Scientists claim to have 'rejuvenated' human eggs in breakthrough that could revolutionise IVF success rates for older women
The landmark research suggests that an age-related defect causing genetic errors in embryos can be corrected by adding a crucial protein to eggs.
When eggs donated by fertility patients were microinjected with the protein, they showed almost twice as few defects as untreated eggs.
If confirmed in wider trials, the approach has the potential to improve egg quality, which is the main cause of IVF failure and miscarriage in older women.
Overall, we can almost halve the number of eggs [with abnormal] chromosome numbers. This is a very significant improvement", said Prof Melina Schuh, director of the Max Planck Institute for Multidisciplinary Sciences in Göttingen and co-founder of Ovo Labs, which aims to commercialise the technique.
Most women have eggs with the wrong number of chromosomes by their early 40s, but almost all eggs have the wrong number of chromosomes. This was the motivation for addressing this problem", added Schuh, whose lab has been studying egg biology for two decades.
The findings will be presented at the British Fertility Society conference in Edinburgh on Friday and are published as a preprint on the Biorxiv website.
Decline in egg quality is the main reason why IVF success rates plummet sharply with a woman's age and is the reason why the risk of chromosomal abnormalities such as Down's syndrome rises with maternal age. For patients under 35, the average live birth rate per embryo transfer in IVF treatment was 35%, compared with just 5% for women aged 43-44, according to the latest figures from the UK.
The average age of fertility patients in the UK who start treatment for the first time is now over 35.
Dr Agata Zylinska, co-founder and co-founder of Ovo Labs, said: "Currently, when it comes to female factor infertility, the only solution available to most patients is to try IVF multiple times to increase your cumulative chances of success. What we envision is that many women will be able to conceive within a single IVF cycle."
The latest approach targets a vulnerability in eggs linked to a process called meiosis, in which sex cells (eggs or sperm) release half their genetic material to be able to combine to create an embryo.
In an egg, this requires 23 pairs of X-shaped chromosomes to line up along one axis of the cell. When fertilised, the cell divides, resulting in chromosome pairs being neatly sliced to create a cell with exactly 23 single chromosomes from the mother, the rest supplied by sperm.
However, in older eggs, chromosome pairs are prone to loosen, slightly misalign or completely separate before fertilisation. In this scenario, the X-shaped structures do not line up properly and move chaotically around the cell, so when the cell divides, they are not sliced symmetrically. This results in an embryo with too many or too few chromosomes.
Schuh and colleagues previously discovered that a protein called Shugoshin 1, which appears to act as glue to keep chromosome pairs together, declines with age. In the latest experiments in mouse and human eggs, they found that microinjections of Shugoshin 1, it seems, corrected the problem of chromosome pairs separating prematurely.
Using eggs donated by patients at a fertility clinic in Bourn Hall, they found the defect fell from 53% in control eggs to 29% in treated eggs. When they looked only at eggs from women over 35, a similar trend was seen (65% vs 44%), although this result was not statistically significant, the scientists say, likely because they only treated nine eggs in this age range.
It's really beautiful that we've identified one protein that declines with age, restored it to young levels, and it has a big effect", said Schuh. "We're just restoring the younger situation with this approach."
This approach will not extend fertility to menopause, when the egg supply is exhausted.
There is currently no treatment involving microinjections into eggs, but the team does not expect safety issues and is negotiating with regulators about a clinical trial. A key question will be whether the apparent improvement in egg quality translates to embryos with fewer genetic errors.
Dr Gunesh Thireen, at the University of Edinburgh, who was not involved in the research, described the findings as "really promising."
"This is really important work because we need approaches that work for older eggs because that's the point where most women come", said he. "If there's a single injection that significantly increases the number of eggs with correctly organised chromosomes, it gives you a better starting point."
