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 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 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 A→T 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.