In Vitro Fertilization and Autistic Spectrum Disorder: Clinical Experience- Review of Literature

Background: In 1978 the first baby was born in Britain after in vitro fertilization, and it was reported as a healthy female neonate. Since then, according to WHO, there are about 8.000.000 children born with IVF. In 1984 for the first time it was possible to transfer frozen embryos and in 1991 it was the first successful intracytoplasmic sperm injection (ICSI) to treat mainly male infertility problems. ICSI is now used in more that 80% of couples treated with IVF. Data for neurodevelopmental outcome of children born with IVF are obscure and inconclusive mainly due to research methodology problems and to factors that can affect outcome such as IVF technique per se, ICSI, culture medium used, transfer of frozen of fresh embryos, the infertility problems and perinatal co factors such as prematurity, multiple birth, parental age. Literature data show a possible link with increased Autistic Spectrum Disorders (ASD) incidence, ADHD, Specific Learning Difficulties (SLDs) and Behavioral problems such as internalizing and externalizing behavior especially with ICSI technique.

Aim: Our aim was to analyze our data from the Developmental and Behavioral Pediatrics Outpatient Clinic and to review current literature.

Material-Methods: We retrospectively analyzed medical records of children referred to our Developmental-Behavioral Pediatrics Outpatient Clinic for evaluation with IVF history and we reviewed recent publications from pubmed library. We excluded extremely and very preterm children, congenital anomalies, syndromes and cerebral lesions such as hemorrhages.

Results: There are no studies or systematic meta analysis to associate increased ASD in relation to IVF. There is a possible link between ICSI and ASD, mental retardation, SLDs. Nevertheless literature studies are of weak methodology mainly due to diagnostic criteria for ASD. In our population we studied medical records of 133 children with IVF history. Boys 61%, girls 39%. The educational level of mother and father was in the middle and upper range in 83 and 86% respectively. Mean paternal and mean maternal age at conception was 37 and 38 years respectively. ASD of any severity was detected in 9.02% of cases and of high severity in 1.5%. The relation between boys and girls in ASD cases was 2:1. ADHD detected in 8.2%, internalizing and externalizing behavior in 33.08% and SLDs in 26.3%

Discussion: In our population we recorded increased ASD incidence amongst children with IVF history (9.02%). Nevertheless the incidence of severe cases were close to the general population (1.5%). In our IVF population there was weaker association between ASD and male sex compared to the general population (2:1 vs 4:1). Literature data need further evaluation regarding entry criteria, methodology and ASD diagnostic criteria in order to come in a clear conclusion between IVF and ASD.