Pre-implantation genetic diagnosis (PGD) is a specialized technique used with in vitro fertilization (IVF). It allows for the genetic profiling of embryos before they are implanted into the uterus, screening for specific genetic conditions. PGD offers an alternative to prenatal diagnosis, as it occurs prior to pregnancy establishment.
What is Pre-implantation Genetic Diagnosis?
PGD serves as a diagnostic tool, identifying genetic abnormalities in embryos created through IVF. It is distinct from prenatal diagnoses like amniocentesis because genetic assessment happens before pregnancy begins. The primary goal of PGD is to help couples at risk of passing on inherited genetic diseases to select unaffected embryos for implantation, reducing the chance of a child being born with a specific genetic disorder.
The PGD Process
The PGD process begins with an IVF cycle, involving ovarian stimulation, egg retrieval, and fertilization. The resulting embryos are then cultured in a laboratory setting for three to five days, allowing them to develop to a suitable stage for biopsy. Embryos are usually biopsied at the blastocyst stage, around day five or six of development, by removing a few cells from the trophectoderm, which is the outer layer that will form the placenta. This method is considered less harmful to the embryo compared to earlier biopsy stages.
The biopsied cells are then sent to a specialized laboratory for genetic analysis. Techniques such as Polymerase Chain Reaction (PCR) are used to detect single-gene disorders by amplifying specific DNA sequences. For chromosomal abnormalities, methods like Next-Generation Sequencing (NGS) or Array Comparative Genomic Hybridization (CGH) examine the number and structure of chromosomes. After the genetic analysis is complete, results guide the selection of embryos that are unaffected by the targeted genetic condition. These unaffected embryos are then transferred into the woman’s uterus, or they can be cryopreserved for future use.
Genetic Conditions Identified by PGD
PGD can detect a range of genetic conditions. One common application is for single-gene disorders, which are caused by a mutation in a single gene. Examples include cystic fibrosis, sickle cell anemia, Huntington’s disease, and Tay-Sachs disease. PGD identifies embryos that do not carry the specific mutation.
PGD also applies to chromosomal structural rearrangements, where parents may carry balanced translocations or inversions. While the parent might be healthy, these rearrangements can lead to unbalanced chromosome sets in offspring, often resulting in non-viable embryos or severe health issues. PGD identifies embryos with a normal chromosomal arrangement. PGD focuses on specific known genetic diseases or rearrangements, differentiating it from Preimplantation Genetic Screening (PGS), now often called PGT-A (Preimplantation Genetic Testing for Aneuploidy). PGS screens for numerical chromosomal abnormalities, such as an extra or missing chromosome, like in Down syndrome, which is a broader screening rather than a targeted diagnosis for a specific inherited disease.
Who PGD Can Help
PGD can benefit several groups of individuals and couples. It is often considered by couples who are known carriers of a genetic disorder, even if they do not exhibit symptoms themselves, to prevent passing the condition to their children. Individuals who personally have a genetic condition and wish to avoid transmitting it to their offspring may also choose PGD. Couples who have previously had a child affected by a severe genetic disease often consider PGD for subsequent pregnancies.
In some situations, PGD is used by couples experiencing recurrent pregnancy loss, particularly when chromosomal abnormalities are suspected as the cause. Although this can overlap with PGT-A, PGD specifically targets known structural rearrangements. A less common, but significant, application of PGD is for human leukocyte antigen (HLA) matching. This allows for the selection of an embryo that is not only free of a specific genetic condition but also has an HLA type compatible with an existing sick child, potentially serving as a stem cell donor.
Important Considerations for PGD
While PGD offers significant benefits, there are several considerations to acknowledge. The procedure is highly accurate, with reported rates around 97%, but it is not entirely foolproof. There is a small possibility of misdiagnosis or the presence of mosaicism, where an embryo contains both normal and abnormal cells. For this reason, post-implantation prenatal testing, such as amniocentesis or chorionic villus sampling, may still be recommended to confirm the diagnosis.
There is a low risk of damage to the embryo during the biopsy procedure itself. Beyond the technical aspects, PGD raises various ethical and moral discussions. These include debates surrounding the selection of embryos, concerns about creating “designer babies” for non-medical traits, and the moral implications of discarding embryos that are found to be affected or unsuitable. The cost of PGD is also a significant factor, as it is an expensive procedure that may not be fully covered by insurance, which can limit accessibility for many couples. The entire IVF and PGD process can also be emotionally demanding for couples, involving physical discomfort and psychological stress.