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HLA typing

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Preimplantation HLA typing is an attractive PGT indication. The first case of preimplantation HLA typing was performed in combination with PGT for Fanconi anemia complementation group C (FA‐C), which resulted in a successful hematopoietic reconstitution in the affected sibling by transplantation of stem cells obtained from the HLA‐matched offspring resulting from PGT.5 To improve access to the HLA‐identical bone marrow transplantation in sporadic bone marrow failures, this approach was then applied with the sole purpose of ensuring the birth of an HLA‐identical offspring, not involving PGT, which also resulted in radical treatment of a sibling with a sporadic Diamond–Blackfan anemia (DBA) by stem cell transplantation from an HLA‐identical child born following preimplantation HLA typing.79 Preimplantation HLA typing has become one of the most useful indications for PGT, performed currently with or without testing for the causative gene.7988

Despite the ethical issues involved,80 preimplantation HLA typing procedures have so far been performed in hundreds of cases with affected children requiring HLA‐compatible stem cell transplantation, including thalassemia, Fanconi anemia, Wiskott–Aldrich syndrome, X‐linked adrenoleukodystrophy, X‐linked hyper‐IgM syndrome, X‐linked hypohidrotic ectodermal dysplasia with immune deficiency, X‐linked chronic granulomatous disease, cancer syndromes, incontinentia pigmenti, leukemias, and inherited and sporadic forms of DBA.8191

We applied PGT‐HLA in 485 cycles, including HLA typing alone, or combined with PGT‐M for 35 different conditions. Overall, 424 HLA‐matched unaffected embryos were detected and transferred in 291 cycles, resulting in 125 clinical pregnancies and birth of 117 HLA‐matched children, as potential donors for their siblings.25, 48, 92 Although the majority of cases were performed for thalassemia, this approach has a great life‐saving potential for affected siblings with congenital immunodeficiency. We performed 135 PGT cycles for 18 different immunodeficiency conditions, resulting in the birth of 54 children free of immunodeficiency, stem cell donors for transplantation treatment of affected siblings, with a total cure, such as Fanconi anemia and hyper‐IgM syndrome.48

Similar experience has been reported from other large series, such as from Istanbul: 626 PGT‐HLA cycles for 312 couples were performed (122 HLA only and 504 with PGT‐M), resulting in the birth of 128 thalassemia‐free children. Stem cells of 66 of these children were used for cord blood or bone marrow transplantation, which resulted in successful bone marrow reconstitution in all but two of them (transplantation treatment of the remaining 57 sibling pending).93, 94

Genetic Disorders and the Fetus

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