December 6, 2022

Predicting an embryo’s future with ‘polygenic risk scores’ is ‘unproven’ and ‘unethical’, say experts

“Advanced embryo genetic testing. Choose your healthiest embryo.” This is the slogan of Genomic Prediction, an American company which is selling polygenic risk scores (PRSs) analyses of embryos to prospective parents.

It claims that its technology is being used in 173 IVF clinics in 37 countries. Its mission is “Choice over chance: helping families have healthy babies.”

However, a critical article in European Journal of Human Genetics says that such claims are both “unproven” and “unethical”.

The authors say that there is no evidence that PRSs can predict the likelihood of as-yet unborn children being liable to a specific disease in the future.

Genetic risk tests already exist and are used to screen out (ie, destroy embryos) for traits like Down syndrome or cystic fibrosis. Such tests work because there is a single, easily detectable gene. But many diseases or valuable traits (like IQ or athletic ability) involve many genes interacting with the environment.

Genomic Prediction, for instance, claims that its tests can predict polygenic conditions like type 1 and type 2 diabetes, breast cancer, testicular cancer, prostate cancer, malignant melanoma, basal cell carcinoma, coronary artery disease, heart attack, hypercholesterolemia, hypertension and schizophrenia.

The geneticists at the ESHG appear to believe that this is rubbish.

“While PRS may identify individuals at risk of a given disease in the general population (where the genetic variability is very wide) there is no evidence that they can be useful for a couple in determining the choice of one embryo over another, as the genetic variability within an individual family is limited,” says Dr Francesca Forzano, of the ESHG.

No information on the value of PRSs to predict disease development in postnatal life is available for embryos. In fact, such studies would be wellnigh impossible to perform in embryos, given that one might have to wait decades for the predicted disorder to appear – or not.

Performing a PRS test for embryo selection would be premature at best, say the authors. Adequate, unbiased information on the risks and limitations of this practice should be provided to prospective parents and the public, and a societal debate must take place before any potential application of the technique in embryo selection.

Such a debate should be focused particularly on what would be considered acceptable regarding the selection of individual traits. Without proper public engagement and oversight, the practice of implementing PRS tests for embryo selection could easily lead to discrimination and the stigmatisation of certain conditions.

“It is also vital to provide prospective parents with a clear understanding of the difference between counselling and marketing,” says Professor Maurizio Genuardi, ESHG President.

Klaus Wiemer, of Poma Fertility, an IVF clinic in Kirkland, Washington, told the online magazine GenomeWeb about a client who asked for a for a second cycle of IVF to get embryos with better risk scores with Genomic Prediction’s testing service.

“Even though the embryos are genetically normal,” said Wiemer, “she was just unhappy with the heritable scores that the embryos got for certain traits. So what happens to all those other embryos that are okay? That’s the problem that we’re starting to face.”