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First IVF Baby with New Embryo Screening Technique

Published: Tuesday, July 09, 2013
Last Updated: Tuesday, July 09, 2013
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The method uses the latest DNA sequencing techniques and aims to increase IVF success rates while being more affordable.

Dr Dagan Wells of Oxford University led the international team which has shown how 'next-generation sequencing' can be used to pick the embryos created by IVF that are most likely to lead to successful pregnancies.

The approach can identify embryos with the correct number of chromosomes and may cut hundreds of pounds off the cost of embryo screening, Dr Wells says, which currently adds £2000–£3000 to IVF treatments.

He will outline the development today at the European Society of Human Reproduction and Embryology's annual meeting in London.

The work was a collaborative effort. It received significant support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, a partnership between Oxford University Hospitals NHS Trust and the University of Oxford. The collaboration also involved industrial partners, in particular the medical diagnostic company Reprogenetics UK.

The majority of embryos produced by IVF aren't able to lead to successful pregnancies, and scientists have sought to find ways of identifying the embryos that should be implanted to give the greatest chance of success.

How an embryo looks and how it develops during the first few days of life give some indication of its viability. However, many embryos turn out to have the wrong number of chromosomes – the packages of DNA we inherit from our parents. Having an incorrect number of chromosomes usually prevents embryos from producing a pregnancy. Until recently, such abnormalities have been hard to detect as they do not affect the appearance of embryos under the microscope.

Dr Wells, of the Institute for Reproductive Sciences in the Nuffield Department of Obstetrics and Gynaecology, explained: 'Many of the embryos produced during infertility treatments have no chance of becoming a baby because they carry lethal genetic abnormalities. Next-generation sequencing improves our ability to detect these abnormalities and helps us identify the embryos with the best chances of producing a viable pregnancy. Potentially, this should lead to improved IVF success rates and a lower risk of miscarriage.'

Recently, a number of trials of various chromosome screening methods have shown that they can improve IVF success rates by around 30%. But the costs of these genetic tests remain a barrier to their widespread use.

This led Dr Wells and colleagues to look at the possibilities of using the latest in DNA sequencing technology to screen embryos for chromosomal abnormalities. In recent years, next-generation sequencing has seen massive reductions in costs, a trend that looks set to continue.

Dr Wells said: 'Results from randomised clinical trials carried out during the last year have suggested that most IVF patients would benefit from embryo chromosome screening. However, the costs of these genetic tests are relatively high, putting them beyond the reach of many patients. Next-generation sequencing could make chromosome testing more widely available, improving access by cutting the costs.'

Next-generation sequencing has been revolutionising research and clinical genetics in many areas, generating vast quantities of data. But it had not yet been applied to embryo screening because of the challenge of applying the techniques to DNA from a single cell. A single cell is all that can be safely taken from a few-day-old embryo for testing.

The researchers' approach involves sequencing DNA from multiple embryos all at the same time. Short DNA tags or 'barcodes' added to the genetic material from each individual embryo mean that the results could be identified uniquely and mapped back to the right embryo.

The researchers explicitly do not read out the whole DNA code for each embryo. They deliberately limit sequencing to around 2% of the embryo's DNA, more than enough to determine the number of chromosomes present, but insufficient to reveal the status of individual genes.

In the future, it should be possible to use the approach to check for chromosomal abnormalities and any serious inherited disorders at the same time, the researchers believe. Dr Wells said: 'Next-generation sequencing provides an unprecedented insight into the biology of embryos.'

An initial validation study showed extremely high accuracy rates for the DNA sequencing approach, says Dr Wells. The study involved seeing whether known chromosome abnormalities, gene defects or mitochondrial DNA mutations could be identified in small numbers of cells from laboratory cell-lines. And cells from 45 embryos, previously shown to be abnormal with another testing technique, were reanalysed by next-generation sequencing where the researchers were 'blinded' to the abnormalities present.

Dr Wells' team then worked with the Main Line Fertility Clinic in Pennsylvania, USA, and the fertility clinic of New York University in New York City to use the method in assessing the chromosomes of embryos produced by two couples undergoing IVF.

Cells sampled from seven five-day-old embryos (known as 'blastocysts') were screened, revealing three chromosomally healthy blastocysts for the first couple and two for the second.

In both cases, transferring one of these embryos led to a healthy pregnancy. The first pregnancy saw a healthy baby boy born in June. The second pregnancy is progressing well and is due to deliver in the next couple of months.

'Our next step is a randomised clinical trial to confirm the true efficacy of this approach,' said Dr Wells. He hopes that might start later this year through the Oxford Fertility Unit and the Lister Fertility Clinic in London.


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