IVF is an assisted reproductive technology that creates embryos outside of the body for transfer into the uterus. While primarily known as a treatment for infertility, IVF alone does not prevent genetic disorders. Prevention is achieved by combining IVF with Preimplantation Genetic Testing (PGT). This combined approach allows parents who are carriers of a known genetic mutation to select an embryo free of that specific condition for transfer. IVF provides the necessary setting to access and analyze the embryo’s genetic material before pregnancy is established.
The Mechanism: Preimplantation Genetic Testing
Preimplantation Genetic Testing (PGT) is a sophisticated technique performed on embryos created through an IVF cycle before implantation. The process involves taking a small sample of cells from the developing embryo and analyzing the DNA for chromosomal or specific gene abnormalities. PGT identifies genetic anomalies, ensuring that only embryos with the highest potential for a healthy outcome are selected for transfer.
PGT addresses genetic issues through two approaches: screening and testing. Screening looks for general chromosomal errors often linked to implantation failure or miscarriage risk. Testing is highly specific, designed to detect a particular inherited disorder when parents carry a known gene mutation. This analysis provides the scientific basis for preventing the transmission of inherited diseases.
The goal is to increase the chance of a successful pregnancy and reduce the likelihood of a child being born with a serious genetic condition. Selecting an unaffected embryo before transfer represents a proactive approach, bypassing the need for later-stage prenatal diagnostic procedures like amniocentesis for the tested conditions.
Distinguishing Types of Genetic Screening
The umbrella term PGT covers several specific tests, the two most common being PGT-M and PGT-A, which target different genetic errors. PGT for Monogenic disorders (PGT-M) prevents the inheritance of a known, single-gene disorder. This test is performed when one or both parents are carriers of a specific gene mutation, causing conditions like Cystic Fibrosis, Sickle Cell Anemia, or Huntington’s disease.
PGT-M is customized for each family’s unique mutation, requiring a specific DNA probe to look for that exact genetic change. This precise testing allows for the selection of embryos that have not inherited the disease-causing gene, preventing the transmission of that particular disorder. PGT-M is the direct method for avoiding a severe, inherited condition with a known genetic cause.
Preimplantation Genetic Testing for Aneuploidy (PGT-A) screens for an incorrect number of chromosomes in the embryo. A normal human cell contains 46 chromosomes; having an extra or missing chromosome (aneuploidy) is a major cause of miscarriage and implantation failure. PGT-A can detect aneuploidies such as Down syndrome (Trisomy 21), which is caused by an extra copy of chromosome 21.
PGT-A is primarily used to improve IVF success rates, especially for women of advanced maternal age, by identifying chromosomally normal embryos. While its main purpose is selecting a viable embryo, it simultaneously prevents the birth of a child with a disorder caused by a chromosome number error.
The PGT Process Steps
The PGT process begins after the egg retrieval and fertilization steps of the standard IVF cycle. Embryos are cultured for five to six days until they reach the blastocyst stage, characterized by 70 to 100 cells. Reaching this stage is crucial because it allows for the safe removal of cells that will eventually form the placenta, leaving the cells that will become the fetus untouched.
An embryologist performs a trophectoderm biopsy, carefully removing a small cluster of five to ten cells from the outer layer of the blastocyst using specialized micromanipulation techniques. This cell sample is sent to a genetics laboratory for DNA analysis. The embryo is then flash-frozen, or cryopreserved using vitrification, while the lab work is carried out.
The genetic analysis typically takes several days to a week, during which the DNA from the biopsied cells is amplified and tested. Once results are returned, the fertility specialist identifies the embryos that are genetically normal (euploid) and free of the specific condition being tested for. A single, selected embryo is then thawed and transferred into the woman’s uterus in a subsequent cycle.
Accuracy and Procedural Limitations
Preimplantation Genetic Testing is highly accurate, particularly in detecting whole-chromosome aneuploidies, resulting in a low misdiagnosis rate when a euploid embryo is transferred. However, the procedure is not 100% accurate, and a small risk of false negatives and false positives exists. Subsequent prenatal testing is often recommended to confirm the genetic status of the ongoing pregnancy, even after PGT.
A significant limitation is embryonic mosaicism, where an embryo contains a mix of both normal and abnormal cells. Since the biopsy only samples a few cells from the outer layer, the results may not perfectly represent the genetic makeup of the entire embryo. This sampling error complicates the diagnosis and transfer decision, reducing the overall diagnostic certainty.
There is a minimal risk of damage to the embryo during the trophectoderm biopsy procedure, estimated to be less than two percent. Furthermore, PGT only tests for the specific genetic issues it is designed to analyze, such as chromosome number or a known single-gene disorder. It cannot screen for all possible congenital defects, birth anomalies, or future genetic mutations that may arise later in life.