Embryo testing could produce babies who might aid sick siblings

Parents with a child requiring stem cell transplantation can have genetic testing done on embryos prior to implantation to determine if the tissue type matches and the ensuing offspring could potentially serve as a donor to the affected child, according to a study in the May 5 issue of The Journal of the American Medical Association (JAMA).

Preimplantation genetic diagnosis (PGD) has become available as an alternative to prenatal diagnosis in order to avoid the risk for pregnancy termination, because PGD allows selection of unaffected embryos before a pregnancy is established, according to background information. Despite the need for ovarian stimulation and in vitro fertilization (IVF) to be part of the procedure, PGD has become an acceptable method for avoiding the birth of children with genetic disorders.

Preimplantation genetic diagnosis is applicable to indications beyond those of prenatal diagnosis, such as Human Leukocyte Antigen (HLA) matching to affected siblings to provide stem cell transplantation. HLA testing, also known as tissue typing, determines the compatibility between donors and recipients for the transplantation of solid organs (i.e. heart, liver, kidney and lung) and bone marrow. Compatibility within the HLA minimizes immune rejection.

Yury Verlinsky, Ph.D., of the Reproductive Genetics Institute, Chicago, and colleagues report the first clinical experience of preimplantation HLA matching not involving identification of a causative gene to demonstrate the feasibility of this approach for stem cell transplantation in siblings with bone marrow failure.

The study consisted of HLA matching procedures conducted during 2002-2003 in an in vitro fertilization program for nine couples with children affected by acute lymphoid leukemia, acute myeloid leukemia, or Diamond-Blackfan anemia (DBA) requiring HLA-matched stem cell transplantation. DNA was removed from embryos following in vitro fertilization and analyzed for HLA genes, and embryos were transferred that were HLA matched to affected siblings.

The researchers found that as a result of testing of a total of 199 embryos, 45 (23 percent) 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.

"The data herein show the potential feasibility of preimplantation HLA matching for couples having a child affected with a bone marrow disorder, who may wish to have another child as a potential HLA-matched donor of stem cells for transplantation to the affected sibling," the authors write. "In addition to sporadic forms of DBA, as well as leukemia, the method may potentially be applied to other conditions; for example, the method might be used by parents who have unsuccessfully sought an HLA-compatible donor for a child with other types of cancer. These expanding indications make preimplantation testing a complement to traditional prenatal diagnosis, allowing parents to avoid inherited conditions and pregnancy termination. At the same time, the evidence suggests that it may now be possible for a pregnancy to have genetic characteristics that may be beneficial for affected individuals in the family." (JAMA. 2004;291:2079-2085. Available post-embargo at JAMA.com)

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