{"paper_id":"2aaaf312-1ed2-445b-8162-05290889a9e4","body_text":"INTRODUCTION \nReview question / Objective Population (P): \nW o m e n w i t h s u r g i c a l l y a n d \nh i s t o p a t h o l o g i c a l l y c o nfir m e d \nendometriosis\nIntervention (I): Detection of specific circulating and \ntissue-based microRNAs (miRNAs)\nComparator (C): Women without endometriosis \n(e.g., asymptomatic or undergoing surgery for \nother benign gynecologic conditions)\nOutcome (O): Diagnostic accuracy and expression \ndifferences of miRNAs\nStudy design (S): Clinical studies (prospective, \nretrospective), randomized trials, meta-analyses\nObjective:\nTo evaluate the diagnostic potential of circulating \nand tissue-specific microRNAs as non-invasive \nbiomarkers for endometriosis by systematically \nreviewing and analyzing the current literature.\nRationale Endometriosis is a prevalent and often \ndebilitating gynecological disorder lacking reliable, \nnon-invasive diagnostic methods. Although \nimaging techniques have improved, laparoscopy \nremains the diagnostic gold standard—an invasive \nand costly procedure. Therefore, identifying \naccurate, reproducible, and non-invasive \nbiomarkers is a clinical priority.\nMicroRNAs (miRNAs), due to their regulatory \nfunctions in inflammation, cell growth, and \nhormonal pathways, and their stability in biological \nfluids, have emerged as promising candidates. \nSeveral studies have suggested miRNAs as \ndiagnostic tools; however, methodological \nheterogeneity and lack of reproducibility limit their \nclinical application.\nThis review aims to critically appraise and \nsynthesize available evidence regarding \ndysregulated miRNAs in endometriosis to \ndetermine whether these molecules can truly serve \nas reliable, non-invasive diagnostic biomarkers. \nCondition being studied Endometriosis is a \nchronic, estrogen-dependent in flammatory \ncondition characterized by the growth of \nendometrial-like tissue outside the uterus, leading \nINPLASY 1\nInternational Platform of Registered Systematic Review and Meta-analysis Protocols\nINPLASYmiRNA in endometriosis- a new hope or illusion\nDryja-Brodowska, A; Obrzut, B; Obrzut, M; Darmochwał-Kolarz, D.\nADMINISTRATIVE INFORMATION  \nSupport -  None. \nReview Stage at time of this submission - Completed but not \npublished. \nConflicts of interest - None declared. \nINPLASY registration number: INPLASY202560027 \nAmendments - This protocol was registered with the International \nPlatform of Registered Systematic Review and Meta-Analysis Protocols \n(INPLASY) on 7 June 2025 and was last updated on 7 June 2025.\nCorresponding author: \nBogdan Obrzut\nbobrzut@ur.edu.pl\nAuthor Affiliation:                   \nDepartment of Obstetrics & \nGynecology, Institute of Medical \nSciences, College of Medical \nSciences, University of Rzeszow, \nRzeszow, 35-959, Poland.\nDryja-Brodowska et al. INPLASY protocol 202560027. doi:10.37766/inplasy2025.6.0027\nDryja-Brodowska et al. INPLASY protocol 202560027. doi:10.37766/inplasy2025.6.0027 Downloaded from https://inplasy.com/inplasy-2025-6-0027/\nINPLASY202560027\ndoi: 10.37766/inplasy2025.6.0027 \nReceived: 6 June 2025\nPublished: 7 June 2025\n\nto pain, infertility, and reduced quality of life. It \naffects up to 10% of reproductive-age women and \noften causes delayed diagnosis due to nonspecific \nsymptoms. Despite its burden, diagnostic \nconfirmation still relies largely on invasive surgical \nmethods, underscoring the urgent need for non-\ninvasive diagnostic alternatives. \nMETHODS \nSearch strategy Electronic databases: PubMed \nand Google Scholar\nSearch period: 2010 to March 2025\nLanguage: English\nKeywords: “microRNA”, “miRNA”, “biomarker”, \n“endometriosis”, “mcRNA”, and their combinations \nusing Boolean operators (AND/OR)\nManual search: Bibliographies of included studies\nNumber of initially identified studies: 727\nFinal included studies: 17 (after screening, \nduplication removal, and applying inclusion/\nexclusion criteria).\nParticipant or population Women of reproductive \nage with surgically and histopathologically \nconfirmed endometriosis. Control participants \nincluded women without endometriosis, often \nundergoing surgery for other gynecological \nconditions or healthy asymptomatic women in \nlimited cases. \nIntervention Evaluation of microRNA (miRNA) \nexpression levels in various biological samples \n(serum, plasma, endometrial tissue) to assess their \ndiagnostic value in detecting endometriosis. \nComparator Control groups included women \nwithout endometriosis—either undergoing \nlaparoscopy for other gynecologic conditions or, in \none study, healthy non-operated women. \nStudy designs to be included Randomized \nclinical trials, meta-analyses, prospective and \nretrospective clinical studies. \nEligibility criteria Inclusion: Human studies in \nEnglish (2010–2025), full-text access, sample size \n≥ 24, studies with blood or endometrial tissue \nsamples, journal Impact Factor ≥ 2\nExclusion: Non-human studies, reviews, languages \nother than English, inaccessible full-texts, sample \nsize < 24, Impact Factor < 2. \nInformation sources PubMed, Google Scholar. \nManual reference list searches from included \narticles. No trial registries or grey literature were \nincluded.\nMain outcome(s) The primary outcome was the \nidentification of specific circulating or tissue-based \nmiRNAs consistently dysregulated in women with \nendometriosis, and their potential as diagnostic \nbiomarkers. The review evaluated expression \npatterns, sensitivity/specificity (if reported), and \nreproducibility across studies. \nAdditional outcome(s) Secondary outcomes \nincluded the impact of sample type (serum, \nplasma, tissue), menstrual cycle phase, validation \nmethods, and geographical distribution of studies \non the reliability of miRNA detection. \nData management Two independent reviewers \nconducted screening and data extraction using a \npredefin e d M i c r o s o f t E x c e l f o r m . A n y \ndisagreements were resolved through discussion. \nData collected included study details, participant \ndemographics, sample types, miRNA expression, \nmenstrual cycle consideration, and main \noutcomes. \nQuality assessment / Risk of bias analysis The \nrisk of bias was assessed qualitatively through \nevaluation of study design, sample size, selection \nof control groups, consideration of biological \nvariables (e.g., menstrual cycle), and transparency \nin validation techniques. \nStrategy of data synthesis Findings were \nsynthesized narratively due to heterogeneity in \nstudy design, miRNA types, and validation \napproaches. Studies were grouped and compared \nbased on sample type, menstrual cycle \nconsideration, and validation method (e.g., RT-\nqPCR, microarray). Tables were used to summarize \nand compare key features and findings.\nSubgroup analysis Subgroup analyses were \nperformed based on:\nSample type (serum vs. plasma vs. tissue)\nGeographical origin of the study\nConsideration of menstrual cycle phase\nValidation method used (RT-qPCR vs. others).\nSensitivity analysis Sensitivity analysis was not \nperformed due to the qualitative nature of the data \nsynthesis and the heterogeneity of study methods \nand outcomes. \nLanguage restriction Sensitivity analysis was not \nperformed due to the qualitative nature of the data \nINPLASY 2Dryja-Brodowska et al. INPLASY protocol 202560027. doi:10.37766/inplasy2025.6.0027\nDryja-Brodowska et al. INPLASY protocol 202560027. doi:10.37766/inplasy2025.6.0027 Downloaded from https://inplasy.com/inplasy-2025-6-0027/\n\nsynthesis and the heterogeneity of study methods \nand outcomes. \nCountry(ies) involved Department of Obstetrics & \nGynecology, Institute of Medical Sciences, College \nof Medical Sciences, University of Rzeszow, \nRzeszow, 35-959, Poland. \nKeywords microRNA, miRNA, endometriosis, non-\ninvasive biomarkers, diagnostics, gene expression, \ngynecology, reproductive health. \nContributions of each author \nAuthor 1 - Anna Dryja-Brodowska - writing- \noriginal draft, conceptualization.\nEmail: anna.dryja5@gmail.com\nAuthor 2 - Bogdan Obrzut - writing- review and \nediting, supervision.\nEmail: bobrzut@ur.edu.pl\nAuthor 3 - Maciej Obrzut - literature search, \nscreened studies for inclusion.\nAuthor 4 - Dorota Darmochwał-Kolarz - The author \nread, provided feedback and approved the final \nmanuscriptreview and supervision.\nEmail: ddarmochwal@ur.edu.pl\nINPLASY 3Dryja-Brodowska et al. INPLASY protocol 202560027. doi:10.37766/inplasy2025.6.0027\nDryja-Brodowska et al. INPLASY protocol 202560027. doi:10.37766/inplasy2025.6.0027 Downloaded from https://inplasy.com/inplasy-2025-6-0027/","source_license":"CC0","license_restricted":false}