Reproductive genetics: are non-invasive preimplantation tests accurate enough?

The 9^th edition of the IVIRMA Congress finishes, after five days in which the best researchers in Assisted Reproduction have presented the latest findings in the field, in an online format due to the pandemic situation. With a more interactive and looking for dynamic formats, the congress has offered different debates, conducted by experts, on the most relevant topics for the future of reproductive medicine and Workshops run by leading figures in Reproductive Medicine. On this occasion, the audience was broadened to add not only medical and research staff, but also other professionals linked to infertility and assisted reproduction, such as psychologists, family doctors and geneticists.

Reprodutive genetics is one of the most important topics at the moment, in constant evolution. “Non-invasive preimplantation genetic tests – are we ready?” is the question posed at the round table discussion moderated by Dr. Nicolás Prados, Director of IVI’s IVF laboratory. Doctors Dagan Wells and Carmen Rubio participate in this round table to analyze the advantages, disadvantages and characteristics of traditional pre-implantation genetic testing and the more recent, non-invasive methods.

Reprodutive genetics: preimplantation tests 

The use of preimplantation genetic tests is common in assisted reproduction treatments, helping to ensure that the embryos transfered to the uterus do not have 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’. If an aneuploid embryo is transferred during an IVF cycle, in most cases it will not implant or will miscarry. Therefore, it is advisable not to transfer chromosomally abnormal embryos if they can be accurately detected”, explains professor Wells.

Dagan Wells is a professor at the University of Oxford, and he has devoted almost three decades to the study of embryonic genetic anomalies and their early detection. In addition, he runs Juno Genetics, a state-of-the-art clinical diagnostic laboratory providing a wide variety of genetic tests related to reproductive medicine. For her part, Dr. Rubio is the Director of Embryo Genetics Research at Igenomix Laboratories.

Invasive tests vs non-invasive tests

Why are traditional preimplantation genetic tests invasive? Prof. Wells attributes it to the technique required. “A small number of cells are removed from the embryo, usually when the embryo is about five days old. The cells are then analyzed using advanced molecular methods. The only problem is that the removal of these cells is a highly skilled procedure. It requires an embryologist who has done a lot of training. It also requires some expensive equipment.”

Skilled professionals are required to perform this, although not all laboratories have them, neither technology nor equipment. This, according to Prof. Wells, reduces patients’ access testing and increases costs, causing “bottlenecks”.

In contrast, non-invasive tests focus their analyses on a tiny amount of genetic material that leaves the cells and passes into the environment in which the embryo is developing. That means that they are carried out without extracting cells from the embryo.

Professor Wells summarizes as follows the significant advantages of these techniques: “Any risk to the embryo associated with the removal of cells wouldn’t exist and the costs of the procedure could diminish. Clinics would not have to pay a very experienced embryologist nor have the expensive equipment required”.

The accuracy of non-invasive preimplantation genetic tests

Nevertheless, the accuracy of the results provided is still not enough, as concludes professor Wells. “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 the embryo has an abnormality but is wrongly classified unaffected. I don’t believe that non-invasive tests are sufficiently reliable.”

Prof. Wells argues that sometimes it is necessary to supplement the test with a follow-up performed using traditional invasive techniques, due to frequent errors in the results of non-invasive tests. This fact “defeats the whole purpose of doing the non-invasive test in the first place”.

That is why he speaks of an “extremely exciting possibility” but insists that for the time being, more precision is needed in the results offered by invasive tests. “I’m still convinced that non-invasive PGT-A has great promise for the future. I just don’t believe it’s ready at this time”, he concluded.