Why female fertility falls with age

Inflammation and a build-up of fibrous tissue in the ovary as it ages is behind the drop in fertility that women experience as they age.

Scientists and doctors have known for decades that, as a woman ages, her likelihood of conceiving falls while the likelihood of her succumbing to genetic problems, such as Down's Syndrome, increases. But why this occurs wasn't known.

Now, Francesca Duncan, who studies female fertility at Northwestern University in the US, has uncovered an important part of the puzzle.

Publishing her findings in the journal Reproduction, she says we've been looking in the wrong place for the answer.

"When we used to study eggs to work out why they were of poorer quality at higher maternal age we would take the eggs in isolation," she explains. "But we need to think about the ovarian tissue that produced that egg in the first place. If the egg is growing and developing in sub-optimal conditions, it's much more likely to have problems."

Instead Duncan thinks that the ageing ovary, where eggs are matured in structures called follicles before ovulation, becomes choked by a build up of fibrous tissue with age. This forms a barrier to the normal nurturing environment, obstructing the normal function and impacting on the egg quality.

Duncan was inspired to think about the problem this way as an early career scientist when she was dissecting ovaries from older animals. "The tissue was much thicker and tougher."

With this in mind she used a special stain that flags up fibrous tissue and added it to ovarian tissue samples from young and old mice. "The older mice had significantly more fibrosis," she explains.

The origin of the fibrosis appears to be an inflammatory process occurring naturally within the ovary.

Each month many eggs begin to develop in preparation for ovulation, but eventually they all die off except just one that will be ovulated. The rest are broken down and consumed by cells called macrophages.

But, as the cells commence the clean up, they trigger low-grade inflammation, which heals with scarring and ultimately the deposition of fibrous tissue.

The discovery is important because it may shed light on mechanisms that can be used to slow down the process of ovarian ageing, which may help individuals choosing to defer parenthood until later in life.

In the nearer term, measurements of the inflammatory signals issuing from the ovary might be a useful fertility barometer. And such measurements are also likely to be more sensitive than just hormones measurements, which give little indication of the quality of the eggs being ovulated.

"If we can pick up those signals in the blood, we can use them to indicate the rate of ovarian ageing, and give information to a woman about her prospects of pregnancy."