Autism and ICSI: An Affair Revealed

Autism is on the rise. And so are test tube babies. Are they linked? Well, a very well done study published recently says yes. This connection may have something to do with sperm.

Facts About Autism

  • The term “autism” was first used in 1943 to describe children who lacked interest in other people but showed an unusual interest in objects
  • It is a neurological disorder that affects thinking as well as communication and social skills
  • 1 in 44 children are affected, and this rate is increasing
  • It appears to be genetic, but no specific genes have been identified
  • Environmental causes are also suspected, but vaccines are not among them

The Study Anatomy

This large study tracked outcomes of all births in Sweden (2.5 million!) over a 25-year period and followed the children for an average of 10 years after birth. Autism and intellectual disability rates in children were tabulated based on accurate national registries. Rates of these disorders were correlated with various conception methods, including at-home conception, IVF and IVF-ICSI. ICSI was further broken down into whether ejaculated sperm or surgically retrieved sperm was used. And the salient findings were:

  • During the study, 1.2% of Swedish births were conceived with IVF
  • 1.5% of IVF births had autistic disorders and 1.1% had intellectual disabilities
  • Overall, IVF births showed no increased risk of autism disorders and a mild increased risk (18%) of intellectual disabilities compared to at-home conceptions
  • IVF-ICSI using surgically retrieved sperm was associated with a 4.6-fold increase in autism disorders and a 2.3-fold increased risk of intellectual disabilities relative to IVF without ICSI
  • IVF-ICSI using ejaculated sperm was associated with a 47% increased risk of intellectual disabilities relative to IVF without ICSI using ejaculated sperm

One neat perk of well-performed epidemiologic research is that you can isolate or “control” for certain conditions and then test to see how they influence outcomes. Interestingly, risk profiles changed dramatically when only singleton births were evaluated in the study (multiple births comprise from 1/4 to 1/3 of IVF births but <1% of at-home conceptions):

  • Among singleton births, IVF showed no difference in autism or intellectual disability rates when compared to at-home conception
  • Among singleton births, the increased risk of autism and intellectual disability described earlier with IVF-ICSI using surgically retrieved sperm did not hold true.

Another factor that warrants consideration in this research is the age of the parents. Couples who use IVF tend to be older than the average parents simply because they have spent considerable time trying to conceive naturally before pursuing IVF. That suggests that older parents have an increased risk of autistic offspring. For better or worse, this parental age variable was considered to some degree in this study.

Behind the Numbers

So what does all of this mean? Honestly, it’s hard to know for sure. Epidemiological research is limited in that it can only make theoretical “associations” between things. It can’t prove that biological relationships truly exist. Taken in this context, this research suggests that autism and intellectual disabilities in children are related to how they are conceived (at-home vs. in a dish), who their father is, which kind of sperm is used, when they are born and how many siblings are born with them.

What I find provocative is that several of these risk factors (multiple births; preterm births, paternal issues) are ones that have been previously deemed significant for autism and intellectual disabilities. Others, however, such as sperm source, are new to the equation. Given that sperm issues still need fleshing out, it is still far too early to heartily recommend changes to current clinical practice.

This research is pretty heavy stuff. What’s comforting here is that the overall occurrence of both disorders is still very low, regardless of conception method. From another angle, I find that in my medical practice, the simple act of clarifying risk is valuable as couples handle this kind of risk very differently when it comes to fertility and offspring. Ultimately, my goal is to provide the most accurate, up-to-date information available and walk the walk with the patients as they make their decision.