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

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.