Preimplantation Genetic Testing (PGT) for non-traditional indications

Since the introduction of PGT, the indications for PGD are gradually expanding. Initially performed mainly for childhood-onset genetic conditions with clearly defined penetrance, severity and disease phenotypes, PGT is now applied to common late onset conditions determined by genetic predisposition, which may be realized with age or not realized in a lifetime. We present here the experience of PGT for these borderline indications in our series of over 17,000 PGT cases, which includes 5,780 PGT-M

Of the521 conditions tested, the borderline indications included71 cycles for cardiac conditions, 461 cycles for HLA matching and 702 cycles for cancer predisposition. Combined, these 1,163 cycles represent 20.1% of the overall cases. The most common cardiac genetic condition was Dilated Cardiomyopathy (DCM), 5causatives genes (over 30 different mutations), as well as Hypertrophic Cardiomyopathy (HCM) with 6 causative genes (over 16 different mutations). These cycles resulted in birth of 32 cardiac disease predisposition free children. The largest group for non-traditional indications was PGT-M for 23 cancer predisposition syndromes (642 cases overall), including BRCA1 and BRCA2, accounting for more than a third of the cases (32.7%; 210/642). These cycles resulted in birth of 271children free of cancer predisposition genes, which is the world's largest series. The number of cases for cancer predisposition syndromes has increased steadily since 1999, after we performed the world's fist PGT. The other group of PGT for non-traditional indications is PGT for HLA matching, which was requested either in combination with PGT-M (73.5% (339/461), or exclusively for HLA typing (26.5% (122/461), with or without PGT-A. Referrals for PGT are becoming increasingly complex as the improving testing technologies identify a wide genetic heterogeneity, variable severity and penetrance of adult onset conditions, for which the application of PGT may present importance ethical problems. However, our experience shows the increasing referral for PGT of such conditions, which was extremely accurate and efficient, allowing couples at risk to produce the offspring free of genes predisposing to common conditions of later life.