A rare in-vitro fertilization technique that addresses male infertility is associated with an increased risk of autism and mental disability in children, compared with standard methods, according to a study that may prompt parents and doctors to take steps to reduce the danger.
The increased risk was among children born as a result of intra-cytoplasmic sperm injection in which a sperm surgically extracted from the testes is injected directly into an egg before being transplanted to the womb. Using the injection method with ejaculated sperm also raised the risks, though not as much, the researchers found. Less than 2 percent of children with either disorder were conceived using IVF, they said.
About 5 million children worldwide have been born by IVF since 1978, and 1.4 percent of total births in the U.S. annually and as many as 4.4 percent in western Europe result from the procedure, according to government and industry figures. Across all types of IVF procedures, compared with spontaneous pregnancies, the study found no increase in the risk of autism and a small increase for mental disability linked only to multiple births, such as twins and triplets.
“A perhaps more unexpected finding was an increased risk for both autism and mental retardation after treatment of more severe and not very common cases of male infertility compared with other ICSI techniques,” said Karl-Goesta Nygren, one of the study authors and associate professor of obstetrics and gynecology at Sweden’s Karolinska Institute, during a briefing today in London.
Babies born using intra-cytoplasmic sperm injection, or ICSI, with extracted sperm had a 4.6-fold increased risk of autism, and more than twice the risk of mental disability, compared with more common IVF methods, according to the study. Deploying the technique using ejaculated sperm had a risk of autism that was 1.2 times higher, and a risk of mental disability about 1.47 times higher, compared with standard IVF procedures.
The findings, mined from data in the Swedish national health registers, were published today in the Journal of the American Medical Association.
Factors such as the age of the patients, their psychiatric history, hormone treatments and duration of infertility couldn’t explain the result, Nygren said.
The concern about ICSI is “whether the risk is associated with the procedure or the indication for the procedure -- male-factor infertility,” Marcelle Cedars, professor and director of the University of California, San Francisco’s Women’s Health Clinical Research Center, said in an editorial accompanying the article. “Continued studies and ongoing surveillance are required.”
The risk of autism from ICSI using surgically extracted sperm wasn’t statistically significant when the analysis excluded twins and triplets. That suggests the risk can be lowered by transferring only one embryo to the womb instead of two or three, said Abraham Reichenberg, another study author at the Institute of Psychiatry at King’s College London.
About 3 percent of women who had IVF treatment in Sweden between 2003 and 2007 used ICSI with surgically extracted sperm, the authors said. The rate is likely to be similarly low in the U.S. and other western European countries, Reichenberg said.
The research, funded by the Swedish Research Council and advocacy group Autism Speaks, included more than 2.5 million children born in the country between 1982 and 2007.
The findings are important for scientists because they may uncover additional factors or mechanisms that lead to autism, said Alycia Halladay, senior director of environmental and clinical sciences at Autism Speaks. The overall results are reassuring for women since there were no elevated risks for those who underwent the most common procedures, she said.
“Most families that are going through IVF are very concerned about the risk factors, but sometimes the benefits outweigh the risks,” she said in a telephone interview. “There was no risk with just the fresh embryo IVF, with ejaculated sperm. That should be comforting for women and families undergoing this procedure.”
Shelly Armstrong of North Little Rock, Arkansas, said she used ICSI in November 2005 after trying to conceive for 18 months with her husband who had a vasectomy reversal. While the procedure, which involved surgical extraction of sperm, successfully resulted in triplets, one of them has autism and another has attention deficit hyperactivity disorder, she said.
“I still am blessed with my kids, and I’m happy to have done it,” said Armstrong, who was 35 when she gave birth. If she were to do it now, “I would definitely think about it, but it would depend on the percentages -- whether it’s a 1 percent chance or a 70 percent chance.”
More than 7 million women and their partners in the U.S., about 12 percent of those in their child-bearing years, suffer with infertility, according to the U.S. Centers for Disease Control and Prevention.
One in 88 children in the U.S. had autism or a related disorder in 2008, the latest period for which data was available, according to the CDC. That was a 23 percent rise from 2006, the agency’s researchers reported, saying it was unclear how much of the increase was due to greater awareness of the disease.
A University of California, Los Angeles study last year found that IVF may significantly increase the risk of birth defects, particularly those of the eyes, heart, reproductive organs and urinary system.
Children of older fathers are known to be more at risk of diseases including schizophrenia and autism as they transmit more new DNA variations to their children than younger dads, according to a study published in Nature last year.