When considering fertility treatments like In Vitro Fertilization (IVF), genetic testing can play an important role in diagnosing causes of infertility and maximizing the chances of a successful IVF pregnancy. Our licensed genetic counselor at Pacific NW Fertility, Lauren Garrett, MS, CGC, has written this guide to the many types of genetic testing and screening options.
For patients navigating infertility, genetic tests can be broadly categorized into two types: preconception genetic testing (testing the people that are planning to conceive typically before trying and before IVF), and preimplantation genetic testing (testing the embryos as a part of conceiving with IVF).
Preconception Genetic Testing (Testing People Conceiving)
The two types of genetic testing on patients:
● Chromosomal Karyotype
● Genetic Carrier Screening/Expanded Carrier Screening
A karyotype is a diagnostic blood test that looks at the size, shape, and number of your chromosomes, which contain your genes. Genes are parts of DNA passed to children from the egg provider and sperm provider. They carry information that determines your unique traits, such as height and eye colors, as well as risk for genetic disease. People typically have 46 chromosomes, divided into 23 pairs. One chromosome in each pair comes from the egg and the other from the sperm.
A karyotype is recommended to some patients receiving fertility treatments based on family history, and/or if they have recurrent pregnancy loss. Karyotypes can often detect structural rearrangements in chromosomes which can increase chances for miscarriage or the birth of child with a chromosome problem. For these patients, IVF with PGT-SR (see below) can be considered as a treatment option. You can read more about the association between balanced translocaitons and other chromosomal rearragments leading to increased risk of miscarriage in Dr. Lora Shahine’s book on miscarriage, Not Broken: An Approachable Guide to Miscarriage and Recurrent Pregnancy Loss.
Genetic Carrier Screening
Genetic carrier screening is a test typically run on DNA extracted from a saliva or blood sample. The goal is to determine if a patient carries a genetic condition that could be passed to their children. There are two main ways that genetic diseases are inherited. Autosomal recessive inheritance is the type of genetic disease that can occur in a baby if both sperm and egg provider carry for the same disease. X-linked inheritance is the type of disease that travels on the X-chromosome, and only the egg or the sperm provider need to carry in order to pass it on to offspring. Screening for these diseases ahead of time can reveal increased reproductive risks. For situations in which both the sperm and egg provider carry for the same genetic disease, PGT-M (see below) may be an option to help reduce these risks.
The American College of OBGYN (ACOG) and American College of Medical Genetics (ACMG) recommend that all patients be offered carrier screening. Depending on ancestral background and family history, these screenings can include high risk disorders such as Spinal Muscular Atrophy, Cystic Fibrosis, Tay Sachs, Fragile X and Hemoglobinopathies.
“Expanded Carrier Screening”
Over time, genetic sequencing technologies have improved in their ability to sequence many genes simultaneously. This has allowed many companies to offer large, multigene panels that include not just the diseases covered by the ACOG & ACMG recommended carrier screenings, but a large number of other, typically panethnic genetic diseases as well. This is commonly known as “expanded carrier screening.” It’s important to note that most expanded carrier screening panels DO NOT include adult onset disorders such as BRCA1 (a mutation associated with increased risk of breast cancer) or Huntington’s Disease (a neurological disorder that presents in middle age), and that these tests can reduce–but not eliminate–the risk for genetic disease. PNWF currently offers expanded carrier screening through SEMA4, which screens for >250 diseases. Ask your team for further questions about the option of carrier screening for your personal situation.
Preimplantation Genetic Testing/PGT (Testing Embryos)
Over the years, the terminology for genetic testing of embryos has changed. There are 3 recognized categories of preimplantation genetic testing, or “PGT”. The current terms as defined by ASRM are:
● PGT-A: Preimplantation Genetic Testing for Aneuploidy (formerly known as CCS or PGS)
● PGT-SR: Preimplantation Genetic Testing for Structural Rearrangement
● PGT-M: Preimplantation Genetic Testing for Monogenic disease (formerly known as PGD)
These are all types of genetic testing performed on what we call a trophectoderm biopsy: a sampling of approximately 10 cells taken from the outer layer of the embryo at the 5 or 6 day blastocyst stage. The biopsied cells are genetically tested prior to when an embryo is transferred, or implanted. Typically, an embryo is frozen (cryopreserved), and results from PGT help your physician select which embryo is the most likely to implant and result in a successful pregnancy.
PGT-A: Preimplantation Genetic Testing for Aneuploidy
Aneuploidy means that PGT found extra or missing chromosomes in the cells of the biopsy. A normal, or “euploid,” embryo has 46 chromosomes: 23 from the sperm and 23 from the egg. “Aneuploid” embryos have missing or extra chromosomes and are unlikely to implant, and/or likely to result in pregnancy loss. A common example of aneuploidy is Trisomy 21, or “Down Syndrome,” in which there are three copies of chromosome 21 instead of two. Some embryos, called “mosaic embryos,” have a combination of normal and abnormal chromosome counts and are sometimes considered for transfer. Because the test looks at all chromosomes, including X and Y, the sex chromosomes, the biological sex of the embryos will be reported as well. Not all patients want to know the sex of embryos and reports do not have to reflect this information. Review with your team whether you want to know this information or not.
PGT-SR: Preimplantation Genetic Testing for Structural Rearrangement
Similar to PGT-A, this test also checks for aneuploidy in embryos. However, it’s more typically ordered when there is a known “structural rearrangement” in the sperm or egg provider. A structural rearrangement is an umbrella term for specific kinds of chromosomal abnormalities. PGT-SR is a more specific type of PGT-A which looks a little closer at the chromosomes involved. It reduces the risk of having a pregnancy or child with an unbalanced structural abnormality, which involves extra or missing genetic material and typically results in a miscarriage.
PGT-M: Preimplantation Genetic Testing for Monogenic Disease
PGT-M is used to help patients reduce their risk of having a child born with a known inherited disorder caused by mutations in a single gene (“monogenic”), such as cystic fibrosis, BRCA1, or Huntington’s disease. Before PGT-M can be performed, there is typically a “probe” development process that can take several weeks. PGT-M test development typically relies on mapping specific genetic variants, and is custom made for each patient/couple based on the disease they are testing. The goal of PGT-M is to identify which embryos are affected with disease so that unaffected embryos can be selected for transfer.
IVF Genetic testing is complicated and complex – it’s understandable to feel overwhelmed by the options. The important thing to remember is that each fertility journey is unique, so you may not need all of the available tests. Our team of doctors and genetic counselors is here to help you understand your options and determine which testing is right for you.