PGD Offers Promising Option for Preventing Genetic Disorders

A new option is now available for couples who have experienced the disappointment of being unable to conceive or carry a child to term because of genetic reasons, or for couples who have already had a child with a genetic or sex-linked disorder. The new technique is called preimplantation genetic diagnosis, or PGD for short, and it was introduced in January through a collaborative effort of Children’s Hospital of Wisconsin, the Medical College of Wisconsin and Froedtert Hospital.

PGD allows genetic testing to be performed on embryos before they are implanted in the uterus and pregnancy develops, and is intended to decrease the likelihood of a chromosomal abnormality or sex-linked disorder.

“Our program uses advanced technology to provide new hope to couples who are at risk of having, or have already had, children with serious genetic disorders – and to couples who have experienced multiple miscarriages or long periods of unexplained infertility,” says Estil Y. Strawn Jr., MD, Associate Professor of Obstetrics and Gynecology at the Medical College and Director of the Division of Reproductive Medicine and Fertility.

Dr. Strawn is one of a staff of 15 professionals involved in the PGD program, including physicians, embryologists, certified genetic counselors, nurses and laboratory technologists. It is the only such multidisciplinary program in the Milwaukee area, Dr. Strawn says, and one of few in the Midwest or even nationally. Other organizations may offer PGD, he says, but no other provider in this area offers a full range of genetic counseling before the procedure is performed and follow-up care afterward.

Chromosome Variations Can Result in Birth Defects
To understand how the PGD procedure works, it’s necessary to review the rudiments of human genetics:
A normal cell in the human body contains 46 chromosomes in 23 pairs. Chromosomes contain all of the genetic information that determines everything from the hair color to the way our bodies function. We inherit one chromosome of each pair from our mother, and the other from our father. Females have two X chromosomes – one from each parent. Males have one X chromosome, from their mother, and one Y chromosome, from their father. Unlike other cells in the body, normal egg cells and sperm cells each contain 23 chromosomes. When they come together at fertilization, the embryo will have 46 chromosomes – 23 pairs – in each cell.

Chromosomal abnormalities in embryos are not unusual, and the frequency of such variations increases as a women age. Few pregnancies carrying an extra or missing chromosome will last all the way to term – most will be miscarried.

When a cell has either too many or too few chromosomes, this abnormality is called chromosomal aneuploidy. The most common example is Down syndrome, or trisomy 21, which involves an extra chromosome 21.

The PGD Procedure
After the couple’s eggs and sperm are extracted and fertilized in vitro, all the resulting embryos are tested before they are transferred into the woman’s uterus. Each embryo is incubated, and after about the second or third day of development, when the embryo has approximately six to eight cells, two of the cells are removed for biopsy and genetic analysis.

The biopsied cells are analyzed using a technique called fluorescence in situ hybridization, or FISH analysis. FISH analysis uses DNA probes that can attach to the chromosomes so that they can be counted. Each probe is labeled with a different fluorescent dye, and the number of chromosomes of various types can be seen when viewed under a fluorescent microscope. By distinguishing cells that have the most common chromosome abnormalities from those that do not, and by determining which sex chromosomes are present, FISH analysis helps identify the embryos that are most likely to result in a successful pregnancy.

Risks and Accuracy of the Procedure
Worldwide experience with the PGD biopsy technique since 1989 has shown that the risk of damage to the embryo is low. Nevertheless, a normal pregnancy outcome cannot be guaranteed. In addition, there is a small risk of inaccuracy due to incorrect identification of the chromosomal makeup or unclear results from the biopsied embryos.

Due to the unavoidable possibility of inaccuracy, plus the possibility of less common chromosome abnormalities that are not included in the PGD analysis, couples are offered the option of prenatal diagnosis and testing early in pregnancy. This includes amniocentesis, in which some of the amniotic fluid surrounding the developing fetus is aspirated and analyzed; and chorionic villus sampling (CVS), in which a small amount of tissue from the developing placenta is removed and tested.

“PGD is not a way to assure that the baby will be perfect,” Dr. Strawn cautions. “This type of testing merely tells us it won’t have the defects we are testing for. For instance, it would not detect a fetus that is developing with four fingers, not five.”

The technique is not for everyone. Some decline the process based on religious or other beliefs. And the cost alone is prohibitive for many: In vitro fertilization costs $9,000, Dr. Strawn says, and the PGD procedure adds another $1,500. This includes the cost of drugs, doctor visits, the extraction of eggs and sperm, and the laboratory analysis.

Although PGD analysis can identify the sex of embryo, it could be used to select the gender of a child before pregnancy – but not with this program, Dr. Strawn says. “As a consortium we have agreed that we will not offer preimplantation genetic diagnosis solely for sex selection, or ‘family balancing,’ as some call it.”

“For women who are 39 or older, for women with recurring miscarriages, or for those who have undergone two cycles of in vitro fertilization without conceiving, PGD can be an especially helpful option,” he notes.

Barbara Abel
HealthLink Contributing Writer

You can learn more about in vitro fertilization and the PGD program provided by Froedtert & Medical College and Children’s Hospital of Wisconsin by calling the Reproductive Medicine Clinic at 414-805-3666 or 800-272-3666 for information or appointments.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.