Pre-implantation genetic diagnosis (PGD)

Reproductive Options

Many couples who find out that the woman or the man is an FMR1 mutation carrier ask “what are my options for the future?” or “How can I increase my chance of having a child without fragile X syndrome or to test a pregnancy in the future?” There are a number of ways to build a family for carriers including conceiving naturally and testing the pregnancy (prenatal diagnosis), testing a fertilized egg outside the woman’s body and implanting only unaffected embryos (PGD), using an egg donor, adoption and conceiving naturally and not doing any testing.

Pre-implantation Genetic Diagnosis (PGD)

PGD is a process whereby a woman achieves a pregnancy by in-vitro fertilization (IVF) with an unaffected embryo. IVF is an assisted reproductive technology in which after stimulating the ovaries to produce multiple eggs for fertilization, the eggs are removed from the ovary, and fertilized in the laboratory. Then several cells from each fertilized egg (embryo) are sent to a PGD laboratory. The cells are tested for the FMR1 mutation and then only those embryos without a mutation are implanted into the woman’s womb. This procedure has been used for other genetic conditions.

One of the difficulties when attempting PGD for Fragile X carriers is that some carriers have ovarian insufficiency (ranging from premature menopause to reduced ovarian functioning). This makes it difficult to stimulate the ovaries to produce multiple eggs necessary for PGD. Another complexity in PGD is that the laboratory technology used, called PCR, does not accurately distinguish between a full and premutation. It will only tell you if the fetus has the normal FMR1 allele or the one with the mutation, not how large the mutation is. The PGD analysis for Fragile X is done by a process called linkage—the lab uses genetic markers very close to the gene to distinguish the mother’s two different X chromosomes. This linkage technique will require blood samples from other family members (such as a sibling, other affected individuals, grandparents or other relatives).

The accuracy of PGD is 95-98 percent; therefore prenatal testing by CVS or amniocentesis is recommended later in the pregnancy. There are two parts to this process. The IVF, which is performed at many infertility centers, is the process of withdrawing and then implanting the fertilized egg. The PGD lab work, i.e. the genetic testing of the egg, is done separately and only at a small number of PGD laboratories in the world.

When undergoing PGD, the woman may have her IVF at a center close to home or at the center performing the PGD analysis. There are only a few centers around the world that offer PGD for Fragile X. Therefore, if the woman has the IVF close to home the IVF center will ship the cells to the PGD center, which will then alert the IVF center as to which embryos that are unaffected and available for implantation.

Prior to any PGD process a woman must have a fertility evaluation to determine her ovarian function and quantity of eggs. Then she will begin medications to stimulate her ovaries prior to the egg removal.