Preimplantation Genetic Diagnosis
The decision to have a child is a weighty choice for any individual or couple. Among the endless questions and concerns could be whether you can support another human being—financially and emotionally—and if your relationship
The decision to have a child is a weighty choice for any individual or couple. Among the endless questions and concerns could be whether you can support another human being—financially and emotionally—and if your relationship is ready for this transition, as well as decisions about education, health and other topics. But if you or your partners know that you carry a genetic risk for cancer, you have another major consideration: Will you pass along a hereditary risk for cancer to your child?
For certain prospective parents with a known genetic mutation, there is a way to answer this question. Preimplantation genetic diagnosis (PGD) is a genetic test that can be performed on embryos created through in vitro fertilization (IVF), a fertility process in which a woman’s egg and a man’s sperm are combined in a laboratory dish. The test can determine if the embryo has a known genetic mutation that may predispose it to increased risk for cancer later in life. The goal of PGD is to prevent certain diseases or disorders from being passed on to the child.
Preimplantation genetic diagnosis tests embryos before they are implanted, so only embryos created through IVF are used. To test for a certain genetic abnormality, embryo biopsy—the removal of one or a small number of cells from a growing embryo—is required. These cells are then tested for the genetic abnormality. Prospective parents can then choose not to have embryos that have the genetic problem implanted and can instead choose to use an embryo that does not have the mutation in question.
“Preimplantation genetic diagnosis is testing of a specific mutation or mutations within a gene that has been identified within a family,” explains Lindsey Campbell, Certified Genetic Counselor for Natera (natera.com), a laboratory that performs PGD. “Therefore PGD is only possible for individuals who have a known hereditary cancer condition who wish to prevent passing on the mutation(s) to their children. It allows a couple to become pregnant with embryos selected to have normal chromosomes and free of a genetic condition in the family.”
Candidates for PGD must have been identified by prior genetic evaluation as high risk for a genetic abnormality that predisposes them to cancer. Common reasons to suspect a genetic link and refer a patient for testing are early onset of cancer (generally considered under age 40 in breast cancer) and a strong family history of cancer.
Nicole Longo, DO, an internist at Cancer Treatment Centers of America® (CTCA) in Philadelphia, Pennsylvania, explains that PGD can also be used to test for genetic disorders other than cancer, such as cystic fibrosis and numerous other conditions. “It’s not just cancer patients who undergo PGD,” she says.
Who Can Benefit
The concern about passing along genetic cancer risk to children is particularly relevant for cancer patients of childbearing age, explains Melanie Corbman, MS, LCGC (Licensed Genetic Counselor) at CTCA® in Philadelphia. People who are diagnosed with cancer as young adults have a higher risk that there is a genetic mutation linked to their diagnosis. For many who carry hereditary risk for cancer, diagnosis will coincide with childbearing years. This can make the question How can I prevent my children from getting cancer? a major concern among survivors who want to start a family. “Testing with PGD,” Corbman says, “is a way that parents can help protect their children.”
Corbman explains that PGD is appropriate for only a “specific population”—people who test positive for a genetic mutation and are of childbearing age. There are so many possibilities in genetic mutations, Corbman explains, that it is impossible to run a general test without searching for a particular mutation. “Otherwise,” she says, “it’s a needle in a haystack.”
Because PGD can be performed only on embryos conceived through IVF, it can be part of the larger discussion about fertility issues associated with cancer. Certain cancers and cancer treatments can affect the ability to conceive a child, so patients diagnosed during childbearing years often consult specialists to learn about ways to preserve fertility. Options include freezing eggs, sperm or embryos and fertilizing through IVF. These patients can then add PGD to the process.
According to Corbman, the big benefit of PGD is in cases where the condition will affect children. For example, familial adenomatous polyposis, an inherited condition that can cause colorectal cancer, may be linked to a type of liver cancer in children; families with this mutation may benefit from PGD. The case for PGD with adult-onset cancers is not as clear. For instance, a mutation in the BRCA1 or BRCA2 gene increases risk for breast cancer; but because breast cancer is unlikely to affect an individual until adulthood (around age 25), prospective parents with a known BRCA mutation may choose to forgo PGD with the hope that research will have substantially improved breast cancer treatment and prevention by the time their child is at risk.
The risk of passing along a genetic disorder to your child is “significantly” reduced with PGD, according to Campbell. And though the test is considered highly accurate, there is a slight chance of a false-negative result, or a test that fails to detect a genetic mutation that’s actually present. She also reminds that PGD is very specific and tests only for a particular known mutation. “Patients must understand that all genetic conditions cannot be ruled out—only the ones being tested,” Campbell explains. “Therefore there is always a risk of a different condition developing later in life.” She adds that ruling out genetic risk for cancer does not rule out all possibility of developing cancer: “Individuals who don’t have a hereditary cancer mutation still may have a population risk for cancer.”
You Will Have Support
Genetic cancer risk and PGD are complex topics that can certainly add more challenge to the already complicated world of a cancer diagnosis or known hereditary risk. There are professionals who specialize in the field, however, and can help you make decisions and understand the process and the results.
Genetic counselors, such as Corbman and Campbell, play an important role by helping determine if you may be at risk for a genetic link to cancer. They do this by considering such factors as your age at diagnosis and family history of cancer. If a genetic counselor finds reason to suspect a genetic mutation, you may be given options for genetic testing. This is a critical part of the PGD process because PGD works by looking for a specific known mutation. Therefore testing must first identify that mutation in the prospective parent or parents.
As an internist, Dr. Longo is also involved in decisions surrounding genetic testing and PGD, making sure that information is accurately shared with the right experts and that patients get the support they need. “I help identify family history,” she explains, “including cancer and non-cancer issues, and I work with genetic counselors and a fertility center to determine if testing’s appropriate.”
What Candidates Need to Know
The decision to pursue PGD is certainly not made lightly. With considerations ranging from the financial burden to the emotional one, candidates have a lot to weigh before moving forward.
Campbell explains that because the PGD process is “customized”—meaning it is based on testing that is tailored for specific mutations and requires the collection of DNA samples—it is very time consuming. “On average it takes approximately eight weeks to develop and validate a custom test for a single gene condition,” she says.
Many labs also require DNA from other relatives, so PGD candidates need to have family members available. “Testing still may be possible if relatives are deceased or unavailable, but it may be more complex and potentially less accurate,” Campbell explains.
Campbell also advises that PGD candidates understand that there is a chance that all embryos will test positive for an abnormality. “In that case,” she says, “none will be recommended for transfer.”
Candidates for PGD, says Corbman, might also face incredibly difficult emotional decisions if an embryo tests positive for a genetic mutation, such as choosing which embryo to use or not use based on that information. An important question for PGD candidates to ask themselves, she says, is How comfortable will I be with that knowledge and acting on it? The answers are, of course, deeply personal.
Corbman adds cost to the list of considerations about PGD. “It’s very expensive,” she says. And because PGD is done in addition to the already costly IVF, the overall price tag is substantial. It is possible that your insurance won’t cover either procedure.
Preimplantation Genetic Diagnosis and Embryo Safety
The embryos used in PGD are very new—only several days old. At this point they have only eight cells, one of which must be removed for test. As a result, “there’s a slight risk to the embryo,” says Corbman.
Campbell adds that there have been recent advancements in the field, including the ability to test multiple cells biopsied with precise lasers from an embryo that has reached a 100- to 150-cell stage. “This minimizes the risk of harm to the embryo and increases the accuracy of test results since more than one cell is available for testing.”
Preimplantation Genetic Diagnosis Versus Prenatal Testing
PGD does not take the place of prenatal testing; the two tests are performed at different stages of embryo development, so parents who have undergone PGD can learn additional, critical information with prenatal testing.
Whereas PGD is performed after the embryo is created through IVF but before it is implanted in the mother’s uterus, prenatal testing is done after implantation. More cells have formed at this point, allowing testing for many more conditions.
“We still recommend prenatal diagnostic testing [in addition to PGD] for absolute confirmation,” says Campbell. Another benefit of prenatal testing, she explains, is that it provides testing for couples who can achieve pregnancy naturally and may not wish to go through IVF.
A Little Peace of Mind
There is no test, crystal ball or magic spell that can guarantee and protect the health of your baby. With PGD, however, prospective parents can take one worry off their list by knowing that they will not pass along a known hereditary risk for cancer.