In the past couple of decades genetic testing options available prior to conception and during pregnancy have rapidly evolved. Patients often feel uninformed about which test(s) they should consider before conceiving and during pregnancy. Each genetic test has benefits and limitations. There is no test that can look for everything. This article will outline genetic testing options that are available to you prior to conception (preconception tests) and during a future pregnancy (prenatal tests).
Genetic screening on prospective parents
Individuals planning to conceive should consider meeting with their OB/GYN for a preconception check-up. During a preconception visit, an OB/GYN will likely discuss the frequency of menstrual cycles and fertile windows, diet and lifestyle habits, current medications, and personal medical history and family history. They will likely offer you a few different blood tests including carrier screening.
Carrier screening is a standard of care genetic test that should be offered to all people considering conception. Both the egg source and the sperm source can undergo carrier screening to best define disease risk for future children. Using a blood sample, carrier screening can detect whether a person is a carrier of a number of autosomal recessive diseases. Autosomal recessive diseases are conditions such as cystic fibrosis and sickle cell anemia, which occur at a significantly increased frequency when both the egg source/mother and the sperm source/father are carriers of the same disease. When both the egg source and sperm source are carriers of the same disease, there is a 25% chance that each embryo or future child will inherit both genetic variants and be at risk to develop that specific disease.
Carrier screening panels can include 200 or more autosomal recessive diseases. Most people are identified to be a carrier of at least one disease on the 200+ disease expanded panels. Carriers of recessive diseases have a second, functional copy of the gene and typically do not experience any symptoms of the disease. While carrier screening is an excellent tool to determine a patient’s risk to have a child with some of the most common recessive diseases, there are thousands of rare recessive diseases that are not included on the panels. In addition, carrier screening cannot determine the risk for chromosomal syndromes, like Down syndrome, or common polygenic diseases such as heart disease or diabetes, which Orchid offers in the Couple Report.
Genetic testing on embryos
While carrier screening should be made available to all people regardless of how they plan to conceive, preimplantation genetic testing (PGT) is a technology that requires an embryo biopsy before the embryo is implanted into the uterus. For that reason, PGT is only available to people planning on undergoing in vitro fertilization (IVF).
IVF involves an egg retrieval and fertilization of each mature egg outside of the body. Embryos will be grown in a lab for about five days before they are biopsied. A biopsy means that an embryo sample of just 3-10 cells can be used to perform a genetic test on embryos. While testing of the biopsy is underway the embryos will be vitrified or frozen and stored at a fertility clinic. Once PGT results are complete, the doctor and patient can use the results to select an embryo with a reduced risk for certain genetic diseases, and that embryo can be thawed and transferred into the patient's uterus. The accuracy of most types of PGT is typically quoted at ~98% so it is a great screening tool. Confirmatory diagnostic testing with better accuracy, such as CVS or amniocentesis, is typically recommended in pregnancies conceived with PGT screened embryos.
Preimplantation genetic testing for aneuploidy (PGT-A) is the most widely utilized type of PGT. With PGT-A embryos are screened for chromosome imbalances known as aneuploidy and it is determined whether there are any missing or extra chromosomes in the embryo sample. By transferring chromosomally normal (euploid) embryos with 46 chromosomes, the chance for a healthy ongoing pregnancy increases and the risk for miscarriage decreases. PGT-A can also determine the biologic sex of each embryo. PGT-A cannot determine the risk for single gene diseases like cystic fibrosis or polygenic diseases like diabetes or Alzheimer’s disease. While PGT-A is a common add-on to IVF cycles, there are other types of preimplantation genetic testing that can be utilized depending on an individual’s personal medical history, family history, and specific concerns.
Preimplantation genetic testing for polygenic diseases (PGT-P) is the most recent and advanced type of preimplantation genetic testing. Orchid offers genetic testing to help determine a future child’s predisposition to common polygenic diseases including heart disease, diabetes, and certain types of cancer. Most common chronic conditions fall under the category of polygenic disease, meaning genetic risk is influenced by a combination of multiple genetic markers. By analyzing hundreds of genetic variants associated with multiple common diseases, Orchid can determine whether certain embryos are at an elevated risk for multiple polygenic diseases. The Embryo Report results can be used by a physician and a patient to help determine which embryo to transfer based on disease risk. Orchid’s Embryo Report cannot determine the risk for all common diseases, but assess the risk for ten common and impactful conditions. PGT-P cannot assess risk for chromosome imbalances or monogenic diseases, but it can be used in combination with PGT-A or PGT-M. The Embryo Report includes PGT-A.
Preimplantation genetic testing for monogenic diseases (PGT-M) can be utilized by a patient or couple who is known to be at risk to have a child with a monogenic disease. A monogenic disease is a condition that is caused by a genetic change in one specific gene. Examples of monogenic diseases include autosomal recessive conditions included on carrier screening and hereditary cancer predisposition genes like BRCA1 and BRCA. There are thousands of monogenic diseases known to humankind, but PGT-M cannot test for them all. PGT-M is custom designed for each patient depending on the specific gene and variant(s) that they are known to be at risk of passing on to their children. If an individual is concerned about a specific disease that runs in their family, they can inform their provider to see if PGT is available for that condition.
Preimplantation genetic testing for structural rearrangements (PGT-SR) is available to individuals when the egg source or sperm source is known to carry a chromosome structural rearrangement such as a translocation or an inversion. Structural changes are a relatively rare finding, likely affecting less than 1% of the general population, so this test is not utilized as frequently as the other types of PGT. Individuals who have structural rearrangements are at an increased risk for infertility, miscarriages, and children with birth defects. PGT-SR can help these individuals reduce their risk for miscarriages and affected children by screening embryos for unbalanced forms of the structural rearrangement.
Once an individual is pregnant, there is a whole host of genetic testing options to consider. The earliest genetic test available in pregnancy is called non-invasive prenatal testing (NIPT). A blood draw at just 9 weeks gestation can be utilized for NIPT. Even though the 9-week baby is only the size of a grape, fragments of DNA from the pregnancy are already circulating in the pregnant person’s blood.
NIPT is primarily used to detect an atypical number of chromosomes, such as trisomy 21 or Down syndrome. Chromosome imbalances are not typically inherited, but occur by random chance during conception. In addition NIPT may be able to detect the sex of the pregnancy and screen for some small chromosome imbalances called microdeletions. Importantly, NIPT is considered a screening tool and there is a chance for misdiagnosis with NIPT. If a chromosome imbalance were to be identified on NIPT, a provider would likely recommend that you confirm the chromosome finding with diagnostic testing available a bit further along in pregnancy.
There are two genetic tests that are considered diagnostic in pregnancy, meaning both tests offer a >99% accuracy for detecting certain chromosome imbalances.Chorionic villus sampling (CVS) utilizes a small sample of the placenta which can be removed through the abdomen or cervix between 11-13 weeks of pregnancy. The sample can be tested to determine whether chromosome imbalances are present and/or to test for a specific monogenic disease if the pregnancy is known to be at an increased risk. Because CVS is invasive, there is a less than 1% chance for miscarriage following the procedure.
Amniocentesis is similar to CVS in that a sample from the pregnancy is used to run genetic testing, but amniocentesis relies on a sample of amniotic fluid. A small sample of amniotic fluid will contain thousands of skin cells that have been shed by the growing baby. Amniocentesis is generally available at 15 weeks of pregnancy or beyond. During the procedure, a provider will use ultrasound to help them guide a thin needle through the abdomen to remove a small amount of amniotic fluid. Depending on the patient’s concerns or results from previous genetic tests, the sample that is collected can be used to test for chromosome imbalances or a specific monogenic disease. Similarly to CVS, there is a less than 1% chance for miscarriage following the procedure. Specific risks and benefits associated with any test should be reviewed with a provider prior to undergoing any procedure.
Deciding what genetic testing to consider can feel daunting, but no person needs to decide this alone. Your OB/GYN or fertility doctor should be able to help you understand your specific risks based on your unique medical history and family history and the genetic testing options that may best suit your needs prior to conception and during a future pregnancy.