title: The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy.
abstract: BACKGROUND
  Due to the growing number of children born following assisted reproduction technology, even subtle changes in the children's health and development are of importance to society at large. The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4-18-month-old children.
  
  
  METHODS
  In this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development.
  
  
  RESULTS
  The NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups.
  
  
  CONCLUSIONS
  We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4-18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.
authors.affiliation: Department of Paediatrics, Division of Developmental Neurology-CA85, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. k.j.middelburg@developmentalneurology.com
authors.forename: K J
authors.initials: KJ
authors.lastname: Middelburg
authors.forename: M J
authors.initials: MJ
authors.lastname: Heineman
authors.forename: A F
authors.initials: AF
authors.lastname: Bos
authors.forename: M
authors.initials: M
authors.lastname: Pereboom
authors.forename: V
authors.initials: V
authors.lastname: Fidler
authors.forename: M
authors.initials: M
authors.lastname: Hadders-Algra
mesh_terms: D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009068:Movement; D009422:Nervous System Diseases / Q000175:diagnosis / Q000209:etiology*; D009460:Neurologic Examination; D010062:Ovulation Induction / Q000009:adverse effects*; D011247:Pregnancy; D013223:Statistics as Topic