De effecten van ovariële hyperstimulatie en de in-vitrofertilisatie procedure op de neurologische ontwikkeling van tweejarige kinderen.

Background: The number of children born following assisted reproduction technologies (ART) is steadily rising. Yet, surprisingly little is known on neurodevelopmental outcome of ART-children after the age of 18 months. Only a limited number of long-term follow-up studies with adequate methodological quality have been reported so far. Aim of the study: to evaluate the neurological condition of 2 years-old children born after ART in comparison to peers born to subfertile couples. Specific attention is paid to the separate effects of ovarian hyperstimulation and the in vitro procedure per se. The focus of the study is on minor neurological dysfunction. Methods: Participants were the singletons of the Groningen ART cohort. They were born after conventional controlled ovarian hyperstimulation IVF (group COH-IVF, n=66), after modified natural cycle IVF (group MNC-IVF, n=56) or they had been born after natural conception of subfertile couples (group sub-NC, n=87). At 2 years children were assessed with the age-specific and standardized neurological examination according to Hempel. This resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification (neurologically normal, simple or complex MND or neurologically abnormal). Primary outcome is the fluency subscore of the neurological optimality score (NOS). A reduction of fluency of movements reflects the most subtle form of minor neurological dysfunction. Additional outcome parameters are the NOS and the clinical neurological classification. Results: None of the children had an abnormal neurological condition such as cerebral palsy. Children of the COH-IVF group tended to show more often MND than the children of the other two groups, but the differences failed to reach statistical significance. The fluency score did not differ between the three group, all groups had a median score of 10. De median scores for the NOS were 48, 49 en 49 for group COH-IVF, MND-IVF en NC respectively. Multivariate analyses confirmed that neurological outcome was similar in the three groups. Conclusions: Neurological development of two-year-old children born after conventional or modified natural cycle ART does not differ from that of naturally conceived children of subfertile couples. Yet, these reassuring findings do not preclude the possibility that ART may have a negative impact on the more complex brain functions which first emerge at older age.