In vitro fertilization (IVF) helps intended parents conceive by fertilizing an egg outside the body and transferring the resulting embryo into the uterus. Integrating genetic testing into the IVF journey is a significant advancement that increases the likelihood of a successful pregnancy and identifies potential risks. This testing involves a series of analyses performed at different stages, focusing on the genetic health of the prospective parents and their embryos. Genetic testing provides insight into chromosomal and single-gene status, guiding the selection of the most viable embryos for transfer.
Genetic Screening for Prospective Parents
Genetic evaluation begins before the IVF cycle with carrier screening, which focuses on the prospective parents. This testing identifies if one or both partners carry a gene for a specific inherited condition that could be passed to their child. Carrier screening is typically performed using a simple blood or saliva sample analyzed for mutations in hundreds of genes.
Many serious genetic conditions, such as Cystic Fibrosis or Spinal Muscular Atrophy (SMA), are inherited recessively, meaning a child must inherit a faulty gene copy from both parents to be affected. A person can be a carrier without showing symptoms, making screening the only way to identify the risk. If both partners are carriers for the same condition, this information is crucial for family planning and informs the need for specific embryo testing.
Preimplantation Genetic Testing on Embryos
Once embryos are created through IVF, Preimplantation Genetic Testing (PGT) can be performed on the embryos themselves. PGT screens embryos for genetic disorders or chromosomal abnormalities before transfer to the uterus. The specific type of PGT used depends on the genetic risks identified in the prospective parents or the couple’s clinical history.
PGT for Aneuploidy (PGT-A)
The most common form is PGT for Aneuploidy (PGT-A), which screens for an incorrect number of chromosomes. Human cells should have 46 chromosomes; having too many or too few (aneuploidy) is a common reason for implantation failure, miscarriage, or genetic syndromes. PGT-A is often recommended for those with recurrent miscarriages, advanced maternal age, or repeated unsuccessful IVF cycles to select embryos with the correct chromosome count.
PGT for Single-Gene Defects (PGT-M)
PGT for Monogenic/Single-Gene Defects (PGT-M) is performed when one or both parents are known carriers of a specific single-gene disorder, as identified during carrier screening. This test is customized to look for the precise mutation that runs in the family, such as those causing Huntington’s or Tay-Sachs disease.
PGT for Structural Rearrangements (PGT-SR)
PGT for Structural Rearrangements (PGT-SR) is designed for couples where one partner carries a structural chromosome abnormality, such as a balanced translocation. PGT-SR ensures that only embryos with a balanced, normal set of chromosomes are considered for transfer, maximizing the chance of a healthy pregnancy.
The Biopsy and Laboratory Process
The physical process of obtaining cells for PGT is a delicate procedure known as a trophectoderm biopsy. This biopsy occurs when the embryo reaches the blastocyst stage, typically five to seven days after fertilization. At this stage, the embryo consists of the inner cell mass (which becomes the fetus) and the trophectoderm (which forms the placenta).
During the biopsy, an embryologist uses a precision laser and micromanipulation tools to carefully remove five to ten cells from the trophectoderm layer. Since these cells form the placenta, removing them does not disturb the inner cell mass and is considered safe for the embryo. The biopsied cells are then sent to a specialized genetics laboratory for analysis, involving DNA amplification and sequencing.
Immediately following the biopsy, the embryo is flash-frozen, or vitrified, and stored until the genetic test results return. Laboratory analysis typically takes seven to ten days, allowing for a frozen embryo transfer cycle in a subsequent month. Freezing the embryo is necessary to allow time for testing and often leads to higher success rates compared to immediate transfers.
Interpreting Results and Transfer Decisions
The results of the PGT-A test classify embryos into distinct categories that guide the transfer decision. An embryo is classified as “euploid” if it has the correct number of 46 chromosomes, indicating the highest potential for a successful pregnancy. Conversely, an “aneuploid” result means the embryo has an abnormal number of chromosomes and is generally not recommended for transfer due to the high risk of implantation failure or miscarriage.
A more complex result is “mosaicism,” which occurs when the biopsied sample contains a mix of both normal (euploid) and abnormal (aneuploid) cells. This finding suggests the embryo may have two or more cell lines with different chromosomal compositions. The clinical management of mosaic embryos is nuanced because the mosaicism detected in the trophectoderm may not perfectly reflect the inner cell mass.
Transferring a mosaic embryo is typically considered only if no euploid embryos are available. The decision depends on the percentage of abnormal cells detected and the specific chromosome involved. Although mosaic embryos have a lower implantation rate than euploid embryos, many can still result in a healthy live birth. Genetic counseling is recommended to help parents understand the risks and benefits associated with transferring any embryo that is not fully euploid.