Preimplantation Genetic Diagnosis (PGD) Explained

In 1992, Chloe O'Brien was the first baby to be born after being genetically screened as an embryo for the genetic defect, cystic fibrosis. Chloe was the first baby born as a product of PGD.

What is PGD?

PGD stands for preimplantation genetic diagnosis, or sometimes referred to simply as embryo screening. The genetic defects being screened for include Down syndrome, cystic fibrosis, Tay Sachs, muscular dystrophy and sickle cell anemia but are not limited to these defects.

Technically speaking, PGD is a poorly chosen phrase because, in medicine, to "diagnose" means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. Therefore it is probably more accurate to refer to preimplantation genetic screening because we are testing for a genetic condition when there is an absence of a symptom of a disease.

PGD is a procedure that is performed on the embryo PRIOR to implantation. (Sometimes PGD can be performed on human eggs/oocytes prior to fertilization, but that is beyond the scope of this article.) The main advantage of PGD is that after PGD testing it is highly likely that the baby will be free of the disease it was tested for. PGD technology improves the likelihood of a successful pregnancy and birth for couples who are at risk for passing on inherited genetic disease to their offspring. If the parents are both carriers of the cystic fibrosis gene, then PGD offers them the opportunity to have a child that does not have the gene and is not a carrier for the gene. Without PGD these parents would need to undergo prenatal diagnosis to determine if their baby is a carrier of the disease or in fact has the disease and consequently most likely will face the decision of terminating their pregnancy.

Who should consider PGD?

There are two categories of patients that should consider PGD:

1. Couples with a history of miscarriage or repeated unsuccessful IVF cycles. (From a statistical point of view, chromosome disorders occur in well over half of all first trimester pregnancy losses.)

2. Couples at risk for passing on a genetic disease to their baby.

How is PGD performed?

Eggs and sperm are placed in a Petri dish and left to fertilize and the resulting embryos are grown until they reach 4-12 cells. This typically takes three days. One or two cells are removed from each embryo through a procedure called embryo biopsy. These cells are analyzed in the PGD Laboratory to determine which embryos are free of genetic abnormalities. Every doctor's office has their own method of tracking the embryo to the one or two cells that was removed from it. Clearly each embryo biopsied and the removed cell(s) must be carefully tracked so that if a defect is detected the correct embryo is identified. Using PGD, embryos that are free of abnormalities are identified for implantation. The healthy embryos are usually implanted into the uterus 4-5 days following the egg retrieval.

In routine genetic analysis there are usually hundreds of cells available for processing; however, with embryo biopsy only one or two cells are available. To enable testing to be done each cell must contain a nucleus with chromosomes present.

The window of opportunity to biopsy an embryo is very narrow. By day 3 the embryo will be composed of between four and 12 cells that are still distinct from each other. After day 3 the embryo begins to compact. This means that the individual cells begin to lose their clear outline and therefore if biopsied harm could be done to the nearby cell. On Day 3 single cells can be individually removed without disrupting the adjacent cells in the embryo.

Are there risks associated with PGD?

The techniques used to biopsy are generally thought to be safe with little risk to the embryo. The risk of accidental damage to the embryo during biopsy is typically thought to be approximately 1%. (Some embryologists have stated that their risk factor is less than 1 %.) There is a slightly lower likelihood of implantation after embryo biopsy compared to an embryo not having been biopsied. (This remains debatable because so many factors need to be taken into consideration when identifying why an implanted embryos did not result in a pregnancy.) Since PGD is a relatively new technology other risks may become apparent over time, but to date appear quite limited and need to be weighed against the potential benefits for each couple. Think of it this way – identical twins means the embryos spit into two equal parts, in other words 50% of the embryo was lost! Finally with PGD there are certain to be some normal embryos that are incorrectly diagnosed as abnormal and discarded.

Should I do PGD?

You need to have this discussion with your physician who will take into consideration your age, fertility history and genetic history of your extended family. PGD is typically recommended most frequently for patients with a history of genetic disease, unexplained infertility, recurrent miscarriages, unsuccessful IVF cycles, advanced maternal age, or male factor infertility. The most likely cause for miscarriage or multiple failed IVF cycles is a chromosome abnormality. PGD can also vastly reduce the risk of a Down syndrome conception. In some cases where a couple has a large number of embryos they may consider PGD as a tool to deciding which embryos to implant. Finally, through PGD the sex will be identified so this procedure offers a couple the opportunity of family balancing.

What disorder can be diagnosed with PGD?

Most cells contain 23 pairs or 46 chromosomes. These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes). Sperm and eggs only contain 23 single chromosomes (one from each chromosome pair). During fertilization, the embryo receives one chromosome of each pair from each parent resulting in a normal male (46, XY) or a normal female (46,XX). If the sperm or egg harbors a chromosome abnormality, this can be transmitted to the embryo resulting in a genetic disorder.

Down syndrome is usually associated with advanced maternal age. Down syndrome is caused by having an extra #21 chromosome (3 instead of 2). It is also referred to as trisomy 21.

Single gene disorders usually show a characteristic family history of a specific genetic disease. Gene mutations can alter the cells normal function due to a lack of a required protein. For example, Cystic Fibrosis (CF) is a common genetic disorder that primarily affects the lungs of CF patients. The CF mutation affects a protein within the cell that reduces the cells ability to function properly. This results in a build up of mucous within the lungs, lung dysfunction and possible death.

Specific chromosomes are tested for specific disorders, including:

Chromosome 13: Breast and ovarian cancers, deafness, Wilson Disease
Chromosome 15: Marfan syndrome, Tay-Sach's Disease
Chromosome 16: Polycystic kidney disease, Alpha thalassemia
Chromosome 17: Charcot-Marie-Tooth Disease
Chromosome 18: Niemann-Pick Disease, pancreatic cancer
Chromosome 21: Down syndrome
Chromosome X: Duchenne muscular dystrophy, Turner's syndrome, Fragile X Syndrome
Chromosome Y: Acute myeloid leukemia

If PGD can reduce the risk of having a child born with a genetic defect, what is the ethical concern regarding PGD?
  • One common concern is that PGD will lead to more emphasis on society valuing "healthy" people over those deemed "unhealthy".

  • Some take issue with the idea of an embryo being created outside of the body and then being destroyed and not been given the opportunity to come to life. PGD test results are not 100% accurate. Even if a chromosomal abnormality is found, it does not guarantee that the child will be born with a particular disease or disorder.

  • The issue of sex selection and PGD is also a problem. While many like the idea of being able to choose how their family will be formed or hope to avoid a sex-linked disorder, others argue that sex selection encourages people to favor one sex over the other. In countries where there is already a social preference towards one sex, often the male, there is worry that allowing couples to choose the sex of their baby would cause an imbalance in the social makeup of that society.


On the other hand, many people elect to participate in PGD because it can detect potential problems before a pregnancy has even begun. Without PGD genetic testing can only be done on a living fetus. Nuchal translucency testing can be performed at around 11 week’s gestation and will most likely indicate if the baby is Down syndrome. CVS and Amniocentesis testing are standard procedures that are usually performed between week 15-19 of gestation. Although these procedures carry a very small risk to the fetus, there is a risk involved. It is perhaps a less emotional decision for a couple to discard an embryo that contains a genetic defect than making the difficult decision once a pregnancy is in existence.

PGD and Pregnancy

Will PGD affect their chances of pregnancy or, more importantly, the health of their embryo? The procedure is done so early in the developmental process, at 4-12 cell development, it is believed that PGD should not cause any harm to the developing embryo. As with most medical procedures, the success rate depends on the skills of the embryologist.

Some people feel that performing PGD and manipulating the embryo in some way is likely to lessen your chances of a pregnancy through IVF occurring. However, others disagree, believing that pregnancy success rates actually increase through the use of PGD. This is because only those embryos that have been shown to be in good health are transferred back to the mother.

Since genetic abnormalities are the most common reason for a miscarriage, transferring only those embryos without any abnormalities decreases the risk of another miscarriage. However, there are only so many genetic disorders and diseases that PGD can detect at this time. It is still possible to transfer an embryo with genetic problems that just can’t be assessed by PGD.

For those couples with 6 or more embryos it is often a difficult decision to decide which embryos to implant. If PGD is performed then those embryos with genetic disease can be excluded and the remaining healthier embryos considered for implantation.

PGD is not automatically performed in IVF procedures. PGD will cost an additional $5,000-$8,000 over and above the costs of the IVF cycle.

It is estimated that over 15,000 children have been born after a preimplantation genetic screening.
To help those of us who are not entirely sure what the difference between cells, chromosomes and genes are here is a quick guide:

Genetics 101

Our bodies are made up of billions of cells. Each cell has a nucleus that contains chromosomes. Humans have 23 pairs of chromosomes (Compared to chimps that have 24 pairs and bananas have 11 pairs.) Here is a drawing of the 23 pairs of human chromosomes:



Each chromosome is made up of string-like structures called DNA sequences. This is often referred to as the double helix. Short segments of DNA segments are called genes.

An important property of DNA is that it can make copies of itself. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell. Sometimes during the copying process a mistake in copying occurs and this could lead to genetic defects.





Genetic defects occur in one of two ways:

1. Inherited from a parent or ancestors – hereditary mutations. These mutations are present in almost every cell of the person's body.

2. Acquired during a person's lifetime. This can occur during fertilization of the sperm and egg or during a person's life or caused by environmental factors.

If a person has a mutation that occurs in every cell of their body it is most likely an inherited mutation. However, if a mutation occurs at the stage of fertilization then that mutation will also occur in almost every cell of the body. The difference is that in the latter case there is no family history of the disorder and therefore it can be concluded that such a mutation occurred just after fertilization. A mutation that occurs during one’s life (but not at the time of fertilization) or are a result of an environment factor will not be present in every cell of the body. Consequently, these acquired mutations cannot be passed on to the next generation.



A search for "genetics 101" on the Internet yields thousands of results. Here are three of the most helpful and easy to comprehend:

http://www.genetichealth.com/G101_Genetics_Demystified.shtml
https://www.23andme.com/gen101/
http://ghr.nlm.nih.gov/handbook/basics/dna