This September, thousands of young doctors wanting to specialise in obstetrics and gynaecology will sit the Part 1 MRCOG examination, a crucial assessment for all O&G trainees in the UK. Last month, the Royal College of Obstetricians and Gynaecologists (RCOG) invited Dr Lisa Levett – HSL’s Director of Genetics and Molecular Pathology – to speak at their Part 1 MRCOG revision course.
Molecular techniques now play an essential role in prenatal diagnosis and screening, from the detection of viral infections and disease predisposition to the diagnosis of genetic disorders. Molecular testing for chromosomal abnormalities is an area of particular interest for Dr Levett. The most common anomalies are those involving whole extra chromosomes, such as trisomy 21 (Down’s syndrome) and trisomy 18 (Edwards syndrome). 15 years ago, cytogeneticists were having to diagnose these disorders by counting chromosomes down the microscope; today, new molecular methods such as PCR and array CGH have transformed this time-intensive method, making diagnosis much quicker and easier.
Dr Levett gave the trainees an overview of the key molecular techniques relevant to O&G from a laboratory perspective. “It’s important that clinicians understand the clinical relevance of the tests they’re requesting, as well as their risks and limitations,” she explains. “So many different molecular techniques can now be performed in the laboratory – but they vary in their clinical significance. A screening test with a high risk result is not the same as receiving a positive diagnosis. It’s vital that doctors understand this difference and can explain it to patients.”
Non-invasive prenatal testing
Non-invasive prenatal testing (NIPT) is the most recent breakthrough in this field. Diagnostic prenatal testing requires mothers to undergo amniocentesis or chorionic villus sampling – both invasive procedures which could result in miscarriage. NIPT, in contrast, involves a simple blood test and carries no risk to the foetus. The Harmony prenatal test is one such example.
Currently performed at HSL’s flagship laboratory, the Halo, the Harmony test involves microarray analysis of cell-free foetal DNA from the mother’s blood. An overabundance of cell-free DNA fragments from a single chromosome suggests foetal trisomy. The Harmony prenatal test is still considered a screening test, rather than a diagnostic one, but is significantly more sensitive than traditional first trimester screening programmes. For Down’s syndrome, for example, the Harmony test has a detection rate of over 99% and a false positive rate of less than 0.1%. This is vastly superior to conventional prenatal screening, which detects only 70-80% of cases and has a false positive rate of 5%.
The future of NIPT
There is no doubt that NIPT is here to stay. With such high sensitivity, NIPT not only detects more cases of foetal trisomy, it also minimises the risk of unnecessary amniocentesis. Yet not all NIPT techniques are the same. “The technology is moving fast, and new NIPTs are coming onto the market,” Dr Levett explains. “Different assays and algorithms can give different results – with different margins of error. Clinicians must understand these complexities when deciding whether or not NIPT is appropriate for their patients.”
While currently not routinely available on the NHS, the UK National Screening Committee recently announced an evaluative implementation of NIPT to assess its impact on the existing NHS foetal anomaly screening programme. TDL Genetics has been offering the Harmony test for the past four years, and Dr Levett has enjoyed watching its progression: “I am just as excited about this test now as I was when it first became available in the US. Awareness of NIPT is increasing among the medical profession and the public, and more and more women are choosing to have this screening test themselves – even if they currently have to pay for it.”