Alignment between expanded carrier screening panels and conditions leading to PGT-M: a real-world cohort study

To assess the extent to which expanded carrier screening (ECS) panels capture the genetic conditions for which preimplantation genetic testing for monogenic diseases (PGT-M) is performed.

A retrospective observational study conducted at a single university-affiliated PGT unit from 2015 to 2023. Women undergoing PGT-M for autosomal recessive or X-linked genetic conditions were included. Genetic conditions were cross-matched with five ECS panels (four commercial panels and one publicly funded ECS panel) and compared with a targeted, population-specific screening. Coverage was assessed at both the woman and gene levels using paired statistical comparisons.

A total of 330 cases were included; seven women underwent PGT-M for two eligible conditions and were therefore counted twice. These cases involved 110 different genes with an uneven distribution: eight genes accounted for 53.2% of cases, while 71 genes were observed in a single case. At the individual-woman level, targeted, population-specific screening showed lower coverage (47.9%) than that of all ECS panels (71.8-91.5%), with overall differences statistically significant (P < 0.001). At the gene level, coverage ranged from 20.9 to 79.1% across panels (P < 0.001). The evaluated ECS panels included 271-787 genes, with the largest panel demonstrating higher case coverage than the other commercial panels.

Expanded carrier screening panels capture most autosomal recessive and X-linked genetic conditions for which PGT-M is performed. These findings support the clinical utility of ECS in identifying couples at risk of having children affected by such conditions.