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‘Rejuvenated’ eggs raise hopes for improved IVF outcomes

Scientists say they have ‘rejuvenated’ human eggs, in work that could improve IVF success rates for older women.
The team reports that an age-related defect causing genetic errors in embryos may be reversed by supplementing eggs with a key protein.
In eggs donated by fertility patients, microinjection of the protein cut the share showing the defect from 53 per cent to 29 per cent.
The findings were presented at the British Fertility Conference in Edinburgh by researchers from the Max Planck Institute for Multidisciplinary Sciences in Göttingen.
The technique is being commercialised by Ovo Labs, co-founded by professor Melina Schuh, who led the research.
The approach targets problems in meiosis, the process where eggs halve their genetic material before fertilisation.
In older eggs, chromosome pairs can loosen and separate too soon, leading to embryos with too many or too few chromosomes, known as aneuploidy.
The researchers found levels of a protein called Shugoshin 1, which helps hold chromosome pairs together, decline with age. Microinjections appeared to restore this “molecular glue” and reduce errors.
Professor Schuh said: “Overall we can nearly halve the number of eggs with [abnormal] chromosomes. That’s a very prominent improvement.
“Most women in their early 40s do have eggs, but nearly all of the eggs have incorrect chromosome numbers. This was the motivation for wanting to address this problem.
“What is really beautiful is that we identified a single protein that, with age, goes down, returned it to young levels and it has a big effect.
We are just restoring the younger situation again with this approach.
Declining egg quality is a major reason IVF success rates fall steeply with age.
UK figures show an average birth rate of 35 per cent per embryo transferred for patients under 35, dropping to 5 per cent for women aged 43 to 44.
Dr Agata Zielinska, co-founder and co-chief executive of Ovo Labs, said: “Currently, when it comes to female factor infertility, the only solution that’s available to most patients is trying IVF multiple times so that, cumulatively, your likelihood of success increases.
“What we envision is that many more women would be able to conceive within a single IVF cycle.”
The approach would not extend fertility beyond menopause.
The team is in talks with regulators about a clinical trial.
Dr Güneş Taylor, of the University of Edinburgh, who was not involved, said: “This is really important work because we need approaches that work for older eggs because that’s the point at which most women appear.
“If there’s a one-shot injection that substantially increases the number of eggs with properly organised chromosomes, that gives you a better starting point.”
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Common cancer marker may play active role in preventing the disease, study finds

Ki-67, a protein used to measure tumour growth, may also help prevent chromosome errors that drive cancer, a study suggests.
The findings could change how scientists view Ki-67, a marker commonly used in breast cancer and other tumours to assess how quickly cancer cells are growing.
Researchers found the protein may help preserve genome stability by maintaining the structural integrity of centromeres, key parts of chromosomes that help ensure DNA is shared correctly during cell division.
The research was led by professor Paola Vagnarelli at Brunel University of London in collaboration with scientists at the University of Edinburgh and the Technical University of Berlin.
Professor Vagnarelli said: “Doctors already measure Ki-67 to see how aggressive a cancer might be. But our results suggest it is actually helping maintain genome stability.
“That means it may be more than a marker. It could potentially also be a therapeutic target.”
The study examined three proteins that attach to chromosomes during cell division and help rebuild the molecular system that tells each new cell what kind of cell it is.
Every human cell carries identical DNA. What makes a liver cell different from a brain cell is which genes are switched on and which are kept inactive.
When a cell divides, that entire system of switches must be rebuilt. The three proteins involved in this process were Ki-67, Repo-Man and PNUTS.
Vagnarelli’s team developed a method that individually removes each protein from a living cell at the precise point of division. Older techniques could not isolate that moment cleanly.
They found that cells rely on all three proteins to reset themselves after division, but each failed in a different way when removed.
Without PNUTS, gene activity spiralled out of control and thousands of genes switched on at once.
Without Repo-Man, cells escaped safety checkpoints that usually stop damaged or abnormal cells from continuing to divide.
“What we didn’t expect was how clean the separation was,” said Vagnarelli.
Each protein fails in its own specific way. There is no redundancy, no safety net. Which means there are three separate points at which this process can go wrong.
“When the system breaks down, cells can emerge with the wrong number of chromosomes. That condition, called aneuploidy, is seen in disorders such as Down syndrome and in many cancers.
“We also found that these chromosome errors can trigger inflammatory signals inside the cell.”
Aneuploidy means a cell has too many or too few chromosomes, which can disrupt normal growth and function.
Inflammatory signals are chemical messages that can make a cell behave as if it is responding to injury or infection.
“These cells behave almost as if they are under attack,” said Vagnarelli.
“The immune response switches on because the genome is unstable.
“That link between chromosome imbalance and inflammation could help explain patterns we see in several diseases.”
The researchers said the findings may help cancer scientists better understand how chromosome instability, loss of gene regulation and cells dividing before they are ready contribute to tumour growth.
They said understanding the normal machinery that prevents these errors may help researchers find ways to push cancer cells into making mistakes they cannot survive.
“We now have a clearer map of the machinery that resets the cell after division,” said Vagnarelli.
“That knowledge gives us a starting point for thinking about new therapeutic approaches.”
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