Autologous Adipose-Derived Stem Cell Therapy for Ovarian and Endometrial Regeneration in Infertile Patients: A Single-Center Pilot Study

Abstract

Background: Diminished ovarian reserve (DOR) and refractory thin endometrium present major therapeutic challenges in assisted reproductive technology (ART). Conventional treatments frequently yield suboptimal outcomes, prompting growing interest in regenerative strategies such as autologous adipose-derived stem cell (ADSC) transplantation. This study aimed to evaluate the clinical efficacy and safety of autologous ADSC transplantation for ovarian function and endometrial regeneration in infertile women with DOR or refractory endometrium undergoing ART.
Methods: In this retrospective, single-center pilot study conducted between July 2023 and January 2026 at a tertiary reproductive center in Tbilisi, Georgia, 25 infertile women were evaluated. Twenty patients with DOR who met the Bologna criteria received transvaginal ultrasound-guided intraovarian ADSC injection, and 5 patients with refractory thin endometrium (<7 mm) received intrauterine catheter-guided delivery. Patients with elevated malignancy markers (CA-125, HE4, or abnormal ROMA index) were excluded. Interventions involved minimally invasive lipoaspiration followed by enzymatic isolation of stromal vascular fraction (SVF) containing ADSCs. Primary outcomes included changes in antral follicle count (AFC), follicular development, and endometrial thickness (EMT). Secondary outcomes included restoration of trilaminar morphology, clinical pregnancy rates, and adverse events.

Results: The mean (SD) age was 40.0 (5.1) years in the ovarian cohort and 42.8 (5.4) years in the endometrial cohort. Following intraovarian ADSC transplantation, mean (SD) AFC increased significantly from 3.0 (2.6) to 3.9 (2.7) (P < 0.01), and mean (SD) dominant follicle count improved from 0.4 (0.6) to 1.6 (0.8) (P < 0.01). In the endometrial cohort, mean (SD) EMT increased from 6.1 (1.3) mm to 7.5 (2.2) mm (P = 0.62), with trilaminar morphology restored in 3 of 5 patients (60%). One clinical pregnancy was achieved in the endometrial cohort, and one ongoing pregnancy was documented in the ovarian cohort. No major procedural complications or serious adverse events occurred.

Conclusions: Autologous ADSC transplantation was associated with improved ovarian activity and  enhanced endometrial development in selected infertile women with DOR or refractory thin endometrium. While these preliminary findings suggest ADSC therapy represents a promising adjunctive regenerative strategy in reproductive medicine, larger prospective randomized controlled studies are required to establish efficacy, long-term safety, and reproductive outcomes.