Reducing Intraoperative Hemorrhage in Type Ⅱ Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT)

Reducing Intraoperative Hemorrhage in Type Ⅱ Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reducing Intraoperative Hemorrhage in Type Ⅱ Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT) Changmei Sang, Qiuling Shi, Lei Zhao, Yanjun Kang, Shuping Zhao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6379195/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Aug, 2025 Read the published version in Trials → Version 1 posted 5 You are reading this latest preprint version Abstract Background The incidence of caesarean scar pregnancy (CSP) has significantly increased due to the increasing prevalence of caesarean deliveries and advances in diagnostic imaging. However, no consensus has yet been reached on the optimal therapeutic approach. Type II CSP leads to disease heterogeneity, characterized by multiple treatment options and the absence of a unified therapeutic approach. Hysteroscopic treatment for CSP has demonstrated a notable success rate, particularly in cases of type I CSP. High-intensity focused ultrasound (HIFU) ablation has emerged as a novel, non-invasive treatment option that minimizes intraoperative blood loss. However, its use may be excessive in low-risk cases. Here, we report a protocol for a randomized clinical trial designed to evaluate the necessity of performing HIFU in CSP treatment when combined with suction curettage under hysteroscopic guidance. Methods We aim to propose a randomized clinical trial that will enroll 140 participants. All participants will undergo surgical suction curettage guided by hysteroscopy, randomized into groups with or without HIFU pretreatment. Data on demographic characteristics, disease characteristics, ultrasound findings, and laboratory test results will be collected before the intervention. The primary outcome will be the intraoperative blood loss. Secondary outcomes will include the incidence of near haemorrhage, therapeutic success rates, subsequent pregnancy outcomes within a 2-year follow-up period. Discussion Hysteroscopy has exhibited favorable therapeutic outcomes in the management of CSP, though it remains associated with a risk of intraoperative hemorrhage. HIFU has shown promise as a preoperative adjuvant modality. However, the comparative clinical advantages of standalone hysteroscopic intervention versus HIFU-assisted protocols are insufficiently explored in prospective clinical studies. This investigation seeks to assess both the standalone efficacy of hysteroscopic resection and the efficacy of combined therapy incorporating HIFU pretreatment for type II CSP. Trial registration: Registration number: ChiCTR2000034332 Registration date: 2nd July 2020 High-intensity focused ultrasound caesarean scar pregnancy suction curettage hysteroscopy intraoperative bleeding Figures Figure 1 Figure 2 Figure 3 Administrative Information Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/). Title {1} Reducing Intraoperative Hemorrhage in Type Ⅱ Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT) Trial registration {2a and 2b}. Registration number: ChiCTR2000034332 Registry name：A randomized controlled clinical trial for the effect of FUAS combined with suction curettage and simple suction curettage in the treatment of type II cesarean scar pregnancy Protocol version {3} Version and Date: V-1.0 29th May, 2020 Funding {4} Foundation of the State Key Laboratory of Ultrasound in Medicine and Engineering (Grant No:2020KFA3002) Author details {5a} a State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China; b School of Public Health and Management, Chongqing Medical University, Chongqing, P.R. China; c Qingdao Women and Children’s Hospital, Qingdao, Shandong, P.R. China Name and contact information for the trial sponsor {5b} Zhibiao Wang, e-mail: [email protected] , State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China Shuping Zhao, e-mail: [email protected] , State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China; Qingdao Women and Children’s Hospital, Qingdao, Shandong, P.R. China Role of sponsor {5c} The role of funding sources in the study design process, encompassing data collection, management, analysis, and interpretation; report writing; and the decision to submit the report for publication - including the ultimate authority over these activities. Introduction Background and rationale {6a} Caesarean scar pregnancy (CSP) is a unique type of ectopic pregnancy in which the gestational sac (GS) is implanted into the scar tissue from a previous caesarean delivery [1,2]. The estimated incidence of CSP ranges from 1 in 1,800 to 1 in 2,216 pregnancies [3,4]. The rising caesarean delivery rate and the increasing use of reliable imaging techniques for CSP diagnosis have led to a significant increase in reported cases over the last decade. CSP is associated with a high incidence of severe maternal morbidity, such as life-threatening haemorrhage, placenta accreta spectrum (PAS), uterine rupture, and even maternal mortality. Achieving optimal management of CSP remains a significant challenge for gynaecologists. The Gynaecology Subcommittee of the Chinese Medical Association issued updated guidelines in the Expert Opinion of Diagnosis and Treatment of Caesarean Scar Pregnancy in 2016 [5]. The treatment principles for CSP are early detection, early diagnosis, and early intervention. The guidelines classify CSP into three types—Type I, Type II, and Type III—based on the growth direction of the gestational sac (GS) and the residual myometrium thickness (RMT) between the GS and the bladder, as assessed by ultrasound, with specific treatment recommendations provided for each type. For type I CSP, ultrasound-guided suction curettage exhibits favourable therapeutic outcomes with a relatively low risk of massive haemorrhage. For type Ⅲ CSP, the risk of residual tissue retention and bleeding during curettage is high, making this procedure unsuitable. Alternatively, pregnancy tissue removal combined with uterine scar repair may be considered. For Type Ⅱ, GS is partially implanted in the uterine scar, and the RMT is less than 3 mm. Despite the availability of various treatment modalities—including medication, dilation and curettage, hysteroscopic and laparoscopic surgery, uterine artery embolization (UAE), high-intensity focused ultrasound (HIFU), and combinations of these approaches—significant risks of complications remain, even when strategies are tailored to individual participants and clinical manifestations. Mounting evidence indicates that CSP is a precursor to abnormally adherent placenta in the second and third trimesters [3], increasing the risk of severe haemorrhage or hysterectomy during operation or delivery. Surgical hysteroscopy provides direct visualization of the competent detachment of the decidua basalis from the steep concavity of the caesarean scar defect (CSD) in CSP. Hysteroscopic surgery has been reported to achieve a high success rate and low complication rate in CSP, particularly in cases with RMT greater than 3 mm [6,7]. However, However, patients with RMT <3 mm undergoing hysteroscopic surgery or curettage may encounter intraoperative uncontrollable bleeding accompanied by a high incidence of required secondary treatment [8]. Pre-assessment of blood loss in CSP is crucial for gynaecologists. Effective preoperative management is essential to minimize the risk of excessive bleeding during surgery. HIFU ablation, a novel non-invasive treatment, has been widely employed in the treatment of various solid tumour and benign disorders, particularly gynaecological diseases, such as uterine fibroids and adenomyosis [9,10,11,12]. During HIFU ablation, ultrasound beams generated by the transducer penetrate through the abdominal skin, subcutaneous tissue, and bladder before focusing on the targeted tissue around the CSP lesion. Coagulative necrosis occurs when the target temperature increases to over 60°C. The cavitation effect of HIFU may also loosen the adhesion between the GS and the myometrium at the uterine scar [13]. Numerous recent studies have demonstrated that HIFU is an effective therapeutic option for participants with type Ⅰ, Ⅱ, and Ⅲ CSP [14,15], reducing intraoperative blood loss [14,16]. In comparison with UAE, HIFU treatment for CSP offers advantages such as lower pain scores, fewer adverse effects, and minimal impact on post-operative menstrual blood loss [17,18]. HIFU is a favourable treatment option for participants with fertility preservation requirements [19,20]. However, HIFU may not be necessary in cases with a low risk of massive haemorrhage. To date, no randomized controlled trials (RCTs) have evaluated intraoperative blood loss and postoperative outcomes of surgical modalities—including suction curettage and hysteroscopy, with or without HIFU pretreatment—in women with type II CSP. Herein, we aim to conduct a prospective RCT to primarily evaluate the necessity of HIFU in the management of type II CSP. Objectives {7} High-Intensity Focused Ultrasound pretreatment combined with Hysteroscopy-Guided suction curettage reduces intraoperative bleeding in type II Caesarean Scar Pregnancy. Trial design {8} This is a single-center open-label, 1:1 parallel-group, superiority-design.This protocol will adhere to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). Trial results will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines, and a flow diagram of this trial is presented in Fig. 1. Methods: Participants, interventions and outcomes Study setting {9} The trial will be conducted at Qingdao Women and Children’s Hospital. Eligibility criteria {10} Diagnostic Criteria The diagnostic criteria for cesarean scar pregnancy will be confirmed through transvaginal ultrasound examination[3].The ultrasound diagnostic report will be reviewed and finalized by two ultrasound physicians. Diagnostic Criteria of CSP[5]: 1. An empty uterine cavity and endocervix; 2. A thin or absent layer of myometrium between the GS and the bladder; 3. GS located anteriorly at the level of the internal os covering the previous lower uterine segment caesarean section scar; 4. An abundant peritrophoblastic blood flow within the area of the GS, as demonstrated by low-pulse repetition Doppler study. Diagnostic Criteria of Type Ⅱ CSP[5]: 1. The gestational sac is partially implanted at the uterine scar site, with a portion or the majority of it lying within the uterine cavity; in rare instances, it may even extend to the fundal region of the uterine cavity; 2. The gestational sac is notably deformed and elongated, with its lower pole forming an acute angle; 3. The myometrium between the gestational sac and the bladder is thinned out, measuring ≤3 mm in thickness; 4. CDFI (Color Doppler Flow Imaging): Trophoblastic blood flow signals (low-resistance blood flow) are detected at the site of the uterine scar. Inclusion Criteria 1. All participants must be at least 18 years old and must voluntarily decide to terminate their pregnancy and sign the surgical informed consent form; 2. Participants with a history of caesarean section; 3. Participants who have experienced menopause (within eight weeks) and have serum β-hCG levels exceeding 10,000 mIU/mL; 4. The maximum diameter of the gestational sac is less than 50mm[21]; 5. Participants must voluntarily agree to participate in this study and sign an informed consent form. Exclusion Criteria 1. Participants with vaginitis or vaginal bleeding exceeding menstrual volume before interventions; 2. Participants with severe coagulation dysfunction, severe internal or external diseases, or contraindications to anaesthesia; 3. Participants with a history of allergy to contrast agents; 4. Participants who are lactating; 5. Participants who do not want to receive surgical treatment; 6.The other types of CSP. Who will take informed consent? {26a} Informed consent will be obtained from authorized investigators, who are required to have more than 6 years of experience in performing induced abortion surgery. Additional consent provisions for collection and use of participant data and biological specimens {26b} n/a Interventions Explanation for the choice of comparators {6b} Eligible participants will be randomly assigned to the control or HIFU groups. The control group will undergo suction curettage guided by hysteroscopy, while the HIFU group will receive HIFU therapy followed by suction curettage guided by hysteroscopy. Intervention description {11a} HIFU Treatment Equipment The HIFU treatment will use a JC200 focused ultrasound tumour therapeutic system (Chongqing Haifu Medical Technology Co. Ltd., Chongqing, P.R. China), which offers real-time sonographic monitoring. Pre-HIFU Treatment Preparation participants will be instructed to undergo bowel preparation, which includes consuming semi-liquid and liquid foods, taking polyethylene glycol (PEG) orally the night before treatment, fasting for 6-8 hours, and abstaining from drinking fluids for 2-4 hours before the procedure. The abdominal wall, from the umbilicus to the upper margin of the pubic symphysis, must be shaved, degreased with 75% ethanol, and degassed using degassed water. A catheter will be inserted into the bladder for volume control. HIFU Treatment Procedure HIFU treatment will be performed by two experienced doctors who have completed over 200 HIFU procedures. During the procedure, participants will be placed in the prone position on the high-intensity focused ultrasound treatment table, with the anterior abdomen in contact with the degassed water. The sagittal ultrasound scanning mode will be used for pre-treatment planning and sonication. A water balloon will be placed between the transducer and abdominal wall to displace the bowel from the acoustic pathway. The point-by-point scan mode will be selected, with the power set between 350 and 400 W. The focus will be adjusted to target the embedding area of the GS, which will be treated from deep to superficial layers. Criteria for terminating HIFU treatment include: (1) Significant large-scale changes or generalized changes observed via real-time ultrasound monitoring; (2) Color Doppler showing a reduction in blood flow grading of the embedding area to grade 0 or grade 1 (Adler grading). A contrast-enhanced ultrasound using a microbubble agent (Sonovue, Bracco, Milan, Italy) will be performed 10 minutes before and immediately after HIFU to evaluate blood supply alterations in the embedding area. The bladder will be infused with cold saline (0-4°C) to lower the local temperature immediately after HIFU, after which the urinary catheter may be removed. Procedure for Suction Curettage and Hysteroscopy Treatments Pre-Treatment Preparation All participants will undergo pre-surgical preparation, including blood transfusion and the establishment of dual intravenous channels, and will be primed for potential conversion to laparoscopic or open surgery if necessary. The surgery will be performed by a single surgeon with extensive experience, including over 10 years in hysteroscopic surgery and more than 100 cases of hysteroscopic treatment for CSP. participants in the HIFU group will undergo curettage guided by hysteroscopy within 0 to 1 day after HIFU ablation. Suction Curettage and Hysteroscopy Treatment The procedure will be performed under general anaesthesia. A prostaglandin drug (Carboprost suppositories, 1 mg, NORTHEAST PHARM) is inserted into the vagina 30 minutes before surgery to prepare the cervix. participants empty their bladder and are placed in the lithotomy position. After sufficient cervical dilation, an 8-mm suction cannula will be gently inserted into the uterine cavity, and the vacuum pressure will be set at 400 mmHg. The cannula will be carefully maneuvered around the GS embedding area to detach the pregnancy tissues. The suction will be applied for 3 to 5 minutes. Following tissue aspiration, oxytocin (10 U in 500mL of 0.9% NaCl, 60 drops/min) will be administered intravenously to promote uterine contractions. A 10-mm electrosurgical hysteroscope with 0.9% NaCl will subsequently be inserted into the uterine cavity. The uterine distention fluid will be injected into the cavity at a pressure ranging from 80 to 100 mmHg. The surgeon will perform a thorough examination of the uterine cavity and subsequently withdraw the hysteroscope to the CSD. The scar flap will be excised electrically with a ring electrode to fully expose the bottom of the incision (Fig. 2). The CSD will be examined systematically in a clockwise or counterclockwise direction. A wire-loop electrode may be utilized to remove retained pregnancy tissues, and electrocoagulation will be employed to control bleeding from the wound surface. If necessary, and provided there are no contraindications to anaesthesia, dilute vasopressin (6 U in 60 mL of 0.9% NaCl) will be injected into the cervix at the 4 o’clock and 8 o’clock positions, with a total volume of 20–60 mL, to control perioperative blood loss. If active uterine bleeding occurs, a Foley catheter balloon injected with normal saline will be promptly employed. Remedial measures 1.For intraoperative active bleeding that is unresponsive to conservative treatment, timely combined use of laparoscopy or UAE is required. 2.For cases where postoperative HCG decreases slowly or rises again after a decrease, and ultrasonic examination reveals a lesion at the scar site, re-hospitalization for supplementary drug (Methotrexate, MTX) treatment or repeat hysteroscopic surgery is necessary. Criteria for discontinuing or modifying allocated interventions {11b} Participants will be withdrawn from the study, and no further data will be collected if they meet the following criteria: 1.Participant experiencing an emergency, such as severe bleeding or intense pain before interventions required by the study , will be withdrawn from this study and carry out intervention immediately, such as UAE; 2.unexpected cancellation of surgery; 3.Intraoperatively, the surgical approach is modified as needed (e.g., by incorporating laparoscopy or UAE); 4.Postoperative pathology indicates gestational trophoblastic neoplasm; 5.Participant asks to withdraw from the study. Strategies to improve adherence to interventions {11c} 1. Pre-Trial Training All study personnel (including nursing staff) will complete standardized training prior to trial initiation. Training modules covered: study protocol and standard operating procedures (SOPs)/ operational steps and safety precautions/data collection methodology/ completion of case report forms (CRFs)/ use of Excel-based data collection templates. 2. In-Trial Process Optimization Progress monitoring: Regular team meetings will held to review trial progress, troubleshoot operational challenges, and implement workflow refinements to enhance efficiency and data quality. Relevant concomitant care permitted or prohibited during the trial {11d} If active uterine bleeding occurs, dilute vasopressin and/or a Foley catheter balloon injected with normal saline will be permitted. Drug treatment (mifepristone or MTX) before surgery or before discharge after surgery is prohibited. Provisions for post-trial care {30} n/a Outcomes {12} Primary Outcome Intraoperative blood loss Secondary Outcomes 1.Ratio of near haemorrhage* *Near haemorrhage is defined as any of the following: an estimated intraoperative blood loss of ≥ 100 mL [20], the utilization of a Foley catheter balloon [22], or a discrepancy in haemoglobin levels before and after the surgical intervention of ≥ 20 g/L [23]. 2. Therapeutic success rates Success is defined as the complete removal of pregnancy tissue, normalization of serum β-hCG levels, and no need for readmission. 3. Subsequent pregnancy outcomes within a 2-year follow-up period. Other data Hospitalization duration, intraoperative complications*, duration of vaginal bleeding after treatment, time to achieve normal β-hCG levels, and time to normal menstrual recovery * Intraoperative complications include sacrococcygeal pain, treatment area pain, haematuria, fluid overload, symptomatic dilutional hyponatremia, uterine perforation, or hysterectomy. Participant timeline {13} Once participants have signed the informed consent form and completed the review of inclusion and exclusion criteria, preoperative preparation will commence. Participants in the HIFU group will undergo hysteroscopic surgery 24 hours after HIFU treatment. On the first postoperative day, blood routine and β-HCG levels will be rechecked. If no special conditions occur, patients will be discharged on the 2nd postoperative days. Following discharge, β-HCG levels will be tested weekly until they return to normal. Ultrasound re-examination will be performed after menstruation concludes. Strict contraception will be required for six months postoperatively. For participants with fertility intentions, a follow-up call will be made two years postoperatively to inquire about pregnancy outcomes.(Fig. 3) Sample size {14} The primary outcome of this study is the intraoperative blood loss. The mean intraoperative blood loss for type Ⅱ CSP treated with suction curettage under hysteroscopic guidance was 32.56 mL (standard deviation (SD) of 25.32 mL) [24], compared to 20.6 mL (SD of 21.8 mL) for cases treated with HIFU followed by suction curettage under hysteroscopic guidance between November 2019 and May 2020 at Qingdao Women and Children’s Hospital. Using an independent sample t-test with a type I error rate of 5%, a type Ⅱ error rate of 20%, the calculated sample size per group was 63. Considering a 10% attrition rate, we will need 70 participants for each group (63/0.9). Attrition factors include withdrawal during the study period, loss to follow-up, non-compliance with study protocols, and invalid or unreliable recorded data. Consequently, this randomized clinical trial is designed to recruit a total of 140 participants diagnosed with type II CSP, who will be randomly assigned to two equally sized groups. Recruitment {15} Recruitment will be carried out through multiple approaches, including direct outreach to potential participants via outpatient clinics and departmental promotion at Qingdao Women and Children’s Hospital, as well as referrals from community hospitals. Participants diagnosed with type Ⅱ CSP will be identified via medical record review. Researchers will then contact eligible candidates through telephone or in-person communication to screen for study eligibility. Assignment of interventions: allocation Sequence generation {16a} A professional statistician will generate random numbers. Concealment mechanism {16b} A professional statistician will compile the random number sequence into an Excel spreadsheet. Study personnel (comprising physicians and nurses) have no access to group assignments prior to participant enrolment. Implementation {16c} Two investigators will simultaneously access the Excel spreadsheet using the participant's enrollment number to verify the participant's assigned group. Assignment of interventions: Blinding Who will be blinded {17a} Blinding was not applicable, as this was an open-label study. Procedure for unblinding if needed {17b} n/a Data collection and management Plans for assessment and collection of outcomes {18a} Following participant recruitment, a trained researcher will collect baseline data. This dataset will include key participant characteristics, such as age; parity; gravidity; number of prior cesarean deliveries; interval since the last cesarean delivery; fertility intentions; history of cesarean scar pregnancy (CSP) or placenta accreta spectrum (PAS); gestational age at admission; gestational sac (GS) size; presence of fetal cardiac activity; residual myometrial thickness (RMT); serum β-hCG levels; and clinical symptoms (e.g., vaginal bleeding or lower abdominal pain). Clinical outcome data will encompass: uterine depth; pituitrin administration and Foley catheter balloon placement; intraoperative blood loss; presence/absence of intrauterine adhesions; surgical duration; length of hospitalization (calculated as discharge date minus admission date); post-treatment vaginal bleeding duration; time to β-hCG normalization; resumption of normal menstruation; and pregnancy outcomes. Data related to HIFU treatment will include total ablation energy, total treatment time, median treatment power, sonication time, and treatment intensity. Safety indicators will include intraoperative complications (e.g., uterine perforation, water intoxication, massive hemorrhage, or surgical procedure modification) and HIFU treatment complications (e.g., lower abdominal pain, sciatica or gluteal pain, hematuria, skin injury, and nerve injury). Adverse events (AEs) will be graded for severity—from mild-to-moderate (Grade 1-2) to severe (Grade 3-5)—according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria[25]. The results of the ultrasound examination will be reviewed and approved by two experienced physicians, while the laboratory tests will be conducted by the hospital's qualified laboratory department. Plans to promote participant retention and complete follow-up {18b} 1.Emphasize the importance of follow-up through repeated communications prior to discharge. 2.Remind participants to attend follow-up appointments via the official WeChat account and hospital follow-up system. 3.Streamline the workflow with advance scheduling, enabling participants to select weekend or off-peak hours for follow-up visits. Data management {19} Research data will be stored in Microsoft Excel files on hospital intranet computers, which are password-encrypted and accessible only to authorized researchers. During data collection and management, researchers will ensure meticulous, timely, accurate, and comprehensive documentation of all relevant study data. Data will undergo regular checks by the quality controller, and participant personal information will not be recorded. Confidentiality {27} Each participant will be assigned a unique study number, which will be utilized across all study-related documentation. Such documentation will remain accessible exclusively to the study investigators. Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} n/a Statistical methods Statistical methods for primary and secondary outcomes {20a} Per-protocol analyses will be conducted. Intercurrent events include: study-unrelated events (such as upper respiratory tract infection) occurring during participants' hospitalization leading to prolonged length of hospital stay, and unplanned pregnancy occurring before the resumption of postoperative menstruation leading to inability to track menstrual resumption time. The secondary outcome indicators of such participants will not be included in the statistical analysis. To be included in the analysis, a participant must provide data from the baseline and the intraoperative blood loss. If a participant meets the withdrawal criteria, no data will be included in the analysis. Normally distributed quantitative data will be expressed as mean and SD. Non-normally distributed variables will be expressed as median (interquartile range). Qualitative data will be expressed as counts and percentages. Comparisons between groups will be conducted using the Student’s t-test, Wilcoxon rank test or c 2 test. Two-sided p < 0.05 will be considered statistically significant. Interim analyses {21b} Given the low risk associated with the study content, interim analysis will not be conducted. Methods for additional analyses (e.g. subgroup analyses) {20b} n/a. Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c} Per-protocol analyses will be conducted. Missing data will be handled using multiple imputation. Results derived from complete-case data (without missing observations) will be compared with those from imputed data to conduct a sensitivity analysis. Plans to give access to the full protocol, participant level-data and statistical code {31c} The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request 3 months after the official publication of the research paper. Oversight and monitoring Composition of the coordinating centre and trial steering committee {5d} Qingdao Women and Children’s Hospital Ethics Committee and the State Key Laboratory of Ultrasound in Medicine and Engineering Academic Committee. Composition of the data monitoring committee, its role and reporting structure {21a} A Data Monitoring Committee (DSM) composed of one clinician, one statistician, and the secretary of the Ethics Committee of Qingdao Women and Children’s Hospital will be established. DSM members will conduct regular study monitoring, with the process maintained independently from investigators. Adverse event reporting and harms {22} All AEs shall be collected, managed proactively in line with established treatment protocols, and serious adverse events (SAEs) reported to the Qingdao Women and Children’s Hospital Ethics Committee in a timely manner. Frequency and plans for auditing trial conduct {23} The frequency and procedures for auditing trial conduct will be annual, and the audit process will be independent of the investigators. Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25} The communication plan for protocol amendments will be developed by researchers, formulated in accordance with internal hospital procedures and Good Clinical Practice (GCP) requirements. This plan aims to ensure transparent dissemination of amendment information to all relevant stakeholders, thereby safeguarding the study's scientific validity as well as the rights and interests of trial participants. Dissemination plans {31a} Data collection is anticipated to be finalized by June 2026. Research findings will be published in alignment with agreements with the funding body and institutional guidelines. Upon acceptance of the research findings for publication, the relevant data will be made publicly accessible via the website at http://www.cpc.unc.edu/projects/china. Discussion In clinical practice, our primary goal has consistently been to identify safe, effective, minimally invasive, and fertility-preserving treatment modalities for participants with CSPs. Treatment decisions must be customized individually, considering the severity of symptoms, future family planning goals, physician expertise, and institutional resources. Hysteroscopy has demonstrated a relatively high success rate in treating type Ⅰ CSP, with surgical bleeding effectively controlled [23]. However, the risk of complications, particularly massive hemorrhage, is heightened during hysteroscopic treatment, especially in grassroots-level hospitals or among physicians with limited clinical experience. HIFU delivers energy precisely to the implantation site of the GS at the cesarean scar through real-time ultrasound monitoring. It destroys trophoblastic cells and damages small blood vessels with diameters less than 2 mm by generating temperatures of 60–100℃ [13]. No statistically significant difference was observed between HIFU and UAE in terms of treatment success rate [14,16]. Furthermore, HIFU has a reduced impact on post-operative menstrual blood loss (MBL), making it a favorable treatment option for participants with fertility intentions [19,20]. Therefore, in this randomized clinical trial, our primary objective will be to assess the necessity of HIFU as a treatment option for type Ⅱ CSP to control intraoperative blood loss. Characteristics such as gestational age, size of the gestational sac, RMT, and pre-treatment serum β-hCG levels are identified as risk factors associated with intraoperative blood loss [26]. Subsequently, we will analyze these characteristics and develop classifications to optimize the treatment strategy. Trial status The protocol version and date: V-1.0 29th May, 2020. The recruitment began on July 12, 2020 and the recruitment work has been completed, but the follow-up of some participants' secondary assessment indicators (the pregnancy outcomes within two years) has not yet been carried out. Abbreviations AE adverse event CRF case report form CDFI color doppler flow imaging GCP GS good clinical practice gestational sac CSD caesarean scar defect CSP caesarean scar pregnancy CTCAE common terminology criteria for adverse events DSM data monitoring committee HIFU high-intensity focused ultrasound MBL menstrual blood loss MTX methotrexate PAS placenta accreta spectrum PEG polyethylene glycol RMT residual myometrium thickness RCT randomized controlled trial SAE serious adverse event SOP standard operating procedure UAE uterine artery embolization Declarations Acknowledgements The authors would like to thank Professor Lian Zhang for editing this manuscript. Authors’ contributions {31b} Author Changmei Sang: designed the study, and wrote the manuscript. Author Qiuling Shi: performed statistical analysis, and reviewed the manuscript. Author Lei Zhao and Yanjun Kang: provided critical feedback on the study design. Author Shuping Zhao: designed the study, provided critical feedback on the study design and edited the manuscript. Author Zhibiao Wang: supervised the project and contributed to the interpretation of results. Funding {4} Foundation of the State Key Laboratory of Ultrasound in Medicine and Engineering (Grant No:2020KFA3002) Availability of data and materials {29} All the researchers and authorized viewers have the right to access the final trial data set. De-identified patient data generated or analyzed during this study are not publicly available due to privacy but may be made available upon reasonable request. Researchers who meet criteria for access to confidential data can contact the corresponding author at [email protected] after obtaining approval from the Institutional Ethics Committee of Qingdao Women and Children’s Hospital. A data sharing agreement will be required to ensure compliance with applicable laws and regulations. Ethics approval and consent to participate {24} This research is fully in accordance with the Declaration of Helsinki. This clinical trial has been approved by Qingdao Women and Children’s Hospital(ethics approval number: QFELL-KY-2020-33).Written informed consent to participate in the study will be obtained from all eligible participants. Consent for publication {32} Patients and the public will not be involved in the design, recruitment, or conduct of this study. There are no plans to disseminate study results to participants, as providing research outcome feedback to participants is not standard practice in China. However, participants will be notified that they may access the final study results through our future published articles.The informed consent form is detailed in the attachment. Competing interests {28} The authors declare that they have no competing interests. Authors’ information (optional) References Miller R, Gyamfi-Bannerman C. Cesarean scar ectopic pregnancy. Society For Maternal Fetal Medicine Consult Series;# 63. Am J Obstet Gynecol. 2022;B9–20. Riaz RM, Williams TR, Craig BM, et al. Cesarean scar ectopic pregnancy: Imaging features, current treatment options, and clinical outcomes. Abdom Imaging. 2015;40:2589–99. Jurkovic D, Hillaby K, Woelfer B, et al. First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment cesarean section scar. Ultrasound Obstet Gynecol. 2003;21:220–7. Seow KM, Huang LW, Lin YH, et al. Cesarean scar pregnancy: Issues in management. Ultrasound Obstet Gynecol. 2004;23:247–53. Family Planning Subgroup, Chinese Society of Obstetrics and Gynocology, Chinese Medical Association. Expert opinion of diagnosis and treatment of cesarean scar pregnancy (2016). Zhonghua fu chan ke za zhi. 2016;51:568–72. Chueh H-Y, Pai AH-Y, Su Y-Y, et al. Hysteroscopic removal, with or without laparoscopic assistance, of first-trimester cesarean scar pregnancy. Fertil Steril. 2022;117:643–5. Hameed MSS, Wright MS, Chern A. Scope and suction: Hysteroscopic-guided suction evacuation of cesarean scar pregnancy – A safe and efficacious treatment for selected participants. Gynecol Minim Invasive Ther. 2023;12:72–6. He Y, Wu X, Zhu Q, et al. Combined laparoscopy and hysteroscopy vs. uterine curettage in the uterine artery embolization-based management of cesarean scar pregnancy: A retrospective cohort study. BMC Womens Health. 2014;14:116. Orsi F, Arnone P, Chen W, et al. High intensity focused ultrasound ablation: A new therapeutic option for solid tumors. J Cancer Res Ther. 2010;6:414–20. Liu L, Wang T, Lei B. High-intensity focused ultrasound (HIFU) ablation versus surgical interventions for the treatment of symptomatic uterine fibroids: A meta-analysis. Eur Radiol. 2022;32:1195–204. Otgontuya A, Jeng C-J, Wu T-N, et al. Comparison of the treatment efficacies of HIFU, HIFU combined with GnRH-a, and HIFU combined with GnRH-a and LNG-IUS for adenomyosis: A systematic review and meta-analysis. Taiwan J Obstet Gynecol. 2023;62:226–38. Lin Z, Gong C, Huang Q, et al. A comparison of results following the treatment of placenta accreta and placenta increta using high-intensity focused ultrasound followed by hysteroscopic resection. Int J Hyperth. 2021;38:576–81. Huang L, Du Y, Zhao C. High-intensity focused ultrasound combined with dilatation and curettage for cesarean scar pregnancy. Ultrasound Obstet Gynecol. 2014;43:98–101. Liu Y, Yin Q, Xu F, et al. Clinical efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treatment of cesarean scar pregnancy (CSP) I and Ⅱ. BMC Pregnancy Childbirth. 2022;22:607. Peng Y, Dai Y, Yu G, et al. Analysis of the type of cesarean scar pregnancy impacted on the effectiveness and safety of high intensity focused ultrasound combined with ultrasound-guided suction curettage treatment. Int J Hyperth. 2022;39:1449–57. Zhang C, Zhang Y, He J, et al. Outcomes of subsequent pregnancies in participants following treatment of cesarean scar pregnancy with high intensity focused ultrasound followed by ultrasound-guided dilation and curettage. Int J Hyperth. 2019;36:926–31. Li Y, Hua C. Is high-intensity focused ultrasound superior to uterine artery embolization in cesarean scar pregnancy and subsequent pregnancy outcomes? A meta-analysis of the Chinese population. J Minim Invasive Gynecol. 2023;30:180–91. Liu Y, Wang L, Zhu X. Efficacy and safety of high-intensity focused ultrasound compared with uterine artery embolization in cesarean section pregnancy: A meta-analysis. J Minim Invasive Gynecol. 2023;30:446–54. Dai Y, Peng Y, Shi Q, et al. Comparison of menstruation recovery after ultrasound-guided suction curettage in participants with cesarean scar pregnancy pretreated using high-intensity focused ultrasound and uterine artery embolization. Int J Hyperth. 2023;40:2241686. Wang X, Yang B, Chen W, et al. Clinical efficacy and re-pregnancy outcomes of participants with previous cesarean scar pregnancy treated with either high-intensity focused ultrasound or uterine artery embolization before ultrasound-guided dilatation and curettage: A retrospective cohort study. BMC Pregnancy Childbirth. 2023;23:85. Zhu X, Deng X, Wan Y, et al. High-intensity focused ultrasound combined with suction curettage for the treatment of cesarean scar pregnancy. Med (Baltim). 2015;94(18):e854. Ban Y, Shen J, Wang X, et al. Cesarean scar ectopic pregnancy clinical classification system with recommended surgical strategy. Obstet Gynecol. 2023;141:927–36. Zhu Q, Tang Y, Tian Q, et al. Clinical efficacy and safety analysis of different treatment options for cervical pregnancy. Int J Hyperth. 2023;40:2255757. Liu B, Chi Y, Hu L, et al. Clinical study on the treatment of partial Ⅱ-type cesarean scar pregnancy by hysteroscopy. Prog Obstet Gynecol. 2020;29:141–3. Common Terminology Criteria for Adverse Events (CTCAE). Version 5. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2017. Wan X, Wang X, Feng Z, Zhou X, Han Z, Wu J, Xu H, Hu T. Analysis of Risk Factors for Intraoperative Bleeding in the Surgical Treatment of Cesarean Scar Pregnancy and Development of Predictive Models. Multidiscip Healthc. 2024;17:2021–30. Supplementary Files SPIRITFillablechecklist15Aug2013.doc Cite Share Download PDF Status: Published Journal Publication published 06 Aug, 2025 Read the published version in Trials → Version 1 posted Reviewers agreed at journal 23 Jun, 2025 Reviewers invited by journal 23 Jun, 2025 Editor assigned by journal 19 Jun, 2025 First submitted to journal 19 Jun, 2025 Editorial decision: Minor revision 04 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6379195","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":475197635,"identity":"72795e23-82d1-4f8f-9b5e-f1c508c2be20","order_by":0,"name":"Changmei Sang","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Changmei","middleName":"","lastName":"Sang","suffix":""},{"id":475197636,"identity":"87835cb0-2512-4098-a94e-0ebe8c889a8c","order_by":1,"name":"Qiuling Shi","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qiuling","middleName":"","lastName":"Shi","suffix":""},{"id":475197637,"identity":"e28d3d05-3d9f-4716-9b3e-178712e8e463","order_by":2,"name":"Lei Zhao","email":"","orcid":"","institution":"Qingdao Women and Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Zhao","suffix":""},{"id":475197638,"identity":"506461fd-97df-4c60-899b-831ab7f604fa","order_by":3,"name":"Yanjun Kang","email":"","orcid":"","institution":"Qingdao Women and Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanjun","middleName":"","lastName":"Kang","suffix":""},{"id":475197639,"identity":"9338f639-af05-4c17-9552-5c1cee9e6a61","order_by":4,"name":"Shuping Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYDACCTBpI8fPzHzwASla0owl29mSDUjRcijR4DyPmQBROuRnNz98+HPHgQTjwwxmDAw1NtEEtTDOOWZszHvmTp7ZYYa0BwzH0nIbCGlhlkgwk2Zse1YM1HLcgLHhMGEtbBLp3yR/th1O3NzM2CZBlBYeiRwzCV6glg3MzGzEaZGQyCkG+iXNWOIwG7NBAjF+kZ+RvhEYYsCo7D//8cGHGhvCWsCAEaYsgSjlKFpGwSgYBaNgFGADAMQcPcdVnCofAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-6081-934X","institution":"Qingdao Women and Children's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shuping","middleName":"","lastName":"Zhao","suffix":""},{"id":475197640,"identity":"91fde536-29a0-4b23-a778-d5214ea5af1f","order_by":5,"name":"Zhibiao Wang","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhibiao","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-04-05 01:06:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6379195/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6379195/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13063-025-08967-8","type":"published","date":"2025-08-06T15:57:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85822558,"identity":"58e9c5c4-5956-4152-9b90-3a099f94e994","added_by":"auto","created_at":"2025-07-02 06:49:37","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34049,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the process\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6379195/v1/65741494375c6c009034ecb5.jpg"},{"id":85821906,"identity":"9e9601e4-4028-491e-a7fc-db4d55114f07","added_by":"auto","created_at":"2025-07-02 06:41:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":87236,"visible":true,"origin":"","legend":"\u003cp\u003eCrucial surgical procedures of hysteroscopy treatment\u003c/p\u003e\n\u003cp\u003eA. Observation of the uterine cavity; B. Observation of CSD; C. Implantation site of the villi in CSD; D-FScar flap of CSD\u003c/p\u003e\n\u003cp\u003eAbbreviation: CSD: caesarean scar defect\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6379195/v1/332ab8d5b3ec92328ee69881.jpg"},{"id":85821905,"identity":"28bea3a4-07d7-4f8c-ba35-f467c92b9ea9","added_by":"auto","created_at":"2025-07-02 06:41:37","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46834,"visible":true,"origin":"","legend":"\u003cp\u003eSPIRIT figure\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6379195/v1/a44edae7078f33ffbfc9ed63.jpg"},{"id":88814069,"identity":"99ca2453-9016-44ac-b6bc-45ca69d14e70","added_by":"auto","created_at":"2025-08-11 16:05:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1769159,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6379195/v1/0cbad4b9-37ad-400a-94d4-192e78452ff5.pdf"},{"id":85822555,"identity":"fa4ed04b-bcc9-48cd-a851-8cab864e00cc","added_by":"auto","created_at":"2025-07-02 06:49:37","extension":"doc","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":126976,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRITFillablechecklist15Aug2013.doc","url":"https://assets-eu.researchsquare.com/files/rs-6379195/v1/9a132292f70edd0fd7159521.doc"}],"financialInterests":"","formattedTitle":"Reducing Intraoperative Hemorrhage in Type Ⅱ Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT)","fulltext":[{"header":"Administrative Information","content":"\u003cp\u003eNote: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"639\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eTitle {1}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003eReducing Intraoperative Hemorrhage in Type\u0026nbsp;Ⅱ\u0026nbsp;Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eTrial registration {2a and 2b}.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003eRegistration number:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eChiCTR2000034332\u003c/p\u003e\n \u003cp\u003eRegistry name：A randomized controlled clinical trial for the effect of FUAS combined with suction curettage and simple suction curettage in the treatment of type II cesarean scar pregnancy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eProtocol version {3}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003eVersion and Date: V-1.0 \u0026nbsp; 29th May, 2020\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eFunding {4}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003eFoundation of the State Key Laboratory of Ultrasound in Medicine and Engineering (Grant No:2020KFA3002)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eAuthor details {5a}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China; \u003csup\u003eb\u003c/sup\u003eSchool of Public Health and Management, Chongqing Medical University, Chongqing, P.R. China;\u003csup\u003ec\u003c/sup\u003eQingdao Women and Children\u0026rsquo;s Hospital, Qingdao, Shandong, P.R. China\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eName and contact information for the trial sponsor {5b}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003eZhibiao Wang, e-mail: [email protected], State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China\u003c/p\u003e\n \u003cp\u003eShuping Zhao, e-mail: [email protected], State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China; Qingdao\u0026nbsp;Women and Children\u0026rsquo;s Hospital,\u0026nbsp;Qingdao, Shandong, P.R. China\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34.1158%;\"\u003e\n \u003cp\u003eRole of sponsor {5c}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65.8842%;\"\u003e\n \u003cp\u003eThe role of funding sources in the study design process, encompassing data collection, management, analysis, and interpretation; report writing; and the decision to submit the report for publication - including the ultimate authority over these activities.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Introduction","content":"\u003cp\u003e\u003cstrong\u003eBackground and rationale {6a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaesarean scar pregnancy (CSP) is a unique type of ectopic pregnancy in which the gestational sac (GS) is implanted into the scar tissue from a previous caesarean delivery\u0026nbsp;[1,2]. The estimated incidence of\u0026nbsp;CSP\u0026nbsp;ranges from 1 in 1,800 to 1 in 2,216 pregnancies\u0026nbsp;[3,4]. The rising caesarean delivery rate and the increasing use of reliable imaging techniques for CSP diagnosis have led to a significant increase in reported cases over the last decade. CSP is associated with a high incidence of severe maternal morbidity, such as life-threatening haemorrhage, placenta accreta spectrum (PAS), uterine rupture, and even maternal mortality. Achieving optimal management of CSP remains a significant challenge for gynaecologists.\u003c/p\u003e\n\u003cp\u003eThe Gynaecology Subcommittee of the Chinese Medical Association issued updated guidelines in the Expert Opinion of Diagnosis and Treatment of Caesarean Scar Pregnancy in 2016\u0026nbsp;[5]. The treatment principles for CSP are early detection, early diagnosis, and early intervention.\u0026nbsp;The guidelines classify CSP into three types\u0026mdash;Type I, Type II, and Type III\u0026mdash;based on the growth direction of the gestational sac (GS) and the residual myometrium thickness (RMT) between the GS and the bladder, as assessed by ultrasound, with specific treatment recommendations provided for each type. For type I CSP, ultrasound-guided suction curettage exhibits favourable therapeutic outcomes with a relatively low risk of massive haemorrhage. For type\u0026nbsp;Ⅲ\u0026nbsp;CSP, the risk of residual tissue retention and bleeding during curettage is high, making this procedure unsuitable. Alternatively, pregnancy tissue removal combined with uterine scar repair may be considered. For Type\u0026nbsp;Ⅱ, GS is partially implanted in the uterine scar, and the RMT is less than 3 mm. Despite the availability of various treatment modalities\u0026mdash;including medication, dilation and curettage, hysteroscopic and laparoscopic surgery, uterine artery embolization (UAE), high-intensity focused ultrasound (HIFU), and combinations of these approaches\u0026mdash;significant risks of complications remain, even when strategies are tailored to individual\u0026nbsp;participants\u0026nbsp;and clinical manifestations.\u003c/p\u003e\n\u003cp\u003eMounting evidence indicates that CSP is a precursor to abnormally adherent placenta in the second and third trimesters\u0026nbsp;[3], increasing the risk of severe haemorrhage or hysterectomy during operation or delivery. Surgical hysteroscopy provides direct visualization of the competent detachment of the decidua basalis from the steep concavity of the caesarean scar defect (CSD) in CSP. Hysteroscopic surgery has been reported to achieve a high success rate and low complication rate in CSP, particularly in cases with RMT greater than 3 mm\u0026nbsp;[6,7].\u0026nbsp;However, However, patients with RMT \u0026lt;3 mm undergoing hysteroscopic surgery or curettage may encounter intraoperative uncontrollable bleeding\u0026nbsp;accompanied by a high incidence of required secondary treatment [8]. Pre-assessment of blood loss in CSP is crucial for gynaecologists. Effective preoperative management is essential to minimize the risk of excessive bleeding during surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHIFU ablation, a novel non-invasive treatment, has been widely employed in the treatment of various solid tumour and benign disorders, particularly gynaecological diseases, such as uterine fibroids and adenomyosis\u0026nbsp;[9,10,11,12]. During HIFU ablation, ultrasound beams generated by the transducer penetrate through the abdominal skin, subcutaneous tissue, and bladder before focusing on the targeted tissue around the CSP lesion. Coagulative necrosis occurs when the target temperature increases to over 60\u0026deg;C. The cavitation effect of HIFU may also loosen the adhesion between the GS and the myometrium at the uterine scar\u0026nbsp;[13]. Numerous recent studies have demonstrated that HIFU is an effective therapeutic option for\u0026nbsp;participants\u0026nbsp;with type Ⅰ,\u0026nbsp;Ⅱ, and\u0026nbsp;Ⅲ\u0026nbsp;CSP\u0026nbsp;[14,15], reducing intraoperative blood loss\u0026nbsp;[14,16]. In comparison with UAE, HIFU treatment for CSP offers advantages such as lower pain scores, fewer adverse effects, and minimal impact on post-operative menstrual blood loss\u0026nbsp;[17,18]. HIFU is a favourable treatment option for\u0026nbsp;participants\u0026nbsp;with fertility preservation requirements\u0026nbsp;[19,20]. However, HIFU may not be necessary in cases with a low risk of massive haemorrhage. To date, no randomized controlled trials (RCTs) have evaluated intraoperative blood loss and postoperative outcomes of surgical modalities\u0026mdash;including suction curettage and hysteroscopy, with or without HIFU pretreatment\u0026mdash;in women with type II CSP. Herein, we aim to conduct a prospective RCT to primarily evaluate the necessity of HIFU in the management of type II\u0026nbsp;CSP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives {7}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHigh-Intensity Focused Ultrasound pretreatment combined with Hysteroscopy-Guided suction curettage reduces intraoperative bleeding in type II Caesarean Scar Pregnancy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial design {8}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a single-center open-label, 1:1 parallel-group, superiority-design.This protocol will adhere to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). Trial results will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines, and a flow diagram of this trial is presented in Fig. 1.\u003c/p\u003e"},{"header":"Methods: Participants, interventions and outcomes","content":"\u003cp\u003e\u003cstrong\u003eStudy setting {9}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial\u0026nbsp;will be\u0026nbsp;conducted at Qingdao Women and Children\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria {10}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Criteria\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe diagnostic criteria for cesarean scar pregnancy\u0026nbsp;will be\u0026nbsp;confirmed through transvaginal ultrasound examination[3].The ultrasound diagnostic report will be reviewed and finalized by two ultrasound physicians.\u003c/p\u003e\n\u003cp\u003eDiagnostic Criteria \u0026nbsp;of CSP[5]:\u003c/p\u003e\n\u003cp\u003e1. An empty uterine cavity and endocervix;\u003c/p\u003e\n\u003cp\u003e2. A thin or absent layer of myometrium between the GS and the bladder;\u003c/p\u003e\n\u003cp\u003e3. GS located anteriorly at the level of the internal os covering the previous lower uterine segment caesarean section scar;\u003c/p\u003e\n\u003cp\u003e4. An abundant peritrophoblastic blood flow within the area of the GS, as demonstrated by low-pulse repetition Doppler study.\u003c/p\u003e\n\u003cp\u003eDiagnostic Criteria \u0026nbsp;of\u0026nbsp;Type\u0026nbsp;Ⅱ CSP[5]:\u003c/p\u003e\n\u003cp\u003e1. The gestational sac is partially implanted at the uterine scar site, with a portion or the majority of it lying within the uterine cavity; in rare instances, it may even extend to the fundal region of the uterine cavity;\u003c/p\u003e\n\u003cp\u003e2. The gestational sac is notably deformed and elongated, with its lower pole forming an acute angle;\u003c/p\u003e\n\u003cp\u003e3. The myometrium between the gestational sac and the bladder is thinned out, measuring \u0026le;3 mm in thickness;\u003c/p\u003e\n\u003cp\u003e4. CDFI (Color Doppler Flow Imaging): Trophoblastic blood flow signals (low-resistance blood flow) are detected at the site of the uterine scar.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. All participants must be at least 18 years old and must voluntarily decide to terminate their pregnancy and sign the surgical informed consent form;\u003c/p\u003e\n\u003cp\u003e2. Participants\u0026nbsp;with a history of caesarean section;\u003c/p\u003e\n\u003cp\u003e3. Participants\u0026nbsp;who have experienced menopause (within eight weeks) and have serum \u0026beta;-hCG levels exceeding 10,000 mIU/mL;\u003c/p\u003e\n\u003cp\u003e4. The maximum diameter of the gestational sac is less than 50mm[21];\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp;Participants\u0026nbsp;must voluntarily agree to participate in this study and sign an informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Participants with vaginitis or vaginal bleeding exceeding menstrual volume before interventions;\u003c/p\u003e\n\u003cp\u003e2. Participants with severe coagulation dysfunction, severe internal or external diseases, or contraindications to anaesthesia;\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp;Participants\u0026nbsp;with a history of allergy to contrast agents;\u003c/p\u003e\n\u003cp\u003e4.\u0026nbsp;Participants\u0026nbsp;who are lactating;\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp;Participants\u0026nbsp;who do not want to receive surgical treatment;\u003c/p\u003e\n\u003cp\u003e6.The other types of CSP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will take informed consent? {26a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent will be obtained from authorized investigators, who are required to have more than 6 years of experience in performing induced abortion surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional consent provisions for collection and use of participant data and biological specimens {26b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003en/a\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExplanation for the choice of comparators {6b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEligible\u0026nbsp;participants\u0026nbsp;will be randomly assigned to the control or HIFU groups.\u0026nbsp;The\u0026nbsp;control group will undergo suction curettage guided by hysteroscopy, while the HIFU group will receive HIFU therapy followed by suction curettage guided by hysteroscopy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention description {11a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHIFU Treatment Equipment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe HIFU treatment will use a JC200 focused ultrasound tumour therapeutic system (Chongqing Haifu Medical Technology Co. Ltd., Chongqing, P.R. China), which offers real-time sonographic monitoring.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePre-HIFU Treatment Preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eparticipants\u0026nbsp;will be instructed to undergo bowel preparation, which includes consuming semi-liquid and liquid foods, taking polyethylene glycol (PEG) orally the night before treatment, fasting for 6-8 hours, and abstaining from drinking fluids for 2-4 hours before the procedure. The abdominal wall, from the umbilicus to the upper margin of the pubic symphysis, must be shaved, degreased with 75% ethanol, and degassed using degassed water. A catheter will be inserted into the bladder for volume control.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHIFU Treatment Procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHIFU treatment will be performed by two experienced doctors who have completed over 200 HIFU procedures. During the procedure,\u0026nbsp;participants\u0026nbsp;will be placed in the prone position on the high-intensity focused ultrasound treatment table, with the anterior abdomen in contact with the degassed water. The sagittal ultrasound scanning mode will be used for pre-treatment planning and sonication. A water balloon will be placed between the transducer and abdominal wall to displace the bowel from the acoustic pathway. The point-by-point scan mode will be selected, with the power set between 350 and 400 W. The focus will be adjusted to target the embedding area of the GS, which will be treated from deep to superficial layers. Criteria for terminating HIFU treatment include: (1) Significant large-scale changes or generalized changes observed via real-time ultrasound monitoring; (2) Color Doppler showing a reduction in blood flow grading of the embedding area to grade 0 or grade 1 (Adler grading). A contrast-enhanced ultrasound using a microbubble agent (Sonovue, Bracco, Milan, Italy) will be performed 10 minutes before and immediately after HIFU to evaluate blood supply alterations in the embedding area. The bladder will be infused with cold saline (0-4\u0026deg;C) to lower the local temperature immediately after HIFU, after which the urinary catheter may be removed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure for Suction Curettage and Hysteroscopy Treatments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePre-Treatment Preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll\u0026nbsp;participants\u0026nbsp;will undergo pre-surgical preparation, including blood transfusion and the establishment of dual intravenous channels, and will be primed for potential conversion to laparoscopic or open surgery if necessary. The surgery will be performed by a single surgeon with extensive experience, including over 10 years in hysteroscopic surgery and more than 100 cases of hysteroscopic treatment for CSP.\u0026nbsp;participants\u0026nbsp;in the HIFU group will undergo curettage guided by hysteroscopy within 0 to 1 day after HIFU ablation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSuction Curettage and Hysteroscopy Treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe procedure will be performed under general anaesthesia. A prostaglandin drug (Carboprost suppositories, 1 mg, NORTHEAST PHARM) is inserted into the vagina 30 minutes before surgery to prepare the cervix.\u0026nbsp;participants\u0026nbsp;empty their bladder and are placed in the lithotomy position. After sufficient cervical dilation, an 8-mm suction cannula will be gently inserted into the uterine cavity, and the vacuum pressure will be set at 400 mmHg. The cannula will be carefully maneuvered around the GS embedding area to detach the pregnancy tissues. The suction will be applied for 3 to 5 minutes. Following tissue aspiration, oxytocin (10 U in 500mL of 0.9% NaCl, 60 drops/min) will be administered intravenously to promote uterine contractions.\u003c/p\u003e\n\u003cp\u003eA 10-mm electrosurgical hysteroscope with 0.9% NaCl will subsequently be inserted into the uterine cavity. The uterine distention fluid will be injected into the cavity at a pressure ranging from 80 to 100 mmHg. The surgeon will perform a thorough examination of the uterine cavity and subsequently withdraw the hysteroscope to the CSD. The scar flap will be excised electrically with a ring electrode to fully expose the bottom of the incision (Fig. 2). The CSD will be examined systematically in a clockwise or counterclockwise direction. A wire-loop electrode may be utilized to remove retained pregnancy tissues, and electrocoagulation will be employed to control bleeding from the wound surface. If necessary, and provided there are no contraindications to anaesthesia, dilute vasopressin (6 U in 60 mL of 0.9% NaCl) will be injected into the cervix at the 4 o\u0026rsquo;clock and 8 o\u0026rsquo;clock positions, with a total volume of 20\u0026ndash;60 mL, to control perioperative blood loss. If active uterine bleeding occurs, a Foley catheter balloon injected with normal saline will be promptly employed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRemedial measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.For intraoperative active bleeding that is unresponsive to conservative treatment, timely combined use of laparoscopy or UAE is required.\u003c/p\u003e\n\u003cp\u003e2.For cases where postoperative HCG decreases slowly or rises again after a decrease, and ultrasonic examination reveals a lesion at the scar site, re-hospitalization for supplementary drug (Methotrexate,\u0026nbsp;MTX) treatment or repeat hysteroscopic surgery is necessary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCriteria for discontinuing or modifying allocated interventions {11b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be withdrawn from the study, and no further data will be collected if they meet the following criteria:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.Participant\u0026nbsp;experiencing an emergency, such as severe bleeding or intense pain\u0026nbsp;before interventions required\u0026nbsp;by the study\u0026nbsp;, will be withdrawn from this study\u0026nbsp;and carry out intervention immediately, such as UAE;\u003c/p\u003e\n\u003cp\u003e2.unexpected cancellation of surgery;\u003c/p\u003e\n\u003cp\u003e3.Intraoperatively, the surgical approach is modified as needed (e.g., by incorporating laparoscopy or UAE);\u003c/p\u003e\n\u003cp\u003e4.Postoperative pathology indicates gestational trophoblastic neoplasm;\u003c/p\u003e\n\u003cp\u003e5.Participant asks to withdraw from the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrategies to improve adherence to interventions {11c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Pre-Trial Training\u003c/p\u003e\n\u003cp\u003eAll study personnel (including nursing staff) will complete standardized training prior to trial initiation. Training modules covered: study protocol and standard operating procedures (SOPs)/ operational steps and safety precautions/data collection methodology/ completion of case report forms (CRFs)/ use of Excel-based data collection templates.\u003c/p\u003e\n\u003cp\u003e2. In-Trial Process Optimization\u003c/p\u003e\n\u003cp\u003eProgress monitoring: Regular team meetings will held to review trial progress, troubleshoot operational challenges, and implement workflow refinements to enhance efficiency and data quality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRelevant concomitant care permitted or prohibited during the trial {11d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIf active uterine bleeding occurs,\u0026nbsp;dilute vasopressin\u0026nbsp;and/or\u0026nbsp;a Foley catheter balloon injected with normal saline will be permitted.\u003c/p\u003e\n\u003cp\u003eDrug treatment (mifepristone or MTX) before surgery or before discharge after surgery is\u0026nbsp;prohibited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProvisions for post-trial care {30}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003en/a\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes {12}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcome\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntraoperative blood loss\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary Outcomes\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.Ratio of near haemorrhage*\u003c/p\u003e\n\u003cp\u003e*Near haemorrhage is defined as any of the following: an estimated intraoperative blood loss of \u0026ge; 100 mL\u0026nbsp;[20], the utilization of a Foley catheter balloon\u0026nbsp;[22], or a discrepancy in haemoglobin levels before and after the surgical intervention of \u0026ge; 20 g/L\u0026nbsp;[23].\u003c/p\u003e\n\u003cp\u003e2. Therapeutic success rates\u003c/p\u003e\n\u003cp\u003eSuccess is defined as the complete removal of pregnancy tissue, normalization of serum \u0026beta;-hCG levels, and no need for readmission.\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp;Subsequent pregnancy outcomes within a 2-year follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHospitalization duration, intraoperative complications*, duration of vaginal bleeding after treatment, time to achieve normal \u0026beta;-hCG levels, and time to normal menstrual recovery\u003c/p\u003e\n\u003cp\u003e* Intraoperative complications include sacrococcygeal pain, treatment area pain, haematuria, fluid overload, symptomatic dilutional hyponatremia, uterine perforation, or hysterectomy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant timeline {13}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOnce participants have signed the informed consent form and completed the review of inclusion and exclusion criteria, preoperative preparation will commence. Participants in the HIFU group will undergo hysteroscopic surgery 24 hours after HIFU treatment. On the first postoperative day, blood routine and\u0026nbsp;\u0026beta;-HCG levels will be rechecked. If no special conditions occur, patients will be discharged on the 2nd postoperative days. Following discharge,\u0026nbsp;\u0026beta;-HCG levels will be tested weekly until they return to normal. Ultrasound re-examination will be performed after menstruation concludes. Strict contraception will be required for six months postoperatively. For participants with fertility intentions, a follow-up call will be made two years postoperatively to inquire about pregnancy outcomes.(Fig. 3)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size {14}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary\u0026nbsp;outcome\u0026nbsp;of this study is\u0026nbsp;the\u0026nbsp;intraoperative blood loss.\u0026nbsp;The mean intraoperative blood loss for type\u0026nbsp;Ⅱ\u0026nbsp;CSP treated with suction curettage under hysteroscopic guidance was 32.56 mL (standard deviation (SD) of 25.32 mL)\u0026nbsp;[24], compared to 20.6 mL (SD of 21.8 mL) for cases treated with HIFU followed by suction curettage under hysteroscopic guidance between November 2019 and May 2020\u0026nbsp;at\u0026nbsp;Qingdao Women and Children\u0026rsquo;s Hospital. Using an independent sample t-test with a type I error rate of 5%, a type\u0026nbsp;Ⅱ\u0026nbsp;error rate of 20%, the calculated sample size per group was\u0026nbsp;63. Considering a\u0026nbsp;10% attrition rate, we will need\u0026nbsp;70\u0026nbsp;participants\u0026nbsp;for each group (63/0.9).\u0026nbsp;Attrition factors include withdrawal during the study period, loss to follow-up, non-compliance with study protocols, and invalid or unreliable recorded data.\u0026nbsp;Consequently, this randomized clinical trial is designed to recruit a total of 140 participants diagnosed with type II CSP, who will be randomly assigned to two equally sized groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment {15}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecruitment will be carried out through multiple approaches, including direct outreach to potential participants via outpatient clinics and departmental promotion at Qingdao Women and Children\u0026rsquo;s Hospital, as well as referrals from community hospitals. Participants diagnosed with type Ⅱ CSP will be identified via medical record review. Researchers will then contact eligible candidates through telephone or in-person communication to screen for study eligibility.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: allocation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSequence generation {16a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA professional statistician will generate random numbers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcealment mechanism {16b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA professional statistician will compile the random number sequence into an Excel spreadsheet. Study personnel (comprising physicians and nurses) have no access to group assignments prior to participant enrolment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation {16c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo investigators will simultaneously access the Excel spreadsheet using the participant\u0026apos;s enrollment number to verify the participant\u0026apos;s assigned group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: Blinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will be blinded {17a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlinding was not applicable, as this was an open-label study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure for unblinding if needed {17b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003en/a\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for assessment and collection of outcomes {18a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFollowing participant recruitment, a trained researcher will collect baseline data. This dataset will include key participant characteristics, such as age; parity; gravidity; number of prior cesarean deliveries; interval since the last cesarean delivery; fertility intentions; history of cesarean scar pregnancy (CSP) or placenta accreta spectrum (PAS); gestational age at admission; gestational sac (GS) size; presence of fetal cardiac activity; residual myometrial thickness (RMT); serum\u0026nbsp;\u0026nbsp;\u0026beta;-hCG levels; and clinical symptoms (e.g., vaginal bleeding or lower abdominal pain).\u003c/p\u003e\n\u003cp\u003eClinical outcome data will encompass: uterine depth; pituitrin administration and Foley catheter balloon placement; intraoperative blood loss; presence/absence of intrauterine adhesions; surgical duration; length of hospitalization (calculated as discharge date minus admission date); post-treatment vaginal bleeding duration; time to\u0026nbsp;\u0026beta;-hCG normalization; resumption of normal menstruation; and pregnancy outcomes. Data related to HIFU treatment will include total ablation energy, total treatment time, median treatment power, sonication time, and treatment intensity.\u003c/p\u003e\n\u003cp\u003eSafety indicators will include intraoperative complications (e.g., uterine perforation, water intoxication, massive hemorrhage, or surgical procedure modification) and HIFU treatment complications (e.g., lower abdominal pain, sciatica or gluteal pain, hematuria, skin injury, and nerve injury). Adverse events (AEs) will be graded for severity\u0026mdash;from mild-to-moderate (Grade 1-2) to severe (Grade 3-5)\u0026mdash;according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria[25].\u003c/p\u003e\n\u003cp\u003eThe results of the ultrasound examination will be \u0026nbsp; reviewed and approved by two experienced physicians, while the laboratory tests will be \u0026nbsp;conducted by the hospital\u0026apos;s qualified laboratory department.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to promote participant retention and complete follow-up {18b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.Emphasize the importance of follow-up through repeated communications prior to discharge.\u003c/p\u003e\n\u003cp\u003e2.Remind\u0026nbsp;participants\u0026nbsp;to attend follow-up appointments via the official WeChat account\u0026nbsp;and hospital follow-up system.\u003c/p\u003e\n\u003cp\u003e3.Streamline the workflow with advance scheduling, enabling\u0026nbsp;participants\u0026nbsp;to select weekend or off-peak hours for follow-up visits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData management {19}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch data will be stored in Microsoft Excel files on hospital intranet computers, which are password-encrypted and accessible only to authorized researchers. During data collection and management, researchers will ensure meticulous, timely, accurate, and comprehensive documentation of all relevant study data. Data will undergo regular checks by the quality controller, and participant personal information will not be recorded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidentiality {27}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEach participant will be assigned a unique study number, which will be utilized across all study-related documentation. Such documentation will remain accessible exclusively to the study investigators.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003en/a\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods for primary and secondary outcomes {20a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePer-protocol analyses will be conducted.\u0026nbsp;Intercurrent events include: study-unrelated events (such as upper respiratory tract infection) occurring during participants\u0026apos; hospitalization leading to prolonged length of hospital stay, and unplanned pregnancy occurring before the resumption of postoperative menstruation leading to inability to track menstrual resumption time. The secondary outcome indicators of such participants will not be included in the statistical analysis.\u003c/p\u003e\n\u003cp\u003eTo be included in the analysis, a participant must provide\u0026nbsp;data from the baseline and\u0026nbsp;the intraoperative blood loss. If a participant meets the withdrawal criteria, no data will be included in the analysis.\u0026nbsp;Normally distributed quantitative data will be expressed as mean and SD. Non-normally distributed variables will be expressed as median (interquartile range). Qualitative data will be expressed as counts and percentages.\u0026nbsp;Comparisons between groups will be conducted using the Student\u0026rsquo;s t-test, Wilcoxon rank test or\u0026nbsp;c\u003csup\u003e2\u003c/sup\u003e test.\u0026nbsp;Two-sided p\u0026nbsp;\u0026lt; 0.05 will be considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterim analyses {21b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the low risk associated with the study content, interim analysis will not be conducted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods for additional analyses (e.g. subgroup analyses) {20b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003en/a.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePer-protocol analyses will be conducted. Missing data will be handled using multiple imputation. Results derived from complete-case data (without missing observations) will be compared with those from imputed data to conduct a sensitivity analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to give access to the full protocol, participant level-data and statistical code {31c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request 3 months after the official publication of the research paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOversight and monitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the coordinating centre and trial steering committee {5d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQingdao Women and Children\u0026rsquo;s Hospital Ethics Committee and the State Key Laboratory of Ultrasound in Medicine and Engineering Academic Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the data monitoring committee, its role and reporting structure {21a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA Data Monitoring Committee (DSM) composed of one clinician, one statistician, and the secretary of the Ethics Committee of Qingdao Women and Children\u0026rsquo;s Hospital will be established. DSM members will conduct regular study monitoring, with the process maintained independently from investigators.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse event reporting and harms {22}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll AEs shall be collected, managed proactively in line with established treatment protocols, and serious adverse events (SAEs) reported to the Qingdao Women and Children\u0026rsquo;s Hospital Ethics Committee in a timely manner.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFrequency and plans for auditing trial conduct {23}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe frequency and procedures for auditing trial conduct will be annual, and the audit process will be independent of the investigators.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe communication plan for protocol amendments will be developed by researchers, formulated in accordance with internal hospital procedures and Good Clinical Practice (GCP) requirements. This plan aims to ensure transparent dissemination of amendment information to all relevant stakeholders, thereby safeguarding the study\u0026apos;s scientific validity as well as the rights and interests of trial participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination plans {31a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collection is anticipated to be finalized by June 2026. Research findings will be published in alignment with agreements with the funding body and institutional guidelines. Upon acceptance of the research findings for publication, the relevant data will be made publicly accessible via the website at http://www.cpc.unc.edu/projects/china.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn clinical practice, our primary goal has consistently been to identify safe, effective, minimally invasive, and fertility-preserving treatment modalities for\u0026nbsp;participants\u0026nbsp;with CSPs. Treatment decisions must be customized individually, considering the severity of symptoms, future family planning goals, physician expertise, and institutional resources.\u003c/p\u003e\n\u003cp\u003eHysteroscopy has demonstrated a relatively high success rate in treating\u0026nbsp;type Ⅰ\u0026nbsp;CSP, with surgical bleeding effectively controlled\u0026nbsp;[23].\u003csup\u003e\u0026nbsp;\u003c/sup\u003eHowever, the risk of complications, particularly massive hemorrhage, is heightened during hysteroscopic treatment, especially in grassroots-level hospitals or among physicians with limited clinical experience. HIFU delivers energy precisely to the implantation site of the GS at the cesarean scar through real-time ultrasound monitoring. It destroys trophoblastic cells and damages small blood vessels with diameters less than 2 mm by generating temperatures of 60\u0026ndash;100℃\u0026nbsp;[13]. No statistically significant difference was observed between HIFU and UAE in terms of treatment success rate\u0026nbsp;[14,16].\u0026nbsp;Furthermore, HIFU has a reduced impact on post-operative menstrual blood loss (MBL), making it a favorable treatment option for\u0026nbsp;participants\u0026nbsp;with fertility\u0026nbsp;intentions\u0026nbsp;[19,20].\u0026nbsp;Therefore, in this randomized clinical trial, our primary objective will be to assess the necessity of HIFU as a treatment option for\u0026nbsp;type Ⅱ\u0026nbsp;CSP to control intraoperative blood loss. Characteristics such as gestational age, size of the gestational sac, RMT, and pre-treatment serum \u0026beta;-hCG levels are identified as risk factors associated with intraoperative blood loss\u0026nbsp;[26].\u0026nbsp;Subsequently, we will analyze these characteristics and develop classifications to optimize the treatment strategy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol version and date: V-1.0 \u0026nbsp; \u0026nbsp;29th May, 2020.\u003c/p\u003e\n\u003cp\u003eThe recruitment began on July 12, 2020 and the recruitment work has been completed, but the follow-up of some participants\u0026apos; secondary assessment indicators (the pregnancy outcomes within two years) has not yet been carried out.\u003cstrong\u003e\u003cbr\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003eadverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003ecase report form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eCDFI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003ecolor doppler flow imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003cp\u003eGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003egood\u0026nbsp;clinical\u0026nbsp;practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003egestational sac\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eCSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003ecaesarean scar defect\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eCSP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003ecaesarean scar pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eCTCAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003ecommon terminology criteria for adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eDSM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003edata\u0026nbsp;monitoring\u0026nbsp;committee\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eHIFU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003ehigh-intensity focused ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eMBL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003emenstrual blood loss\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eMTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003emethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003ePAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003eplacenta accreta spectrum\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003ePEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003epolyethylene glycol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eRMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003eresidual myometrium thickness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003erandomized controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eSAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003eserious adverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eSOP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003estandard operating procedure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eUAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003euterine artery embolization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Professor Lian Zhang for editing this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions {31b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthor Changmei Sang:\u0026nbsp;designed the study, and wrote the manuscript.\u003c/p\u003e\n\u003cp\u003eAuthor Qiuling Shi:\u0026nbsp;performed statistical analysis, and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eAuthor Lei Zhao and Yanjun Kang: provided critical feedback on the study design.\u003c/p\u003e\n\u003cp\u003eAuthor Shuping Zhao:\u0026nbsp;designed the study,\u0026nbsp;provided critical feedback on the study design and edited the manuscript.\u003c/p\u003e\n\u003cp\u003eAuthor Zhibiao Wang:\u0026nbsp;supervised the project and contributed to the interpretation of results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding {4}\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFoundation of the State Key Laboratory of Ultrasound in Medicine and Engineering (Grant No:2020KFA3002)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials {29}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the researchers and authorized viewers have the right to access the final trial data set.\u0026nbsp;De-identified patient data generated or analyzed during this study are not publicly available due to privacy but may be made available upon reasonable request. Researchers who meet criteria for access to confidential data can contact the corresponding author at [email protected] after obtaining approval from the Institutional Ethics Committee of Qingdao Women and Children\u0026rsquo;s Hospital. A data sharing agreement will be required to ensure compliance with applicable laws and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate {24}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research is fully in accordance with the Declaration of Helsinki. This clinical trial has been approved by Qingdao Women and Children\u0026rsquo;s Hospital(ethics approval number: QFELL-KY-2020-33).Written informed consent to participate in the study will be obtained from all eligible participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication {32}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients and the public will not be involved in the design, recruitment, or conduct of this study. There are no plans to disseminate study results to participants, as providing research outcome feedback to participants is not standard practice in China. However, participants will be notified that they may access the final study results through our future published articles.The informed consent form is detailed in the attachment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests {28}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003einformation (optional)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMiller R, Gyamfi-Bannerman C. Cesarean scar ectopic pregnancy. Society For Maternal Fetal Medicine Consult Series;# 63. Am J Obstet Gynecol. 2022;B9\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiaz RM, Williams TR, Craig BM, et al. Cesarean scar ectopic pregnancy: Imaging features, current treatment options, and clinical outcomes. Abdom Imaging. 2015;40:2589\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJurkovic D, Hillaby K, Woelfer B, et al. First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment cesarean section scar. Ultrasound Obstet Gynecol. 2003;21:220\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeow KM, Huang LW, Lin YH, et al. Cesarean scar pregnancy: Issues in management. Ultrasound Obstet Gynecol. 2004;23:247\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFamily Planning Subgroup, Chinese Society of Obstetrics and Gynocology, Chinese Medical Association. Expert opinion of diagnosis and treatment of cesarean scar pregnancy (2016). Zhonghua fu chan ke za zhi. 2016;51:568\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChueh H-Y, Pai AH-Y, Su Y-Y, et al. Hysteroscopic removal, with or without laparoscopic assistance, of first-trimester cesarean scar pregnancy. Fertil Steril. 2022;117:643\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHameed MSS, Wright MS, Chern A. Scope and suction: Hysteroscopic-guided suction evacuation of cesarean scar pregnancy \u0026ndash; A safe and efficacious treatment for selected participants. Gynecol Minim Invasive Ther. 2023;12:72\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe Y, Wu X, Zhu Q, et al. Combined laparoscopy and hysteroscopy vs. uterine curettage in the uterine artery embolization-based management of cesarean scar pregnancy: A retrospective cohort study. BMC Womens Health. 2014;14:116.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrsi F, Arnone P, Chen W, et al. High intensity focused ultrasound ablation: A new therapeutic option for solid tumors. 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Outcomes of subsequent pregnancies in participants following treatment of cesarean scar pregnancy with high intensity focused ultrasound followed by ultrasound-guided dilation and curettage. Int J Hyperth. 2019;36:926\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Hua C. Is high-intensity focused ultrasound superior to uterine artery embolization in cesarean scar pregnancy and subsequent pregnancy outcomes? A meta-analysis of the Chinese population. J Minim Invasive Gynecol. 2023;30:180\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Wang L, Zhu X. Efficacy and safety of high-intensity focused ultrasound compared with uterine artery embolization in cesarean section pregnancy: A meta-analysis. J Minim Invasive Gynecol. 2023;30:446\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDai Y, Peng Y, Shi Q, et al. Comparison of menstruation recovery after ultrasound-guided suction curettage in participants with cesarean scar pregnancy pretreated using high-intensity focused ultrasound and uterine artery embolization. Int J Hyperth. 2023;40:2241686.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Yang B, Chen W, et al. Clinical efficacy and re-pregnancy outcomes of participants with previous cesarean scar pregnancy treated with either high-intensity focused ultrasound or uterine artery embolization before ultrasound-guided dilatation and curettage: A retrospective cohort study. BMC Pregnancy Childbirth. 2023;23:85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu X, Deng X, Wan Y, et al. High-intensity focused ultrasound combined with suction curettage for the treatment of cesarean scar pregnancy. Med (Baltim). 2015;94(18):e854.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBan Y, Shen J, Wang X, et al. Cesarean scar ectopic pregnancy clinical classification system with recommended surgical strategy. Obstet Gynecol. 2023;141:927\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu Q, Tang Y, Tian Q, et al. Clinical efficacy and safety analysis of different treatment options for cervical pregnancy. Int J Hyperth. 2023;40:2255757.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu B, Chi Y, Hu L, et al. Clinical study on the treatment of partial Ⅱ-type cesarean scar pregnancy by hysteroscopy. Prog Obstet Gynecol. 2020;29:141\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCommon Terminology Criteria for Adverse Events (CTCAE). Version 5. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWan X, Wang X, Feng Z, Zhou X, Han Z, Wu J, Xu H, Hu T. Analysis of Risk Factors for Intraoperative Bleeding in the Surgical Treatment of Cesarean Scar Pregnancy and Development of Predictive Models. Multidiscip Healthc. 2024;17:2021\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"High-intensity focused ultrasound, caesarean scar pregnancy, suction curettage, hysteroscopy, intraoperative bleeding","lastPublishedDoi":"10.21203/rs.3.rs-6379195/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6379195/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe incidence of caesarean scar pregnancy (CSP) has significantly increased due to the increasing prevalence of caesarean deliveries and advances in diagnostic imaging. However, no consensus has yet been reached on the optimal therapeutic approach. Type II CSP leads to disease heterogeneity, characterized by multiple treatment options and the absence of a unified therapeutic approach. Hysteroscopic treatment for CSP has demonstrated a notable success rate, particularly in cases of type I CSP. High-intensity focused ultrasound (HIFU) ablation has emerged as a novel, non-invasive treatment option that minimizes intraoperative blood loss. However, its use may be excessive in low-risk cases. Here, we report a protocol for a randomized clinical trial designed to evaluate the necessity of performing HIFU in CSP treatment when combined with suction curettage under hysteroscopic guidance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe aim to propose a randomized clinical trial that will enroll 140 participants. All participants will undergo surgical suction curettage guided by hysteroscopy, randomized into groups with or without HIFU pretreatment. Data on demographic characteristics, disease characteristics, ultrasound findings, and laboratory test results will be collected before the intervention. The primary outcome will be the intraoperative blood loss. Secondary outcomes will include the incidence of near haemorrhage, therapeutic success rates, subsequent pregnancy outcomes within a 2-year follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHysteroscopy has exhibited favorable therapeutic outcomes in the management of CSP, though it remains associated with a risk of intraoperative hemorrhage. HIFU has shown promise as a preoperative adjuvant modality. However, the comparative clinical advantages of standalone hysteroscopic intervention versus HIFU-assisted protocols are insufficiently explored in prospective clinical studies. This investigation seeks to assess both the standalone efficacy of hysteroscopic resection and the efficacy of combined therapy incorporating HIFU pretreatment for type II CSP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegistration number: ChiCTR2000034332\u003c/p\u003e\n\u003cp\u003eRegistration date: 2nd July 2020\u003c/p\u003e","manuscriptTitle":"Reducing Intraoperative Hemorrhage in Type Ⅱ Caesarean Scar Pregnancy: A Study Protocol Comparing High-Intensity Focused Ultrasound (HIFU) Pretreatment vs. Hysteroscopy-Guided Suction Curettage - An Open-Label, 1:1 Parallel-Group, Superiority-Design Investigator-Initiated Trial (IIT)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-02 06:41:32","doi":"10.21203/rs.3.rs-6379195/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-06-23T13:20:22+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-23T13:20:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-19T11:35:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-06-19T05:15:44+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor revision","date":"2025-06-04T10:33:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cf88cd8e-7fa8-4650-bffb-8e341b73b0d0","owner":[],"postedDate":"July 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-11T15:59:09+00:00","versionOfRecord":{"articleIdentity":"rs-6379195","link":"https://doi.org/10.1186/s13063-025-08967-8","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2025-08-06 15:57:01","publishedOnDateReadable":"August 6th, 2025"},"versionCreatedAt":"2025-07-02 06:41:32","video":"","vorDoi":"10.1186/s13063-025-08967-8","vorDoiUrl":"https://doi.org/10.1186/s13063-025-08967-8","workflowStages":[]},"version":"v1","identity":"rs-6379195","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6379195","identity":"rs-6379195","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}