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Study Links Male Infertility Procedure to Increased Risk of Autism

Associated risk remains modest; no increased risk seen with most forms of in vitro fertilization
July 02, 2013

Using a large Swedish health registry, researchers have broken down the autism risk associated with different types of in vitro fertilization (IVF). They found that most forms of IVF do not increase the risk of autism. They found a small increased risk only with procedures that involve surgical sperm retrieval, a treatment for male infertility. However, this risk disappeared entirely when the researchers excluded children born prematurely or as multiples (twins, triplets, etc.).

The study also associated IVF procedures, in general, with increased risk of intellectual disability. Here, too, the association was strongest with procedures involving surgical sperm retrieval.

The findings appear today in the Journal of the American Medical Association (JAMA). Autism Speaks and the Swedish Research Council funded the research, which involved scientists at New York’s Mount Sinai School of Medicine, King’s College London and Sweden’s Karolinska Institute.

Putting risk into perspective
Previous scientific reports have been mixed on whether IVF increases the risk of autism. This is the first study sample large enough to allow researchers to tease apart the risks associated with specific procedures, explains Alycia Halladay, Ph.D., Autism Speaks senior director of environmental and clinical sciences.

[Also see our Q&A with Dr. Halladay: Autism and Infertility Treatment: Your Questions Answered."]

This isn’t about assigning blame for autism, she emphasizes. It’s about identifying a group of children who may be at modestly increased risk, so parents and physicians can be alert to early signs and intervene if needed.

“Parents undergoing any type of assisted reproductive technology are concerned about the risks on the health and well-being of their future children,” Dr. Halladay adds. "Couples may want to include the new information in discussions with their physicians."

For instance, the results suggest that the associated risk might be reduced by avoiding multiple embryo transplants after IVF, says the study’s senior investigator, Avi Reichenberg, Ph.D., of Mount Sinai’s Seaver Autism Center. However, more research is needed to understand what’s behind the increased risk associated with this particular IVF procedure when it results in multiple or preterm births. Dr. Reichenberg did much of the research while at King's College London.

Tapping into Sweden’s vast health registry
Using Sweden’s national health registry, the investigators analyzed more than 2.5 million birth records from 1982 and 2007. They also followed up on the children’s development.

When comparing natural conception to all IVF treatments, the researchers found no increased autism risk. However, they found differences when they looked at specific types of IVF procedures. These included sperm injection, which involves injecting a single sperm into an extracted egg.

A significantly increased risk of autism emerged only when sperm injection involved surgically retrieved sperm. Surgically removing sperm is generally done when vasectomy or another cause of male infertility prevents collecting sperm through ejaculation.

The procedure appeared to more than quadruple autism risk. However, this increased risk disappeared when the researchers excluded premature and multiple births (twins, triplets, etc.). Preterm and multiple births carry their own increased risk of autism.

The overall increase in risk for intellectual disability with IVF varied between 51 and 71 percent – depending on procedures. Here, too, the researchers saw the highest risk among children born prematurely or as multiples.

“While intellectual disability or autism remain a rare outcome for IVF, being aware of the increased risk associated with specific types of IVF means offspring at risk can be identified and potentially monitored for developmental disorders,” Reichenberg says. “In this way, parents and physicians can ensure that these children receive early detection and appropriate support and care.”

More study is needed to understand the mechanism by which IVF with surgical sperm extraction increases the risk of autism, the researchers agree.

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