Why does a woman's fertility start to diminish in her 30s well before Menopause?

It has been demonstrated that utilising drugs that fight fibrosis and support mitochondrial health, ovarian ageing in mice can be reversed.

Australian researchers have shown that when mice age, they develop higher amounts of ovarian fibrosis, which is brought on by mitochondrial failure, inflammation, and excessive collagen buildup.

Reduced fertility results from the modifications, stiffening the ovarian architecture and affecting ovulation. They contend that this mechanism could account for why, years before menopause, a woman’s fertility can start to diminish in her 30s.

‘One challenge we faced was convincing our clinical colleagues that ovarian fibrosis (the excess inflammation and collagen) could actually be preventing egg release from ovaries’ said study leader Professor Rebecca Robker from the University of Adelaide, Australia. ‘Currently, clinical treatments for triggering ovulation in women involve administering very high doses of hormones to make the egg-containing follicles grow and mature, and the search for new therapies has been all about finding new hormones or treatment protocols to stimulate these follicles.’

The findings, which were reported in Science Advances, demonstrated that fibrosis began much earlier than previously believed in the ovaries of 12-month-old mice (equivalent to around 35 human years). Additionally, obese mice showed increased ovarian fibrosis and a decline in fertility similar to that seen in old animals.

According to the study, ovulation rates were increased when ovarian fibrosis was treated with medications, such as those that enhance mitochondrial activity and lessen inflammation. Although the results need to be confirmed in humans, this study is the first to explore non-hormonal ways to enhance ovarian function.

Professor Richard Anderson from the MRC Centre for Reproductive Health at the University of Edinburgh, who was not involved in the study, noted that women are increasingly wanting to have children later in their reproductive lives and that improving the function of the ovaries at that time would be beneficial.

There are many unanswered issues regarding the potential applicability of this study to people, but we do know that older human ovaries contain more collagen, and that this can influence both mouse and human ovaries’ ability to generate eggs.