It is now possible for physicians to offer preimplantation genetic diagnosis for human leukocyte antigen (HLA) matching to a couple whose biological child is in need of an HLA-matched hematopoietic progenitor cell (HPC) transplant, or bone marrow transplant. The PGD procedure allows genetic screening to be performed on early embryos before implantation and pregnancy development for the purpose of selecting only those embryos that are HLA matched to the affected child.
Children’s Hospital of Wisconsin, Froedtert Hospital and the Medical College of Wisconsin offer PGD for the purpose of HLA matching. For definitions of any terms on this page, please see our glossary.
PGD for HLA Matching
When a couple has a child with a disease that requires an HPC transplant, they learn that the optimal source of cells needed for transplant is an HLA-matched sibling. Donor cells need to be HLA-matched to an affected child to significantly decrease the chance that the transplanted cells will react against the child’s body (graft vs. host disease). Many of these children do not have an HLA-matched sibling, so their physicians look for an unrelated HLA-matched donor through the bone marrow registry and cord blood registry. Some couples have undertaken a pregnancy in the hope of having a child who is an HLA match to their affected child. With each pregnancy, these couples have a 1 in 5 chance of conceiving a child who is an HLA match to their affected biological child.
A new alternative is now available to couples using in vitro fertilization (IVF) to find an HLA match. Following IVF, preimplantation genetic diagnosis can be used for the purpose of HLA matching by selecting for and transferring only the embryos that are HLA matched to your affected child. Each embryo has a 1 in 5 chance of matching the affected biological child. With PGD, the goal is to select those embryos that are a match and transfer them. In this process, we can significantly increase the chance for a couple to have a child that is HLA-matched to the affected child.
PGD Process for the Purpose of HLA Matching
A couple and their affected child will be asked to undergo blood tests. These blood tests will determine whether the preimplantation genetic diagnosis process will be feasible. If these tests show that PGD is possible, the parents will undergo an IVF cycle to form embryos.
The embryos formed are sampled on the third day of development when they have approximately 6 to 8 cells. One or two cells are then taken from the embryo for testing, and the embryo is incubated until testing is complete. PGD is performed on cells from each embryo for the purpose of identifying those embryos that are an HLA match to the affected child.
Risks of PGD
The techniques used in PGD for HLA matching compares the mother’s DNA and father’s DNA to that of the affected child. It is imperative that both parents are the biologic/genetic parents of the affected child to ensure that it is possible to find HLA-matched embryos. If non-paternity or non-maternity is discovered, pursuit of an HLA-matched embryo will not be successful.
The sampling technique required to perform PGD has been in use since 1990. The likelihood of damage to an embryo during the removal of cells is low, but it can occur. This can result in a decreased chance of embryo survival. When compared to IVF without PGD, there is a somewhat decreased chance for embryo survival among embryos that have undergone PGD. IVF with PGD is not known to lead to an increased chance for congenital abnormalities, birth defects, mental retardation, or other abnormal development when compared to natural pregnancies. However, a normal pregnancy outcome is not guaranteed.
Accuracy of PGD
Overall, PGD is an accurate process for determining whether the HLA type of an embryo matches that of an affected child. There is a small risk of error or technical limitation that will prevent us from determining whether the sampled embryos and the affected child are HLA matched. Because of this and the fact that we do not test for genetic conditions or chromosome problems, the option of testing early in pregnancy through prenatal diagnosis is available.
Preventive Measures During PGD Cycle
It is important for a couple undergoing PGD to alter their sexual activity during the PGD cycle. The couples must refrain from intercourse until the cycle is complete.
Cost of PGD
IVF with PGD is expensive. Insurance companies generally do not cover the cost of IVF with or without PGD. We will provide you with a detailed cost analysis for IVF and PGD.
Use of Umbilical Cord Blood
It is expected that the cord blood from the matched sibling will be used for transplantation. Because the cord blood sample may fall short of the required number of cells for transplantation we expect that 70 percent of cord bloods may need supplementation with other progenitor cell sources such as bone marrow or peripheral blood stem cells.
Requests for information regarding the Children’s Hospital of Wisconsin, Froedtert Hospital and the Medical College of Wisconsin PGD program and IVF can be obtained by contacting the Reproductive Medicine Clinic at 414-805-7370 or by using our Contact Us form. Information regarding PGD for the purpose of HLA matching can be discussed in more detail with our geneticist or genetic counselor.
PGD — Preimplantation genetic diagnosis — This is the process of testing the genetic make up of an embryo formed through in vitro fertilization (IVF).
HLA — Human leukocyte antigen — These are the proteins on white blood cells that are matched in order to do a Blood or Bone Marrow Transplant.
HLA Matching — This is a process that compares the Human Leukocyte Antigen type of two individuals. When they have the same HLA type they are said to be a match.
IVF — in vitro fertilization — This is the process of using eggs and sperm to form embryos in the laboratory.
PCR — Polymerase Chain Reaction — This is a process that takes a small amount of DNA, such as the DNA from a single cell and makes many copies of it. This copied DNA can be used to determine the HLA status of an embryo.
Hematopoietic Progenitor Cell (HPC) — These are the seed cells that can re-grow a bone marrow. They are found in bone marrow, umbilical cord blood, or peripheral (circulating) blood.
Hematopoietic Progenitor Cell (HPC) Transplant — Most commonly known as a “bone marrow transplant,” an HPC transplant is the use of chemotherapy and/or radiation therapy followed by infusion of HPC in order to regrow the bone marrow.
Embryo Transfer — The process of returning the embryo to the uterus