Scientists claim to have “rejuvenated” human eggs for the first time in a move they predict could revolutionize ECO success rates for older women.
A pioneering study suggests an age-related defect that causes genetic errors in embryos could be reversed by adding a vital protein to eggs. When eggs donated by infertility patients were microinjected with protein, they were almost half as likely to develop a defect as untreated eggs.
If confirmed in larger studies, this approach could improve egg quality, a leading cause of IVF failure and miscarriage in older women.
“Overall we can almost halve the number of eggs using [abnormal] chromosomes. This is a very noticeable improvement,” said Professor Melina Schuh, director of the Max Planck Institute for Interdisciplinary Sciences in Göttingen and co-founder of Ovo Labs, which aims to commercialize the technique.
“Most women around age 40 do have eggs, but almost all eggs have the wrong chromosome number,” added Shu, whose lab has been researching egg biology for the past two decades. “That was the motivation to solve this problem.”
The results will be presented at UK Fertility Conference in Edinburgh on Friday and were published as a preprint on the Biorxiv website.
Declining egg quality is the main reason why IVF success rates plummet as a woman ages, and why the risk of chromosomal disorders such as Down syndrome increases as the mother ages. For patients under 35 years of age, the average fertility rate per IVF embryo transferred was 35%, compared with just 5% for women aged 43-44 years, according to the study. latest UK data. The average age of infertility patients starting treatment for the first time in the UK is now over 35 years.
Dr Agata Zielinska, co-founder and co-CEO of Ovo Labs, said: “Currently, when it comes to female factor infertility, the only solution available to most patients is to try IVF several times, so that cumulatively the likelihood of success increases. We anticipate that many more women will be able to conceive within a single IVF cycle.”
The latest approach targets eggs' vulnerabilities associated with a process called meiosis, in which sex cells (eggs or sperm) shed half of their genetic material so they can combine to create an embryo.
In eggs, this requires 23 pairs of X-shaped chromosomes to be aligned along the same axis of the cell. At fertilization, the cell divides, causing pairs of chromosomes (ideally) to come together neatly at their centers, forming a cell containing exactly 23 individual chromosomes from the mother, with the rest supplied by the sperm.
However, in older eggs, pairs of chromosomes tend to become loose in the middle, coming loose slightly or separating completely before fertilization. In this scenario, the X-shaped structures do not line up properly and move around the cell randomly, so they do not close symmetrically when the cell divides. As a result, the embryo has too many or too few chromosomes.
Shu and his colleagues previously found that levels of the protein Shugoshin 1, which appears to act as glue for chromosome pairs, decline with age. In recent experiments in mice and human eggs, they found that microinjections of Shugoshin 1 appear to solve the problem of premature separation of chromosome pairs.
Using eggs donated by patients at Bourne Hall Fertility Clinic in Cambridge, they found that the number of defects decreased from 53% in control eggs to 29% in treated eggs. When they looked only at eggs from women over 35, there was a similar trend (65% compared to 44%), although this result was not statistically significant, which the scientists said was likely due to the fact that they only processed nine eggs in that age range.
“What's really exciting is that we identified a single protein that declines with age, brought it back to youthful levels, and it has a big effect,” Shu said. “With this approach, we are simply restoring a younger situation again.”
This approach will not prolong fertility after menopause, when the supply of eggs dries up.
Apart from intracytoplasmic sperm injection (ICSI), there are currently no treatments involving microinjection into eggs, but the team does not foresee safety concerns and is in talks with regulators about clinical trials. An important question will be whether the apparent improvement in egg quality will result in embryos with fewer genetic errors.
Dr Gunesh Taylor from the University of Edinburgh, who was not involved in the study, called the results “really promising”.
“This is really important work because we need approaches that work for older eggs, because that's when most women come in,” she said. “If there is a single injection that significantly increases the number of eggs with correctly organized chromosomes, that gives you a better starting point.”
