Ovarian ageing : where are we now? and where to next?

From the mid-1980s, the scientific community has demonstrated irrefutable evidence for the age-related decline in female fertility (Menken et al., 1986) [1], supporting observations in animals and humans of maternal ageing, increased incidence of miscarriage and congenital abnormality dating back to the mid-20th Century (Warburton, 1970) [2]. Although, it was not until 2005 that a report arising from the European Society of Human Reproduction and Embryology sought to address ovarian ageing as the primary contributing factor to this decline and its profound influence on the success of assisted reproduction. Over the resulting two decades, researchers have endeavoured to define and quantify the genetic, molecular and cellular factors directly responsible for ovarian ageing and subsequently female age-related infertility, seeking to ultimately improve diagnostics and treatments. In this review, we undertake a closer investigation of the ‘usual suspects’ and speculate on the role of synergistic inflammaging and finally address the question of whether in 2020 we are really any closer to finding the culprits underpinning the ageing ovary.