{"paper_id":"6fc84cd4-9e81-4364-a6dc-e802c06a5876","body_text":"INTRODUCTION \nReview question / Objective This study \naims to evaluate the safety and efficacy of \nHerbal Medicine in managing symptoms \nand enhancing recovery after HIFU treatment in \npatients with adenomyosis. \nRationale There are several studies evaluating the \nefficacy of herbal medicine for adenomyosis. \nHowever, research on herbal medicine for \nsymptom management after HIFU treatment \nremains limited. A meta-analysis by Li (2023), \nwhich included studies published as of May 2022, \nincorporated only five RCTs (excluding grey \nliterature), making it difficult to draw definitive \nconclusions regarding e fficacy. Since the \npublication of that study, several randomized \ncontrolled trials (RCTs) have been conducted, \nwhich are expected to provide a stronger evidence \nbase for more conclusive findings. \nCondition being studied Adenomyosis (AM) is an \nestrogen-dependent condition characterized by \nthe infiltration of endometrial tissue into the \nmyometrium, leading to symptoms such as \nmenorrhagia and progressively worsening \ndysmenorrhea. Currently, hysterectomy is the only \ndefinitive treatment, but it is not suitable for \nwomen who wish to preserve their uterus or \nmaintain fertility. Therefore, effective, minimally \ninvasive treatment options with fewer side effects \nand lower recurrence rates are being actively \nexplored, with High-Intensity Focused Ultrasound \n(HIFU) emerging as a recommended approach in \nclinical guidelines. HIFU is a non-invasive \ntechnique that induces coagulative necrosis in \ntargeted tissues through thermal energy, offering \nadvantages such as high efficacy, minimal adverse \neffects, and rapid recovery. It is suitable for \npatients who have fertility planning and desire to \nconserve the uterus. However, due to the deep \ninfiltration of AM lesions, HIFU alone often leaves \nresidual lesions, which may contribute to symptom \nrecurrence, posing a major challenge in long-term \ndisease management.\nINPLASY 1\nInternational Platform of Registered Systematic Review and Meta-analysis Protocols\nINPLASYSafety and Efficacy of Herbal Medicine for Symptom \nManagement After HIFU Treatment in Adenomyosis: \nA systematic review and meta-analysis\nKim, EJ; Shim, YS; Min, SY .\nADMINISTRATIVE INFORMATION  \nSupport -  None. \nReview Stage at time of this submission - Formal screening of search \nresults against eligibility criteria. \nConflicts of interest - None declared. \nINPLASY registration number: INPLASY202530088 \nAmendments - This protocol was registered with the International \nPlatform of Registered Systematic Review and Meta-Analysis Protocols \n(INPLASY) on 21 March 2025 and was last updated on 21 March 2025.\nCorresponding author: \nEun-Jin Kim\nutopialimpid@naver.com\nAuthor Affiliation:                   \nDongguk University Bundang \nKorean Hospital.\nKim et al. INPLASY protocol 202530088. doi:10.37766/inplasy2025.3.0088\nKim et al. INPLASY protocol 202530088. doi:10.37766/inplasy2025.3.0088 Downloaded from https://inplasy.com/inplasy-2025-3-0088/\nINPLASY202530088\ndoi: 10.37766/inplasy2025.3.0088 \nReceived: 21 March 2025\nPublished: 21 March 2025\n\nHerbal medicine has shown promising efficacy in \nmanaging AM, and combining it with HIFU is being \nexplored to enhance treatment outcomes. This \nstudy aims to compare HIFU alone with HIFU \ncombined with herbal medicine in terms of uterine \nand lesion volume reduction, symptom relief, \nrecurrence rate reduction, and overall safety. A \nsystematic review and meta-analysis of existing \nstudies will be conducted to provide evidence-\nbased insights into the clinical benefits of herbal \nmedicine with HIFU for AM treatment. \nMETHODS \nSearch strategy We will search electronically on \nEnglish databases, Chinese databases and Korean \ndatabases. We used the search terms \" \nadenomyosis \" and \"herbal medicine,\" which were \nadapted to suit the language specifications of each \ndatabase. \nParticipant or population  \n[Inclusion Criteria] \nPatients diagnosed with adenomyosis according to \nthe diagnostic criteria outlined in Obstetrics and \nGynecology\n[Exclusion Criteria] \nPatients with contraindications to ultrasound \nablation.\nPatients requiring surgical treatment or those with \nsevere gynecological diseases (such as malignant \ntumors).\nPatients with severe hepatic or renal impairment, \ncardiovascular diseases, or other serious systemic \nconditions.\nPregnant or lactating women.\nIntervention The experimental group received \nHIFU combined with herbal medicine (with no \nrestrictions on the specific type of herbal medicine \nused, such as oral, external application, and \nenema formulations). The control group received \nHIFU treatment alone. Conventional Western \nmedicine was allowed, provided that both groups \nreceived the same treatment. \nComparator The control group received HIFU \ntreatment alone. Conventional Western medicine \nwas allowed, provided that both groups received \nthe same treatment. \nStudy designs to be included All the randomized \ncontrolled trials (RCTs) were included. \nEligibility criteria All randomized controlled trials \n(RCTs) on the efficacy of HIFU combined with \nherbal medicine in the treatment of adenomyosis \n(AM) were included. Non-RCTs, RCT protocol, \nanimal studies, case reports, thesis, survey and \nreviews were excluded. \nInformation sources We will electronically search \n11 following databases. Three English databases \n(MEDLINE via PubMed, EMBASE, the Cochrane \nCentral Register of Controlled Trials), three Chinese \nd a t a b a s e s ( C h i n a N a t i o n a l K n o w l e d g e \nInfrastructure, Wanfang data, and VIP), and five \nKorean databases (such as Oriental Medicine \nAdvanced Searching Integrated System, Korean \nstudies Information Service System, Korea Citation \nIndex, Research Information Sharing Service, and \nKorean Medical database) without any language \nrestrictions.\nMain outcome(s)  \n1)Uterine volume (or Lesion volume) assessed by \ntransvaginal ultrasound.\n2)CA125 in peripheral blood.\n3)Dysmenorrhea assessed by visual analogue \nscale. \nAdditional outcome(s)  \n1)Total effective rate\n2)Menstrual bleeding volume assessed by pictorial \nblood loss assessment chart\n3)Adverse events. \nQuality assessment / Risk of bias analysis \nQuality assessment will be performed using Risk of \nbias (Rob2) tool from the Cochrane Handbook for \nSystematic Reviews of Interventions. The tool \nincludes bias arising from the randomization \nprocess, bias due to deviations from intended \ninterventions, bias due to missing outcome data, \nbias in the measurement of the outcome, and bias \nin the selection of reported results. \nStrategy of data synthesis The data will be \nsynthesized using Review Manager 5.4 software. \nDichotomous outcomes will be summarized using \nRisk Ratios (RR) with 95% Confidence Intervals \n(CI). Continuous outcomes will be presented as the \nstandard mean di fference (SMD) or mean \ndifference (MD) with 95% CI. Heterogeneity was \nevaluated using the Higgins I2 index, with I2 ≥ \n50% indicating potential heterogeneity, and I2 ≥ \n75% indicating significant heterogeneity.\nSubgroup analysis If the meta-analysis shows \nsignificant heterogeneity, subgroup analyses will \nbe conducted. Subgroup analyses will also be \nperformed based on the compositions of herbal \nmedicines, both with and without conventional \ntreatment, provided that a sufficient amount of \ndata is available. \nINPLASY 2Kim et al. INPLASY protocol 202530088. doi:10.37766/inplasy2025.3.0088\nKim et al. INPLASY protocol 202530088. doi:10.37766/inplasy2025.3.0088 Downloaded from https://inplasy.com/inplasy-2025-3-0088/\n\nSensitivity analysis A sensitivity analysis was \nperformed by excluding one study at a time to \nassess the robustness of the meta-analysis results. \nLanguage restriction No language restriction. \nCountry(ies) involved Republic of Korea. \nKeywords adenomyosis; high intensity focused \nultrasound; herbal medicine; Systematic review; \nMeta-anaylsis. \nDissemination plans adenomyosis; high intensity \nfocused ultrasound; herbal medicine; Systematic \nreview; Meta-anaylsis. \nContributions of each author \nAuthor 1 - Eun-Jin Kim - Conceptualization, Data \ncuration, Formal analysis, Methodology.\nEmail: utopialimpid@naver.com\nAuthor 2 - Youngshin Shim - Conceptualization, \nData curation, Formal analysis, , Visualization.\nEmail: simyoungshin@naver.com\nAuthor 3 - Sang Yeon Min - Project administration, \nSupervision.\nEmail: bubblem@dongguk.ac.kr\nINPLASY 3Kim et al. INPLASY protocol 202530088. doi:10.37766/inplasy2025.3.0088\nKim et al. INPLASY protocol 202530088. doi:10.37766/inplasy2025.3.0088 Downloaded from https://inplasy.com/inplasy-2025-3-0088/","source_license":"CC0","license_restricted":false}