IMPACT OF EXPANDED CARRIER SCREENING (ECS) ON UPTAKE OF PREIMPLANTATION GENETIC TESTING FOR MONOGENIC DISORDERS (PGT-M)

One of important problems in the health care application of technological developments in genomics is the availability of prospective identification of those at need for these technologies. The development and implementation of prospective carrier screening programs in the last few years is expected to increase the uptake of PGT-M. But most of couples at genetic risk are unaware of their genetic profiles to request PGT, which has been improved with the upgrade of traditional ethnicity-based screening to the expanded carrier screening (ECS). Recent advances in genomic technologies allow for multiplexed platforms with ability to screen for thousands of mutations and variants at a reasonable cost. The present ECS panels differ greatly in scope and include over thousand conditions and variants of variable penetrance, which are commercially available, offering the possibility of a more comprehensive and efficient risk evaluation. However, although the potential ECS to increase the number of couples presenting for PGT-M is obvious, no data are available to evaluate their actual impact. So this report evaluates the impact of ECS on the uptake of PGT-M, based on our ongoing PGT-M experience, which represents the world's largest series in one center. A total of 643 (54.6%) PGT-M cases were performed through ECS referral during the years 2016-2018, as part of our overall PGT-M practice of 1188 cases, including referrals through traditional approach during the same period of time. To evaluate the impact of ECS on the PGT-M uptake, we analyzed the dynamics of increase of at-risk couples presenting for PGT-M through ECS overall, as well as separately for each genetic condition tested, compared to the baseline referrals through the traditional approach. The analysis showed an increase of ECS based referrals to PGT-M from 35.1% (133 of 322 cases) in 2016 to 53.8% (210 of 392 total) in 2017, and 63.3% (300 of 474) in 2018. Among the most frequently referred conditions were cystic fibrosis (CFTR) (131 of 182, 72%), the uptake of which increased from 50% in 2016 to 82.7% in 2018; Deafness (GLB2) (65 of 81, 80.2%) with the uptake growing from 31.2% in 2015 to 86.4% in 2018; Fragile X (FMR1) (102 of 128, 80%), the uptake growing from 73% in 2016 to 84% in 2018; Thalassemia and sickle cell disease (HBB) (58 of 99, 58.6%), increasing from 45.8% in 2016 to 60.9% in 2018. So, the overall number of prospective PGT-M cases for the last three years more than doubled after ECS-based referral, with a similar dynamics for each condition tested (up to 80% increase of referrals through ECS). This may become the major source for performing PGT-M in the near future, allowing to offer PGT-M prospectively before the birth of an affected child. The data show significant increase of the PGT-M uptake following ECS, demonstrating the utility for offering PGT-M prospectively to the couples at risk.