutional appartenece of \nthe authors contribution.\nBulletti et al. INPLASY protocol 202560103. doi:10.37766/inplasy2025.6.0103\nBulletti et al. INPLASY protocol 202560103. doi:10.37766/inplasy2025.6.0103 Downloaded from https://inplasy.com/inplasy-2025-6-0103/\nINPLASY202560103\ndoi: 10.37766/inplasy2025.6.0103 \nReceived: 25 June 2025\nPublished: 25 June 2025\n\nimported into a reference manager (Zotero) and \nscreened for duplicates. \nParticipant or population Eligibility Criteria. Only \ncomparative studies—prospective, retrospective, \nrandomized controlled trials, and meta-analyses—\nwere eligible. Studies had to fulfill the following \ninclusion criteria: Reported fertility outcomes \n(spontaneous pregnancy and/or IVF results); \nIncluded women with surgically or radiologically \nconfirmed endometriosis; Provided data on \nendometriosis stage, when available; Included a \ncomparison group (medical vs surgical, treatment \nvs control)\nExclusion criteria included case reports, studies \nfocused exclusively on pain without reproductive \noutcomes, non-comparative designs, and studies \nnot available in English or as full text. \nIntervention This study was conducted as a \nsystematic review and meta-analysis, in \naccordance with the PRISMA 2020 guidelines.¹ All \nstages of selection, screening, inclusion, and \nanalysis were performed independently by two \nreviewers, with discrepancies resolved by \nconsensus or third-party adjudication. \nComparator 1. Medical Treatment vs Controls\no Stratified by endometriosis stage\no Focus on disease suppression and IVF outcomes\n2. Surgical Treatment vs Controls\no Focused on fertility-related indications only (not \npain)\no Reporting spontaneous pregnancy and IVF \nsuccess rates\n3. Medical vs Surgical Interventions\no Comparison of spontaneous fertility and IVF \nsuccess\no Analysis of impact of surgical complications on \nreproductive decision-making.\nStudy designs to be included This study was \nconducted as a systematic review and meta-\nanalysis, in accordance with the PRISMA 2020 \nguidelines.¹ All stages of selection, screening, \ninclusion, and analysis were performed \ni n d e p e n d e n t l y b y t w o r e v i e w e r s , w i t h \ndiscrepancies resolved by consensus or third-party \nadjudication. \nEligibility criteria Only comparative studies—\nprospective, retrospective, randomized controlled \ntrials, and meta-analyses—were eligible. Studies \nhad to fulfill the following inclusion criteria: \nReported fertility outcomes (spontaneous \npregnancy and/or IVF results); Included women \nwith surgically or radiologically con firmed \nendometriosis; Provided data on endometriosis \nstage, when available; Included a comparison \ngroup (medical vs surgical, treatment vs control)\nExclusion criteria included case reports, studies \nfocused exclusively on pain without reproductive \noutcomes, non-comparative designs, and studies \nnot available in English or as full text. \nInformation sources The databases PubMed, \nEmbase, Scopus, and the Cochrane Library.\nMain outcome(s)  \n• Spontaneous pregnancy rate\n• IVF outcomes, including clinical pregnancy and \nlive birth rates\n• Surgical complications, including ovarian reserve \nreduction or procedure-related morbidity\n• Cost-effectiveness (reported only when explicitly \nassessed in eligible studies).\nData management Statistical Analysis. Meta-\nanalysis was performed using a random-e ffects \nmodel to account for inter-study variability. \nHeterogeneity was assessed with the I² statistic. \nFor each comparison group, pooled odds ratios \n(OR) and 95% confidence intervals (CI) were \ncalculated. Subgroup analyses were performed by:\n• Endometriosis stage (I–IV)\n• Type of treatment (medical vs surgical)\n• Outcome (spontaneous conception vs IVF-\nrelated)\nForest plots were generated to visually represent \neffect sizes, and funnel plots were used to assess \npublication bias. All analyses were conducted \nusing RevMan 5.4 and R.\nQuality assessment / Risk of bias analysis Risk \nof bias was evaluated using the ROBINS-I tool for \nnon-randomized studies and the Cochrane Risk of \nBias 2.0 for randomized trials.²⁻³ Certainty of \nevidence was assessed using the GRADE \napproach across outcomes.⁴ \nStrategy of data synthesis Analysis is conducted \nby the help of an analyst statistician.\nSubgroup analysis Meta-analysis was performed \nusing a random-effects model to account for inter-\nstudy variability. Heterogeneity was assessed with \nthe I² statistic. For each comparison group, pooled \nodds ratios (OR) and 95% confidence intervals (CI) \nwere calculated. Subgroup analyses were \nperformed by:\n• Endometriosis stage (I–IV)\n• Type of treatment (medical vs surgical)\n• Outcome (spontaneous conception vs IVF-\nrelated)\nForest plots were generated to visually represent \neffect sizes, and funnel plots were used to assess \nINPLASY 2Bulletti et al. INPLASY protocol 202560103. doi:10.37766/inplasy2025.6.0103\nBulletti et al. INPLASY protocol 202560103. doi:10.37766/inplasy2025.6.0103 Downloaded from https://inplasy.com/inplasy-2025-6-0103/\n\npublication bias. All analyses were conducted \nusing RevMan 5.4 and R.\nSensitivity analysis Meta-analysis was performed \nusing a random-effects model to account for inter-\nstudy variability. Heterogeneity was assessed with \nthe I² statistic. For each comparison group, pooled \nodds ratios (OR) and 95% confidence intervals (CI) \nwere calculated. Subgroup analyses were \nperformed by:\n• Endometriosis stage (I–IV)\n• Type of treatment (medical vs surgical)\n• Outcome (spontaneous conception vs IVF-\nrelated)\nForest plots were generated to visually represent \neffect sizes, and funnel plots were used to assess \npublication bias. All analyses were conducted \nusing RevMan 5.4 and R.\nLanguage restriction English. \nCountry(ies) involved Italy. \nKeywords endometriosis, infertility, spontaneous \npregnancy, IVF , medical therapy, laparoscopy, \nGnRH, comparative studies. \nDissemination plans article in journal. \nContributions of each author \nA u t h o r 1 - F r a n c e s c o M a r i a B u l l e t t - \nConceptualization and first and final drafti.\nEmail: bulletti@icloud.com\nAuthor 2 - Maria Elisabetta Coccia - methods.\nEmail: mariaelisabetta.coccia@unifi.it\nAuthor 3 - Maurizio Guido - Analysis and literature \nsearch.\nEmail: maurizio.guido@unical.it\nAuthor 4 - Evaldo Giacomucci - Literature \nscreening and manuscript contribution.\nEmail: evaldo.giacomucci@mail.bologna.it\nAuthor 5 - Antonio Palagiano - data collection and \nanalytical process.\nEmail: palagiano@gmail.com\nAuthor 6 - Carlo Bulletti - oversaw the study’s \nconceptual development and coordinated the final \nmanuscript revision.Final Draft.\nEmail: carlobulletti@gmail.com\nINPLASY 3Bulletti et al. INPLASY protocol 202560103. doi:10.37766/inplasy2025.6.0103\nBulletti et al. INPLASY protocol 202560103. doi:10.37766/inplasy2025.6.0103 Downloaded from https://inplasy.com/inplasy-2025-6-0103/","source_license":"CC0","license_restricted":false}