Intracytoplasmic sperm injection and fetal origins of autism spectrum disorder: an intriguing, though controversial association.

Latest knowledge assigns the origins of autism spectrum disorder (ASD)-currently affecting 1% of children- to intrauterine life, when fetal brain develops. Besides genetics, environmental factors, responsible for epigenetic changes contributed to its rising incidence. In vitro fertilization (IVF) and the most widely used intracytoplasmic sperm injection (ICSI) are implicated in epigenetic changes. A series of studies examined the impact of ICSI on ASD in the offspring. Results are usually conflicting, due to inherent problems of study design and power, mixed IVF/ICSI cases and not exclusively ASD diagnoses included. Furthermore, preterm birth, low birthweight infants, advanced parental age, hormonal disturbances, all associated with ICSI, are known factors affecting ASD. While solid data supporting ICSI contribution to currently alarming ASD increase are lacking, exploration of underlying molecular mechanisms would strengthen possible associations. In the meanwhile, ICSI use should be restricted to male-factor infertility cases.