Contemporary prenatal genetic diagnosis for congenital adrenal hyperplasia: preimplantation genetic testing and maternal cell-free DNA

Preventing genital atypia in a fetus affected with congenital adrenal hyperplasia (CAH) by administration of dexamethasone to the mother early in pregnancy is an effective treatment option. However, strategies to identify at-risk pregnancies continue to evolve. Traditionally, first trimester chorionic villus sampling (CVS) or second trimester amniocentesis to detect an affected female fetus were conducted, and are still conducted today. Invasive prenatal procedures carry low but finite risks of pregnancy loss (1/455 after CVS; 1/400 after amniocentesis). Invasive methods are not applicable before 9–10 weeks, and treatment with dexamethasone should start before 9 weeks of gestation in order to prevent genital virilization in affected female fetuses. Ideally, prenatal diagnosis is made before 9 weeks and by noninvasive methods. This would avoid the need to treat male fetuses and unaffected female fetuses. Contemporary methods now offer such options. One approach is embryo selection using preimplantation genetic testing to select an unaffected embryo to transfer. A second approach involves cell-free DNA in maternal plasma, which contains both maternal cell-free DNA and fetal/embryonic cell-free DNA. In addition, at-risk couples are increasingly identified by panethnic carrier screening increases, benefitting from noninvasive cell-free DNA testing utilizing maternal blood.