Understanding oocyte ageing: can we influence the process as clinicians?

Abstract

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.