IVF May Be Linked to Rare Eye Tumor

Dutch Study Shows Cluster of Retinoblastoma Cases

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Jan. 23, 2003 -- Children who are conceived through in vitro fertilization (IVF) may be at increased risk for a rare cancer of the eye, new research from the Netherlands suggests. But the authors and others urge caution in interpreting the findings from the small study.

Researchers identified five cases of the ocular tumor retinoblastoma among Dutch children conceived through IVF during a 15-month period between 2000 and 2002. By comparing these cases with children with retinoblastoma who were not conceived through IVF, they calculated that children conceived through IVF are five to seven times more likely to develop the cancer. Their findings are reported in the Jan. 24 issue of TheLancet.

Retinoblastoma is a malignant tumor of the retina that usually occurs in children under the age of 6. Roughly one child in 17,000 develops the cancer, which is caused by a mutation in the Rb tumor suppressor gene. This gene suppresses tissue growth, but a mutated version leads to uncontrolled growth of cells, resulting in cancer. The abnormal gene is passed from parent to child in about 40% of cases, but there is no hereditary link in the majority of cases.

Pediatric ophthalmologist David BenEzra, MD, PhD, who wrote the accompanying commentary in the journal, began tracking ocular problems among children conceived through IVF in the mid-1990s after noticing what appeared to be an increase in eye malformations in these children. He has also identified a case of retinoblastoma in an Israeli IVF child, but he warns that the evidence linking assisted reproduction to the tumor is far from conclusive. He tells WebMD that larger studies finding no association between IVF and an increase in cancer risk are reassuring.

"We know from these studies that if there is an association it is probably very limited," says BenEzra, who is a professor of pediatric ophthalmology at Jerusalem's Hadassah Hebrew University. "But this still has to be studied further so that we get an idea of the true incidence of this tumor in these children."

In the Dutch study, researcher Annette C. Moll, MD, PhD, and colleagues compared the occurrence of retinoblastoma in the IVF population with that in the general population, and then estimated the risk for all children conceived through assisted reproduction.

None of the five children with retinoblastoma identified by the researchers had a family history of the disease, and all of the children were successfully treated.

Moll and colleagues agree that larger studies are needed to confirm the association between IVF and retinoblastoma and to explore potential causes.

"Whether treatment with ovulation-inducing drugs increases the risk of childhood cancer is an important matter, especially with the rising number of women undergoing treatment for subfertility," the researchers wrote. "Future investigators should consider the number of IVF treatments, other fertility drugs given before IVF, and the possibility that serious disorders in children conceived by IVF are diagnosed earlier than those in other children who do not have such close medical surveillance."

In a news release issued Friday, an association representing more than 4,000 European fertility specialists urged caution in interpreting the Dutch study. The European Society of Human Reproduction and Embryology release also cited the larger studies showing no increased occurrence of cancer among almost 20,000 IVF children.

Society chairman Hans Evers says the Dutch study could easily have overestimated the risk because it was so small.

"Of course, this does not exclude a connection between assisted reproduction techniques and childhood cancer, and everyone involved in fertility treatment agrees that it is extremely important to follow these children right through their childhood," Hans Evers says in the news release. "But the present report should be treated cautiously for now."

BenEzra agrees that this study may have overestimated the risks of retinoblastoma in this population.

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SOURCES: The Lancet, Jan. 24, 2003 • Annette C. Moll, MD, PhD, department of ophthalmology, VU Medical Center, Nijmegen, Netherlands • David BenEzra, Pediatric Ophthalmology Unit, Hadassah Hebrew University, Jerusalem • Hans Evers, MD, chairman, European Society of Human Reproduction and Embryology.
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