Preimplantation Genetic Testing (PGT) for Non-Lethal Correctable Conditions Through Population Carrier Screening

An increasing number of patients without family history of genetic disease are referred for preimplantation genetic testing of monogenic disorders (PGT-M) after ascertainment through population (expanded) carrier screening (ECS), increasing the proportion of non-lethal correctable genetic conditions in PGT-M indication profile. The aim of this paper is to analyze the current dynamics of these changes in our PGT-M series, which is the world’s largest PGT-M experience. This was analyzed using our PGT-M for two prevalent examples of non-lethal correctable genetic conditions, phenylketonuria (PKU) and hereditary hearing loss (HHL) during the period of 2005-2022. During this period, 91 PGT-M cycles were performed for PKU, involving testing for 108 mutant alleles in PAH gene, and 262 PGT-M cycles for HHL, involving testing for up to 300 mutations in 13 different genes causing hearing loss. PGT-M for these non-lethal correctable conditions resulted in the birth of 54 babies free of PKU and 134 children free of HHL. Dynamics of PGT-M referrals during this period of 17 years demonstrated the shift from retrospective to prospective application of PGT-M for both conditions, with 87% of prospective PGT-M performed for PKU, and 82% for HHL, performed for couples who had no affected relatives with PKU or HHL. These at-risk couples were ascertained through ECS in the last decade, making it possible to provide the option of prospective PGT-M for these non-lethal correctable conditions.