Clinical implications of expanded carrier screening for pregnancy-related care and individual health

To evaluate the incidence of expanded carrier screening (ECS) results with possible clinical implications on patient health and/or pregnancy-related treatment planning.

Single academic center, retrospective, cohort study.

A total of 3,136 patients underwent ECS between January 2018 and December 2020.

All patients were screened using the same ECS, comprising 283 genes.

Rates of positive ECS results and carrier-carrier couples were reported, excluding carrier-carrier couples without a reproductive risk for a serious clinical outcome (i.e., alpha thalassemia single-gene deletions). Results with possible ramifications for an individual patient's health were recorded. This included individuals identified through ECS to be potentially affected with a genetic condition due to homozygous or compound heterozygous findings, and those with heterozygous findings associated with a personal health risk, such as elevated risk for premature ovarian insufficiency, metabolic crisis, neurological disease, cardiovascular disease, or malignancy.

Expanded carrier screening was performed and resulted in 3,136 patients; 2,280 (72.7%) carried at least one condition. Fifty-four patients (1.7%) were homozygous or compound heterozygous for a recessive genetic condition. Another 68 patients (2.2%) were high-risk heterozygote carriers of a recessive disease: Gaucher (n = 34), familial hypercholesterolemia (n = 14), fumarase deficiency (n = 9), ataxia-telangiectasia (n = 7), and fragile X premutation (n = 4). Ten female carriers of X-linked conditions were identified (0.4%). When restricting analysis to couples who both completed ECS (n = 905 couples), 58 couples (6.4%) carried the same genetic condition, although only 21 (2.3%) were considered clinically significant disease-causing combinations and recommended for preimplantation genetic testing for monogenic conditions.

A small proportion (1.7%) of total ECS results impact clinical fertility care by triggering recommendations for in vitro fertilization with preimplantation genetic testing for monogenic conditions. A larger proportion of results (3.9%) had implications for patients' personal health, which may not be sufficiently addressed in the consent process and can affect eligibility for benefits such as life and disability insurance.