Preimplantation Genetic Diagnosis
PGD for Down Syndrome, Chromosomal Abnormalities
Chromosomes contain all of the genetic information that determines everything from the color of our hair to the way our body functions. A normal cell in the human body contains 46 chromosomes in 23 pairs. We inherit one chromosome of each pair from our mother and the other chromosome from our father. Females have two X chromosomes, while males have one X and one Y chromosome. Each egg cell and sperm cell contain 23 chromosomes and when they come together at fertilization the embryo will then have 46 chromosomes.
Chromosomal aneuploidy is a type of chromosome abnormality that occurs when a cell has either too many or too few chromosomes. The most common example of a chromosomal aneuploidy is Down syndrome, or trisomy 21, which involves an extra chromosome 21. Other common chromosomal aneuploidies are trisomy 13, trisomy 18, Turner syndrome and Klinefelter syndrome, which can result in liveborn children with a range of birth defects and cognitive disability. Other chromosomal aneuploidy includes an extra chromosome 15, 16, or 22, which results in a miscarriage early in pregnancy.
Risk of Chromosomal Abnormalities Increases With Maternal AgeAs a woman ages, the chance of having an aneuploid pregnancy increases. There is a significant rate of chromosome abnormalities in embryos, and the frequency of these abnormalities increases with age. Only a few pregnancies carrying an extra or missing chromosome will go to term; most will be miscarried.
The likelihood of delivering an affected child is shown in the chart below*.
|Maternal Age at Delivery
||Risk of Aneuploidy in Liveborn Child |
||1 in 385 (or 0.26%)|
||1 in 192 (or 0.52%)|
||1 in 102 (or 0.98%)|
||1 in 66 (or 1.5%) |
||1 in 21 (or 4.8%)|
||1 in 8 (or 12.5%) |
*Hook EB. Cross PK. Schreinemachers DM. (1983) Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA, 249(15):2034-8. *Hook EB. (1981) Rates of chromosomal abnormalities at different maternal ages, Obstetrics & Gynecology, 58(3):282-5.
The goal of preimplantation genetic diagnosis for chromosomal aneuploidy is to select for and maximize the chance of transferring only chromosomally normal embryos to achieve more pregnancies, reduce the number of pregnancy losses, and reduce the number of affected offspring.
PGD for Sex-Linked DisordersMost couples at risk for a sex-linked condition are identified by review of the family history or the birth of an affected child. The majority of sex-linked conditions are caused by a change, or mutation, in a gene on the X chromosome and typically affect only males. This is because males have only one X chromosome, inherited from their mother, while they get a Y chromosome from their father. Since a male has only one X chromosome, if it has a mutated gene he will develop the disorder. It is this type of inheritance that causes disorders such as Duchenne Muscular Dystrophy, hemophilia, and some types of hydrocephalus (water on the brain).
Females are usually not affected because they have two X chromosomes. Females with one normal X chromosome and one mutated X chromosome generally do not have symptoms of the disease because of the presence of the normal gene. These females are referred to as “carriers” and are at risk for passing on the gene mutation to their children. If that child is a girl who inherits the gene, she also will be a carrier. Once the sex of the embryo is determined, female embryos, which would not be at risk for a sex-linked disorder, would be transferred. A technology called Microsort® can significantly increase the chance of conceiving a female child by selecting for sperm that have an X chromosome.
PGD ProcedureCouples who have PGD will undergo an in vitro fertilization (IVF) cycle to create embryos. Genetic analysis will then be performed on cells from each embryo prior to transfer into the woman’s uterus. To analyze an embryo, we biopsy the embryo around the third day of its development when the embryo has approximately 6-8 cells. One or two cells are taken from the embryo. The embryo is incubated until testing is complete.
The cells are then carefully analyzed to discover specific genetic problems, such as Down syndrome. Using the latest technology from Gene Security Network, our lab looks at all 24 chromosomes, rather than just a few. With this analysis, we can distinguish cells that have chromosome abnormalities from those that do not. We won’t transfer embryos that are found to have a chromosome abnormality. We will not reveal the gender of any embryos, except for couples who undergo PGD for a family history of an X-linked condition. (In families who are at risk for an X-linked disease, only female embryos will be transferred.) You can learn more about the latest techniques in chromosome analysis by visiting Gene Security Network.
Preventive Measures During PGD CycleIt is important for a couple undergoing PGD to alter their sexual activity during the PGD cycle. Beginning with day five of treatment with follicle stimulating hormones (FSH), the couple must refrain from sexual intercourse until cycle completion (regular menstruation or positive blood pregnancy test). Intercourse during this time could lead to a pregnancy with an embryo that has not been tested.
Risks of PGDIt is important to know that there may be no embryos available for embryo transfer. The biopsy technique required to perform PGD has been in use since 1990. From use of the technique since that time, it seems the chance of accidental damage to an embryo during the removal of cells is very low. The risks of biopsy to an embryo include but are not limited to decreasing the embryo’s chance for survival and continued development prior to implantation. Embryo biopsy is not known to lead to an increase in children born with congenital abnormalities, birth defects, mental retardation, or other possible problems with development following natural fertilization. PGD may reveal that all embryos are chromosomally abnormal. However, a normal pregnancy outcome cannot be guaranteed whether or not there is an embryo biopsy.
Accuracy of PGDOverall, PGD is an accurate process for determining the chromosomal content of a cell from an embryo. There is a small risk of inaccuracy (incorrect identification of the chromosomal make-up) and/or unclear results in the biopsied embryo(s).
Some embryos are a mixture of normal and abnormal cells (mosaicism). If we analyze a cell that has normal chromosomal content, while unanalyzed cells have a chromosome abnormality, we could inaccurately identify that embryo as being chromosomally normal. Therefore, the analyzed cell may not be representative of the cells as a whole. Due to the unavoidable possibility of inaccuracy and the possibility of less common chromosome abnormalities for which we do not test, the option of testing early in pregnancy through prenatal diagnosis is available.
Cost of PGDThe PGD costs are in addition to the cost of in vitro fertilization (IVF) and embryo transfer. They include the cost of the DNA probes, FISH analysis, the biopsy procedure and professional physician fees. Insurance companies generally do not cover the cost of PGD. We will be happy to provide you with a detailed cost analysis for PGD.
Contact InformationRequests for information regarding the Children’s Hospital of Wisconsin, Froedtert & The Medical College of Wisconsin PGD and IVF program can be obtained by contacting the Reproductive Medicine Center at 262-253-9220. Information regarding preimplantation genetic diagnosis can be discussed in more detail with a genetic counselor.
Last Review Date: March 8, 2013
Online Editor(s): Shannon Krause