Questions to Ask About Genetic Screening and Testing

Most genetic counseling appointments involve a discussion of your family medical history, as well as any genetic tests that may be recommended for you. Gathering family medical history information from your and your partner’s immediate relatives beforehand will help the genetic counselor perform a thorough evaluation. For this type of evaluation, “immediate relatives” includes multiple generations, so think about your parents, siblings, nieces, nephews, aunts, uncles, grandparents, etc. You may also want to prepare any questions you have regarding your family history or genetic testing options that have been previously mentioned by your healthcare provider.

A karyotype, or chromosome analysis, is a test that may be performed on individuals with unexplained infertility or recurrent pregnancy loss. The purpose of this test is to determine if someone has the correct number and structure of chromosomes, which are the packages of genetic material contained in all of our cells. Having extra, missing, or rearranged genetic material can explain some cases of infertility or pregnancy loss.

Carrier screening is commonly offered to any individual who is of reproductive age and/or planning a pregnancy. Carrier screening is explained in detail below.

Preimplantation genetic testing (PGT) is a test performed on embryos following IVF which may screen for genetic changes or chromosome abnormalities. PGT is explained in detail below.

Additional genetic tests may also be offered to you depending on your personal medical or family history.

Carrier screening is a test to determine if you carry any misspellings, known as mutations, in your DNA that are associated with recessive genetic conditions. These conditions may be inherited in either an autosomal recessive or X-linked recessive manner.

An autosomal recessive condition is one that affects both men and women and is caused by having a mutation in both copies of a particular gene. A person with the condition typically inherits a mutation from each of their parents. Having one copy of a gene with a mutation is known as being a carrier. Carriers usually have no symptoms of the disease. If both parents are carriers, they have a 1 in 4, or 25%, chance to both pass the mutation and therefore have a child with the disease.

An X-linked recessive genetic condition is one in which the disease-causing gene is on the X chromosome, one of our sex-related chromosomes. Women have two X chromosomes and men have an X and a Y chromosome. A woman with a mutation in a gene on one X chromosome is known as being a carrier. She typically has no symptoms of the disease as she has a working copy of the gene on her other X chromosome. Men with a mutation in a gene on their X chromosome will have the disease. Carrier testing for X-linked conditions is therefore typically offered to women. A woman that is a carrier has a 50% chance to pass the mutation. Sons with the mutation will have the disease whereas daughters will be carriers like their mother.

Many professional medical societies, such as the American Society for Reproductive Medicine, American College of Obstetricians and Gynecologists, and the National Society of Genetic Counselors, recommend that carrier screening for certain disorders be offered to individuals who are planning a pregnancy. However, the decision to undergo carrier screening is up to you and your partner. A discussion of carrier testing options with a genetic counselor may help you make an informed decision.

Genetic disorders that are commonly included in carrier screening panels include: cystic fibrosis, spinal muscular atrophy (SMA), and inherited blood disorders such as sickle cell anemia or beta-thalassemia. Testing may also be offered for fragile X syndrome. Because fragile X syndrome is an X-linked disorder (see previous), testing for this is typically offered to only the female partner. Carrier screening tests vary in the number of diseases screened with some including over 300 genetic conditions.

Yes! It is important to note that the majority of individuals who are carriers of genetic disorders do not have a family history of that condition. In fact, one publication suggested that 80% of couples who had a child with a recessive disorder had no family history of that disorder. This is why it is important to consider carrier screening for anyone who is planning a pregnancy, regardless of their family history. If you happen to have a family history of a particular genetic condition, it is important to address that history with your genetic counselor as well to ensure the appropriate testing is conducted.

The chance that you could be a carrier for any specific genetic disorder varies by disorder as well as by ethnicity. For example, for white individuals, there is a 1 in 25 chance they are a carrier for cystic fibrosis. For African American individuals, the chance they are a carrier for sickle cell anemia is approximately 1 in 10. Being a carrier of a genetic disorder is common. We are all likely carriers for multiple disorders. As being a carrier should not affect our health, carrier status should only be of concern if our partner is also a carrier of the same autosomal recessive disorder.

If you are identified as a carrier of an autosomal recessive disorder, the next step is to consider screening your reproductive partner for that particular condition(s). This will help to determine whether your future children may be at an increased risk for that condition, as well as what reproductive options may be available to you. If you are a carrier of an X-linked recessive disorder, reproductive options should be discussed.

Insurance coverage for genetic testing is enormously variable by insurer, plan, individual deductible, and test required. In some cases, a prior authorization for testing may need to be coordinated with your doctor. You may also wish to speak with your insurance provider regarding your coverage before testing.

Genetic testing for embryos falls under the umbrella term “preimplantation genetic testing” (PGT). There are currently three types of PGT: PGT-A, PGT-SR, and PGT-M.  PGT-A tests for aneuploidy, a condition in which there is an extra or missing chromosome, and for extra or missing pieces of a chromosome. Embryos with these chromosome issues can fail to implant in the uterus, can result in an ongoing pregnancy that ends in loss, or can result in a child born with a chromosome disorder.

A well-known example of aneuploidy is trisomy 21, or Down syndrome, which causes various physical symptoms and intellectual disability. PGT-SR (SR = structural rearrangement) tests embryos for known changes in how a patient’s chromosomes are arranged, such as a translocation or inversion. These may be identified as part of a fertility workup using a karyotype (see previous). PGT-M (M = monogenic disease) tests for known single-gene disorders in the family. A risk for one of these disorders may be identified by family history or on carrier screening. PGT technologies continue to evolve. Your doctor will advise if there are additional tests she/he wishes to consider for your embryos.

Most current forms of PGT require a sample from the embryo obtained via an embryo biopsy. When an embryo is biopsied, an embryologist removes one or more cells from the embryo before either transfer or freezing. Typically, these cells are removed from the part of the embryo that will become the support structures for the pregnancy, such as the placenta and sac, not the baby. In most cases, embryos resume growing normally following biopsy. Sometimes embryos may be damaged during this process and not resume growing. Risk percentages are both center and embryologist specific and may be available from your doctor’s office.

All genetic tests are not created equal. For example, a genetic test to estimate one’s ancestry will not provide information about carrier status. In addition, the quality of data provided between a direct-to-consumer laboratory and a clinically validated (CAP and CLIA certified) laboratory may vary. Currently, DTC test results need to be confirmed by a certified lab, so repeat testing may be necessary. A genetic counselor can work with you to review your previous test results and determine what was previously tested and what additional work-up is appropriate.

Preconception and preimplantation genetic testing are not replacements for routine prenatal screening with your OB/GYN and prenatal genetic counselor. It is best to forward any genetic testing results from your IVF doctor to your OB/GYN. During your first trimester appointments, you will speak with your OB/GYN and genetic counselor about available prenatal screening and diagnostic tests. These will typically include evaluations for fetal aneuploidy (extra or missing chromosomes) and ultrasound exams for fetal anatomy. As PGT is not 100% accurate, a follow-up evaluation of the pregnancy is recommended.