Preimplantation genetic diagnosis and screening: genetic testing for embryos
Genetic testing of embryos is a powerful technology available only to those who are doing in vitro fertilization. To perform these tests, a small number of cells (usually about five or fewer) are taken from an embryo in a process called a biopsy; the genetic makeup of these cells are then evaluated in a genetics lab. Typically, after testing, only genetically normal and healthy embryos are chosen to be transferred into the uterus for a potential pregnancy.
Here, we’ll go over the two types of genetic testing for embryos—preimplantation genetic screening (PGS; also known as PGT-A in the newest nomenclature) and preimplantation genetic diagnosis (PGD; also known as PGT-M in the newest nomenclature)—as well as the biopsy process, risks, benefits, and more.
Preimplantation genetic screening (PGS or PGT-A) for genetically normal embryos
Preimplantation genetic screening—PGS, also known as PGT-A—evaluates embryo health by testing for the presence or absence of the normal number of chromosomes (that’s 46 in humans, more on that below). PGS increases the chance of pregnancy in an IVF cycle and lowers the chance of miscarriage by ensuring that doctors are only transferring embryos that are genetically healthy and able to develop. This type of testing is especially useful for older women, who have lower egg quality (meaning, they have a higher percentage of genetically abnormal eggs, and therefore the embryos their eggs produce are more likely to have genetic errors).
Understanding chromosomes
A chromosome contains a molecule of DNA, the genetic code that provides all of the instructions for the body. The DNA inside your chromosomes determines everything from your eye color to what diseases you may get. A normal human cell contains 23 pairs of chromosomes, one set from each parent, for a total of 46. This concept—getting 50% of our genetic code from each parent—is the foundation of sexual reproduction, and is really beneficial for the human species because it creates genetic variation and makes us more likely to survive.
An embryo is created from the joining of two gametes, or reproductive cells: an egg and a sperm. Each gamete contains half of the required chromosomes, or 23, which should combine to create a healthy embryo with 46-chromosome cells. (Chromosome number 23 is the one that determines the baby’s sex.) Healthy embryos are called euploid.
But that doesn’t always go as planned. Sometimes, one or more of the biological parents have low quality gametes, meaning their egg or sperm cells contain errors in their DNA (more on this below). Sometimes, something goes awry in the process of fertilization and cell division, and the cells don’t get copied properly.
However it happens, a genetically abnormal embryo, called aneuploid, is unlikely to survive and thrive; it most likely won’t implant in the embryo and lead to pregnancy, but could also result in a miscarriage later on in the pregnancy or, in very rare cases, lead to a genetic disorder in the baby.
Egg quality, aneuploidy, and age
Aneuploid embryos may be caused by low egg quality, a term that refers to the state of an egg as genetically normal or abnormal. The eggs inside the ovaries are “primordial,” or immature eggs. During ovulation, they go through another phase of cell division, known as meiosis. Older eggs are more likely to accumulate errors in their DNA during that division process, leading to genetically abnormal eggs, and therefore abnormal embryos.
More than 70% of embryos from women in their 20s are typically normal, while women in their 40s are likely to end up with less than 25% normal embryos. The decrease in egg quality is why why natural fertility declines with age, and why we see infertility, miscarriage, and genetic disorders more often with women over 35. It also means that women over 35 are especially good candidates for preimplantation genetic screening.
Learn more about egg quality.
Potential PGS results
If you choose to do preimplantation genetic screening, you’ll receive an embryo “report card” with the genetic status of each of your embryos. Here are some terms you might see on that report:
- Normal or euploid: This means that the cells retrieved from the embryo contain the proper number of chromosomes. This is the best result! Often, this embryo status is reported along with sex chromosomes—XX is female, and XY is male—meaning you can choose, or choose to know, the sex of the embryo you transfer.
- Abnormal: There are a few ways that an embryo could be abnormal.
- Aneuploid means the cells biopsied contained the wrong number of chromosomes. That could be because:
- One entire chromosome pair is missing (nullisomy),
- There’s an extra copy of one entire chromosome pair (disomy),
- There’s only one of a pair of chromosomes (monosomy),
- There’s an extra copy of one in a pair of chromosomes (trisomy), or
- There’s a missing or extra piece of a chromosome (as opposed to the entire chromosome).
While most aneuploid embryos will simply fail to develop, there are some rare conditions caused by specific genetic defects. Down syndrome, for example, is caused by trisomy in chromosome 21.
- Mosaic means that, among the cells biopsied from the embryo, there were some normal and some abnormal cells. Mosaic embryos may have anywhere from 20% to 80% abnormal cells. These embryos have a very small chance—around 15%—of resulting in a live birth.
- Aneuploid means the cells biopsied contained the wrong number of chromosomes. That could be because:
PGS and recurrent pregnancy loss
The majority of miscarriages, especially those that happen in the first trimester, are due to embryo aneuploidy. Those who are experiencing recurrent pregnancy loss, characterized by 3 or more consecutive miscarriages, may benefit from PGS.
Learn more about pregnancy loss.
Not only can preimplantation genetic screening help identify the potential cause of the aneuploidy that’s resulting in miscarriage (hugely beneficial when most who experience miscarriage don’t get a clear answer as to why), it can help couples get and stay pregnant by ensuring doctors transfer an embryo they know is genetically healthy and more likely to survive and thrive.
Preimplantation genetic diagnosis (PGD or PGT-M) for genetic disease
As opposed to PGS, which is a general screening for embryo normalcy, preimplantation genetic diagnosis (PGD) is a test for a specific genetic disease.
Single-gene disorders
Preimplantation genetic diagnosis can test for what are called single-gene disorders, or diseases that are caused by or linked to one gene.
Most, but not all, single-gene disorders require both biological parents to be carriers of the abnormal gene. (In this case, the parents have a 25% chance of passing along the disorder to each of their children) Parents might know this because they have a family history of a specific disorder, because they had an older child with the condition, or because they’ve done genetic “carrier” testing.
There are also disorders that rely on just one defective gene. In this case, only one parent needs to be a carrier in order for the child to be at risk; in this case, there’s a 50% chance the child will inherit the disorder.
PGD testing
Preimplantation genetic diagnosis can test for over 400 different single-gene disorders, including cystic fibrosis, sickle cell anemia, Tay-Sachs, and Huntington’s disease. PGD can test for both disorders that would be fatal to the fetus or baby as well as illnesses that may not affect children until they are older. It can also test for genetic defects that make someone much more likely to get a specific disease, like BRCA-1, which predisposes the carrier to breast and ovarian cancer. The idea behind PGD is to prevent heritable disease by first, creating and testing multiple embryos (some of the embryos will inherit the undesired gene and some will not, just by chance) and then transferring only embryos that don’t carry the genes for disease.
It’s important to understand that preimplantation genetic diagnosis is not a general screening. This testing examines one specific gene for a known potential disorder. It’s not yet possible, though it may be one day, to get a full genetic workup on an embryo from just a few cells. It’s a common but very untrue myth that PGD leads to so-called “designer babies.” While PGS and PGD will both allow you to know the sex of the embryo, PGD doesn’t test for hair color, eye color, height, or anything other than the presence of a specific genetic defect.
The embryo genetic testing process
Preimplantation genetic diagnosis and screening can both happen as part of in vitro fertilization. They’re not automatically performed; this testing is optional, but common, and your doctor will talk with you about whether or not genetic testing is right for you.
Here’s what happens after one or more embryos is created with IVF:
Embryo biopsy
The embryo biopsy is the process by which a few cells are taken from each embryo for testing. The biopsy is done at the blastocyst stage, typically the fifth, sixth, or sometimes seventh day of the embryo’s development. At this point, each embryo has about 100 or more cells, and the removal of 5 or so from the outer layer, or trophectoderm (which eventually becomes the placenta) does not impact its development, so long as it’s performed by an experienced embryologist in a high quality lab.
The cells are then sent to a genetics laboratory for testing. This testing typically takes 10–14 days.
Embryo freezing
The embryos are frozen after the biopsy as they await genetic testing results. Like eggs, embryos are frozen using vitrification, a flash freezing technology. Embryos are very likely to survive being vitrified and thawed (survival rates are nearly 100% here at Extend Fertility).
Learn more about embryo freezing.
Frozen embryo transfer of healthy embryo(s)
When results are in and the parents are ready for the next step, one of the healthy embryos is thawed in the lab and transferred into the uterus. Hopefully, it will implant there and result in a pregnancy.
Cost of preimplantation genetic diagnosis/screening
*Note all pricing is reflective of 2020 rates. Please refer to the links below for the most up to date pricing*
| Embryo biopsy | Genetic testing |
| $300 per embryo / $3,000 for 11 or more embryos | Approximately $225 per embryo |
| Fee goes to the IVF lab | Fee goes to the genetics lab |
The total cost of genetic screening for all the embryos created in one cycle can be $3,000 or more. This is in addition to the costs of IVF, embryo freezing, and frozen embryo transfer. PGD and PGS are not typically covered by insurance.
Learn more about Extend Fertility pricing.
| Age | Cycle type | Ongoing pregnancy rate |
| 36–37 | PGS | 66.7% |
| No testing | 43.5% | |
| 38–40 | PGS | 78.1% |
| No testing | 58.3% | |
| 41–42 | PGS | 50% |
| No testing | 0% |
The overall pregnancy rate per IVF cycle that uses PGS testing is 71%, according to a study of 241 embryos with an average maternal age of 35.7.
Lower chance of miscarriage
Because most miscarriages are due to embryo aneuploidy, and PGS allows doctors to only transfer euploid embryos, this screening lowers the risk of miscarriage signficantly.
In one study, it was determined that PGS reduced miscarriage rates for all maternal ages over 35. The most significant reduction was in mothers over 40; for 41-year-old mothers, PGS reduced the miscarriage rate from close to 30% to lower than 15%. For 43-year-old mothers, the risk was reduced from around 43% to around 17%.
PGS has also been shown to cut down the risk of miscarriage in younger patients, though not to the degree it does in older patients (reducing it from around 15% down to 10%).
Given the emotional, physical, and financial setbacks involved in pregnancy loss, many patients are motivated to reduce their chance of experiencing it.
More efficient IVF
Because it greatly increases your chance of getting pregnant on the first “shot,” PGS can save you money, time, and heartbreak during the IVF process. Let’s look at one example: a PGS cycle in which 6 embryos are tested and just one is transferred, vs. a non-PGS cycle that requires three transfers to achieve a pregnancy.
| PGS cycle | |
| IVF cycle with embryo freezing | $11,000 |
| Medication | $4,000 |
| Embryo biopsy for 6 embryos | $1,800 |
| PGS testing for 6 embryos | $1,350 |
| Supplementation before ET | ~$500 |
| Frozen embryo transfer | $3,000 |
| Total | $21,650 |
| Non-PGS cycle + multiple embryo transfers | |
| IVF cycle with embryo freezing | $11,000 |
| Medication | $4,000 |
| Supplementation before ET x 3 | ~$1,500 |
| Frozen embryo transfer x 3 | $9,000 |
| Total | $25,550 |
Learn more about Extend Fertility pricing.
As you can see, PGS can be “worth it” financially—and this is not taking even into consideration the stress and time associated with three embryo transfers and multiple failed cycles.
Results of preimplantation genetic diagnosis
PGD is able to diagnose single-gene disorders in embryos with 98% accuracy, significantly reducing or in most cases eliminating the chance that the offspring is affected by that disorder.
Risks of preimplantation genetic diagnosis or screening
There was a time when biopsy was done on day 3 of the embryo’s development, when the embryo had far fewer cells, which posed risks to the embryo.
Today, the biopsy is done on day 5, 6, or 7, when the embryo is in the blastocyst stage and has over 100 cells. The cells used for genetic testing are taken from the trophectoderm, the outermost layer of the embryo which will become the placenta. When performed by an experienced embryologist, trophectoderm biopsy does not affect the embryos.
Who should do preimplantation genetic diagnosis/screening?
Preimplantation genetic diagnosis or screening can be a powerful tool in your fertility treatment toolbox. These patients should consider embryo genetic testing:
- Patients over age 35 (PGS)
- Patients with a history of recurrent pregnancy loss (PGS)
- Patients with concerns about single-gene defects (PGD), because:
- Both biological parents are carriers of a “defective” gene (or one parent, in the case of rare diseases that only require a single parent to carry the gene)
- A previous biological child of the same parents has been affected by a genetic disorder
- Any patient who wants to harness technology to prioritize the transfer of embryos that are more likely to be genetically healthy.
