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.