PGS and PGD are types of genetic tests used during in vitro fertilization (IVF) to test an embryo for extra or missing chromosomes and/or inherited diseases. The goal of both PGS and PGD testing is to find out which embryos are most likely to result in a healthy pregnancy.
Both PGS and PGD are done on an embryo biopsy as part of an IVF cycle. PGS screens embryos for whole extra or missing chromosomes. PGD tests embryos for a specific genetic disease or small extra or missing pieces of chromosomes.
PGS or PGD tests are done after fertilization by removing a single cell or multiple cells from a developing embryo for testing. The biopsy is performed by an embryologist at an IVF center. It can be done either 3 days or 5 days after fertilization.
Preimplantation Genetic Diagnosis (PGD) – also referred to as preimplantation genetic testing – is screening for genetic diseases. PGD is the process of removing one cell from an embryo developing in vitro for genetic testing. The embryo’s cell is analyzed for the presence of a gene mutation or an unbalanced chromosome. PGD is recommended when one of the parents is known to have a genetic disease history.
Preimplantation Screening – PGS
Preimplantation Screening (PGS) is the process of removing cells from an embryo developing in vitro to be screened for aneuploidy – the condition of having too many or too few chromosomes – evidence of a genetic defect. PGS is recommended for parents whose genes are known or presumed to be chromosomally normal.
Humans have 23 pairs of chromosomes. As a women ages, her lower quality of eggs raises the chances of producing an embryo with an abnormal number of chromosomes.
These groups of women should seriously consider genetic testing:
Women over 35 who are undergoing In Vitro Fertilization (IVF)
Women who’ve experienced recurrent miscarriages
Women who’ve experienced multiple failed IVF cycles
Parents who are known carriers of a genetic disease
Parents who have a child with a genetic disease
In some cases you may be a carrier for a disease without having the disease yourself. PGD tests for:
- Translocations of genes (exchange of chromosomal materials or other structural rearrangements), which can cause birth defects, mental retardation, or miscarriage
- Huntington disease
- Marfan syndrome
- Recessive genetic diseases such as cystic fibrosis or Tay-Sachs disease
- Genetic diseases carried on the X chromosome, such as hemophilia or Duchenne muscular dystrophy
- Gender, which allows you to avoid an X-linked genetic disease (mostly boys have those), or balance your family
- Abnormalities in the number of chromosomes
There are several different ways of testing embryos before implantation.
FISH Methods– This is the older method that has been widely used until recently. It typically only tests between 5 – 10 chromosomes, rather than all of the chromosomes. So, it is possible to pass testing with FISH method and still have some chromosomal abnormalities. These biopsies in the past have been typically done on day 3, and only biopsy a single cell. Although this can be the better choice for select PGD situations, for standard PGS (where we are not testing for a specific defect but testing for overall competency), the concern is that that not all chromosomes are evaluated. Also, some experts believe that there may be some false positives or uncertain results, or even that in some cases an embryo that tests positive for a defect on day 3 might have been able to self-correct by day 5. The added concern with a day 3 biopsy is that some feel there is possibly a higher risk of damaging the embryo (since they are typically only around 8 cells by day 3). With the day 3 biopsy, the results are typically back in time for a fresh blastocyst transfer on day 5.
CCS – Comprehensive Chromosomal Screening. CCS is a form of PGS and simply means you are screening all pairs of human chromosomes rather than a limited set tested with FISH methods. Now, just to make it more confusing, there is also more than one way of evaluating all chromosomes with CCS – common methods are CGH (also known as array CGH or aCGH), SNP and qPCR.
With CCS, you can do a day 3 biopsy (again, only a single cell like is often used with FISH testing) or also a day 5 biopsy, which allows you to biopsy a few cells, giving them more material to analyze. The experts are still uncertain as to whether a day 3 or day 5 biopsy is better, but some feel that the embryo may be better able to tolerate the day 5 biopsy. An advantage of day 3 biopsy is that most labs can have the results back in time for a fresh blastocyst transfer on day 5. The disadvantage to day 3 biopsy is having only one cell to evaluate; whereas with day 5 biopsy there are a few cells to help re-verify any positive or unclear result. When doing a day 5 biopsy, many clinics are then immediately freezing the embryos (typically with vitrification so that the thaw rate is 95+%) and then waiting for the CCS results, and then doing the transfer in a later frozen cycle.
There are two potential additional advantages to freezing the embryo after a day 5/blastocyst biopsy and doing a frozen transfer. The first is in an own egg cycle, if waiting for a frozen transfer the woman’s body can recover from the stimulation medication and be in a more natural hormonal state at the time of transfer which is thought to possibly enhance the likelihood of implantation and recent studies indicate that it may improve overall pregnancy outcomes. That benefit doesn’t necessarily extend to a donor egg cycle, since the medications are similar to the recipient for a fresh or frozen transfer. The second potential benefit is that by batching embryos together, the overall cost of testing may be lower
How accurate is PGS or PGD?
On occasion, misdiagnosis may occur, so patients undergoing PGD/PGS are usually offered traditional prenatal diagnostic tests (chorionic villus sampling-CVS or amniocentesis) to confirm the results. The rates of misdiagnosis in PGD range from 1% to 9%. Embryos from which no diagnostic information is obtained are usually discarded rather than risk embryo transfer, although this policy varies from clinic to clinic. The other risks of PGD/PGS are the same as those associated with any cycle of IVF, including multiple pregnancy and OHSS.