Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, P. O Box: 16635-148, Royan Allay, Eastern Hafez St, Banihashem Sq., Resalat Highway, Tehran, Iran.
Department of Regenerative Medicine, Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P. O Box: 16635-148, Shaghayegh Alley, Banihashem Sq., Resalat Highway, Tehran, Iran.
J Ovarian Res. 2021 Jan 6;14(1):5. doi: 10.1186/s13048-020-00743-3.
Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients.
This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 10, 10 × 10, or 15 × 10 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation.
Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 10 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 10 and 10 × 10 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 10 and 10 × 10 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05).
We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT.
NCT02603744 , Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov.
卵巢早衰（POF）是指 40 岁以前卵巢活动丧失。干细胞治疗具有创造再生微环境的能力，并且由于成年卵巢中存在更新的卵泡发生和生殖细胞，因此被提议用于治疗与 POF 相关的不孕。在这项研究中，我们评估了自体脂肪来源的基质细胞（ADSCs）的安全性、可行性、疗效和剂量调整，以及其改善 POF 患者卵巢功能的能力。
这是一项非随机临床试验，I 期。9 名被明确诊断为 POF 的女性被分为三组（每组 3 名），在一侧卵巢中分别接受 5×10、10×10 或 15×10 个自体 ADSC 悬浮液移植。在移植后 24 小时、1 周和 2 周、1、2、3、6 和 12 个月对参与者进行随访。主要目的是评估 ADSC 移植的安全性。次要目标包括 ADSC 移植对恢复月经、激素水平（卵泡刺激素（FSH）和抗苗勒氏管激素）、卵巢功能（通过超声评估的窦卵泡计数和卵巢体积）以及剂量递增的影响。
参与者在随访期间均未出现任何早期可能的副作用和继发性并发症。4 名患者出现了月经恢复，持续了几个月。在 15×10 组中，有 2 名 POF 患者在干预后第二个月出现月经恢复。另外 2 名 POF 患者在 5×10 和 10×10 细胞组中报告在干预后 1 个月出现月经恢复。我们观察到 4 名患者的血清 FSH 水平低于 25IU/l。在 5×10 和 10×10 细胞组的 2 名患者中，血清 FSH 在 ADSC 移植后 1 年的随访中表现出不一致的下降。卵巢体积、AMH 和 AFC 在随访期间均有变化，细胞组之间无显著差异（p>0.05）。
我们表明 ADSC 的卵巢内嵌入是安全可行的，并与血清 FSH 的不一致下降有关。这需要进一步用大 RCT 进行研究。
NCT02603744，2015 年 11 月 13 日注册 - 回顾性注册，http://www.Clinicaltrials.gov。
