Human eggs ‘rejuvenated’ in advance that could boost IVF success rates | Biology

Scientists claim to have “rejuvenated” human eggs for the first time, a breakthrough they say could revolutionize IVF success rates in older women.

Groundbreaking research suggests an age-related defect that causes genetic errors in embryos could be reversed by supplementing eggs with an essential protein. When eggs donated by fertility patients received microinjections of protein, they were almost half as likely to have the defect as untreated eggs.

If confirmed in further trials, this approach could potentially improve egg quality, which is the leading cause of IVF failure and miscarriage in older women.

“Overall, we can reduce the number of eggs by almost half with [abnormal] chromosomes. This is a very important improvement,” said Professor Melina Schuh, director of the Max Planck Institute for Multidisciplinary Sciences in Göttingen and co-founder of Ovo Labs, which aims to commercialize the technique.

“Most women in their early 40s have eggs, but almost all eggs have an incorrect number of chromosomes,” added Schuh, whose lab has studied egg biology for two decades. “That’s what motivated us to want to solve this problem.”

The results will be presented on Friday at the British Fertility Conference in Edinburgh and have been published as a pre-print article on the Biorxiv website.

Declining egg quality is the main reason why IVF success rates decline sharply with a woman’s age and is why the risk of chromosomal disorders such as Down syndrome increases with maternal age. For patients under 35, the average birth rate for each embryo transferred during IVF treatment was 35%, compared to just 5% for women aged 43 to 44, according to the most recent UK figures. The average age of fertility patients starting treatment for the first time in the UK is now over 35.

Dr Agata Zielinska, co-founder and co-CEO of Ovo Labs, said: “Currently, when it comes to female infertility, the only solution available for most patients is to try IVF multiple times so that, cumulatively, your chances of success increase. What we envision is that many more women would be able to conceive during 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) shed half of their genetic material so they can unite to form an embryo.

In eggs, this requires 23 pairs of X-shaped chromosomes to line up along a single axis in the cell. During fertilization, the cell divides, causing pairs of chromosomes to be – ideally – carefully broken at their centers to create a cell with precisely 23 unique chromosomes from the mother, with the rest delivered by the sperm.

However, in older eggs, chromosome pairs tend to become loose in the middle, detaching slightly or detaching completely before fertilization. In this scenario, the X-shaped structures fail to align properly and move chaotically within the cell. So when the cell divides, they are not broken symmetrically. This results in an embryo with too many or too few chromosomes.

Schuh and his colleagues previously found that a protein, Shugoshin 1, which appears to act as a glue for chromosome pairs, declines with age. In the latest experiments on mouse and human eggs, they found that microinjections of Shugoshin 1 appeared to reverse the problem of premature separation of chromosome pairs.

Using eggs donated by patients at the Bourn Hall Fertility Clinic in Cambridge, they found that the number with the defect decreased from 53% in control eggs to 29% in treated eggs. When they looked only at eggs from women over 35, a similar trend was observed (65% versus 44%), although this result was not statistically significant, which the scientists said was likely because they only processed nine eggs in that age range.

“What’s really beautiful is that we identified a single protein that with age declines, brought it back to youthful levels and that has a big effect,” Schuh said. “With this approach, we are only restoring the situation of young people. »

This approach would not extend fertility beyond menopause, when the egg supply becomes depleted.

Aside from intracytoplasmic sperm injection (ICSI), there are currently no treatments involving microinjections into eggs, but the team does not anticipate any safety concerns and is in discussions with regulators about a clinical trial. An important question will be whether apparent improvements in egg quality result in embryos with fewer genetic errors.

Dr Güneş Taylor, of the University of Edinburgh, who was not involved in the research, described the results as “really promising”.

“This is really important work because we need approaches that work for older eggs, because that’s when most women appear,” she said. “If there is a single injection that significantly increases the number of eggs with properly organized chromosomes, that gives you a better starting point.”