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Sunday, July 7, 2013

IVF baby born using revolutionary genetic-screening process

Next-generation sequencing could enable IVF clinics to determine the chances of children developing diseases
David Levy and Marybeth Scheidts holding their baby Connor Levy
Baby Connor Levy with his parents David Levy and Marybeth Scheidts
The first IVF baby to be screened using a procedure that can read every letter of the human genome has been born in the US.
Connor Levy was born on 18 May after a Philadelphia couple had cells from their IVF embryos sent to specialists in Oxford, who checked them for genetic abnormalities. The process helped doctors at the couple's fertility clinic in the US select embryos with the right number of chromosomes. These have a much higher chance of leading to a healthy baby.
The birth demonstrates how next-generation sequencing (NGS), which was developed to read whole genomes quickly and cheaply, is poised to transform the selection of embryos in IVF clinics. Though scientists only looked at chromosomes – the structures that hold genes – on this occasion, the falling cost of whole genome sequencing means doctors could soon read all the DNA of IVF embryos before choosing which to implant in the mother.
If doctors had a readout of an embryo's whole genome, they could judge the chances of the child developing certain diseases, such as cancer, heart disease or Alzheimer's.
Marybeth Scheidts, 36, and David Levy, 41, had tried another fertility treatment, called intrauterine insemination (IUI), three times without success before they signed up for IVF at Main Line Fertility clinic in Pennsylvania.
As part of an international study with Dagan Wells, a fertility specialist at Oxford University, the couple were offered NGS to check their IVF embryos for abnormal chromosomes. Abnormal chromosomes account for half of all miscarriages.
The chances of an embryo having the wrong number of chromosomes rises with the mother's age, and potentially with the father's. For women in their 20s, one in 10 embryos may have the wrong number of chromosomes, but for women in their 40s, more than 75% can be faulty.
Most of the time, embryos with abnormal chromosomes fail to implant in the womb. Those that do are usually miscarried. The portion that survive to full term are born with genetic disorders, such as Down's syndrome and Turner syndrome.
After standard treatment at the US clinic, the couple had 13 IVF embryos to choose from. The doctors cultured the embryos for five days, took a few cells from each and sent them to Wells in Oxford for genetic screening. Tests showed that while most of the embryos looked healthy, only three had the right number of chromosomes.
"It can't make embryos better than they were in the beginning, but it can guide us to the best ones," said Wells.
Based on the screening results, the US doctors transferred one of the healthy embryos into Scheidts and left the rest in cold storage. The single embryo implanted, and nine months later Connor was born. Details of the study will be given at the European Society of Human Reproduction and Embryology (Eshre) meeting in London on Monday.
"I think it saved us a lot of heartache," Scheidts told the Guardian. "My insurance covered me for three cycles of IVF. We might have gone through all three without the doctors picking the right embryos. I would not have a baby now."
A second baby who had the same genetic screening is due to be born next month, after a US couple had IVF at New York University fertility centre.
Doctors can already screen embryos for abnormal chromosomes using a technique called Array CGH, but the procedure adds more than £2,000 to the cost of IVF. Wells said NGS could bring the cost down by a third. To check the number of chromosomes is much simpler than reading all of the DNA accurately.
"It is hard to overstate how revolutionary this is," said Michael Glassner, who treated the couple at the Main Line Fertility clinic. "This increases pregnancy rates by 50% across the board and reduces miscarriages by a similar margin. It will be much less expensive. In five years, this will be state of the art and everyone who comes for IVF will have it."
In Britain, doctors are banned from selecting embryos for anything other than the most serious medical reasons. But as scientists learn more about genetic causes of disease, the urge to choose embryos to avoid cancer and other diseases later in life will intensify.
"You can start to have a very scary picture painted if you talk about height and hair colour and so on," said Glassner. "We have to make sure this is used judiciously."
The prospect of "designer babies" is remote for now, even if it were made legal. IVF produces only a dozen or so embryos at best, so the odds that one has all the traits a couple desires are very low. "IVF is still expensive and uncomfortable with no guarantee of a baby at the end. I can't imagine many people wanting to go through the strains of IVF for something trivial," said Wells.
The Oxford team now plans a large trial of the screening procedure to assess how much it boosts pregnancy rates, and which age groups it benefits the most.
Scheidts still has two screened embryos in cold storage, but has not yet decided whether to use them. "We haven't even thought about that. We'll see how the first year goes."

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