Finding suggests relationship but does not prove IVF procedure -- used in 1 percent of all births in the United States -- is cause of birth defects.
Babies conceived through in vitro fertilization (IVF), a method of assisted reproduction, have a slightly increased risk of major birth defects, such as heart or muscle and skeletal defects, compared to babies conceived naturally, according to a University of Iowa study.

The risk for IVF babies was 6.2 percent compared to 4.4 percent for naturally conceived babies. While the finding suggests a relationship between IVF and slightly more birth defects, it does not prove that the IVF procedure itself is the cause.

However, questions raised by the investigation are important to address because nearly 1 percent of all children born in the United States are conceived through IVF, said Brad Van Voorhis, M.D., the F.K. "Ted" Chapler Professor of Reproductive Endocrinology in the UI Roy J. and Lucille A. Carver College of Medicine and a study author.

"The finding indicates that the vast majority of IVF-conceived babies are not affected by major birth defects," Van Voorhis said. "Most appear to be fine, at least up to age 1, which was our study limit. However, the question remains whether the slight increased risk for IVF babies is caused by the treatment itself, by factors in infertile couples who seek IVF or by some combination of the treatment and these factors."

The team did the study because reports from other countries found a slight increase in the risk of major birth defects in babies conceived after IVF procedures, but no similar study had been done in the United States. The UI investigation results appear in the November 2005 issue of the journal Fertility and Sterility. The issue also includes a Finnish study on assisted reproduction and major birth defects, as well as several other articles and letters on the topic.

The UI study was based on births in Iowa from 1989 to 2002 and used assisted reproduction records from UI Hospitals and Clinics and birth defects records from the Iowa Registry for Congenital and Inherited Disorders (formerly known as the Iowa State Birth Defects Registry), which is housed in the Department of Epidemiology in the UI College of Public Health.

Data revealed major birth defects in 90 of 1,462 IVF-conceived children, 17 of 343 children conceived through intrauterine insemination or IUI (a less complex procedure in which sperm is injected into the uterus to fertilize an egg) and 369 of 8,422 naturally conceived children. The comparative birth defect rates were: 6.2 percent for IVF babies, 5 percent for IUI babies and 4.4 percent for naturally conceived babies.

Van Voorhis said the team studied babies born from assisted production procedures aside from IVF to help determine if the increased rate was associated with the IVF procedure itself or factors in couples being treated for infertility.

He explained, "Had we seen lower risk for IUI-conceived babies, suggesting that another form of assisted reproduction had no increased risk compared to natural conception, it might have pointed toward IVF as a culprit. But the risk of major birth defects was slightly higher for IUI babies than for those naturally conceived.

"Had we seen a higher risk rate for IUI than for IVF, we would have thought there were issues with the couples being treated rather than with the IVF procedure itself. Yet the IUI rate was in between the rates for IVF and natural conception, so it remains unclear. IVF babies may have increased risk partly due to procedures and partly due to conditions affecting the parents who come to us as patients," Van Voorhis added. "We are not trying to assign 'blame' for the problem but rather are hoping to pinpoint areas of the IVF treatment that could be changed to improve the safety for children."

While the team had the advantage of using one of the most comprehensive and respected birth defect registries in the nation, it would take a much larger study involving multiple states and registries to answer questions about causes, Van Voorhis said.

In discussing potential limits of the Iowa study, Van Voorhis noted that selection of the control group of naturally conceived babies was restricted to counties from which patients treated in the UI infertility clinic delivered their babies. Thus, it is possible that a small number of the "naturally conceived" controls were actually conceived using infertility treatment at another clinic.

"It's possible that focusing on our referral area underestimated the risk a little bit for IVF-conceived babies," Van Voorhis said. "In another consideration, some of the apparent increased risk in IVF babies could be the result of parents, doctors or both looking more carefully for birth defects, resulting in a slightly higher detection rate."

A known risk factor for major birth defects is a multiple birth -- in which there are twins, triplets or even more babies in one pregnancy. Multiple births have become more commonplace through IVF when two or more embryos are commonly transferred to a woman's uterus. However, a few centers, including UI Hospitals and Clinics, are more frequently implanting only one embryo in an IVF cycle to reduce the risk of multiple birth and the problems of premature delivery and birth defects.

"Overall, the study should reassure people that there is not a huge increased risk in using IVF. However, at centers like ours we are always careful in our practice of assisted reproduction, and studies like this indicate treatment needs to be done in specialized centers that pay attention to these types of concerns," Van Voorhis said.

In addition to Van Voorhis, the study included researchers in the Department of Obstetrics and Gynecology and the Department of Pediatrics in the UI Carver College of Medicine and the Department of Epidemiology in the UI College of Public


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