Christopher Chen Oocyte Biology Research Laboratory, UQ Centre for Clinical Research, The University of Queensland, Brisbane, Herston, Queensland, Australia.
Curr Opin Obstet Gynecol. 2021 Jun 1;33(3):218-224. doi: 10.1097/GCO.0000000000000708.
Oocyte quality is rate-limiting for pregnancy success and declines with age. Here, I review animal-study evidence showing dramatic reversal of oocyte ageing with mitochondrial nutrients and explore clinical evidence related to their usage.
Oocyte ageing is strongly tied to mitochondrial dysfunction and oxidative stress. Quality-defining events occur over a protracted period (2-3 months in humans) when oocyte volume increases over 100-fold. Treating mice during the growth phase with mitochondrial modifiers such as CoQ10 combats oocyte ageing. Exciting new work shows that raising oocyte NAD+ levels also dramatically rejuvenate aged oocytes. However, evidence that any of these agents can reproducibly improve quality in humans is lacking. This is largely because there has been a focus on patients with poor ovarian response during IVF and/or low ovarian follicular pool size, rather than patients with poor oocyte quality. In addition, studies have used short-term treatment during ovarian stimulation after oocyte growth is already complete.
Mitochondrial therapeutics such as NAD+-boosting used during the oocyte's growth phase markedly improve oocyte quality in mice. Evaluating them in humans should focus on patients with poor oocyte quality and utilise per-oocyte (rather than per-cycle) endpoints after adequate treatment that captures the growth phase when quality is defined.
卵子质量是妊娠成功的限速因素，并且会随着年龄的增长而下降。在这里，我回顾了动物研究证据，证明了线粒体营养物质可以显著逆转卵子老化，并探讨了与它们的使用相关的临床证据。
卵子老化与线粒体功能障碍和氧化应激密切相关。质量定义事件发生在一个较长的时期（人类为 2-3 个月），在此期间，卵子体积增加了 100 多倍。在生长阶段用线粒体修饰剂（如 CoQ10）治疗小鼠可以对抗卵子老化。令人兴奋的新工作表明，提高卵子 NAD+水平也可以显著恢复老化的卵子。然而，缺乏任何这些药物能够在人类中重复改善质量的证据。这主要是因为人们关注的是接受体外受精治疗的卵巢反应不良患者和/或卵巢卵泡池小的患者，而不是卵子质量差的患者。此外，研究使用的是在卵子生长完成后进行卵巢刺激期间的短期治疗。
在卵子生长阶段使用线粒体治疗药物，如 NAD+ 促进剂，可以显著改善小鼠的卵子质量。在人类中评估它们应该侧重于卵子质量差的患者，并在充分治疗后使用每个卵子（而不是每个周期）的终点，以捕获定义质量的生长阶段。
