EXPANDED CARRIER SCREENING AND CLINICAL DECISION MAKING IN 2020

Abstract

To assess how often clinical management is altered using expanded carrier screening (ECS) panels that analyze 283 genes. All couples who underwent expanded carrier screening with one test provider (SEMA4) in 2020 at a large assisted reproductive center were evaluated, with a focus on those with at least one partner with a positive carrier screen at risk for disease. A high-risk result was defined as any result that provided patients with information that was medically actionable, including the potential use of PGT-M for the selection of an unaffected embryo. The overall rate of positive ECS results and the number of couples who were considered high-risk were evaluated. From this data set, the proportion that underwent preimplantation genetic testing for monogenic/single gene disorders were analyzed. A total of 9,444 individuals were tested, with 4,722 couples tested in total. Of those, 3,471 (73.5%) of the couples had a positive result for at least one gene in one of the partners. 391 patients (11% of those with at least one positive test) were considered high-risk for genetic disorders that were potentially actionable. Some patients/couples had multiple actionable results. Out of the couples with at least one partner with an abnormal ECS, 145 (4% of positive tests, 37% of high-risk) underwent PGT-M testing. Five couples declined PGT-M even though they were considered high-risk, however they all underwent preimplantation genetic testing for aneuploidy (PGT-A). From this data, expanded carrier screening informed and/or affected clinical decision making 4.1% of the time, 391 times after 9,444 tests with 4,722 couples. The utilization of expanded carrier screening continues to increase in reproductive medicine populations. Prior studies have suggested that ECS will identify at least 1/300 couples (0.3%) who will have risk for a severe genetic disease for which PGT-M will prevent transmission. With our dataset, expanded carrier screening identifies approximately four percent of couples who have increased reproductive risk or personal health risk. The rate of positivity for at least one gene is likely to increase as ECS providers continue to expand testing panels. Further research is needed to understand the decision-making regarding couples who are eligible to do PGT-M but choose to proceed with only PGT-A.