Maternal age and IVF
|Pregnancy rate declines with maternal age. What can we do about it?|
Maternal age and IVF – what’s it all about?
Have you ever asked why doctors always go on about your age when you seek assisted reproduction?
Why do they keep on at me when there are so many over 40’s that get pregnant either naturally – or after assisted conception?
And why do they tell me I have a 10% chance of conceiving with my eggs but an 80% chance with donated eggs?
Well, it’s not really a personal attack but just real advice on your probable chance of success. Just looking at someone doesn’t give clinicians much information about their success rate, medical examinations help a bit but the only strong indicator of your maximum chances to conceive is the female age.
So why? Are clinicians chauvinist? Are they saying women should just make babies?? Why not men as well??
No, actually it’s your biology speaking.
So what’s the biological link between maternal age and reproduction?
Unfortunately, all of the body is subject to damage in everyday use. Whereas an engine wears out through friction, our body wears out through the toxic side effect of energy production. This happens in small parts of the cells termed ‘mitochondria’. These mitochondria produce most of the energy needed in the body, but their activity causes the production of free radicals which attack the mitochondria themselves and damage them. Since mitochondria have their own DNA and regenerate themselves through this template, a damaged template means lower quality mitochondria and problems for future cells. There is no solution to this problem, but destruction and regeneration of the cell stock itself appears to alleviate it and prolong the quality curve.
Our body is never constant, but instead millions of cells are being generated and destroyed every day. This keeps us in top condition since any problems within cells are eliminated quickly – just like a quality check in a factory. However, some parts of our body simply cannot do this. This is either because it would be dangerous to destroy and replace cells (in the brain for example connections are involved in memory and learning, so replacing them would mean loss of memory) or because the cells are formed before birth and waiting their turn (eggs for example). This is where we come to the maternal age effect.
The maternal age effect is then simply the fact that your eggs are formed before birth and the stock then consumed throughout life. This means your eggs have your own age. As you get older and go through the mitochondrial effect described above, your eggs go through the same process. As mitochondria lose quality, less energy is produced, therefore the eggs must compensate with alternate, inefficient sources of energy, until a deficit cannot be recuperated. This leads to secondary effects such as aneuploidies (Downs’ syndrome is a classic example) and low pregnancy rates.
Why not males? Not because God is a chauvinist, but because the testicles produce sperm continually throughout life. This turnover means damaged mitochondria are eliminated, and sperm are therefore subject to the much lower buildup of damaged mitochondria.
What can we do about it?
Because mitochondrial activity and toxicity are so intertwined, we can’t do much about ageing actually. The following ideas are the best solutions at the present time.
1) Freeze eggs during youth
Women could freeze a stock of their eggs in the prime of their life, in order to use them once their career was established and a suitable partner found. An excellent solution, but for women it’s not so easy to produce eggs because this requires a hormonal therapy AND operation in a clinic. Until now, very few women have considered this option, probably because the best time to do it is at an age in which few are even thinking about having a baby; perhaps it’s an idea for future generations.
2) Freeze ovarian tissue
Without undergoing ovarian stimulation, a biopsy of the ovary can be quickly performed (still in an operating theatre). This would be cryopreserved. When required, this tissue could then be transplanted onto the ovary, to create a source of young eggs since cryopreservation suspends time.
In the case that no eggs have been conserved in youth, your ‘aged’ eggs can be partially rejuvenated with the technique of cytoplasmic donation. This entails injecting some cytoplasm (the eggs nutrients) from a young donor egg into your own eggs. The fresh cytoplasm increases the energy production in your eggs and can help people conceive. Unfortunately, it is poorly considered as a clinical technique in the USA and other countries due to theoretical incompatibilities between the mitochondrial sources. However, it is still available in some areas of the world.
4) Freeze egg stem cells
An ovarian biopsy is performed, and dissected for the removal and conservation of egg stem cells. When required, these can be used as a homologous source of mitochondria to perform cytoplasmic donation. This technology is in development from the company OvaScience. We hope it will be clinically offered in the future, however it still requires people to ‘prepare’ for reproduction at an age in which they have no interest in the subject.
5) Egg donation
Why do egg donation programs offer an 80% chance of getting pregnant when I may be estimated to have a 40% chance? No, it’s not that donated eggs are treated in a special way, just statistics. A young female can be considered to have a 60% chance of getting pregnant, then decreasing with respect to age. When their fertility is known (i.e. a baby has already resulted from their eggs), we can add an extra 20% chance, hence 80%.
Take a course of dietary supplements including L-Carnitine or Coenzyme Q10. Eat fruit and vegetables and generally try to improve your lifestyle. This may have a small short term effect but remember that it cannot compensate for a long-term effect such as ageing. However, in reproduction, even short term effects can be sufficient to create the conditions for pregnancy.