In-vitro fertilization (IVF) treatments for the most severe forms of male infertility may be linked to an increased risk of intellectual disability and autism in children, according to a new study published in the Journal of American Medicine Association.

While autism and intellectual disability remain a rare outcome of IVF, and while some of the risk is associated with the presence of multiple births, the study provides important evidence, according to the international team of researchers, for parents and clinicians on the relative risks of modern IVF treatments.

The study was conducted using anonymous data from the Swedish national registers: in all, researchers analyzed more than 2.5 million birth records from 1982 and 2007 and followed-up on whether children had a clinical diagnosis of autism or intellectual disability (defined as having an IQ below 70) up until 2009.

Of the 2.5 million children, 1.2 percent (30,959) were born following IVF, and of the 6,959 diagnosed with autism, 103 were conceived using IVF. Meanwhile, of the 15,830 with intellectual disability, 180 were born after IVF.

Multiple pregnancies, however, are a known risk factor for pre-term birth and some neurodevelopmental disorders, so the researchers also compared single to multiple births.

Sven Sandin, co-author of the study from King's College London's Institute of Psychiatry explained in a statement that, given the variety of IVF treatments, the researchers were forced to examine subgroups in order to determine the true effects of IVF on mental development.

"IVF treatments are vastly different in terms of their complexity," Sandin said. "When we looked at IVF treatments combined, we found there was no overall increased risk for autism, but a small increased risk of intellectual disability."

Taking this one step further, however, when the scientists separated the different IVF treatments, they found that "'traditional" IVF was "safe," but that IVF involving intra-cytoplasmic sperm injection (ICSI), which is often recommended in the case of paternal infertility, was associated with an increased risk of intellectual disability and autism in children.

Children born after IVF with ICSI using surgically extracted sperm and fresh embryos, furthermore, faced a 360 percent increased risk of autism, though, once again, the association disappeared when multiple births were taken into account.

In conclusion, Dr. Avi Reichenberg, who led the study from King's College London's Institute of Psychiatry and Mount Sinai School of Medicine, explains: "Our study shows that treatments developed to manage male infertility are associated with an increased risk for developmental disorders in the offspring. The exact mechanism is unclear, but there are a number of risk factors, from selection of IVF procedures, to multiple embryos, and to preterm birth. Whilst 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, ensuring they receive early detection and appropriate support and care."