ARC® Fertility Articles

Preimplantation Genetic Testing

James Goldfarb, MD.©
www.uhhospitals.org/fertility
University Hospitals Fertility Center at Ahuja
UH Ahuja Medical Center
Kathy Risman Pavilion
1000 Auburn Drive, Suite 310
Beachwood, OH 44122
216-285-5028
Fax: 216-201-5385

It is now possible to test embryos created by In Vitro Fertilization (IVF) for genetic diseases by utilizing Preimplantation Genetic Testing (PGT). The primary goal of PGT is to identify genetic defects in embryos created through IVF before transferring them to the uterus, thus decreasing pregnancy terminations and births with genetic abnormalities.

There are two types of Preimplantation Genetic Testing that can be performed

  1. Preimplantation Genetic Diagnosis (PGD)
    Parent(s) carry a genetic condition and testing is performed to determine whether that condition has been transmitted to the egg or embryo
  2. Preimplantation Genetic Screening (PGS)
    Parents have no known genetic abnormalities and their embryos are screened for chromosomal abnormalities (aneuploidy)

The Process of PGT 
As with so many procedures PGT begins with careful patient counseling. If patients are candidates and desire to proceed, an IVF cycle is initiated. Embryos produced by IVF can have one or more cells analyzed for the condition in question. One to three embryos (depending mainly on the woman’s age) that are determined to not be affected with the condition in question are transferred to the uterus with a procedure that is similar to that of a Pap test.

Experience with PGT
Women in their later 30′s and 40′s have a significantly lower pregnancy rate than younger women. It is thought that the lower pregnancy rate is due in large part to the higher incidence of aneuploidy (chromosomally abnormal) embryos. It was assumed that PGS would, by allowing transfer of chromosomally normal embryos, lead to higher pregnancy rates and lower miscarriage rates in this age group. Thus, when we first started doing PGS in the mid 2000′s we were offering PGS to couples going through IVF if the woman was more than 38 years old. However, we noted a much higher than expected number of embryos reported as chromosomally abnormal; of the first 271 embryos we tested only 58 (21%) were reported to be normal. Other IVF programs had similar experience and it became clear that there were many false positive results in doing PGS. As reported in the New England Journal in July 2007, the high number of false positive results decreased the number of morphologically normal embryos available for embryo transfer resulting in lower, rather than higher, pregnancy rates for patients undergoing PGS. Because of these unexpected and disappointing results, the use of PGS has decreased greatly. Recently newer ways of performing PGS are being evaluated to determine if the historic problems with PGS can be minimized.

In contrast to PGS, the experience with PGD has been very encouraging; pregnancy rates are very good and the tests are very accurate. PGD can be utilized to prevent babies being born with any disease for which the causative gene has been indentified. Common diseases for which PGD is performed include cystic fibrosis, muscular dystrophy and hemophilia PGD allows to avoid having children with these and other devastating diseases.

PGD can also help couples who have a child with diseases such as leukemia and who need a hematopoietic cell transplant. Often there are no matches for the child among the family, and the parents were planning on having more children. In this case the couple can go through IVF and have the embryos undergo HLA typing. Embryos that are an HLA match with the child with the disease can be transferred. Cord blood from the IVF pregnancy can then be used for transplant to the affected sibling.

Although controversial, PGD obviously has the capability of being utilized for sex selection for family balancing.

Clearly, like many technologies, PGT raises many ethical issues but it also provides the chance for couples to have what is most important to them – a healthy family.

James Goldfarb, MD, is board-certified in reproductive endocrinology and infertility and director of the University Hospitals Fertility Center at UH Ahuja Medical Center in Beachwood.

©Copyright James Goldfarb, MD