The use of non-invasive embryo testing has many advantages, but current methods need to overcome significant limitations until they are ready for clinical use, says Prof. Dagan Wells.
Are we ready for non-invasive pre-implantation genetic testing? This is the question posed at a roundtable discussion chaired by Dr. Nicolás Prados, Director of IVI’s IVF laboratory, on the final day of the 9th edition of the IVIRMA Congress. The discussion compared the use of traditional pre-implantation genetic testing to more recent, non-invasive methods. Doctors Dagan Wells and Carmen Rubio participated in the roundtable to analyse the advantages, disadvantages and characteristics of both.
Dagan Wells is a professor at the University of Oxford who has devoted almost three decades to the study of embryonic genetic anomalies and their early detection. He currently manages the state-of-the-art clinical diagnostic laboratory Juno Genetics, which provides a wide variety of genetic tests related to reproductive medicine. Dr. Carmen Rubio is the Director of Embryo Genetics Research at Igenomix Laboratories.
During the debate, Prof. Dagan Wells described non-invasive testing of IVF embryos as a ”revolutionary approach which offers a great deal of promise”. However, he cautioned that such methods are not yet ready for use in clinics because the results they provide do not match the same levels of accuracy as invasive methods. “We should be providing the best possible care for our patients and I don’t believe that non-invasive tests are sufficiently reliable at this time. For example, there are too many false positives: embryos that are labelled abnormal when in fact they are unaffected by the genetic abnormality being tested. There are also too many false negatives, cases in which an embryo has an abnormality but is mistakenly classified as unaffected”.
Prof. Wells argues that such errors in the results of non-invasive tests are sometimes so frequent that it is considered necessary to supplement the test with a follow-up performed using the traditional invasive method, which Prof. Wells added “defeats the whole purpose of having done the non-invasive test in the first place”.
Detection of chromosomal abnormalities
The use of pre-implantation genetic testing is common in assisted reproduction treatments, helping to ensure that the embryos chosen for transfer do not contain any chromosomal abnormalities. “Embryos generated during an IVF cycle quite often have a chromosome missing or a duplicated one. This is a situation known as ‘aneuploidy’. In most cases, if a chromosomally abnormal embryo – an aneuploid embryo – is transferred during an IVF cycle, it will not implant or it will miscarry. Therefore, it is advisable not to transfer chromosomally abnormal embryos if they can be accurately detected”, explained Wells.
Pre-implantation testing is traditionally performed using a technique that is considered invasive and requires skilled professionals, as Prof. Wells describes: “A small number of cells are removed from the embryo, usually when the embryo is about five days old. The cells are then analysed using advanced molecular methods. The removal of these cells is a highly skilled procedure: it requires an embryologist who has done a lot of training and it also requires some expensive equipment.”
Not all laboratories have the required technology, equipment or skills, which according to Prof. Wells, causes “bottlenecks” that reduce access to testing for patients and increase costs. In contrast, non-invasive tests can be carried out without the need to extract cells from the embryo. Instead, they focus their analyses on a tiny amount of genetic material that leaves the cells and is released into the external environment in which the embryo is developing.
“Any risk to the embryo associated with the removal of cells would be eliminated and the costs of the procedure could be reduced, as clinics would not have to pay a very experienced embryologist nor have to have access to the expensive equipment required”, added Prof. Wells. Among these advantages of non-invasive testing, Wells describes an “extremely exciting possibility” but insists that more precision is needed in the results obtained, which only invasive tests offer at this time. “I’m still convinced that non-invasive PGT-A has great promise for the future but I don’t believe it’s ready at this time”, he concluded.