Image: First Test Tube Baby
Louise Brown, the world's first "test-tube" baby, is shown shortly after she was born at Oldham General Hospital in England on July 25, 1978.
By MSNBC contributor
msnbc.com

In the 25 years since the birth of the world’s first “test-tube” baby, about a million children around the globe have been conceived with the help of medical technology, and experts say most of them are doing just fine. But with a growing number of studies suggesting these kids may have elevated rates of rare birth defects or other health problems, U.S. doctors have formed a panel to take a careful look at the safety of fertility techniques.

Born in England on July 25, 1978, Louise Brown was the first child to be conceived through in vitro fertilization. Since then, IVF and other forms of assisted reproductive technology, or ART, have become an option for many couples struggling with infertility. In 2000, the latest year for which statistics are available, about 35,000 American babies were born using ART, accounting for 1 percent of all births in the United States.

Studies have yielded conflicting results on the safety of these techniques, with some reports showing that children conceived through ART are no different health-wise than their naturally conceived peers while other studies have raised concerns.

"What we needed was a group of experts to really do an assessment about the strength and power of the studies and what conclusions we could reasonably draw about the risks," says genetics expert Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University in Baltimore and former assistant director of the National Human Genome Research Institute.

Hudson partnered with the American Society for Reproductive Medicine and the American Academy of Pediatrics to convene a panel of experts who are now analyzing the available research.

"Anytime a technique has been associated, even suggested to be associated, with a problem, I think it's important to look at that association to see if it's real," says Dr. Sandra Ann Carson, president of the ASRM and a professor of obstetrics and gynecology at Baylor College of Medicine in Houston. "Right now, we're not sure if it's real."

Suspected problems
Among the more recent reports that have triggered some alarm over the techniques are two large-scale studies published in The New England Journal of Medicine over a year ago.

One study conducted in Australia found that babies conceived through IVF or another technique known as intracytoplasmic sperm injection, or ICSI, were more than twice as likely as naturally conceived infants to have major birth defects (9 percent vs. 4.2 percent), including problems with the heart and urinary or genital tracts.

During IVF, doctors place egg and sperm together in a petri dish and then transfer one or more of the resulting fertilized embryos into a woman's uterus. With ICSI, a modification of IVF that was developed in the early 90s to overcome male factor infertility, doctors inject a single sperm -- which may be immobile or misshapen -- into an egg.

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The second study by U.S. health officials showed that full-term singleton babies conceived through all forms of ART were more than twice as likely as infants in the general population to be born underweight (6.5 percent vs. 2.5 percent), putting them at risk for breathing difficulties and other potentially deadly health problems at birth as well as developmental difficulties down the line.

Several other studies followed. Last January, two reports published in genetics journals found that children with Beckwith-Wiedemann syndrome were four to six times more likely to have been conceived through IVF or ICSI than not. The syndrome, which normally affects one in 15,000 newborns, can cause an oversized tongue and internal organs, high birthweight and a greater risk of some cancers.

Also in January, a report in The Lancet implicated IVF with a five- to seven-fold increased risk of a rare form of eye cancer known as retinoblastoma among children born in the Netherlands.

And, in the April issue of the Journal of Urology, Johns Hopkins researchers concluded that babies conceived though IVF were seven times more likely to be born with a set of rare urological birth defects that include the formation of the bladder outside the body.

Other case reports linked ICSI with Angelman syndrome, yet another rare condition that can cause developmental problems and speech impairment.

To date, there have been about 300 published reports involving children conceived with ART, says Hudson, and the panel of experts will be looking at all of them. They plan to issue a report in the coming months with their conclusions and possible directions for future research.

Britain, too, is taking steps to better understand any potential dangers to children from these techniques. Last fall, the government's Human Fertilization and Embryology Authority and the Medical Research Council announced the creation of a working group to explore the issue.

'Small differences'
While the studies linking ART with health problems may seem scary, experts emphasize that most of the observed abnormalities are uncommon to begin with and are still uncommon even if the risk is magnified several times.

"You could hypothesize that if there were a particular health problem that's very common, it would have been recognized early," says Hudson.

"The risks that do exist, if they do exist, are rare," she maintains.

Dr. Arnold Strauss, chief of pediatrics at Vanderbilt University Medical Center in Nashville and a member of the U.S. panel analyzing the data, agrees.

"Common sense would say that a lot of people have been through this and most of their children are doing well," says Strauss.

"It's really a question of subtlety and small differences," he says.

What is clear is that ART has not produced anywhere near the catastrophic results some predicted a quarter century ago when Brown was born.

Possible factors
Doctors do know that because multiple embryos often are implanted during an IVF cycle to boost the odds of success, a woman has an increased risk of having twins, triplets or other multiples. These babies are at risk for being born prematurely and underweight.

But it's not known precisely why singletons might be at risk for low birthweight or some of the various birth defects or other problems that have been identified in studies.

"Is it the disease, the infertility, resulting in the birth defect or is it the technique itself?" asks Carson.

Infertile couples who undergo ART may have characteristics, such as defective sperm or eggs, that put them at greater risk of having children with abnormalities, experts speculate.

Strauss said he can see how actual ART procedures could theoretically pose a risk.

"The speculation would be that you're dealing with cells that are put into conditions that they would never normally see," he says, referring to egg and sperm cells in a culture medium in a lab dish. "Cells do change" in culture, he adds.

Experts say potential problems could stem from other aspects of infertility treatment, including the use of drugs to stimulate the ovaries or maintain a pregnancy, the freezing and thawing of embryos, or possible damage to an egg resulting from the injection of sperm during ICSI.

As fertility specialists sort out the risks, they say parents of children conceived through ART or those contemplating fertility treatments should not be overly concerned.

Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York-Presbyterian Hospital in New York City, says he explains to his patients that ART is still relatively new and "while we don't see a glaring increase in the abnormality rate" there may be some, unclear degree of risk.

Both Rosenwaks and Dr. Alan DeCherney, a professor of obstetrics and gynecology at the University of California at Los Angeles and editor of the journal Fertility and Sterility, say their patients aren't deterred when they hear about some of the recent studies.

"They're interested in getting pregnant," says DeCherney.

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