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Injecting a boost for IVF

Scientists at UK fertility clinic CARE can now screen for chromosomal abnormalities in an ovum before it is fertilised under IVF - could this be the breakthrough that advances the field and bypasses ethical concerns?

Last year, Louise Brown, the first baby to be born after successful in-vitro fertilisation (IVF) turned 30 years old. Before then childless couples could only hope to have children if they had a medical condition which could be treated - for example a hormonal insufficiency which could be reversed through drugs.

However, one adversary against which medicine traditionally has been powerless is the mighty gene. It is known that about 20% of miscarriages are caused by a chromosomal defect either in the sperm or in the ovum. This problem is frequently non-recurrent, i.e. it is a spontaneous chromosomal defect which will not affect all the zygotes, therefore there is no reason why successive pregnancies would not be successful. However, for couples who suffer from other infertility problems, for example a low sperm count - a chromosomal defect would mean that the low chances of getting pregnant are compounded by a higher risk of miscarriage.

Early this year, scientists at UK fertility clinic CARE developed a novel method which screens for chromosomal abnormalities in the woman's ovum before it is fertilised under IVF. The technology which makes this possible is called array comparative genomic hybridisation (array CGH). Array comparative genomic hybridisation (also CMA, Chromosomal Microarray Analyisis, Microarray-based comparative genomic hybridisation, array CGH, a-CGH, aCGH, or Virtual Karyotype) detects genomic copy number variations at a higher resolution level than chromosome-based comparative genomic hybridization (CGH). Array CGH as an infertility treatment is currently not available anywhere in the world except here in the UK.

The main principles of this technique are:

1. A laser cuts a hole in the edge of the egg and the polar body is sucked out using a pipette.
2. The chromosomes inside the polar body are the image of those still inside.
3. The polar body chromosomes are analysed so that scientists can work out what is left behind in the egg without disturbing it.
4. By analysing the chromosome in the polar body the team may find that, for example, there is a missing chromosome and that therefore that egg is destined, if it becomes fertilised, of ending in a miscarriage.

Detecting chromosomal abnormalities of the egg before IVF treatment means that only eggs with a full complement of chromosomes are selected for IVF, thereby doubling its chances of success. This screening can be carried out within 24 hours, and also it removes the ethical dilemma of screening and rejecting embryos as array CGH screening is done at the pre-fertilisation stage.

Dr Simon Fishel, managing director of CARE Fertility Group said: "One of the main reasons why IVF doesn't work is chromosomal abnormality. Full chromosome analysis offers huge hope to many couples who have a poor chance of conceiving, those who have had many failures, and for those who want to maximise their chance at each attempt. We now have the best tool for achieving this - 'array CGH'. This screening method has the potential to improve birth rates, minimise the incidence of miscarriage and birth defects caused by chromosomal irregularity."

Array CGH provided a much better look at the gene content on the chromosomes of human embryonic stem cells, with a resolution about 100 times better than standard clinical methods. Traditionally this method had been used by clinical specialists who commonly generate a karyotype to examine the chromosomes of cancer cells or for amniocentesis in prenatal diagnosis, which has a much lower resolution than Array CGH, said Michael Teitell - a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

The creation of multiple-embryos in IVF has long been an ethical battlefield. Many pro-life and religious groups argue that life is created at the fertilisation of the egg, and therefore discarding embryos created during IVF rounds are seen akin to abortion. However, the principles behind this technique are very simple - screen eggs before fertilisation and only use the eggs that have a higher chance of success. As the ovum is screened before conception it bypasses the controversial embryo screening ethical issue, and it also means that as only eggs which are chromosomally guaranteed to succeed are used in the IVF process fewer embryos need to be created. Potentially you would only need to create the exact number of desired embryos as technically the embryo will be viable.

However, this is not going to appease the die-hard pro-life campaigners who consider IVF morally wrong. Although the application of array CGH in IVF is mired in moral complications, its potential benefits cannot be overlooked. This technique is capable of helping women who have been unsuccessful with natural conception or conventional IVF. However there continues to be room for improvement, for the further refinement of current procedures to make them even better and more successful. Dr Simon Fischel, director of the CARE Fertility group, said: "Ultimately we could reach the holy grail of one cycle of IVF, one egg, one embryo and one baby."

Case study:

Looking at the two grey blobs moving on the ultrasound monitor, Nadia felt the familiar wave of excitement, but this time it was marred by the knowledge that at any point she cold lose her babies. Until the age of 30 Nadia had been happily single, concentrating on a flying career in banking and making the most of her bonuses. At 35 she had met Adam and after 6 months they had married on a beach in an idyllic Greek island. When Nadia was nearing her 38th birthday she discussed having children with her husband and they decided to start trying. A year passed with not one positive pregnancy test they went to the GP. After a long list of invasive tests they were told the devastating news that Nadia suffered from chronic anovulation, a condition where the ovaries fail to release an oocyte, therefore ovulation was not taking place. After several months on clomid she started ovulating and her eggs were harvested ready for IVF. Nadia underwent several IVF attempts and on three occasions became pregnant, however she miscarried all of them before the 7th week. The reason for her miscarriages are unknown and experts suspect that a chromosomal abnormality is causing the high failure rate. By now, aged 42, Nadia and her husband had to come to terms that unless this pregnancy carried to full term, the chances of her becoming pregnant again were very remote.

Array CGH could offer Nadia and her husband a glimmer of hope. If they could obtain a donor egg, and the eggs screened for chromosomal abnormalities, it is very likely that with the right treatment she could not only become pregnant but also successfully carry the pregnancy to term.

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