Status
Conditions
Treatments
About
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.
Full description
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
Exclusion criteria
Withdrawal criteria
Interventions
The patient undergoes lower abdominal liposuction (with an aspirate volume of approximately 100-360 mL) under general anesthesia administered. Immediately after the procedure at the operating room bedside, ADRCs are prepared using Celution® system (Cytori Therapeutics, Inc., Shanghai, China) and subjected to quality control as follows:
Firstly, under aseptic technique, the lipoaspirate is injected into the processing container. Following the device's prompts, the automatic cleaning procedure is initiated. The volume of composite enzyme indicated by the device is aspirated and added to the processing container. The automated system then proceeds to handle key steps including separation, centrifugation, and resuspension of the cellular fraction, ensuring standardized and consistent processing of ADRCs. Following 90-120 minutes of automated processing, the operator draws up a measured 5mL aliquot of ADRCs suspension. Of this volume, 0.5mL is retained for quality control testing, including assessments of cell count, viability, and surface marker expression; the remaining 4.5mL is used for injection into both of the patient's ovaries, with 2-2.5mL administered per ovary.
After the procedure, the patient remains supine for 30 minutes, with close monitoring for local reactions (e.g., abdominal pain, bleeding) or systemic reactions (e.g., allergic reactions). The patient is discharged if no abnormalities are observed.
Safety evaluation and AEs Monitoring To assess the safety profile of this trial, all adverse events including local or systemic reactions, will be closely tracked with detailed documentation of their onset, duration, severity, and frequency.
Risk mitigation strategies
The trial encompasses three key procedures: abdominal liposuction, automated preparation of ADRCs, and intraovarian ADRCs injection. Targeted strategies are implemented to mitigate risks across these steps:
For abdominal liposuction and intraovarian injection, preoperative measures include establishing intravenous access to enable rapid emergency response, while operators are required to master local anatomical details to avoid critical blood vessels and nerves. Intraoperatively, gentle manipulation is emphasized to reduce vascular injury and prevent accidental intravascular entry of adipose tissue or ADRCs; prior to injection, aspiration is performed to confirm the needle is not within a vessel, and a retrograde injection technique is adopted for ADRCs delivery.
In the automated ADRCs preparation process, standardized material preparation and pre-procedural equipment checks (conducted by designated staff) are mandatory. The automated system undergoes regular maintenance and calibration to ensure stable operation. Should equipment or consumable issues arise during preparation, the manufacturer's technical support team will be promptly consulted for troubleshooting.
Surveillance and management of potential AEs
Potential adverse events may arise from liposuction, injection, or ADRCs preparation, with corresponding management protocols in place:
For events related to liposuction or injection, fat embolism-though extremely rare-represents a critical concern, potentially presenting as chest tightness, visual impairment, or severe localized pain. Upon such presentation, the procedure will be halted immediately, and clinicians will administer symptomatic treatment.
Other potential reactions include bleeding, infection, abdominal pain, or allergic responses. Bleeding will be managed with hemostatic agents as needed, while infection prevention relies on strict adherence to aseptic techniques. Mild abdominal pain typically resolves with rest, but severe pain may require analgesics after definitive diagnosis. Allergic reactions, though rare, will be monitored closely, with protocols in place to address severe manifestations.
For AEs linked to ADRCs preparation, equipment or consumable malfunctions that could compromise product quality will be documented, and the manufacturer's support team will be engaged immediately to resolve issues, ensuring ADRCs safety before injection.
Continuous monitoring will be maintained throughout the procedure and post-procedural recovery to enable timely identification and management of any adverse events, prioritizing participant safety.
Outcome Measurements Primary composite endpoints
Secondary endpoints
Safety endpoint Incidence of treatment-emergent adverse events (TEAEs) related to ADRCs injection within 12 months post-treatment.
Statistical Analysis Methods The statistical analysis plan will be developed by the biostatistician and principal investigator based on the study protocol and finalized as a document prior to database lock. The primary endpoints are "Clinical Pregnancy" or "FSH, AMH, and AFC levels at various post-procedural time points". The full analysis set will be used for data analysis, which includes all enrolled subjects. For subjects who discontinue the study, data from their last follow-up visit will be carried forward as the final data point for analysis (Last Observation Carried Forward). Statistical analyses will be performed using SAS or R software.
Primary endpoint analysis
Secondary endpoint analysis
Safety Analysis
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
25 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal