Although IVF is becoming increasingly common, with about 1% of births in the US coming through IVF and as many as 4% in Denmark, concerns about its safety linger, according to a report in Nature Medicine. In an overview of recent research, the journal says that some scientists worry that initiating reproduction outside the body may cause genetic changes that manifest as congenital birth defects. So far, there is no direct evidence for this, but epidemiological studies suggest that IVF is associated with some rare genetic syndromes in newborns.

These include Beckwith-Wiedemann syndrome, a condition marked by premature birth, an enlarged tongue and heightened susceptibility to tumors, respiratory and speech defects. The normal prevalence worldwide is 1 in 12,000 newborns, but a 2003 study found that 3 out 65 US children afflicted with the syndrome had been conceived through IVF. "There appeared to be more children with the syndrome conceived through ART [assisted reproductive technology] than we might have expected by chance alone," says Eamonn Maher, a geneticist at the University of Birmingham, UK.

One possible cause is a failure in DNA imprinting. "The concern is that while the embryo is being cultured in the [IVF] lab, maybe the imprint marks are being changed. We know for sure that happens in mice," says Carmen Williams, a clinical investigator at the US National Institute of Environmental Health Sciences in North Carolina.

Unfortunately there are few long-term studies of the health of babies conceived through the technology. One Canadian study reported at the Society for Maternal-Fetal Medicine's conference in 2007 found that babies conceived through IVF were nearly 60% more likely to develop birth defects than naturally conceived ones. Another study, from the University of Iowa, found birth defects in about 6.2% of about 1,500 IVF-conceived children, in contrast to 4.4% among naturally conceived ones.

Dr Williams suggests that in the future IVF clinicians ought to avoid certain invasive procedures, such as biopsies of implanted embryos, culturing embryos in the lab longer than the minimal time period and using ICSI in the absence of male fertility problems.

And a recent study appears to confirm that problems do exist. Writing in the journal Human Reproduction, researchers at the US Centers for Disease Control and Prevention say that babies conceived with IVF are between 2 and 4 times more likely to be born with certain defects than babies conceived naturally. These include certain heart defects, cleft lip (with or without cleft palate) and some types of gastrointestinal defects. ~ Nature Medicine, November; Medical News Today, Nov 18