Cognitive development of singletons born after intracytoplasmic sperm injection compared with in vitro fertilization and natural conception

Objective: To investigate cognitive development of singletons conceived by intracytoplasmic sperm injection (ICSI) at 5-8 years of age. Design: Follow-up study. Setting: University medical center, assessments between March 2004 and May 2005. Patient(s): Singletons born between June 1996 and December 1999 after ICSI at the Leiden University Medical Center were compared with matched singletons born after IVF and natural conception (NC). Intervention(s): Mode of conception. Main Outcome Measure(s): Intelligence quotient (IQ) was measured with the Revised Amsterdam Child Intelligence Test (short form). The investigators were blinded to conception mode. Result(s): Singletons conceived by ICSI (n = 83) achieved lower IQ scores than IVF singletons (n = 83) (adjusted mean difference IQ: 3.6 [95% confidence interval (CI) -0.8, 8.0j). After categorizing IQ outcomes (<85, 85-115, > 115), no significant difference in the distribution of IQ was found. Singletons conceived by ICSI (n = 86) achieved lower IQ scores than NC singletons (n = 85); the adjusted mean difference varied between 5 and 7 points (5.6 [95% CI 0.9, 10.31; 7.1 [95% CI 1.7, 12.5]) depending on the covariates included in the model. Adjustment for prematurity did not change the results. Percentages in IQ categories <85, 85-115, and > 115 were 12%, 64%, and 24% for ICS] and 6%, 54%, and 40% for NC, respectively. Conclusion(s): In the relatively limited sample investigated, cognitive development among ICSI singletons was lower than among IVF and NC singletons. Infertility factors or unmeasured confounders may play a role.