Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS)
PGD and PGS are the two forms of genetic testing used to evaluate embryos for genetic defects that can result in birth defects or pregnancy failure. Individuals and couples may need genetic tests due to hereditary diseases, recurrent miscarriages or repeated in vitro fertilization (IVF) failures. Genetic screening is also appropriate for older women and for couples wishing to identify the sex of their embryo, which is called sex selection.
PGD looks for one specific genetic defect such as the one that causes cystic fibrosis. PGS evaluates for any chromosomal abnormality, such as the one that results in Down syndrome. PGS is by far the more commonly recommended test.
Preimplantation genetic diagnosis (PGD)
In PGD we evaluate cells from the embryo for a particular genetic disease one or both of the parents are suspected to be at risk for passing on. Embryos without that defect can be implanted in the mother’s womb for pregnancy.
PGD decreases the risk of a child having a genetic disease but it does not completely eliminate it. We recommend confirmation during pregnancy via amniocentesis or chorionic villus sampling.
Patients may elect to have PGD to study their DNA for a known inherited disease in their family, which puts them at high risk for a particular genetic condition. For example, if each parent has been screened, and one or both carry a DNA gene mutation, they will then know that they could have a baby with the related disease (see below). A couple might also undergo PGD if they have already had a pregnancy with an inherited genetic condition and wish to dramatically reduce the chances of this happening again.
PGD actually involves a more complex process than that of PGS, as the couples’ own DNA must be assessed and a “probe” made for their specific disorder. More common diseases that are amenable to this kind of screening include certain types of muscular dystrophy, thalassemia, cystic fibrosis, Huntington’s disease and sickle cell anemia. Hundreds of disorders can be eliminated with PGD.
Most frequently diagnosed diseases and disorders detected by PGD
- Cystic fibrosis
- Sickle cell anemia
- Spinal muscular atrophy
- Tay-Sachs disease
- Huntington’s disease
- Charcot-Marie tooth disease
- Fragile X syndrome
- Duchenne muscular dystrophy.
Preimplantation genetic screening (PGS)
PGS checks for chromosome abnormalities and detects major errors in the numbers of chromosomes, whereas PGD detects only one tiny chromosomal mutation. PGS decreases the risk of chromosomal errors causing miscarriage, birth defects, fetal death and other issues. Since the percentage of embryos with a chromosomal abnormality increases with female age, PGS may increase the success rates for IVF in women over 35.
We all have 23 pairs of chromosomes. The sex chromosomes are either XX in a female or XY in a male. If patients use preimplantation genetic screening, they can establish the normalcy of their embryos and identify gender.
The scientific analysis of the chromosomes in PGS is carried out at one of the few national centers. There is a considerable amount of time, skill and equipment involved to set up a program to allow preimplantation genetic testing.
During PGS, chromosomal material is expanded and counted. At least half of the embryos in many cases are aneuploid, which means having an abnormal number of chromosomes, either too few or too many, rather than the two in a normal chromosome pair. Aneuploidy arises from errors in the production of chromosomes by the egg before the sperm arrives.
Through amazingly precise scientific tools, all chromosomes are tested for aneuploidy, translocations (incorrect chromosome position) and other structural alterations. Those embryos found to possess such an abnormality are not implanted in the mother.
Common aneuploidy examples are trisomy (triple chromosome) or monosomy (single chromosome), when there should be pairs of chromosomes. In either of these cases, if an implantation occurs from such an embryo, we would expect either a miscarriage or an abnormal offspring, such as a child with Down syndrome – also known as trisomy 21 because it occurs in chromosome pair #21.
PGS diagnoses are correct 99 percent of the time. There can be times when the chromosomal material is not reflective of the actual outcome, but this is quite uncommon. A few years ago, using the technology available, it was only possible to test up to five chromosome pairs in one embryo. Now, all 23 pairs of chromosomes can be tested.
PGS is a dramatic breakthrough that enables us not only to determine the gender of the embryos for people desiring gender selection, but also to lower the miscarriage risk. It also largely eliminates the possibility of babies born with conditions such as Down syndrome.
Process & limitations for PGD & PGS
First, both female and male partners should be screened for their fertility potential. This involves looking at the ovaries with an ultrasound and testing the AMH (anti-Müllerian hormone), which is a predictor of ovarian reserve. Some young women are surprised to find that they have relatively low reserve, which impacts the number of eggs that will be retrieved.
After IVF, which involves retrieving eggs using transvaginal ultrasound and successfully fertilizing one or more to create embryos, the genetic testing occurs. On day five of embryo development, an embryologist biopsies the barely visible embryos and uses a micromanipulator to take a few cells without damaging the blastocysts (as the embryo is called at this stage). The genetic scientists can take this infinitesimally small bit of tissue and expand the DNA to determine the chromosomal complement of the embryo.
The embryos are frozen during the time this scientific analysis is being carried out. Thus the complete treatment involves a second cycle for thawing and replacing healthy embryos. Unused embryos that are chromosomally normal remain frozen, and their disposition and fate need to be discussed. We strongly encourage the donation of any embryos that are not utilized by the family.
The next month, the mother is placed on estrogen and progesterone in a sequential manner, so that an embryo or embryos can be placed in her uterus about three weeks later. We strongly suggest consideration of single embryo transfer since the implantation rates of these healthy embryos can be quite high. This reduces the risk of twins, which needs to be discussed thoroughly.
Risks of PGD & PGS
Using preimplantation genetic testing with IVF involves the same risks associated with IVF without genetic testing. These include pain, discomfort and nausea caused by overstimulation of the ovaries, multiple pregnancy (twins or more) and birth defects not related to the genetic test. Genetic testing is not 100 percent accurate, so there is a risk of pregnancy failure or having a child born with a genetic birth defect.
Read more about genetic testing and sex selection in our Fertility Blog: