What is Preimplantation Genetic Diagnosis and How Can It Help Those with Lynch syndrome?
Preimplantation genetic diagnosis (PGD) was introduced in 1990 and has provided a way to screen embryos for genetic conditions, chromosomal abnormalities, and mitochondrial disorders. This method enables couples to perform an embryo genetic analysis before transferring the embryo to the uterus during an in vitro fertilization (IVF) cycle. Before the introduction of PGD, the only option available to couples with a hereditary genetic condition was to naturally conceive and then perform prenatal testing, such as a chorionic villus sampling (CVS) or an amniocentesis. Then the couple had the choice of continuing the pregnancy or selective abortion if the pregnancy was affected. With PGD, a couple does not have to make the decision to terminate an affected pregnancy, but rather select for unaffected embryos before pregnancy.
The process of PGD begins with IVF. In IVF, there are several rounds of hormone cycles performed to extract eggs from women. After joining of sperm and egg, or fertilization, the single cell starts to divide and grow. At day 3 after fertilization, embryos consist of 6-8 cells. One of these cells can be removed for testing. While there are many different forms of biopsy, removing one cell at day 3 is the most common form of biopsy, called a cleavage stage biopsy. Removing more than one cell can cause damage to the embryo, therefore one cell is only removed.
Once that cell is removed, PGD can be used to look at the genetic material of that cell. There are several different techniques available depending on what the embryo is being screened for. In the case of a parent with Lynch syndrome or another type of cancer syndrome, typically a process called polymerase chain reaction (PCR) is used to specifically look at the DNA of the cell to read through the code of the DNA and look for the mutation or genetic change that the parent has. While PGD is not perfect, it is continually improving its ability to accurately detect affected embryos at such a young stage.
There are many reasons why a couple will be referred for PGD. If a couple has had genetic testing and is known to carry a genetic mutation, then it is appropriate for them to be referred to PGD. Autosomal recessive conditions where both parents are known to be carriers for the genetic condition, such as Tay Sachs disease, Cystic Fibrosis, or sickle cell disease is appropriate.
In addition, autosomal dominant conditions like Lynch syndrome or Huntington’s disease, where there is a 50/50 chance of passing on the genetic mutation to posterity, is also indicated for referral to PGD. Lastly, it is common to be referred to PGD for X-linked conditions and parental balanced chromosomal inversions/translocations. It is not appropriate to pursue PGD if the parents have a medical condition but no definitive genetic diagnosis, or if a couple wants to test for non-medical physical traits like hair color or eye color.
There are benefits and limitations to using PGD, and for some couples this is a great option, and for others it is not. For a couple who is already undergoing IVF, the cost of PGD might be justified. However, IVF and PGD is quite expensive, and insurance does not always cover these costs. For some patients, the option of PGD will spare them the difficult decision to terminate an affected pregnancy or continue an affected pregnancy. In addition, there are ethical dilemmas that PGD causes as well.
One major ethical objection to PGD emerges from the need to create and then select embryos based on their genetic status. Some people will view this as “playing God” or having too much control of a child’s fate. Others view such a young embryo as too rudimentary in development to not take control of the child’s outcome. In addition, the unwanted embryos are usually discarded, which also raises ethical questioning. Some people’s religious or moral beliefs raise conflicts against discarding embryos, or even selecting for wanted embryos. However, PGD does prevent selective abortion of pregnancies, which can go against individual’s moral and religious beliefs as well.
While PGD has its advantages and disadvantages, this technique can provide a door for Lynch syndrome patients to remove the burden of passing on their cancer risks to their children. This decision to pursue PGD is personal to each individual family and should be carefully considered in relation to other family members and future children. If a family is considering pursuing PGD, speak with your doctor or certified genetic counselor about receiving more information.
- Wu, P., Whiteford, M.L., & Cameron, A.D. (2014). Preimplantation genetic diagnosis. Obstetrics, Gynaecology, and Reproductive Medicine, 24(3):67-73.
- Robertson, J.A. (2003). Extending preimplantation genetic diagnosis: the ethical debate. Human Reproduction, 18(3):465-471
Kendra Frome is currently a Northwestern genetic counseling student. She will graduate in March of 2017 with a Masters degree in genetic counseling. She has experience working with cancer, prenatal, and pediatric genetics. She has a special interest in fertility preservation and techniques for cancer patients, and is currently working on her thesis regarding partner perspectives on fertility preservation. She is originally from Oregon and enjoys spending time outdoors hiking, doing sports, and swimming.
A couple of great new, informative videos about Lynch syndrome are out in English and Spanish. Please click on the links below and feel free to share!
October is Breast Cancer Awareness Month.
If you have:
- a strong family history of breast cancer or other cancers, especially before the age of 50
- multiple family members on the same side of family with the same type of cancer
- bilateral or multiple breast cancers in the same individual
- both breast and ovarian cancer
- male breast cancer or other rare cancers
- Ashkenazi Jewish ethnic background
- Other cancers associated with hereditary breast cancer syndromes
Please talk to your doctor and ask for referral to a certified genetic counselor to see if Breast True High Risk Panel Testing by Pathway Genomics is right for you. It is a next generation sequencing test that includes deletion/duplication analysis to detect mutations in seven high-risk breast cancer susceptibility genes, including BRCA1, BRCA2, and PALB2. For more information on the Breast True High Risk Panel, please go here: https://www.pathway.com/breasttrue/.
Recent studies of breast cancer have shown that approximately 70 percent of the mutations identified were BRCA 1/2 mutations. Approximately 4 percent had germline mutations in other cancer susceptibility genes, including high risk genes. These additional high-risk genes include CDH1, PALB2, PTEN, STK11, and TP53. Breast True High Risk Panel by Pathway Genomics analyzes all of these genes.
Movie presentation of Pink & Blue: Colors of Hereditary Cancer
For more information: https://www.tugg.com/events/pink-blue-colors-of-hereditary-cancer-ertt
Founder and Executive Director of ihavelynchsyndrome.org