Safety and Efficacy of Autologous Adipose-Derived Regenerative Cells (ADRCs) Injection for Improving Diminished Ovarian Reserve (ARISE) - A Single-arm Self-controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 25
- 主要终点
- Cumulative Clinical Pregnancy Rate
研究概览
简要总结
Diminished Ovarian Reserve (DOR) poses significant challenges to fertility and hormonal health, with limited effective treatments. This prospective, self-controlled clinical study evaluates the safety and efficacy of intraovarian injection of autologous Adipose-Derived Regenerative Cells (ADRCs) to improve ovarian function in reproductive-aged women with DOR.
The ARISE trail enrolled 25 women aged <40 years meeting clinical criteria for DOR, excluding those with severe comorbidities. Autologous adipose tissue was harvested via liposuction, and ADRCs were isolated using the Celution® system before bilateral ovarian medulla injection. Participants underwent follow-up at multiple time points up to 12 months post-procedure.
Primary outcomes included cumulative clinical pregnancy rates (natural or via ART) within 12 months and 1-, 2-, 3-, 6-month changes in ovarian reserve markers (FSH, AMH, antral follicle count) in non-pregnant patients. Secondary outcomes encompassed ovarian reserve markers at 12 months, as well as menstrual pattern recovery and ovarian volume changes at 1, 2, 3, 6, 12 months. Adverse events (AEs) will be monitored at each time point.
Statistical analyses followed standard principles, including mixed models for repeated measures and appropriate tests for subgroup comparisons. Sample size was determined based on feasibility and prior effect size estimates to ensure adequate power.
This study provides novel insights into regenerative therapies for DOR, emphasizing safety and functional restoration.
详细描述
Trial design and setting This prospective, self-controlled clinical trial aims to evaluate the efficacy and safety of autologous ADRCs injection in improving DOR. A total of 25 patients diagnosed with DOR at the outpatient clinic of the Reproductive Medicine Center, Peking University People's Hospital, who meet the predefined inclusion and exclusion criteria, will be enrolled in the study.
Autologous adipose tissue will be harvested from patients via liposuction, and the automated autologous adipose tissue processing system Celution® system will be applied to process the adipose tissue for autologous ADRCs isolation and concentration. Subsequently, autologous ADRCs will be injected into the medulla of both ovaries (2-2.5 mL per ovary). Patients will undergo follow-up assessments at 1, 2, 3, 6, and 12 months to evaluate the safety and efficacy of the treatment.
Eligibility Criteria Potential subjects will undergo assessments within 4 weeks prior to the intervention, including medical history and physical examination, menstrual pattern assessment, and ovarian reserve testing (on days 2-5 of the menstrual cycle) involving transvaginal ultrasound for ovarian volume and AFC measurement, as well as serum hormonal assays to quantify AMH and FSH.
Inclusion criteria
- Female patients aged 20-39 years.
- Diagnosed with DOR, defined as AFC < 7 and/or AMH ≤ 1.1 ng/mL.
- FSH ≤ 40 U/L.
- Have signed informed consent for the clinical trial.
- In good general health and able to tolerate local anesthesia, liposuction, oocyte retrieval, as well as pregnancy and childbirth.
- Without relative contraindications to fertility such as hereditary tumor-related diseases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients aged 20-39 years.
- •Diagnosed with DOR, defined as AFC < 7 and/or AMH ≤ 1.1 ng/mL.
- •FSH ≤ 40 U/L.
- •Have signed informed consent for the clinical trial.
- •In good general health and able to tolerate local anesthesia, liposuction, oocyte retrieval, as well as pregnancy and childbirth.
- •Without relative contraindications to fertility such as hereditary tumor-related diseases.
排除标准
- •Presence of thyroid disorders.
- •Body Mass Index (BMI) < 18 kg/m².
- •Confirmed pregnancy (positive β-hCG with ultrasound confirmation of embryo implantation).
- •History of autoimmune diseases.
- •Family history of ovarian tumors.
- •Prior pelvic or systemic radiotherapy for cancer treatment.
- •Positive serology/virology results for human immunodeficiency virus (HIV), Hepatitis C, Hepatitis B, Syphilis, human papillomavirus (HPV), or abnormal ThinPrep cytology (TCT).
- •DOR caused by genetic disorders.
- •Reproductive system pathologies including polycystic ovary syndrome (PCOS), adenomyosis, uterine fibroids ≥ 5 cm, endometrial carcinoma, or uterine malformations.
- •Contraindications to liposuction.
- •Abnormal semen analysis of the male partner precluding natural conception or conception via assisted reproductive technology (ART).
- •Malignancy-related conditions such as active malignancy without complete remission or chemotherapy administration within the past 6 months.
结局指标
主要结局
Cumulative Clinical Pregnancy Rate
时间窗: 12 months
Cumulative Clinical Pregnancy Rate within 12 months post-treatment: Conception via natural pregnancy or assisted reproductive technology which is confirmed by fetal cardiac activity on ultrasound. Subgroup analysis will compare natural pregnancy with conception via assisted reproductive technology.
Change in Ovarian Reserve Markers for non-pregnant patients
时间窗: 1 month, 2 months, 3 months, 6 months
Measured at 1, 2, 3, and 6 months, with parameters assessed on menstrual days 2-5 including FSH, AMH and AFC. These will be analyzed using a repeated-measure mixed-effects model, with data censoring applied after pregnancy.
次要结局
- 12-Month Change in Ovarian Reserve Markers for non-pregnant patients(12 months)
- Menstrual Pattern Recovery for non-pregnant patients(1 month, 2 months, 3 months, 6 months, 12 months)
- Ovarian Volume Change for non-pregnant patients(1 month, 2 months, 3 months, 6 months, 12 months)