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Is assisted reproduction linked to birth defects?
By Kimberly Leydig Scientists from Washington and Johns Hopkins universities have discovered that in vitro fertilization (IVF) appears to be associated with a rare combination of birth defects characterized by excessive growth of various tissues. After studying data from a national registry of patients with Beckwith-Wiedemann Syndrome (BWS), the researchers found that IVF-initiated conception was six times more common in those patients than in the general population.
Children born with BWS -- which may predispose them to Wilms' tumor, hepatoblastoma, neuroblastoma or other cancers -- would likely represent only a tiny fraction of babies conceived via IVF if the findings are confirmed, the researchers emphasized. The results should stimulate further investigation -- not change prospective parents' decisions -- they stressed. "At this point, we simply have a strong association between BWS and IVF," said lead author Michael R. DeBaun, M.D., assistant professor of pediatrics. "We need additional data to verify our findings, and if confirmed, to understand why there is an association." "This analysis should not affect people's decisions about whether to have IVF, because our findings still need to be validated," added co-author Andrew Feinberg, M.D., the King Fahd Professor of Medicine at Johns Hopkins and a member of the university's McKusick-Nathans Institute for Genetic Medicine. "What is learned might improve the health of all children." BWS occurs in about one in 15,000 births. Currently, IVF is not thought to result in birth defects at a higher rate than natural conception, according to the Society for Assisted Reproductive Technology. DeBaun started the Beckwith-Wiedemann Syndrome Registry in 1994 as part of an effort with Feinberg to find links between altered genes and different versions of BWS. Prior to June 2001, four of the 279 BWS patients in the registry were known to be conceived by IVF. Suspecting an association, DeBaun began collecting details about conception methods for new patients entering the registry. Subsequently, three of 65 BWS patients added to the registry were conceived through IVF. In the United States, roughly 0.8 percent of births are due to assisted reproductive technology, including IVF. But the incidence is 4.6 percent among BWS patients who have been entered into the registry since June 2001. The researchers note that they did not specifically recruit parents who had used IVF in order to have a baby, but they can't exclude the possibility that these parents may have been more likely to participate. BWS and other syndromes characterized by excessive growth are frequently due to so-called epigenetic changes -- alterations to the gene other than to the DNA sequence itself. BWS is often caused by abnormal "imprinting" -- biochemical marks on DNA that tell the cell whether the gene copy came from the father or mother. For imprinted genes, the cell uses only the copy from a particular parent (the mother or the father, depending on the gene) to make proteins. If imprinting marks are lost, the cell may make proteins using both copies or neither, causing abnormal growth, such as in BWS or cancer. Abnormal imprinting of two genes, LIT1 and H19, normally accounts for about half of BWS cases. At least five of the seven known registry patients conceived through IVF had such changes. While the association still needs to be confirmed, the researchers suggest that some aspect of culture conditions or the method of combining the sperm and egg could possibly affect the epigenetics of embryos, based on reports of others' experience with animals. |
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