卵巢早衰(POF)是一种普遍且严重的疾病,损害女性健康,但目前尚无有效的治疗方法来恢复卵巢功能。人羊膜上皮细胞(hAEC)在临床前模型中表现出卵巢保护作用。因此,我们进行了单臂,1期临床试验,以评估同种异体hAECs治疗POF的安全性和有效性。
■共有35例患者通过卵巢动脉接受了6×107hAECs,并从2020年12月30日至2022年1月31日完成了为期五个月的随访。在hAECs治疗后的不同时间间隔进行随访评估,包括一个月(访问-1,V-1),三个月(访问-2,V-2),治疗后5个月(访视-3,V-3)。主要终点是不良事件(AE)的发生率,和临床上显著的实验室异常。次要终点包括经阴道超声结果的评估,性激素水平,更年期生活质量(MENQOL)问卷,以及生殖指标。该试验已在www上注册。clinicaltrials.gov作为NCT02912104。
■在整个5个月的随访期间未观察到严重的AE。最常见的AE是血肿(7/35,20.00%),其他不良事件包括盆腔疼痛(4/35,11.43%),发烧(2/35,5.71%),过敏反应(2/35,5.71%),肝毒性(1/35,2.86%)。hAECs移植(hAECT)后,子宫内膜厚度水平显著改善,左卵巢体积,性激素(促卵泡激素(FSH)和雌二醇(E2)),5个月随访期间所有患者的MENQOL评分。其中,13名参与者(37.14%)经历了自发性月经出血,20.00%(7/35)报告hAECT后一次以上的月经出血。在这个响应小组中,子宫内膜厚度显著改善,左卵巢体积,FSH水平,E2,抗苗勒管激素(AMH),与hAECT前相比,hAECT后一个月的MENQOL评分。
■经卵巢动脉的HAECT是安全的,耐受性良好,可暂时改善子宫内膜厚度,卵巢大小,激素水平,POF患者的更年期症状。有必要对具有较长随访时间和较大样本量的hAECs进行进一步的随机对照试验。
■国家自然科学基金(编号:82271664),上海交通大学跨学科项目(YG2022ZD028),上海市卫生健康委员会(202240345),上海市胚胎原始疾病重点实验室(编号Shelab2022ZD01),上海市教育委员会(编号:20152236),和国家重点研究发展计划(编号:2018YFC1004802),上海细胞治疗临床研究中心,中国(编号23J41900100)。
UNASSIGNED: 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 of allogenic hAECs in treating POF.
UNASSIGNED: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-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 five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant 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.
UNASSIGNED: No serious AEs were observed throughout the five-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 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 five-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 improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT.
UNASSIGNED: 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.
UNASSIGNED: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).