A closer look at expanded carrier screening from a PGD perspective

Abstract

Conventionally, the search for carrier status was based on ethnicity and/or family history and targeted to a restricted number of genetic conditions and mutations. This is now being replaced by extended panels testing for hundreds of genetic disorders with a broad range of phenotypes, in what is called ‘expanded carrier screening’. While the ultimate aim of these panels is to increase the reproductive autonomy of the individuals and couples by providing preconception knowledge that could lead to the broadest range of available options, including PGD, we argue that: (i) Given the number and heterogeneity of the conditions included in panels, it cannot be guaranteed that a couple who tests positive for one of those conditions will be eligible for PGD; patients should be informed of this potential limitation before undertaking screening. (ii) Family history is typically lacking in couples identified through panels as being at high-risk for certain disorders. This should promote a reflection on the inclusion of personal experience with a condition as a consideration for PGD in disorders with incomplete penetrance or for which treatment options are available. (iii) With the advent of next-generation sequencing panels, cases of couples in which one member carries a disease-causing variant and the other has a variant of uncertain significance found in the same gene are likely to become more common and need to be discussed from the PGD perspective. (iv) With comprehensive panels where healthy individuals are likely to be identified as carriers for several conditions, testing of carrier status for embryos and prioritisation of the embryos to transfer needs reassessing. We believe that these points should be included in the discussion on expanded carrier screening and that all stakeholders, patients included, must be aware of the challenges and limitations that may come with a positive result.