From ScienceDaily
http://www.sciencedaily.com/releases/2002/11/021118065310.htm


Source:   Johns Hopkins Medical Institutions
Date:   11/18/2002


Assisted Reproduction May Be Linked To Birth Defect Syndrome

Scientists from Johns Hopkins and Washington University School of Medicine
in St. Louis 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 than in the general population. The
findings are slated for the January issue of the American Journal of Human
Genetics, and should be online by the end of November.

Children born with BWS, which may predispose them to Wilms' tumor,
hepatoblastoma, neuroblastoma and other cancers, would likely represent only
a tiny fraction of babies conceived via IVF if the findings are confirmed,
the researchers emphasize. The results should stimulate further
investigation, not change parents' decisions, they say.

"This analysis should not affect people's decisions about whether to have
IVF, because our findings still need to be validated," says Andrew Feinberg,
M.D., King Fahd Professor of Medicine at Johns Hopkins and a member of the
school's McKusick-Nathans Institute for Genetic Medicine. "What is learned
might improve the health of all children."

"At this point, we simply have a strong association between BWS and IVF,"
adds Michael R. DeBaun, M.D., M.P.H., assistant professor of pediatrics at
Washington University School of Medicine and a staff physician at St. Louis
Children's Hospital. "We need additional data to verify our findings, and if
confirmed, to understand why there is an association."

BWS occurs in about 1 in 15,000 births overall. 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. "While our
study has its limitations, we believe it's time to begin looking at these
issues more formally," says Feinberg, who has been studying imprinting's
role in disease, particularly cancer, for some time.

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 BWS patients in the
registry were known to have been conceived by IVF (out of 279). 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. The incidence is 4.6 percent among
BWS patients 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 child, but they can't exclude the possibility that such 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, says Feinberg.

While the association still needs to be confirmed, Feinberg suggests 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.

 ### Authors on the paper are Michael DeBaun of Washington University School
of Medicine (St. Louis, Mo.), and Emily Niemitz and Andrew Feinberg of The
Johns Hopkins University School of Medicine. Funding for the research was
provided by the National Institutes of Health and the March of Dimes (both
to Feinberg), and the Robert Wood Johnson Minority Faculty Development
Program and the Doris Duke Clinical Scientific Foundation

On the Web:

This paper should be online by the end of November.
http://www.journals.uchicago.edu/AJHG/index.html

Backgrounder: Epigenetics and Imprinting
http://www.hopkinsmedicine.org/press/2002/November/epigenetics.htm

For more information: The March of Dimes: http://www.modimes.org

The Society for Assisted Reproductive Technology, a division of the American
Society for Reproductive Medicine: http://www.sart.org

The Beckwith-Wiedemann Support Network: http://www.geocities.com/bwsn/

Editor's Note: The original news release can be found here.


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