A standardized protocol for autologous stromal vascular fraction therapy in refractory thin endometrium and a prospective single-arm clinical study.

backgroundThin endometria are still a big obstacle in fertility treatments and often lead to poor pregnancy outcomes. Stromal vascular fraction (SVF) therapy has shown promise in the improvement of endometrial thickness. However, its preparation and treatment protocols lack standardization, and its efficacy and safety in assisted reproductive technology (ART) need to be further investigated.

methodsThrough the collaboration of plastic surgery, obstetrics and gynecology as well as Good Manufacturing Practice (GMP) laboratory teams, an efficient protocol was developed for the completion of liposuction, hysteroscopy, SVF preparation, quality control and intrauterine infusion on the same day of treatment. This single-center, prospective, self-controlled prospective cohort study was performed at Peking University Third Hospital. Eligible participants (aged 20-45) were patients who had an endometrial thickness of < 7 mm on the day of ovulation or endometrial transformation in hormone replacement cycles. The primary outcome was the proportion of patients whose endometrial thickness increased to 7 mm. All participants were followed up during the first three menstrual cycles after treatment via hospital follow-up visits and then by telephone for the next two years. All adverse events related to the operation were recorded. Outcomes, including menstrual volume, endometrial thickness, pregnancy rate and offspring health, were measured. This study was registered with Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000035126.

resultsStandard SVF preparation and treatment procedures can be efficiently completed within six hours. From December 4, 2020 to August 5, 2022, 35 patients were treated with SVF intrauterine perfusion, and 30 were followed up after the intervention. Participants were aged 35.6 ± 3.85 on average. They had a mean body mass index (BMI) of 24.88 ± 2.05 kg/m2 and a mean pre-treatment endometrial thickness of 5.1 ± 0.94 mm. The SVF used for treating patients had a cell viability of over 90%. After SVF therapy, the mean endometrial thickness at three cycles after treatment was 5.8 ± 0.85 mm, 6.9 ± 1.33 mm and 6.8 ± 1.68 mm, respectively, with a significant increase compared with pre-treatment thickness (p < 0.05). At three months, 18 (51%) of 35 patients achieved an endometrial thickness of 7 mm or above. This increased to 21 (60%) patients two years later. Notably, 11 participants conceived, among whom six gave birth. No adverse events were reported.

conclusionsA streamlined and efficient protocol was established for SVF preparation and treatment, which ensured the effective patient management and consistent production of high-quality SVF. Autologous SVF intrauterine infusion is promising as a safe and effective therapeutic option for patients with refractory thin endometrium. The absence of adverse effects within this cohort over the two-year follow-up period indicates a good safety profile for SVF therapy.