Preimplantation diagnosis for fanconi anemia combined with HLA matching

Context The advent of single-cell polymerase chain reaction (PCR) has prese nted the opportunity for combined preimplantation genetic diagnosis (PCD) a nd HLA antigen testing, This is a novel and useful way to preselect a poten tial donor for an affected sibling requiring stem cell transplantation. Objective To perform in vitro fertilization (IVF) and preimplantation HLA m atching combined with PGD for Fanconi anemia (FA), Design DNA analysis for the IVS 4+4 A -->T (adenine to thymine) mutation in the FA complement C (FANCC) gene in single blastomeres, obtained by biopsy of embryos, to identify genetic status and HLA markers of each embryo befo re intrauterine transfer. Setting In vitro fertilization programs at large medical centers in Chicago , ill, and Denver, Colo. Participants A couple, both carriers of the IVS 4+4 A -->T mutation in the FANCC gene with an affected child requiring an HLA-compatible donor for cor d blood transplantation. Main Outcome Measures DNA analysis of single blastomeres to preselect unaff ected embryos representing an HLA match for the affected sibling. Results Of 30 embryos tested in 4 IVF attempts, 6 were homozygous affected and 24 were unaffected. Five of these embryos were also found to be HLA-com patible, of which 2 were transferred in the first and 1 in each of the othe r 3 cycles, resulting in a pregnancy and birth of an unaffected child in th e last cycle. Conclusion To our knowledge, this is the first PGD with HLA matching, demon strating feasibility of preselecting unaffected embryos that can also be an HLA-compatible source for stem cell transplantation for a sibling.