Novel approaches to fertility restoration in women with premature ovarian insufficiency

Abstract

The diagnosis of premature ovarian insufficiency (POI) brings with it the loss of fertility, an immediate concern for many affected women, and a future one for many others. While there is a low natural conception rate, for most the choice is between oocyte donation and alternative methods of family building such as adoption. There is, however, a lot of research into novel methods for increasing or restoring the fertility of women with POI, which are discussed in this review. Many approaches involve the use of mesenchymal stem cells, from a variety of sources including bone marrow, placenta and umbilical cord, and menstrual blood. These seem to have efficacy in animal models of POI, although through unclear mechanisms. Activation of remaining primordial follicles is also being explored, through physical or chemical manipulation of key regulatory pathways, notably the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and Hippo pathways. Much of the clinical data are uncontrolled, and mostly in women with a reduced ovarian reserve rather than POI, as are the results thus far for administration of platelet-rich plasma. Clinical studies with appropriate controls are needed to substantiate the preliminary claims of effectiveness of these approaches.

早发性卵巢功能不全女性生育力恢复的新方法 摘要

早发性卵巢功能不全（premature ovarian insufficiency, POI）的诊断带来了生育力的丧失, 这是许多受影响的女性的当务之急, 也是许多其他女性未来的担忧。自然受孕率很低, 对大多数人来说, 最多的选择是卵母细胞捐赠和其他家庭建立方法, 例如收养。然而, 有许多关于增加或恢复POI女性生育力的新方法的研究, 本文对此进行讨论。许多方法涉及采用间充质干细胞, 来源多种多样, 包括骨髓、胎盘、脐带以及月经血。这些似乎在POI的动物模型中有效, 尽管机制尚不清楚。通过物理或化学操作关键调控通路, 特别是磷脂酰肌醇3-激酶（PI3K）/AKT/哺乳动物雷帕霉素靶标（mTOR）和Hippo通路, 也正在探索剩余原始卵泡的激活。许多临床数据是不受控制的, 而且大多数是卵巢储备减少的女性, 而不是POI, 迄今为止注射富血小板血浆的结果也是如此。需要有适当对照的临床研究来证实这些方法的初步有效性。

Keywords:

• Premature ovarian insufficiency
• treatment
• mesenchymal stem cell
• platelet-rich plasma
• primordial follicle activation

Potential conflict of interest

R.R. declares no conflict of interest. R.A.A. has participated in advisory boards and received speaker’s or consultancy fees from Roche Diagnostics, Ferring Pharmaceuticals, IBSA, Merck Serono, KaNDy Therapeutics, and Sojournix Inc. outside the submitted work.

Additional information

Funding

The authors’ work in this field is support by grants from the Medical Research Council [G1100357 to R.A.A.], [MR/N022556/1 to the MRC Centre for Reproductive Health]; Wellbeing of Women [PRF005 to R.R.].