In Vitro Linked to Rare Bladder Defects

Disorder Among Conditions Linked to Babies Born Through In Vitro Fertilization

From the WebMD Archives

March 19, 2003 - More than 1 million babies worldwide have been born through in vitro fertilization, and the overwhelming majority are perfectly healthy. But recent studies suggest the popular 25-year-old technology may increase the risk of various rare birth defects and medical problems.

The latest: A finding by Johns Hopkins researchers that in vitro-conceived babies may be seven times more likely to be have rare urological birth defects -- including having their bladders outside of their bodies.

While this exstrophy-epispadias complex is extremely rare -- affecting only three per 100,000 births -- researchers at the Johns Hopkins Children's Center noticed that among the 78 patients treated for it over a four-year period, four were conceived through in vitro fertilization. The Hopkins facility treats about one in seven of all American children with this birth defect.

"Considering how rare bladder exstrophy is, when you see four in vitro fertilization children with it over a short period of time, it makes you take notice," says John P. Gearhart, MD, director of pediatric urology. "I mentioned this observation to some colleagues in Europe, and they said, 'We've seen the same thing.'" Both teams of researchers are now collaborating on a large study.

Bladder exstrophy is the most common birth defect of this complex, characterized by the bladder protruding through the abdominal wall -- being exposed outside the body. Another bladder defect allows the inner lining of this hollow organ to be exposed. . Other defects affect pelvic bones, the urethra, and genitals. These birth defects can be detected with a high-level ultrasound during pregnancy -- a procedure Gearhart recommends for all women with in vitro-conceived pregnancies.

"Exstrosphy babies are good babies -- they have good lungs, good spines, good heads. They just happen to be born with their bladder on the outside. But it's fixed with surgery and they go on with their lives," Gearhart tells WebMD. "We continue to encourage people who are childless to have in vitro pregnancy, but take that extra bit of caution, that extra bit of care, and get a high-level ultrasound during pregnancy performed by a trained neonatologist to look for this condition. This should not discourage couples from having in vitro fertilization."

But his finding, published in the April issue of the Journal of Urology, is the latest discouraging news associating in vitro fertilization to a host of medical problems. In January, Dutch researchers reported in The Lancet that in vitro fertilization babies are up to seven times more likely to have a rare cancer of the retina that affects about one in 17,000 births. And last March, two studies in The New England Journal of Medicine suggested that low birth weight and defects such as Down syndrome were twice as high for babies born to mothers who undergo either in vitro fertilization or intracytoplasmic sperm injection (ICSI). And just one month earlier, another Lancet study linked in vitro fertilization with higher rates of various brain disorders, including cerebral palsy.

In vitro fertilization, retrieved eggs and sperm from the parents are placed together in a laboratory dish to enhance the likelihood of fertilization. If it occurs, the eggs are transferred back into the woman's uterus, where implantation and embryo development would hopefully occur as in a normal pregnancy.

There are various theories on why in vitro fertilization-conceived children seem to have a higher risk of medical problems -- from problems with the preserving solution in the dish that houses the sperm and egg to mistakes in the procedure itself. "Our theory is that bladder exstrosphy and other defects could result from mishandling of the fertilized egg during implantation or some kind of metabolic problem induced by the procedure of implantation itself," Gearhart tells WebMD.

But Robert Brzyski, MD, PhD, president of the professional association representing in vitro specialists at 370 clinics across the U.S., has his own theory. "We cannot discount the lab environment or other factors, but something in the couple's inability to naturally have a child may predispose them to adverse outcomes in general," says Brzyski, of the Society for Assisted Reproductive Technologies and an ob-gyn at the University of Texas Health Science Center at San Antonio.

Like other assisted reproductive techniques, in vitro fertilization is usually reserved for couples who cannot conceive a child naturally for at least a year.

Another theory under investigation is the fact that many in vitro fertilization conceptions end with multiple births, which are historically more vulnerable to birth defects. Of the 78% in vitro fertilization-assisted pregnancies that result in a live birth, 50% produce a single child, 24% produce twins and 5% are triplets or more, reports the American Society of Reproductive Medicine.

"Even before in vitro fertilization, there was a recognition that children that were the result of multiple birth had a higher risk of birth defects," Brzyski tells WebMD. "So now that we have a technology that is associated with increased risk of multiple births, it's hard to know if it's the technology itself or the natural expression of some process involved in multiple births that may be causing these defects. But when you talk about an extremely rare condition, even with a seven-fold increase, that condition is still extremely rare."

Some 45,000 American children have been born through in vitro fertilization since the first procedure was done in the U.S. in 1981; worldwide, more than 1 million babies followed the 1978 birth of the first so-called "test tube baby," Louise Brown.

"The vast majority of in vitro fertilization babies are healthy, robust, and wonderful infants," says Gearhart. "At the end of day, in vitro pregnancy has been a wonder for couples who have waited years to have a baby."

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SOURCES: Journal of Urology, April 2003. The Lancet, Jan. 25, 2003. The New England Journal of Medicine, March 7, 2002. The Lancet, Feb. 8, 2002. American Society of Reproductive Medicine. John P. Gearhart, MD, director, Division of Pediatric Urology, Johns Hopkins Children's Center and Brady Urological Institute; professor of urology, Johns Hopkins School of Medicine, Baltimore. Robert Brzyski, MD, PhD, president, Society for Assisted Reproductive Technologies; associate professor, obstetrics and gynecology, University of Texas Health Science Center at San Antonio.
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