ChiCTR2500114010 版本V1.0 版本创建时间2025/12/05 11:19:20 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2500114010 

最近更新日期：

Date of Last Refreshed on：

 2025-12-05 11:19:14 

注册时间：

Date of Registration：

 2025-12-05 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

卵巢低反应患者自体细胞卵巢注射随机对照研究

Public title：

A Randomized Controlled Study on Autologous Cell Ovarian Injection in Patients with Poor Ovarian Response

注册题目简写：

English Acronym：

研究课题的正式科学名称：

卵巢低反应患者自体细胞卵巢注射随机对照研究

Scientific title：

A Randomized Controlled Study on Autologous Cell Ovarian Injection in Patients with Poor Ovarian Response

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

张馨雨 

研究负责人：

马彩虹 

Applicant：

Xinyu Zhang 

Study leader：

Caihong Ma 

申请注册联系人电话：

Applicant telephone：

 +86 176 1023 1860

研究负责人电话：

Study leader's
telephone：

+86 176 1023 1860

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 xinyu_zhang9284@pku.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 macaihong@bjmu.edu.cn

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

北京海淀区花园北路49号

研究负责人通讯地址：

北京海淀区花园北路49号

Applicant address：

49 North Garden Rd.,Haidian District Beijing 100191,P.R.China

Study leader's address：

49 North Garden Rd.,Haidian District Beijing 100191,P.R.China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

北京大学第三医院

Applicant's institution：

Peking University Third Hospital

研究负责人所在单位：

北京大学第三医院

Affiliation of the Leader：

Peking University Third Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 (2025)医伦审第(777-02)号

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

北京大学第三医院医学科学研究伦理委员会

Name of the ethic committee：

Peking University Third Hospital Medical Science Research Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-11-25 00:00:00

伦理委员会联系人：

洪雪

Contact Name of the ethic committee：

Xue Hong

伦理委员会联系地址：

北京海淀区花园北路49号

Contact Address of the ethic committee：

49 North Garden Rd.,Haidian District Beijing 100191,P.R.China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 10 8226 6872

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

北京大学第三医院

Primary sponsor：

Peking University Third Hospital

研究实施负责（组长）单位地址：

北京海淀区花园北路49号

Primary sponsor's address：

49 North Garden Rd.,Haidian District Beijing 100191,P.R.China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

北京大学第三医院

具体地址：

北京海淀区花园北路49号

Institution
hospital：

Peking University Third Hospital

Address：

49 North Garden Rd.,Haidian District Beijing 100191,P.R.China

经费或物资来源：

北京研究型病房卓越计划项目（BRWEP2024W094090102）

Source(s) of funding：

Beijing Research Ward Excellence Program(BRWEP2024W094090102)

研究疾病：

卵巢低反应  

Target disease：

Poor ovarian response

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

卵巢低反应（Poor ovarian response, POR）是卵巢对促性腺激素刺激反应不良的病理状态, 主要表现为在卵巢刺激周期中发育的卵泡少、周期取消率高、获卵数少和临床妊娠率低。早发性卵巢功能不全（POI）是其中的特殊类型，临床最难治疗的不孕症疾病之一。POR及POI在我国育龄女性的发病率逐年上升，是生殖医学领域的重点和难点问题。新型卵巢局部细胞治疗可以改善卵泡发育微环境、促进“休眠”的原始卵泡发育及排卵、改善卵母细胞质量。本研究拟对POR及POI患者进行自体脂肪血管基质组分（SVF）或自体富血小板血浆（PRP）卵巢局部注射治疗，开展前瞻性探索研究评估该临床技术的安全性，随后开展前瞻随机对照试验评估自体脂肪血管基质组分（SVF）或自体富血小板血浆（PRP）卵巢局部注射治疗对改善卵巢储备及IVF-ET结局的安全性和有效性。该研究有望从自体细胞治疗的角度，改善POR患者的生育力。自体SVF和PRP卵巢注射技术不涉及伦理障碍，易于诊疗流程及操作体系规范化，适用于临床转化及推广。  

Objectives of Study：

Poor ovarian response (POR) is a pathological state where the ovaries do not respond well to the stimulation of gonadotropins. It is mainly characterized by a small number of developing follicles, a high cancellation rate of the ovarian stimulation cycle, a low number of retrieved oocytes, and a low clinical pregnancy rate. Premature ovarian insufficiency (POI) is a special type of this condition and is one of the most difficult infertility diseases to treat. The incidence of POR and POI in reproductive-aged women in China is increasing year by year, making them key and challenging issues in reproductive medicine. New local ovarian cell therapy can improve the microenvironment for follicle development, promote the development and ovulation of "dormant" primordial follicles, and improve the quality of oocytes. This study intends to conduct autologous fat vascular matrix components (SVF) or autologous platelet-rich plasma (PRP) local injection therapy for patients with POR and POI, and conduct a prospective exploratory study to evaluate the safety of this clinical technique. Subsequently, a prospective randomized controlled trial will be conducted to evaluate the safety and efficacy of autologous fat vascular matrix components (SVF) or autologous platelet-rich plasma (PRP) local injection therapy in improving ovarian reserve and IVF-ET outcomes. This study is expected to improve the fertility of patients with POR from the perspective of autologous cell therapy. The autologous SVF and PRP local injection techniques do not involve ethical barriers, are easy to standardize the diagnosis and treatment process and operation system, and are suitable for clinical translation and promotion.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1、在北医三院生殖医学中心就诊拟进行IVF治疗的有生育要求的女性 2、年龄≤45岁，不孕年限≥1年 3、符合POI诊断标准或符合POR的波塞冬诊断标准 4、既往控制性促排卵获卵数≤3个和（或）无可移植胚胎和（或）既往胚胎着床失败≥2次 5、子宫及双侧附件健全 6、 BMI 22-29kg /㎡ 7、受试者须对本研究知情同意，并自愿签署书面知情同意书。

Inclusion criteria

1. Women who have fertility requirements and are seeking IVF treatment at the Reproductive Medicine Center of Peking University Third Hospital 2. Age <= 45 years old, infertility duration >= 1 year 3. Meeting the diagnostic criteria for POI or the Poseidon diagnostic criteria for POR 4. Previous controlled ovarian stimulation resulted in no more than 3 oocytes retrieved and/or no transplantable embryos and/or previous embryo implantation failure >= 2 times 5. Uterus and bilateral adnexa are intact 6. BMI 22 - 29 kg/m^2 7. Participants must have given informed consent for this study and voluntarily signed a written informed consent form.

排除标准：

1、先天性生殖器官发育异常 2、脓毒血症、血小板功能障碍综合征和重度血小板减少等凝血功能障碍或其他血液系统疾病 3、患有自身免疫性疾病或其他内分泌疾病，甲状腺功能异常且未控制 4、附件区有尚未明确良恶性质的肿块 5、合并严重的心脑血管疾病、恶性肿瘤、造血系统疾病及精神疾病者，重要器官功能不全患者 6、近2周内使用全身皮质激素者、近48h内使用阿司匹林等抗血小板药物者 7、处于急性炎症期 8、筛选期间合并有静脉血栓或肺栓塞病史者

Exclusion criteria：

1. Congenital abnormalities of reproductive organs 2. Septicemia, platelet dysfunction syndrome and severe thrombocytopenia and other coagulation disorders or other hematological diseases 3. Suffering from autoimmune diseases or other endocrine diseases, with abnormal thyroid function and uncontrolled condition 4. Having a mass in the adnexal area with an unclear benign or malignant nature 5. Complicated with severe cardiovascular and cerebrovascular diseases, malignant tumors, hematological diseases and mental disorders, patients with impaired function of important organs 6. Those who have used systemic corticosteroids within the last 2 weeks, or used antiplatelet drugs such as aspirin within the last 48 hours 7. In the acute inflammatory stage 8. Those with a history of venous thrombosis or pulmonary embolism during the screening period

研究实施时间：

Study execute time：

从 From 2025-12-15 00:00:00至 To 2027-11-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-12-15 00:00:00 至 To 2027-11-01 00:00:00

干预措施：

Interventions：

组别：

对照组

样本量：

 66

Group：

Control Group

Sample size：

干预措施：

按照常规方案进行，进入IVF周期。

干预措施代码：

Intervention：

Following the conventional protocol, proceed to the IVF cycle.

Intervention code：

组别：

PRP组

样本量：

 66

Group：

PRP Group

Sample size：

干预措施：

于月经周期第7-9天在超声引导下，经阴道穿刺，双侧卵巢皮质下注射进行PRP给药，每侧卵巢3个给药点，每个点位0.5ml，每侧卵巢给药体积共计1.5ml，连续注射1-3个周期，根据患者具体病情决定。注射后受试者平卧2h，观察有无不良事件。随后进入IVF周期。

干预措施代码：

Intervention：

On the 7th to 9th day of the menstrual cycle, under ultrasound guidance, a transvaginal puncture was performed to inject PRP into the cortical layer of both ovaries. There were 3 injection points on each side of the ovary, with 0.5ml injected at each point. The total volume injected for each side of the ovary was 1.5ml. This process was repeated for 1 to 3 cycles, depending on the specific condition of the patient. After the injection, the subjects were required to lie flat for 2 hours and the occurrence of adverse events was observed. Then, they entered the IVF cycle.

Intervention code：

组别：

SVF组

样本量：

 66

Group：

SVF Group

Sample size：

干预措施：

手术当天，首先进行下腹部脂肪抽吸术（100ml，最终以实际获得数量为准），用于制备SVF，对SVF内细胞进行计数，并在北医三院干细胞中心完成SVF制备和质检。检查完毕后，在阴道超声引导下，经阴道穿刺、双侧卵巢局部给药；给细胞量为（1-2）×107/每侧卵巢。每侧卵巢3个给药点，每个点位330±10μl，每侧卵巢给药体积共计1ml。注射后受试者平卧2h，观察有无不良事件。

干预措施代码：

Intervention：

On the day of the surgery, the first procedure was the lower abdominal fat aspiration (100ml, with the actual amount to be determined), which was used to prepare SVF. The cells within the SVF were counted, and the SVF preparation and quality inspection were completed at the Stem Cell Center of Peking University Third Hospital. After the examination, under vaginal ultrasound guidance, a vaginal puncture was performed and local administration was given to both ovaries; the amount of cells administered to each ovary was (1-2) × 107 per side. There were 3 administration points on each ovary, with 330 ± 10 μl at each point, and the total volume of administration for each ovary was 1ml. After the injection, the subjects were asked to lie flat for 2 hours and the occurrence of adverse events was observed.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China

Province：

Beijing

City：

单位(医院)：

 北京大学第三医院 

单位级别：

 三甲 

Institution
hospital：

Peking University Third Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

获卵数

指标类型：

主要指标

Outcome：

Number of retrieved oocytes

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

血抗苗勒氏管激素（AMH）水平

指标类型：

次要指标

Outcome：

Blood anti-Müllerian hormone (AMH) level

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

窦卵泡数量（AFC）

指标类型：

次要指标

Outcome：

Number of antral follicles (AFC)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

临床妊娠率

指标类型：

次要指标

Outcome：

clinical pregnancy rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

颗粒细胞

组织：

Sample Name：

Granule cells

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 45 岁 years

性别：

女性

Gender：

Female

随机方法（请说明由何人用什么方法产生随机序列）：

随机分配方案的制定：采用区组随机分配方案，区组长度动态的采用4和6，利用R软件生成随机表， SVF治疗组和对照组的比例为1:1。

Randomization Procedure (please state who generates the random number sequence and by what method)：

The formulation of the random allocation scheme: A block random allocation scheme was adopted. The block length was dynamically set to 4 and 6. A random table was generated using R software. The ratio of the SVF treatment group to the control group was 1:1.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

由于治疗方案的特殊性，本研究对评估者采用盲法，即术后随访中采集病史的随访人员及超声评估医师，隐藏分组结果。对受试者和研究者无法采用盲法。

Blinding：

Due to the particularity of the treatment plan, in this study, a blind method was adopted for the assessors, that is, the interviewers who collected the medical history during the postoperative follow-up and the ultrasound assessment physicians concealed the group results. However, this blind method could not be applied to the subjects and the researchers.

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

否

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

None

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

数据管理质量控制：制定CRF表及专人填写、定期审查，基因测序数据云存储、记录、标识等，确保数据的准确性、真实性、完整性。随访管理质量控制：建立多途径随访方式(门诊随访、医患沟通群、电话随访等)，专人负责并及时做好随访记录，失访率应控制在20%以内。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Data management quality control: Develop CRF forms and have designated personnel fill them out, conduct regular reviews, store, record, and identify genetic sequencing data in the cloud, ensuring the accuracy, authenticity, and completeness of the data. Follow-up management quality control: Establish multiple follow-up methods (outpatient follow-up, doctor-patient communication groups, telephone follow-up, etc.), have dedicated personnel responsible for it and promptly complete the follow-up records, with the loss rate controlled within 20%.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2025-12-05 11:19:14