ChiCTR2500102829 版本V1.0 版本创建时间2025/05/20 16:54:56 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：

 ChiCTR2500102829 

最近更新日期：

Date of Last Refreshed on：

 2025-05-20 16:54:49 

注册时间：

Date of Registration：

 2025-05-20 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

富血小板血浆及其衍生细胞外囊泡修复子宫内膜损伤治疗女性不孕症的机制研究和临床转化

Public title：

Mechanism and Clinical Transformation of Platelet-rich Plasma and Its Derived Extracellular Vesicles to Repair Endometrial Injury in Female Infertility

注册题目简写：

English Acronym：

研究课题的正式科学名称：

富血小板血浆及其衍生细胞外囊泡修复子宫内膜损伤治疗女性不孕症的机制研究和临床转化

Scientific title：

Mechanism and Clinical Transformation of Platelet-rich Plasma and Its Derived Extracellular Vesicles to Repair Endometrial Injury in Female Infertility

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：

董丹彤 

研究负责人：

张弘 

Applicant：

Dong Dantong 

Study leader：

Zhang Hong 

申请注册联系人电话：

Applicant telephone：

 +86 188 4576 5159

研究负责人电话：

Study leader's
telephone：

+86 138 1488 2907

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：

 dantongdong26@163.com

研究负责人电子邮件：

Study leader's E-mail：

 Szzhanghong126@126.com

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：

江苏省苏州市姑苏区三香路1055号

研究负责人通讯地址：

江苏省苏州市姑苏区三香路1055号

Applicant address：

No. 1055, Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province

Study leader's address：

No. 1055, Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province

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：

苏州大学附属第二医院

Applicant's institution：

The Second Affiliated Hospital of Soochow University

研究负责人所在单位：

苏州大学附属第二医院

Affiliation of the Leader：

The Second Affiliated Hospital of Soochow University

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：

 JD-LC2024023-I01

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：

苏州大学附属第二医院伦理委员会

Name of the ethic committee：

The Ethics Committee of The Second Affiliated Hospital of Soochow University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-04-23 00:00:00

伦理委员会联系人：

顾逸飞

Contact Name of the ethic committee：

Gu Yifei

伦理委员会联系地址：

江苏省苏州市姑苏区三香路1055号

Contact Address of the ethic committee：

No. 1055, Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 67784919

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：

苏州大学附属第二医院

Primary sponsor：

The Second Affiliated Hospital of Soochow University

研究实施负责（组长）单位地址：

江苏省苏州市姑苏区三香路1055号

Primary sponsor's address：

No. 1055, Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏省

市(区县)：

苏州市

Country：

China

Province：

Jiangsu Province

City：

Suzhou City

单位(医院)：

苏州大学附属第二医院

具体地址：

江苏省苏州市姑苏区三香路1055号

Institution
hospital：

The Second Affiliated Hospital of Soochow University

Address：

No. 1055, Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province

经费或物资来源：

自筹

Source(s) of funding：

Self-raised

研究疾病：

不孕症  

Target disease：

Infertility

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：

主要目的：探究富血小板血浆及其衍生细胞外囊泡治疗子宫内膜损伤性不孕症的临床疗效，为子宫内膜损伤的不孕患者需求新型疗法，提高其妊娠率及活产率。 次要目的：阐明子宫内膜损伤患者与内膜正常者的子宫内膜免疫细胞差异，并构建体外内膜炎症模型和内膜损伤的小鼠模型，验证PRP及PEVs是否通过靶向炎症部位而发挥修复子宫内膜损伤的功能，并探究其背后的治疗机理。努力推动PRP临床研究并力争实现新型内膜损伤性疾病免疫疗法的临床应用及转化。  

Objectives of Study：

Main Objective: To explore the clinical efficacy of platelet-rich plasma and its derived extracellular vesicles in the treatment of infertility caused by endometrial injury, in order to improve the pregnancy rate and live birth rate of infertility patients with endometrial injury. Secondary objective: To elucidate the differences of endometrial immune cells between patients with endometrial injury and those with normal endometrial injury, and to construct an in vitro endometrial inflammation model and a mouse model of endometrial injury, to verify whether PRP and PEVs can repair endometrial injury by targeting inflammation sites, and to explore the underlying therapeutic mechanism. To promote the clinical research of PRP and strive to realize the clinical application and transformation of novel immunotherapy for endometrial injury diseases.

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.治疗组：年龄20~40岁就诊于苏州大学附属第二医院生殖医学中心门诊，无避孕措施且规律性生活至少1年未孕的薄型子宫内膜患者，病例选择既往补充足量雌激素排卵期子宫内膜厚度仍＜7mm，无盆腔、内分泌及男方等其他不孕因素，既往有正常排卵，能规律行超声下监测排卵者，共80例。根据随机表法分为PRP组和PEVs组。 2.实验组：年龄20~40岁就诊于苏州大学附属第二医院生殖医学中心门诊患者，既往无避孕措施且规律性生活至少1年未孕，共20例。根据病史分为：（1）内膜损伤组：因内膜损伤性疾病，如中重度宫腔粘连、薄型子宫内膜、阿氏曼综合征等拟于我院行宫腔镜手术的患者，无盆腔、内分泌及男方等其他不孕因素者。（2）内膜正常组：因非内膜损伤原因，如输卵管梗阻、盆腔粘连等拟于我院行宫腹腔镜联合手术的患者，无内分泌及男方等其他不孕因素者。

Inclusion criteria

1. Treatment group: 20~40 years old patients with thin endometrium who were admitted to the outpatient clinic of the Reproductive Medicine Center of the Second Affiliated Hospital of Soochow University, had no contraceptive measures and had regular sexual life for at least 1 year, and the thickness of the endometrium during ovulation was still <7mm during ovulation supplemented with sufficient estrogen, and there were no other infertility factors such as pelvis, endocrine and man, and there were normal ovulation in the past, and ovulation was monitored regularly under ultrasound, a total of 80 cases. According to the randomization method, they were divided into PRP group and PEVs group. 2. Experimental group: 20 patients aged 20~40 years old who were admitted to the Reproductive Medicine Center of the Second Affiliated Hospital of Soochow University, who had no contraceptive measures and had no pregnancy for at least 1 year. According to the medical history, they were divided into: (1) endometrial injury group: patients who were to undergo hysteroscopic surgery in our hospital due to endometrial injury diseases, such as moderate to severe intrauterine adhesions, thin endometrium, Achmann's syndrome, etc., and those who did not have other infertility factors such as pelvis, endocrine and male side. (2) Normal endometrial group: patients who intend to undergo laparoscopic combined hysteroscopic surgery in our hospital due to non-endometrial injury, such as fallopian tube obstruction, pelvic adhesions, etc., without other infertility factors such as endocrine and male partners.

排除标准：

1.生殖系统先天或后天病变，如子宫颈解剖异常、子宫肌瘤、子宫畸形、子宫内膜结核、子宫内膜恶性病变等； 2.患有严重免疫系统、凝血系统疾病患者； 3.夫妇任意一方存在染色体异常或不明原因性不孕患者； 4.患有卵巢早衰、高泌乳素血症等内分泌异常的患者； 5.男方不孕因素如男方无精症、中重度少弱精症者； 6.心、肺、肝、肾等重要器官有严重原发性器质性病变的患者； 7.有激素依赖性恶性肿瘤者； 8.有精神疾病者。

Exclusion criteria：

1. Congenital or acquired lesions of the reproductive system, such as anatomical abnormalities of the cervix, uterine fibroids, uterine malformations, endometrial tuberculosis, endometrial malignant lesions, etc.; 2. Patients with severe immune system and coagulation system diseases; 3. Patients with chromosomal abnormalities or unexplained infertility in either spouse; 4. Patients with endocrine abnormalities such as premature ovarian failure and hyperprolactinemia; 5. Male infertility factors such as male azoospermia, moderate to severe oligoasthenospermia; 6. Patients with severe primary organic lesions of heart, lung, liver, kidney and other important organs; 7. Patients with hormone-dependent malignant tumors; 8. People with mental illness.

研究实施时间：

Study execute time：

从 From 2024-04-01 00:00:00至 To 2026-04-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-07-15 00:00:00 至 To 2026-01-01 00:00:00

干预措施：

Interventions：

组别：

治疗组-PRP组

样本量：

 40

Group：

Treatment group -PRP group

Sample size：

干预措施：

排除禁忌症后抽取患者外周静脉血20ml制作富血小板血浆（PRP），经B超引导下将制作好的PRP经子宫颈灌注入子宫腔中，宫腔灌注48小时后B超测量子宫内膜厚度、形态、血流及卵泡大小。

干预措施代码：

Intervention：

After excluding contraindications, 20ml of peripheral venous blood was extracted from the patient to make platelet-rich plasma (PRP).The prepared PRP was injected into the uterine cavity through the cervix under the guidance of B-ultrasound.The prepared PRP was injected into the uterine cavity through the cervix under the guidance of B-ultrasound.

Intervention code：

组别：

治疗组-PEVs组

样本量：

 40

Group：

Treatment group -PEVs group

Sample size：

干预措施：

排除禁忌症后抽取患者外周静脉血20ml制作血小板细胞外囊泡（PEVs）。经B超引导下将制作好的PEVs经子宫颈灌注入子宫腔中。宫腔灌注48小时后B超测量子宫内膜厚度、形态、血流及卵泡大小。

干预措施代码：

Intervention：

After excluding contraindications, 20ml of peripheral venous blood was extracted from the patient to make extracellular platelet vesicles (PEVs).The prepared PEVs was injected into the uterine cavity through the cervix under the guidance of B-ultrasound.The prepared PEVs was injected into the uterine cavity through the cervix under the guidance of B-ultrasound.

Intervention code：

组别：

实验组-内膜损伤组

样本量：

 10

Group：

Experimental group - endometrial injury group

Sample size：

干预措施：

取患者手术中部分子宫内膜组织，检测其淋巴细胞浸润及炎症因子分泌情况

干预措施代码：

Intervention：

Lymphocyte infiltration and secretion of inflammatory factors were detected by taking part of endometrial tissue during operation

Intervention code：

组别：

实验组-正常内膜组

样本量：

 10

Group：

Experimental group - normal endometrium group

Sample size：

干预措施：

取患者手术中部分子宫内膜组织，检测其淋巴细胞浸润及炎症因子分泌情况

干预措施代码：

Intervention：

Lymphocyte infiltration and secretion of inflammatory factors were detected by taking part of endometrial tissue during operation

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江苏省 

市(区县)：

 苏州市 

Country：

China

Province：

Jiangsu

City：

Suzhou

单位(医院)：

 苏州大学附属第二医院 

单位级别：

 三甲 

Institution
hospital：

The Second Affiliated Hospital of Soochow University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

临床妊娠

指标类型：

主要指标

Outcome：

Clinical pregnancy

Type：

Primary indicator

测量时间点：

排卵后或胚胎移植后28天

测量方法：

血HCG检测、经阴道超声

Measure time point of outcome：

After ovulation or 28 days after embryo transfer

Measure method：

Blood HCG detection,transvaginal ultrasound

指标中文名：

子宫内膜厚度

指标类型：

次要指标

Outcome：

Endometrial thickness

Type：

Secondary indicator

测量时间点：

宫腔灌注后48小时

测量方法：

经阴道超声

Measure time point of outcome：

48 hours after intrauterine perfusion

Measure method：

Transvaginal ultrasound

指标中文名：

子宫内膜类型

指标类型：

次要指标

Outcome：

Endometrial type

Type：

Secondary indicator

测量时间点：

宫腔灌注后48小时

测量方法：

经阴道超声

Measure time point of outcome：

48 hours after intrauterine perfusion

Measure method：

Transvaginal ultrasound

指标中文名：

子宫内膜下血流分型

指标类型：

次要指标

Outcome：

Subendometrial blood flow classification

Type：

Secondary indicator

测量时间点：

宫腔灌注后48小时

测量方法：

经阴道超声

Measure time point of outcome：

48 hours after intrauterine perfusion

Measure method：

Transvaginal ultrasound

指标中文名：

生化妊娠

指标类型：

次要指标

Outcome：

Biochemical pregnancy

Type：

Secondary indicator

测量时间点：

排卵后或胚胎移植后14天

测量方法：

血HCG检测

Measure time point of outcome：

After ovulation or 14 days after embryo transfer

Measure method：

Blood HCG detection

指标中文名：

卵泡大小

指标类型：

次要指标

Outcome：

Follicle size

Type：

Secondary indicator

测量时间点：

宫腔灌注后48小时

测量方法：

经阴道超声

Measure time point of outcome：

48 hours after intrauterine perfusion

Measure method：

Transvaginal ultrasound

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

静脉血

Sample Name：

Blood

Tissue：

Venous blood

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

子宫内膜组织

组织：

子宫腔

Sample Name：

Endometrial tissue

Tissue：

Uterine cavity

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：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 20 岁 years
最大 Max age 40 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）：

简单随机法，由研究团队固定成员用随机数字表法产生随机数列

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

Simple randomization method, a random sequence of numbers is generated by a fixed member of the research team using a random number table method

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：

对研究参与者和评估者设盲

Blinding：

Study participants and evaluators were blinded

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

是Yes

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）：

研究结束后，通过ResMan(www.medresman.org.cn)方式共享

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

After the end of the study, it was shared by ResMan (www.medresman.org.cn).

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：

CRF;EDC

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

CRF;EDC

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-05-20 16:54:49