Could enhancing mitochondrial function improve egg quality in woman over 40?

I had my kids later in life.  My last child was born when I was 42.  My mother would call that a “change of life” baby.  Hahah. About a third of my patients hoping to conceive are also women over the age of 40.  After 40 the main issue, no matter how healthy the woman, is poor egg quality. 

I am currently on vacation in New Harris on Cape Breton Island in Nova Scotia.  If you google map it, the app just says “middle of no where.”  It really is.  There are no people here, possibly because of how remote it is and possible because of the black flies.

In any case, it’s raining so I am browsing scientific journals. I find many of the studies interesting but the ones of egg quality always draw my attention.  What can we do to help woman have better eggs as they age?  Healthier eggs means more natural and IVF pregnancies and healthier babies.

The biggest predictor of IVF success is how well the egg performs in the first 5-6 days after fertilization.  That performance is heavily dependant on cell energy.  Does it have enough energy to properly divide the chromosomes, to divide into robust cells, to grow and expand?  Energy comes largely from mitochondria in the cell.  Mitochondrial function relies on a couple of molecular pathways (e.g. Kreb cycle) to make energy.  Those pathways involve oxidation and reduction hence we put people on antioxidants to help those pathways (e.g. coenzyme Q10).  

To help eggs with mitochondrial function it makes sense to transplant more mitochondria into the egg cell.  People have tried this with the woman’s own mitochondria (no success) and donor egg mitochondria (some success but this is prohibited in Canada and the USA).

How else can we help aging eggs perform better?  A research group recently examined the cells surrounding the egg (called cumulus cells - CC).  They found that the mitochondria in cumulus cells (CCs) also play a roll in egg health. Eggs surrounded by CCs with abnormal or dysfunction, mitochondria were of lower quality than eggs surrounded by CC with normal mitochondrial function. It’s possible that this is just a marker of poor egg health (no surprise that CC have poor mitochondria around old eggs) or it is a causal factor. If it’s a causal factor then we could extract heathy mitochondrial from a donor’s CC and bathe eggs in those cells (which would not be prohibited) to improve egg health. Now, that would be promising.

Reference: Lu X, Liu Y, Xu J, Cao X, Zhang D, Liu M, Liu S, Dong X, Shi H. Mitochondrial dysfunction in cumulus cells is related to decreased reproductive capacity in advanced-age women. Fertil Steril. 2022 Aug;118(2):393-404.