Why consider preimplantation genetic testing for sickle cell disease?

Families with a child who has sickle cell disease may be looking for ways to go beyond managing the disease’s effects on their child and instead explore curative therapies. One curative option for genetic diseases of blood and immunity such as sickle cell disease is matched sibling donor bone marrow transplantation (MSD-BMT). If a child with sickle cell disease has a brother or sister without sickle cell disease, that brother or sister could donate their bone marrow to be used for a curative therapy, even if this sibling has sickle cell trait.

If two parents have already produced a child who has sickle cell disease, there is a 1 in 4 chance (25%) that another child they produce will have sickle cell disease. In addition, there is a 1 in 4 chance that this sibling would be a “match.” Doing the math, this combination of chances means that a sibling born to the same mother and same father of a child with sickle cell disease by natural methods has only a 19% chance of being a candidate donor for MSD-BMT. 

Preimplantation genetic testing (PGT) is a process to increase the chance of having a baby without sickle cell disease that is also a match to the child with sickle cell disease who could then serve as a bone marrow donor.

What is PGT?

If parents want to pursue MSD-BMT, they can undergo in-vitro fertilization (IVF) with PGT to potentially have a baby without sickle cell disease.

For IVF, the mother’s eggs and the father’s sperm are placed together to make embryos in a laboratory. An embryo — the early cell grouping that can become a baby — could then be placed into the mother’s uterus. But first, PGT is performed to determine if the embryo carries the sickle cell gene. Based on the tests, an embryo without the disease is then tested for being an HLA match.  An embryo that does not have sickle cell disease and is found to be an HLA match is then placed in the mother’s uterus to grow into a baby.

The IVF with PGT process

For Children's Hospital of Philadelphia (CHOP) patients, IVF with PGT is performed by our partners at Penn Medicine. These are the steps it entails:

Hormone injections: The woman gets hormone injections to stimulate her ovaries to make multiple eggs.

1. Egg removal: The woman has a minor surgical procedure to remove her eggs.
2. Fertilization: The man’s sperm is injected into each egg in the laboratory, often resulting in multiple embryos.
3. Embryo biopsy: A few cells of each embryo in the laboratory are removed for testing.
4. Preimplantation genetic testing: PGT determines whether each embryo has sickle cell disease and whether they are an HLA match.
5. Embryo placement: The chosen embryo is placed in the woman’s uterus. Other embryos without sickle cell disease can be safely frozen.

Factors to consider when deciding to pursue IVF with PGT

Success rate: The process is not always successful. IVF is less successful in older women. Many couples must go through more than one IVF cycle to have a healthy baby. In our experience at CHOP, the success rate for families willing to pursue at least two to three cycles of IVF with PGD is about 20%–30%. The most difficult part of the selection is identifying an embryo that is an HLA match, though even if a match is not found, PGT can be used to select an embryo that does not have sickle cell disease.

Cost: Each IVF cycle can be quite expensive and is generally not covered by insurance.

Other treatment options: Unrelated donor bone marrow transplants or experimental gene therapy are other curative approaches for sickle cell disease. While MSD-BMT has been considered the optimal therapy, the outcomes for the other two therapeutic options have been steadily improving in recent years. Unrelated donor bone marrow transplants or experimental gene therapy also do not involve the expense and time of IVF with PGT.

If IVF with PGT is successful, what happens next?

After the baby is born, we bank the infant donor's cord blood to enable a smaller bone marrow collection from the donor when that procedure is performed.

We wait until the donor sibling is 1 year old before performing MSD-BMT.