Safety and efficacy fi cacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial

Background Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy fi cacy of allogenic hAECs in treating POF. Methods A total of 35 patients received 6 x 107 7 hAECs via ovarian artery and completed a fi ve-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and fi ve months (Visit-3, V-3) posttreatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant fi cant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings No serious AEs were observed throughout the fi ve-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/ 35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant fi cant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the fi ve-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant fi cant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-M{llerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted.