Article: Preimplantation genetic diagnosis and hereditary cancer

​Contents

Background on PGD:

Preimplantation genetic diagnosis (PGD) is testing that is used in combination with in vitro fertilization (IVF) to help to identify genetic defects within embryos before they are transferred to a womb. The goal of PGD is to prevent inherited genetic diseases or disorders from being passed on from the parent to a child. The technology was first developed in the 1990s and has advanced over time.

There are a number of situations in which patients may benefit from PGD, including when one or both partners has a history of an inherited genetic disorder or when one or both partners tests positive for a mutation that could cause disease in their offspring. Examples include recessive genetic diseases, (i.e. Tay-Sachs or cystic fibrosis), X-linked genetic diseases (i.e. hemophilia or Duchenne muscular dystrophy), and dominant genetic diseases, (i.e Huntington’s disease or a BRCA mutation).

Preimplantation genetic screening (PGS) is another DNA screening technique which identifies chromosomally normal (46 chromosomes) embryos prior to embryo transfer. Those who may benefit from PGS include women who are over the age of 35, have a history of failed IVF, or couples with a history of recurrent miscarriages. Couples with a predisposition to a genetic disorder undergoing PGD to prevent having a child with the disorder may also undergo PGS at the same time to determine if the embryo is chromosomally normal.

Joseph’s article highlights the story of a woman with a BRCA1 mutation who, before undergoing surgery to remove her ovaries, underwent fertility preservation and ended up with only one viable embryo. After PGD she knew the frozen embryo carried the BRCA1 mutation, but she chose to go ahead and have the embryo implanted in her womb. She currently has a healthy son, and while concerned about the fact that since he carries a BRCA1 mutation he is at higher risk of cancer or may possibly pass on the BRCA1 mutation to his children, she is very happy that she went through with the pregnancy.  

Things to consider about PGD:

Not everyone is comfortable with the concept of PGD and screening embryos for mutations. Nevertheless, it is an option available to patients and an increasing number of people with inherited disorders are undergoing IVF and PGD. For this reason, it is important for people considering these procedures to understand what they entail.

For parents who carry a BRCA or other genetic mutation who are considering fertility treatments, it is important to know that:

• You, your partner and the clinician are usually involved in decision-making. Considerations include what a clinician is comfortable doing, and what the potential parent or parents want — and couples don't always agree. 
• There is no guarantee that an embryo will result in a live birth.
• Having a genetic mutation does not guarantee a diagnosis. For example, PGD can tell parents if an embryo carries a BRCA1 mutation, but it cannot tell them if or when an adult child may develop cancer.
• Insurance does not typically cover the cost of IVF or PGD. While there are some resources available to help defray costs, many are available only to cancer survivors and not previvors.

As genetic testing is moving out of a clinical setting and directly into the hands of consumers it is increasingly important for prospective parents to understand the limitations of genetic testing. Not all genetic information is equally useful for making real-life medical decisions.

Ethical considerations

Joseph reports that although doctors in the United Kingdom are not permitted to transfer embryos with abnormalities that may cause serious diseases or disabilities unless there are no other viable embryos, the United States has no regulations regarding when to transfer embryos with genetic abnormalities. In a paper published earlier this year, Daar, Klipstein, and colleagues on the American Society for Reproductive Medicine’s ethics committee highlighted the ethical concerns involved in transferring embryos with genetic anomalies including patient autonomy, the rights and well-being of the offspring, and clinician choice among them. Their goal was to at least provide a foundation for ways to think about the issues.  

There is some disagreement among some experts and advocates as to whether PGD should be available for all inherited mutations. Concerns have been raised over whether some diseases do not impact overall health enough to justify PGD. Clinicians may encounter patients who will want to select an embryo with a certain genetic trait. While this is rare, experts state this sometimes happens in cases where the parents are deaf or have dwarfism and want their children to have the same traits.

It is important to make sure that as experts debate the issues, the patient perspective is considered as well. In 2009, FORCE and colleagues from the University of South Florida and Moffitt Cancer Center conducted and published results of a survey of people with hereditary cancer on knowledge of, and attitudes about PGD.

What does this mean for me?

PGD can test for more than 100 different genetic conditions. The procedure is performed before implantation which allows the couple to decide if they wish attempt a pregnancy. The procedure enables couples who might not have otherwise pursued biological children to do so.  

For families with inherited disorders who have witnessed the devastating impact of inherited disease, this may be strong motivation for choosing PGD.

However, there are concerns with testing as well. For other families, these technologies may be equated with “playing God.” People who believe that life begins at conception may consider the destruction of an embryo as the destruction of a person. While PGD helps to reduce the chances of conceiving a child with a genetic disorder, it cannot completely eliminate this risk. Also, keep in mind that PGD does not replace the recommendation for prenatal testing.

As Judith Daar, a bioethicist and clinical professor at University of California, Irvine, School of Medicine states in the piece, “The technology is marvelous and can be predictive and accurate, but we’re probably at a very nascent stage of understanding the impact of what the genetic findings are on health.”

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Posted 11/08/17