{"paper_id":"837eca38-58ea-4e37-98e9-0bf4965a9ff4","body_text":"INTRODUCTION \nReview question / Objective The aim of this \nsystematic review is to evaluate the impact \nof high-intensity focused ultrasound (HIFU) \ntreatment on pregnancy outcomes in patients with \nadenomyosis. \nCondition being studied  Based on Lynn’s \nconcept of using High-Intensity Focused \nUltrasound (HIFU) for non-invasive surgeries in \n1942, China successfully developed the world’s \nfirst “High-Intensity Focused Ultrasound Tumor \nTreatment System” in 1996, marking the beginning \nof clinical applications of HIFU. HIFU employs brief \nyet intense ultrasound waves, typically raising \ntemperatures above 55℃ momentarily, causing \nirreversible thermal damage to crucial and \nsensitive proteins within cells, severely impacting \ncellular physiological functions, and even leading \nto cell death. Combining thermal e ffects with \nvarious mechanisms such as acoustic cavitation, \nradiation force, shear force, and microstreaming, \nHIFU can coagulate and ablate lesions within the \nbody from outside, achieving a “surgical strike” \neffect. Its non-invasive nature significantly reduces \nrecovery time, alleviates patient su ffering, and \ndelivers better cosmetic results, opening up \nexciting new dimensions in treatment and \ndemonstrating effectiveness in a range of \ndiseases.\nAdenomyosis, as a common and challenging \ngynecological condition, poses the urgent question \nof how to effectively alleviate symptoms, prevent \nrecurrence, particularly improve pregnancy rates, \nand enhance pregnancy outcomes. A series of \nreview articles on HIFU treatment for uterine \nadenomyosis, with follow-up periods ranging from \n3 to 40 months (mostly within 12-18 months), \nsuggest the effectiveness of HIFU in improving \nsymptoms. It is promoted as the ‘preferred’ \ntreatment method for adenomyosis patients \nseeking fertility, due to its short-term uterine repair \nafter surgery, catering to patients with urgent \nfertility desires. However, there is a lack of long-\nterm follow-up data and information on fertility \nINPLASY 1\nInternational Platform of Registered Systematic Review and Meta-analysis Protocols\nINPLASYHIFU babies: Dose the high-intensity focused \nultrasound (HIFU) treatment of adenomyosis \nimprove pregnancy?\nChen, YS1; Wang, ZH2; Xie, X3; Yi, JS4; Lin, SH5; Guo, SW6.\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: INPLASY202390097 \nAmendments - This protocol was registered with the International \nPlatform of Registered Systematic Review and Meta-Analysis Protocols \n(INPLASY) on 28 September 2023 and was last updated on 28 \nSeptember 2023.\nCorresponding author: \nYishan Chen\nys.chen@outlook.com\nAuthor Affiliation:                   \nFujian Maternity and Child Health \nHospital, Fujian Medical University, \nFuzhou, Fujian, China.\nChen et al. INPLASY protocol 202390097. doi:10.37766/inplasy2023.9.0097\nChen et al. INPLASY protocol 202390097. doi:10.37766/inplasy2023.9.0097 Downloaded from https://inplasy.com/inplasy-2023-9-0097/\nINPLASY202390097\ndoi: 10.37766/inplasy2023.9.0097 \nReceived: 28 September 2023\nPublished: 28 September 2023\n\noutcomes after HIFU treatment. There is a concern \nthat residual or incompletely absorbed lesions may \nregrow under the in fluence of estrogen. \nAdditionally, there are worries that lesions close to \nthe endometrial or serosal surface may lead to \nexcessive damage to adjacent endometrial or \nserosal tissue. Furthermore, there is a risk of \nexcessive energy accumulation or prolonged \ntreatment duration, regardless of the lesion’s \nproximity to the endometrial or serosal surface. \nTherefore, it is crucial to o ffer careful \nrecommendations to patients.\nThis article conducts a systematic review of post-\ntreatment fertility outcomes in uterine adenomyosis \npatients who have undergone High-Intensity \nFocused Ultrasound (HIFU) therapy. It also \nevaluates the effect of HIFU treatment of patients \nwith adenomyosis on the pregnancy outcome. \nMETHODS \nSearch strategy We will search the following \ndatabases: PubMed, Web of Science, The \nCochrane Library, EMBASE, CNKI, and Wanfang. \nO u r s e a r c h t e r m s w i l l i n c l u d e \n‘Adenomyosis,’ ‘Adenomyoma,’ ‘High-intensity \nfocused ultrasound,’ ‘Pregnancy,’ and ‘Gestation.’ \nArticles published in both English and Chinese will \nbe considered. Our goal is to identify all relevant \nstudies published up to the date of the initial \nsearch. The search will be re-run just before the \nfinal analysis, and further studies meeting our \ncriteria will be included. \nParticipant or population This article conducts a \nsystematic review of post-treatment pregnancy \noutcomes in uterine adenomyosis patients who \nhave undergone High-Intensity Focused \nUltrasound (HIFU) therapy. \nIntervention HIFU treatment in patients with \nadenomyosis. \nComparator Adenomyosis patients. \nStudy designs to be included We will search the \nfollowing databases: PubMed, Web of Science, \nThe Cochrane Library, EMBASE, CNKI, and \nWanfang. Our search terms will include \n‘Adenomyosis,’ ‘Adenomyoma,’ ‘High-intensity \nfocused ultrasound,’ ‘Pregnancy,’ and ‘Gestation.’ \nArticles published in both English and Chinese will \nbe considered. Our goal is to identify all relevant \nstudies published up to the date of the initial \nsearch. The search will be re-run just before the \nfinal analysis, and further studies meeting our \ncriteria will be included. \nEligibility criteria The exclusion criteria: (1) \nReviews, animal experiments, case reports, \nconference abstracts, conference proceedings, \neditorial letters, guidance or comments; (2) \nrepeated studies; (3) studies where full text is not \navailable. \nInformation sources We will search the following \ndatabases: PubMed, Web of Science, The \nCochrane Library, EMBASE, CNKI, and Wafang. \nO u r s e a r c h t e r m s w i l l i n c l u d e \n‘Adenomyosis,’ ‘Adenomyoma,’ ‘High-intensity \nfocused ultrasound,’ ‘Pregnancy,’ and ‘Gestation.’\nMain outcome(s) A total of 26 studies involving \n4,299 patients were retrieved and evaluated. All \narticles were conducted in Asian, including China \n(18/26, 69.2%), South Korea (19.2%), India (7.7%), \nand Japan (3.8%). The authors of three articles \nwere affiliated with HIFU research institutions or \nmedical companies as shareholders or employees. \nAnd only 1 article actively disclosed conflicts of \ninterest, while the Chinese articles did not mention \nwhether conflicts of interest existed.\nAmong these studies, 10 reported the number of \nplanned pregnancies. The overall pregnancy rate \namong patients who underwent HIFU treatment \nwas 22.7% (95%CI 13.9%, 32.7%), while the \npregnancy rate among those with planned \npregnancies was 53.7% (95%CI 39.5%, 67.5%). \nAmong these, there were 168 natural pregnancies, \nwith a natural pregnancy rate of 21.9% (95%CI \n8.2%, 39.4%). There were 41 pregnancies through \nassisted reproduction, and 243 cases did not \nmention the method of pregnancy. The average \ntime from treatment to pregnancy was 11.6±6.3 \nmonths. The miscarriage rate was 13.7% (95%CI \n6.3%, 22.7%). The live birth rate was 61.9% \n(95%CI 46.4%, 76.6%), and the full-term \npregnancy rate was 50.1% (95%CI 40.1%, \n60.1%). Among the 214 patients who had live \nbirths, 118 underwent cesarean birth, resulting in a \ncesarean birth rate of 56.3% (95%CI 42.9%, \n69.3%), while 86 had vaginal deliveries, and 10 \ncases did not report delivery outcomes. There \nwere 21 cases of complications during pregnancy \nor delivery (21/214, 9.8%), including 9 cases of \npostpartum hemorrhage (4.2%), 8 cases of \nplacental abnormalities (3.7%), 3 cases of preterm \npremature rupture of membranes, and 1 case of \nhypertensive disorders of pregnancy. No cases of \nuterine rupture were reported. \nQuality assessment / Risk of bias analysis Two \ninvestigators screened titles and abstracts for \neligibility as well as the full text of each eligible \nstudy, to confirm the inclusion criteria. The quality \nevaluation criteria of individual studies were \nINPLASY 2Chen et al. INPLASY protocol 202390097. doi:10.37766/inplasy2023.9.0097\nChen et al. INPLASY protocol 202390097. doi:10.37766/inplasy2023.9.0097 Downloaded from https://inplasy.com/inplasy-2023-9-0097/\n\nassessed using the Newcastle-Ottawa Scale (NOS) \nof Cohort studies, MINORS of single-arm clinical \ntrials, and Cochrane of RCT. \nStrategy of data synthesis State 17.0 (Stata \nCorp. LLC, College Station, TX, USA) was used for \nthe data analysis by two review authors (YSC and \nSWG). The heterogeneity of included studies was \nassessed using the Q test (I2 value). If P > 0.1 and \nI2 ≤ 50%, a fixed-effects model was used; \notherwise, a random-effects model was used. For \nsingle-arm studies, the effect sizes were directly \ncombined, while for two-arm studies, the e ffect \nsizes were combined as standardized mean \ndifferences (SMD) or weighted mean differences \n(WMD), and their 95% confidence intervals were \ncalculated. Publication bias was assessed using a \nfunnel plot, which visually represents the potential \nbias in the publication of studies. Sensitivity \nanalysis was conducted to evaluate the stability of \nthe study results. A significance level of P < 0.05 \nwas considered statistically signi ficant for all \nstudies.\nSubgroup analysis According to the sub-group \nanalysis based on patient age (≤40 years or ≥40 \nyears), treatment modality (HIFU alone or HIFU \ncombined with GnRH-a and/or LNG-IUS), NPV% \n(≤70% 0r≥70%), uterine volume (<10weeks \ngestation or ≥10weeks gestation), and lesion size \n(diameter ≤6cm or 26cm), the pregnancy rates \nwere evaluated. \nSensitivity analysis Publication bias was \nassessed using a funnel plot, which visually \nrepresents the potential bias in the publication of \nstudies. Sensitivity analysis was conducted to \nevaluate the stability of the study results. A \nsignificance level of P < 0.05 was considered \nstatistically significant for all studies. \nCountry(ies) involved China. \nKeywords HIFU, Adenomyosis, Pregnancy. \nContributions of each author \nAuthor 1 - Yishan Chen - The author provided \nstatistical expertise and drafted the manuscript.\nEmail: ys.chen@outlook.com\nAuthor 2 - Zhenhong Wang - The author \ncontributed to the development of the selection \ncriteria, and the risk of bias assessment strategy.\nAuthor 3 - Xi Xie - The author read and provided \nfeedback.\nAuthor 4 - Jingsong YI - The author read and \nprovided feedback.\nAuthor 5 - Shunhe Lin - The author contributed to \nthe development of the selection criteria, and the \nrisk of bias assessment strategy.\nAuthor 6 - Sun-Wei Guo - The author provided \nstatistical expertise and approved the final \nmanuscript.\nEmail: hoxa10@outlook.com\nINPLASY 3Chen et al. INPLASY protocol 202390097. doi:10.37766/inplasy2023.9.0097\nChen et al. INPLASY protocol 202390097. doi:10.37766/inplasy2023.9.0097 Downloaded from https://inplasy.com/inplasy-2023-9-0097/","source_license":"CC0","license_restricted":false}