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Yury Verlinsky, PhD; Svetlana Rechitsky, PhD; William Schoolcraft, MD; Charles Strom, MD,PhD; Anver Kuliev, MD,PhD

JAMA. 2001;285:3130-3133.

Context  The advent of single-cell polymerase chain reaction (PCR) has presented the opportunity for combined preimplantation genetic diagnosis (PGD) and HLA antigen testing. This is a novel and useful way to preselect a potential donor for an affected sibling requiring stem cell transplantation.

Objective  To perform in vitro fertilization (IVF) and preimplantation HLA matching combined with PGD for Fanconi anemia (FA).

Design  DNA analysis for the IVS 4 + 4 AT (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 before 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 AT mutation in the FANCC gene with an affected child requiring an HLA-compatible donor for cord blood transplantation.

Main Outcome Measures  DNA analysis of single blastomeres to preselect unaffected 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-compatible, of which 2 were transferred in the first and 1 in each of the other 3 cycles, resulting in a pregnancy and birth of an unaffected child in the last cycle.

Conclusion  To our knowledge, this is the first PGD with HLA matching, demonstrating feasibility of preselecting unaffected embryos that can also be an HLA-compatible source for stem cell transplantation for a sibling.

Author Affiliations: Reproductive Genetics Institute, Chicago, Ill (Drs Verlinsky, Rechitsky, Strom, and Kuliev); and Colorado Center for Reproductive Medicine, Denver (Dr Schoolcraft).

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