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.
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.
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.
Single group
Autologous Adipose-Derived Regenerative Cells (ADRCs) Intraovarian Injection
DeviceUnder general anesthesia, patients undergo lower abdominal liposuction (aspirate: 100-360 mL). ADRCs are immediately prepared bedside using the Celution® system (Cytori Therapeutics): Lipoaspirate is processed in a sterile container with automated separation, centrifugation, and resuspension (90-120 min). From the 5mL ADRCs suspension obtained, 0.5mL is reserved for QC (cell count/viability/surface markers); 4.5mL is injected bilaterally into ovarian stroma (2-2.5mL/ovary). Post-procedure, patients are monitored supine for 30 min for local/systemic reactions before discharge if stable.
Cumulative Clinical Pregnancy Rate
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
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.
12-Month Change in Ovarian Reserve Markers for non-pregnant patients
FSH, AMH, and AFC (assessed on days 2-5 of menstruation) will be compared with baseline and analyzed by paired t-test.
Menstrual Pattern Recovery for non-pregnant patients
It will be documented at 1, 2, 3, 6, and 12 months post-treatment and analyzed using Cochran's Q test for binary outcomes ("recovered" vs. "not recovered").
Ovarian Volume Change for non-pregnant patients
The average bilateral ovarian volume (measured by ultrasound) will be measured at 1, 2, 3, 6, and 12 months post-treatment and analyzed via repeated-measure mixed-effects model
Safety endpoint
Incidence of treatment-emergent adverse events (TEAEs) related to ADRCs injection within 12 months post-treatment.
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Cytori Therapeutics
Lead sponsor
Peking University People's Hospital
Collaborator
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