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Yury Verlinsky, PhD; Svetlana Rechitsky, PhD; Tatyana Sharapova, MS; Randy Morris, MD; Mohammed Taranissi, MD; Anver Kuliev, MD, PhD

JAMA. 2004;291:2079-2085.

Context  Preimplantation genetic diagnosis (PGD) has become an option for couples for whom termination of an affected pregnancy identified by traditional prenatal diagnosis is unacceptable and is applicable to indications beyond those of prenatal diagnosis, such as HLA matching to affected siblings to provide stem cell transplantation.

Objective  To describe preimplantation HLA typing, not involving identification of a causative gene, for couples who had children with bone marrow disorders at need for HLA-matched stem cell transplantation.

Design, Setting, and Participants  HLA matching procedures conducted at a single site during 2002-2003 in an in vitro fertilization program for 9 couples with children affected by acute lymphoid leukemia, acute myeloid leukemia, or Diamond-Blackfan anemia requiring HLA-matched stem cell transplantation. In 13 clinical cycles, DNA in single blastomeres removed from 8-cell embryos following in vitro fertilization was analyzed for HLA genes simultaneously with analysis for short tandem repeats in the HLA region to select and transfer only those embryos that were HLA matched to affected siblings.

Main Outcome Measures  Results of HLA matching and pregnancy outcome.

Results  As a result of testing a total of 199 embryos, 45 (23%) HLA-matched embryos were selected, of which 28 were transferred in 12 clinical cycles, resulting in 5 singleton pregnancies and birth of 5 HLA-matched healthy children.

Conclusion  This is the first known experience of preimplantation HLA typing performed without PGD for a causative gene, providing couples with a realistic option of having HLA-matched offspring to serve as potential donors of stem cells for their affected siblings.

Author Affiliations: Reproductive Genetics Institute, Chicago, Ill (Drs Verlinsky, Rechitsky, Morris, and Kuliev and Ms Sharapova); and Assisted Reproduction and Gynaecology Center, London, England (Dr Taranissi).

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