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PGT for late‐onset disorders with genetic predisposition was first applied for a couple with inherited cancer predisposition, determined by p53 tumor suppressor gene mutations,⁷⁴ which are known to determine a strong predisposition to many cancers. Traditionally, these conditions have not been considered as an indication for prenatal diagnosis that would lead to pregnancy termination, which is not justified on the basis of genetic predisposition. Rather, the possibility of choosing embryos free of genetic predisposition for transfer would obviate the need for considering pregnancy termination, as only potentially normal pregnancies are established. Although the application of PGT for these conditions is still controversial, it has been performed for an increasing number of disorders with genetic predisposition that present beyond early childhood and may not even occur in all cases, including inherited cancers and heart disease.^{6, 7, 25, 74–77}

We have performed a total of 874 cycles for 56 different forms of cancers, the most frequent being breast cancer (284 cycles) caused by BRCA1 (159 cycles) and BRCA2 (125 cycles) mutations. A total of 199 PGT cycles for BRCA1/2 resulted in transfer of one or two embryos, yielding 131 pregnancies and birth of 134 children free from genes predisposing to breast cancer.⁴⁸

The other largest group of cancers for which PGT was performed was neurofibromatosis type 1 and type 2 (NF1/2), for which 103 cycles resulted in transfer of 138 genetic predisposition‐free embryos in 88 cycles, 53 clinical pregnancies, and 55 children born free from genes predisposing to neurofibromatosis.

Other cancers representing frequent indications for PGT were different types of Fanconi anemia (83 cycles), colorectal cancer (52 cycles), tuberous sclerosis types 1 and 2 (44 cycles) (see Figure 2.2), familial adenomatous polyposis (42 cycles), multiple endocrine neoplasia (34 cycles), and retinoblastoma (31 cycles); under 30 PGT cycles were performed for various other cancers. Overall, 966 genetic predisposition‐free embryos were transferred in 634 cycles, resulting in 387 (61.0%) clinical pregnancies and birth of 407 children free from the risk of developing these cancers.^{25, 48}

The other emerging PGT‐M indication has been inherited cardiac disease, for which 109 cycles were performed relating to 23 different diseases. The most frequent indications were familial hypertrophic cardiomyopathy, CMH4 (22 cycles), dilated cardiomyopathy, CMD1A (17 cycles), Holt–Oram syndrome, HOS (8 cycles), acyl‐CoA dehydrogenase very‐long‐chain deficiency, ACADVLD (6 cycles), familial hypertrophic cardiomyopathy 1, CMH1 (6 cycles), long QT syndrome 1, LQT1 (6 cycles) and Noonan syndrome 1, NS1 (6 cycles); PGT for another 16 cardiac conditions were performed in five or less number of cycles. Overall, 123 embryos free of genes predisposing to cardiac disease were transferred in 89 cycles (1.38 embryos per transfer on the average), resulting in 55 clinical pregnancies (61.7 percent) and birth of 54 children free from inherited predisposition to these cardiac diseases. If not prevented, many of these conditions may manifest despite presymptomatic diagnosis and follow‐up, with their first and only clinical occurrence being a premature or sudden death.⁷⁸ The couples at risk for producing progeny with inherited cardiac disease usually request PGT prospectively, with no previous pregnancies attempted, given one of the partners being a carrier of the specific mutation. Many couples already going through IVF for fertility treatment may have questions about the implications of genetic susceptibility factors for offspring, and the appropriateness of using PGT in testing for susceptibility to inherited cardiac disease.^{25, 48}

Of special interest are PGT indications for late‐onset disorders with inherited predisposition to neurological disorders, including neurodegenerative conditions. A total of 960 PGT cycles were performed for these conditions, including 610 for intellectual disability, 210 for Huntington disease, 42 for different movement disorders, such as torsion or myoclonic dystonia, nine for Alzheimer disease, and nine for Prion disease. As many as 1,110 unaffected or genetic predisposition‐free embryos were transferred in 738 cycles (1.5 embryos per transfer on average), yielding 412 clinical pregnancies and birth of 406 infants unaffected or free of the genes predisposing to the above conditions.⁴⁸ Thus, PGT provides a nontraditional option for patients who may wish to avoid the transmission of a mutant gene predisposing to late‐onset disorders in their future children. Because such diseases that present beyond early childhood and even later may not be expressed in 100 percent of cases, the application of PGT for this group of disorders is still controversial. However, for diseases with no current prospect for treatment, PGT may still be offered as the only relief for at‐risk couples.