Carrier screening and PGT for an autosomal recessive monogenic disorder: insights from virtual trials

To assess the costs and benefits of carrier screening and preimplantation genetic testing (PGT) for recessive autosomal monogenic disorders for couples attempting assisted conception.

A simulated first full cycle for women less than 35 years transferring embryos one at a time. The effect of testing on pregnancy outcomes was evaluated for different reporting scenarios. A Monte Carlo method utilising 1000 trials for 10,000 couples, testing 4, 16 and 38 genes, was used to assess the numbers likely to be at high risk and to estimate the incremental cost of screening and PGT to avoid an affected child.

PGT for high-risk couples: testing embryos only for the monogenic condition avoided 1 affected pregnancy for 4 cycles started. Combined with testing for chromosomal aneuploidy: ranking test results avoided 1 adverse pregnancy (affected, biochemical, clinical miscarriage) from 3 cycles started; 1 in 2 when excluding from transfer all embryos with an abnormal test result, within 1 in 25 fewer women achieving an unaffected live birth. Carrier screening for 4, 16 and 38 gene scenarios, where 1:250, 1:196 and 1:29 couples were at high risk: the incremental cost to prevent 1 affected live birth was estimated to be less than GBP 1,150,000 (US $1,587,000), < 836,642 (1,154,566) and < 137,794 (190,156), respectively, in 95% of trials.

Carrier screening combined with PGT, with and without testing for unrelated chromosomal abnormalities, for couples attempting assisted conception is complex but likely to be effective and also expensive.