Genetic testing is an integrated part of the In Vitro Fertilization (IVF) process, helping to enhance the likelihood of a successful pregnancy and reduce the risk of passing on certain conditions. IVF is an advanced reproductive technology where eggs are retrieved and fertilized by sperm outside the body in a laboratory setting. This process allows for the examination of the genetic makeup of reproductive cells and resulting embryos before a pregnancy is established. Genetic analysis provides families with information to make decisions about their reproductive care. This testing is broadly used to screen for chromosomal abnormalities and specific inherited diseases.
Genetic Screening of Prospective Parents
The first step in genetic assessment often involves screening the prospective parents or gamete donors before the IVF cycle begins. This process, known as carrier screening, analyzes the DNA of the intended parents to identify if they carry recessive genes for various disorders. Many individuals can be carriers without showing symptoms, as a recessive disorder only manifests if a child inherits an altered gene copy from both parents.
Standard carrier screening panels look for mutations associated with conditions such as Cystic Fibrosis, Spinal Muscular Atrophy, and Tay-Sachs disease. If both partners are carriers for the same recessive condition, the chance of their child being affected is 25% with each pregnancy. Identifying this shared risk allows families to consider preimplantation genetic testing of their embryos. Carrier screening is performed using a simple blood draw or saliva sample, providing information to guide the subsequent steps of the IVF treatment plan.
Preimplantation Genetic Testing for Aneuploidy
Preimplantation genetic testing for aneuploidy, known as PGT-A, is the most common form of genetic testing performed on embryos during an IVF cycle. Aneuploidy refers to having an abnormal number of chromosomes, such as an extra copy (Trisomy) or a missing copy (Monosomy). Humans typically have 46 chromosomes, arranged in 23 pairs. Having too many or too few chromosomes can lead to implantation failure, miscarriage, or the birth of a child with a genetic syndrome like Down syndrome (Trisomy 21).
The procedure involves growing the embryos in the laboratory for five to six days until they reach the blastocyst stage. An embryologist performs a biopsy, carefully removing a small sample of cells from the trophectoderm, the outer layer that will eventually form the placenta. The embryos are cryopreserved while the biopsied cells are sent for analysis to determine the number of chromosomes.
The goal of PGT-A is selecting embryos that are euploid, meaning they contain the correct 46 chromosomes. This selection process helps prioritize embryos with the highest potential for successful implantation and a healthy ongoing pregnancy. PGT-A is frequently recommended for all IVF patients, particularly for women of advanced maternal age, because the risk of producing eggs with chromosomal errors increases significantly with age. The test acts as a powerful screening tool to identify the most viable embryos for transfer.
Preimplantation Genetic Testing for Inherited Conditions
While PGT-A screens for chromosome number, other types of preimplantation genetic testing detect specific inherited disorders. Preimplantation genetic testing for monogenic disorders, or PGT-M, is performed when one or both parents have a known single-gene mutation they wish to avoid passing to their child. This testing is highly specific and looks for particular conditions caused by a mutation in a single gene, such as Huntington’s disease, Cystic Fibrosis, or Sickle Cell Anemia.
Another targeted test is Preimplantation Genetic Testing for Structural Rearrangements, or PGT-SR. This is utilized when a parent is a known carrier of a chromosomal structural issue. These structural rearrangements, which include translocations or inversions, can cause an embryo to have missing or extra genetic material, often leading to recurrent miscarriage or failed implantation. Unlike the broad screening of PGT-A, both PGT-M and PGT-SR are targeted tests pursued only when a specific genetic risk has been identified in the family. For PGT-M, a custom test probe must often be developed in advance, tailored to the exact mutation carried by the parents.
Understanding Test Results and Clinical Decisions
The results of preimplantation genetic testing categorize embryos as euploid (normal chromosome number), aneuploid (abnormal chromosome number), or mosaic. Aneuploid embryos are typically not considered viable for transfer due to their low potential for success. Mosaicism arises when an embryo biopsy sample contains a mixture of both chromosomally normal and abnormal cells.
Embryos with a mosaic result present a complex clinical scenario. The abnormal cells in the trophectoderm may not accurately reflect the genetic status of the inner cell mass, which develops into the fetus. Mosaic embryos are categorized by the percentage of abnormal cells found. While they may have a lower implantation rate than euploid embryos, successful pregnancies and healthy live births have resulted from their transfer.
Genetic counselors play a significant role in interpreting these results for prospective parents. They provide guidance on the potential risks and benefits associated with transferring a mosaic embryo. This specialized counseling ensures that clinical decisions regarding which embryos to transfer, freeze, or not use are made with a full understanding of the genetic information.