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In a significant scientific achievement, physicians and scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have successfully employed preimplantation genetic diagnosis (PGD) for retinoblastoma. The result was the world's first babies genetically predisposed to this disease to be born free of the deadly eye cancer. The news appears in this month's issue of the American Journal of Ophthalmology.

Preimplantation genetic diagnosis, or embryo biopsy, is a diagnostic technique used with in vitro fertilization (IVF) to determine the genetic status of embryos before implantation. The technique allows parents to know with reasonable certainty that their child will be normal before the mother is even carrying the child. Moreover, PGD can virtually eliminate the risk of passing on a genetic trait from parent to offspring, and forever end a family's history of dealing with a deadly disease.

Retinoblastoma, the most common primary cancer of childhood, is one such disease transmitted between a parent and their offspring. If a parent has bilateral retinoblastoma (in both eyes), there is a 50 percent chance of a child being affected with each pregnancy, with often devastating results. Children with the gene typically develop retinal tumors and are more likely to succumb to other forms of cancer as well. Among these are osteosarcomas of the skull or extremities, soft-tissue sarcomas, and melanomas (skin cancer).

Retinoblastoma occurs 1 in 15,000 births; one child is born with the disease every day in the United States. It is fatal if untreated.

The interdisciplinary team from NewYork-Presbyterian/Weill Cornell was led by Dr. Zev Rosenwaks, Director of the Center for Reproductive Medicine and Infertility; Dr. David H. Abramson, Director of the Ophthalmic Oncology Center; and Dr. Kangpu Xu, a noted embryologist and expert in PGD technology. Other key contributors included Dr. Ina Cholst, Dr. Lucinda Veeck, and Katherine Beaverson, MS.

Dr. Antonio M. Gotto, Jr., Dean of Weill Cornell Medical College, says: Our breakthrough with retinoblastoma is a wonderful achievement. Our team has used this relatively new technology to combat a number of genetic defects and chromosomal abnormalities, leading to a relief of pain and suffering.

Dr. Herbert Pardes, President and CEO of NewYork-Presbyterian Hospital, observes: Such an achievement can only be realized in an academic medical center, such as ours, where specialized, multidisciplinary teams of physicians and scientists can create a unique synergy between bench and bedside, between research and patient care.

In the case reported herein, the physician-scientists used leuprolide acetate and gonadotropins to hyperstimulate the mother's ovaries, and the resulting eggs were harvested and fertilized, using an in vitro fertilization technique that Dr. Rosenwaks helped popularize a few years earlier. After several days, a single cell or blastomere was biopsied from each resultant embryo and its DNA examined. Testing was done using polymerase chain reaction (PCR) and restriction enzyme analysis. Embryos that were determined not to carry the retinoblastoma gene defect were implanted within the mother's uterus. The mother had two successful pregnancies and births through PGD, resulting in a baby girl, now 1½ years old and a baby boy, now 7 months.

In contrast, the couple's first child -- conceived without PGD screening 3½ years ago -- was born with the genetic defect and went on to develop retinoblastoma, or tumors of the retina, at a young age. She is currently undergoing treatment for a brain tumor.

The father himself, who carries the genetic defect, was born with retinoblastoma and treated as a child. He has reduced vision in one eye as the result of his disease.

It is the prevention of a serious disease like this that is perhaps the team's most significant achievement. We've eliminated a life of consistent worry about what might happen next, says Dr. Abramson. As a physician, it's very rewarding.

Previous methods for detecting retinoblastoma have had their limits, notes Dr. Rosenwaks. Chorionic villus sampling (CVS), amniocentesis, or percutaneous umbilical sampling all require tissue or fluid to be taken from around the developing fetus. Then, for couples with a positive test result, a difficult, often traumatic, decision results: to terminate the pregnancy or give birth to a child genetically prone to develop cancer.

Currently at NewYork-Presbyterian/Weill Cornell, preimplantation genetic diagnosis is offered to couples who suffer from genetic disorders and chromosomal abnormalities, including Tay Sach's disease, cystic fibrosis, sickle-cell anemia, hemophilia, thalassemia, and Fanconi's anemia, among others.

Among other notable advances with PGD, NewYork-Presbyterian/Weill Cornell's Center for Reproductive Medicine and Infertility achieved America's first PGD baby, America's first baby born free of hemophilia, and the world's first baby born free of sickle cell.