Preimplantation genetic testing (PGT) is a specialized procedure used during In Vitro Fertilization (IVF) to analyze the genetic makeup of embryos before transfer to the uterus. This testing helps identify genetic or chromosomal abnormalities that could lead to implantation failure, miscarriage, or the birth of a child with a genetic disorder. By examining the DNA of the developing embryo, PGT allows fertility specialists to select those embryos with the highest potential for a healthy pregnancy.
The Mechanics of Preimplantation Genetic Testing
The PGT process is integrated into the standard IVF cycle, with the genetic analysis requiring a small sample of cells from the developing embryo. Fertilized eggs are monitored in the laboratory until they reach the blastocyst stage, which typically occurs five to seven days after fertilization.
A trained embryologist performs a trophectoderm biopsy, carefully removing a cluster of about five to ten cells from the outer layer of the blastocyst. The trophectoderm is the part of the embryo that will eventually develop into the placenta, meaning this process ideally leaves the inner cell mass, which forms the fetus, undisturbed. Following the biopsy, the embryo is cryopreserved (frozen) while the genetic material is sent to a specialized laboratory for analysis.
The laboratory analysis uses advanced technology to examine the DNA from the biopsied cells. The most common method for PGT analysis is Next-Generation Sequencing (NGS), which offers a comprehensive way to screen all 23 pairs of chromosomes. This technique allows for the detection of changes in chromosome number and structure. The embryos remain frozen during the one to two weeks it takes to complete the genetic testing and receive the results.
Categorizing PGT: Screening for Different Genetic Issues
PGT is categorized into three main types, each designed to screen for a different genetic concern. The specific test chosen depends on the reproductive history and genetic risk factors of the prospective parents.
The most common form is PGT for Aneuploidy (PGT-A), which screens for embryos with an incorrect number of chromosomes. A euploid embryo should have 46 chromosomes, arranged in 23 pairs. Embryos with missing or extra chromosomes (aneuploidies) are a major cause of miscarriage and IVF failure. PGT-A is often recommended for individuals with advanced maternal age or a history of recurrent pregnancy loss.
Another category is PGT for Monogenic Disorders (PGT-M), designed to detect specific known inherited diseases caused by a single gene mutation. This test is personalized and requires a custom work-up based on the family’s specific genetic variant. Examples of conditions screened by PGT-M include cystic fibrosis, sickle cell anemia, and Huntington’s disease.
The third type is PGT for Structural Rearrangements (PGT-SR), used when one or both parents carry a structural abnormality in their chromosomes. These structural issues, such as translocations or inversions, mean that parts of the chromosomes are incorrectly organized. Although the parent carrying the rearrangement may be healthy, they have an increased risk of creating embryos with unbalanced genetic material.
Interpreting PGT Test Results
PGT results use specific terminology to guide the decision about which embryos are suitable for transfer. The most desirable result is a euploid embryo, meaning the biopsy sample contained the correct number of 46 chromosomes. Euploid embryos are associated with the highest rates of successful implantation and live birth.
Conversely, an aneuploid result indicates an abnormal number of chromosomes, such as having an extra chromosome (trisomy) or a missing chromosome (monosomy). These embryos are not recommended for transfer due to a low chance of survival and a high risk of miscarriage or severe genetic disorder. The abnormality is usually caused by an error in cell division during the formation of the egg or sperm.
A more complex result is mosaicism, describing an embryo containing a mixture of both euploid (normal) and aneuploid (abnormal) cells in the biopsied sample. This occurs when an error in cell division happens after fertilization, resulting in different cell lines within the same embryo. The proportion of abnormal cells determines the level of mosaicism, and embryos with a lower percentage of abnormal cells may still be considered for transfer following genetic counseling.
Clinical Scope and Broader Implications
PGT represents a significant advancement in reproductive medicine, but it has limitations. The testing procedure is invasive, and while the risk is low, the biopsy could potentially damage the embryo. Furthermore, the test is not perfect and can produce inconclusive results, false positives, or false negatives, requiring careful interpretation.
The financial burden of PGT is substantial, adding considerable cost to an already expensive IVF cycle. Insurance coverage varies widely; PGT-M may be covered more frequently when there is a documented history of a serious genetic disease. However, PGT-A is often considered elective and may not be covered, limiting access to the technology for many individuals.
The expanded use of PGT also raises complex ethical and social questions. As technology advances, there is discussion around testing for adult-onset conditions or conditions with milder symptoms, introducing debates about the scope of embryo selection. While PGT-M and PGT-SR are indicated for specific medical needs, the use of PGT-A in all IVF patients remains a topic of scientific debate.