Assisted reproductive technologies and risk for autism spectrum disorder

The current estimated prevalence of autism spectrum disorder (ASD)is approximately 1:100-150, which reflects a 15-fold increase fromstudies published a half-century ago. The exact cause of ASD is stillunknown and it is now believed that, despite the strong genetic origin,environmental factors may modulate phenotypical expression. Pre-andperinatal events are now the focus of research into risk factors for ASD.Assisted reproductive technology (ART) now accounts for 1-3% of alllive births in the western world. Several procedures that may be used inthe ART process, such as hormonal stimulation, egg retrieval, in vitrofertilization (IVF), intra-cytoplasmic sperm injection (ICSI), micromanipulationof gametes and exposure to culture medium, could subjectthe gametes and early embryos to environmental stress. Although thesetechniques are considered safe, in recent years evidence has beenaccumulating that ART may be associated with an increased risk of birthdefects, low birth weight (LBW), and genetic imprinting disorders.Children arising from ART are also at higher risk for epigenetic andimprinted disorders. Epigenetics refers to heritable modifications of DNA that do not alter the underlying sequence. DNA methylation and histonemodification are examples of epigenetic modifications that may lead toimprinting disorders. The majority of evidence regarding the effect ofART on imprinting involves DNA methylation. A possible associationbetween the increase in ART procedures and the increase in ASDprevalence has been investigated. Previous studies have reportedconflicting results concerning the association between assisted conceptionand the risk for ASD. This chapter will address the recent literature on theassociation between the use of hormonal induction and/or assistedreproductive technologies and the risk for autism. Possible contributingmechanisms will be discussed.