Human Reproduction Update Advance Access published online on March 26, 2008
Human Reproduction Update, doi:10.1093/humupd/dmn005
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Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI–a systematic review
1 Department of Paediatrics, Division of Developmental Neurology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands 2 Department of Obstetrics and Gynaecology, University Medical Center Groningen, Groningen, The Netherlands 3 Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands 4 Department of Paediatrics, Division of Neonatology, University Medical Center Groningen, Groningen, The Netherlands
To whom correspondence should be addressed at: 5 Correspondence address. Tel: +31-50-3614247; Fax: +31-50-3615918; E-mail: k.j.middelburg{at}developmentalneurology.com
BACKGROUND: The effect of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) on the developing human brain is unclear. The objective of this study is to evaluate neurodevelopmental (ND) outcome of children born following these techniques.
METHODS: This systematic review includes studies which compare a group of children born following IVF/ICSI to children born after natural conception by assessing outcome in terms of neuromotor development, cognition, speech/language and behaviour. Specific attention is paid to the studies’ methodological quality based on study design, attrition, blinding of the assessor, validity of ND tests used, confounders included and group size or power analysis.
RESULTS: Twenty-three out of 59 studies had a good methodological quality including 9 register-based (RB) and 14 controlled studies. RB studies suggested that IVF/ICSI per se does not increase the risk for severe cognitive impairment (i.e. mental retardation) or neuromotor handicaps such as cerebral palsy (CP), the association of IVF/ICSI and CP being brought about by the association of assisted conception with risk factors, like preterm birth. In general, controlled studies of good quality did not report an excess of ND disorders in IVF/ICSI-children. However, the majority of studies followed the children during infancy only, thereby precluding pertinent conclusions on the risk of ND disorders that come to the expression at older ages, such as fine manipulative disability or dyslexia.
CONCLUSIONS: A negative effect of assisted conception on the developing human brain is not identified; however, further research of high methodological quality in children beyond pre-school age is needed.
Key words: children / follow-up / ICSI / IVF / neurodevelopmental outcome
Received on June 20, 2007; revised December 20, 2007; accepted on January 17, 2008