Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS) allow us to test your embryos for genetic disease and chromosomal abnormalities prior to getting pregnant.
Preimplantation Genetic Diagnosis: PGD is a tool to test an embryo prior to the embryo being placed in the uterus (preimplantation) for a specific genetic disorder, such as cystic fibrosis, spinal muscular atrophy or sickle cell anemia. There are hundreds of single gene disorders than can be tested, if we know to look for them ahead of time. Couples that have a child with devastating genetic disorder, often consider PGD prior to having a second child.
Preimplantation Genetic Screening: PGS is a tool to test an embryo prior to the embryo being placed in the uterus (preimplantation) for a major chromosome abnormalities, such as Down syndrome. Healthy children and adults have 46 chromosomes, 23 chromosomes from the egg and 23 chromosomes from the sperm (there are rare exceptions). A person with Down syndrome has 47 chromosomes from an extra chromosome #21, which usually occurs in an older egg that has 24, instead of 23, chromosomes. Down syndrome is also called Trisomy 21. Women over 35 years old, and particularly women over 40 years old, are at risk of having abnormalities in their older eggs and may consider PGS.
Preimplantation Genetic Testing: PGT is a new term meant to lump both PGD and PGS.
Both PGS and PGD are performed on embryos to help patients determine which embryos will make the best candidates for embryo transfer with in vitro fertilization (IVF). Both PGD and PGS are performed on the embryo before it is implanted into the uterus so PGD and PGS are relatively non-invasive for the mother, as opposed to other routine pregnancy screenings such as amniocentesis or chorionic villus sampling (CVS).
Another advantage of PGS and PGD? These tests are done before a woman is pregnant, rather than after, which makes for a much easier decision-making process if the results are undesirable. If we determine one or more of the embryos have chromosomal abnormalities – or if an embryo tested positive for genes known to cause life-threatening genetic disorders – the embryos are not placed in the uterus and prevented from developing further. Embryos with normal test results remain vitrified (cryopreserved/frozen) for future implantation (more on that later).
Compare PGD or PGS with the most common chromosome/genetic screens offered to pregnant women. In the case of first-trimester screening (around week 10), CVS (around week 12) or amniocentesis (around week 15), a woman has already lived with the developing embryo inside her body for months before the results are back. Thus, pregnant couples must decide whether to proceed with the pregnancy, or terminate it, and this can be a very stressful and heartbreaking scenario.
Both PGD and PGS start off the same way, with IVF. With every IVF cycle we watch the embryos grow and divide under the microscope until they embryos are 5 days old, at which time the embryos have divided from a 1 cell embryo (a fertilized egg) to about 100 cells. A healthy 5-day old embryo is called a blastocyst. At the blastocyst stage the embryo either must attach to a uterus and establish its own blood supply to continue growing, or we can freeze (vitrify) embryos at the blastocyst stage. Therefore, with every IVF cycle, watching the embryos grow and divide normally is one way that we can choose the best embryo to transfer into the uterus and which embryos are worth cryopreserving for a future baby.
If either PGD or PGS is planned then about 5 placental cells are removed from each embryo that grows into a blastocyst. The 95-cell embryo is then cryopreserved with a process called vitrification[link] and remain in our laboratory and the other 5 cells from each blastocyst embryo are sent to a very specialized lab for either PGS or a combined PGD/PGS analysis.
It is important to note that there is no way to screen for a “perfect child.” PGD and PGS are not a 100% guarantee of a child’s health. However, PGD and PGS do give us a very good way to identify and prevent some of the most common and terrible problems. Currently, there is no way to screen for things like autism, heart defects or other developmental defects that occur after implantation.
The following are some of the differences between PGS and PGD screenings.
One way that all embryos are screened during IVF is to watch the embryo grow and divide in the laboratory for five days. If an embryo stops growing or clearly looks abnormal that embryo will not develop into a baby.
PGS is available as a second-layer of screening, in addition to watching the embryos divide. After 5 days in the laboratory an embryo reaches more than 100 cells and is called a blastocyst. In a blastocyst stage embryo, 50 of the 100 cells will continue growing into a baby, and the other 50 will form the placenta. PGD and PGS tests are done on five of the 50 placental cells, called trophectoderm biopsy. In the case of PGS, we are examining the chromosome pairs contained in the nucleus of each of these five cells.
Healthy embryos have 23 pairs of chromosomes (46 chromosomes total). Half of the chromosomes come from the mother and half come from the father. There should be no more, and no less than 46 chromosomes. In 99% of cases, chromosomal abnormalities are not compatible with life. These normal looking embryos with an abnormal number of chromosomes will also either never attach to the uterus, or will usually be miscarried early in the pregnancy.
However, there are certain chromosomal abnormalities, like Down Syndrome (Trisomy 21), that are compatible with life but can result in a baby born with serious defects.
The results from PGS take about 10 days. So, women who go this route will complete their egg retrieval process and egg fertilization will take place as it always does for any IVF cycle. The difference is that the embryos will be vitrified (frozen) after the PGS and/or PGD trophectoderm biopsy is complete.
Once the results are in, we time the first embryo transfer with the patient’s menstrual cycle so the 5-day old blastocyst embryo is transferred into a uterus that is 5-days post-ovulation. For women that do not have normal menstrual cycles we can prepare the uterus to think it is 5 days after ovulation, with estrogen and progesterone hormones.
PGS is often recommended for women who are near 40-years or older because most of their eggs are abnormal and older women have the highest risk of failed IVF cycles using their own eggs, miscarriages and children born with chromosomal abnormalities. It is also recommended for couples who would prefer to grow one healthy embryo into a healthy baby, rather than taking the risk of implanting two embryos and that both embryos implant and develop into twins.
Remember that our goal is to help women and their partners carry and give birth to one healthy baby at a time: without PGS, we sometimes recommend transferring two embryos. With PGS, we recommend transferring one embryo at a time. The live birth outcomes are about the same in older women that transfer two untested embryos versus one PGS tested embryo, but the twin rates are much lower when only one embryo is transferred.
When we transfer two embryos, younger women have a 40% chance of having twins. When we transfer a single embryo, the chances of having twins is only 1% to 2% (in this case the one embryo that was transferred splits in the uterus and the result is identical twins).
The risks associated with PGS are minimal. There is a 1% chance of causing harm to the embryo, which is very low, and 98% of fetuses survive the vitrification (freezing) and warming (thawing) process.
Another risk (or benefit) is that we learn the gender of each embryo. It’s like having a 99.9% accurate ultrasound to discover the gender of the baby before you ever get pregnant.
This is a much more detailed genetic test that screens the 5-placenta cells from the blastocyst for specific, single gene mutation. For example, cystic fibrosis (the most common genetic disorder diagnosed in Caucasian babies) or sickle cell anemia (the most common genetic disorder diagnosed in African American babies) can be prevented with PGD.
The process of preimplantation genetic diagnosis can automatically include PGS, but it doesn’t work the other way around.
As with PGS, the goal of PGD is to help patients/couples get pregnant and give birth to a single, healthy baby. Typically, preimplantation genetic diagnosis is recommended for couples who have:
Typically, the PGS process adds between $3,000 and $5,000 to the total IVF cycle costs. However, it’s important to keep in mind that the process also increases a couple’s chances of IVF success. While the extra price tag is expensive, it is more affordable than the cost of repeat cycles.
The cost for PGD is roughly the same (and should automatically include PGS), but the price can go up depending on the rarity of the gene mutation you want to screen for.
PGD is recommend for all patients/couples that are known to be at risk of having a child with a serious birth defect. Although PGS is an option for anyone going through IVF it is not always necessary, especially for younger women. As medical technology continues to move forward, we will be able to test for more genetic mutations increasing the success rates of our goal: one healthy baby at a time.