Cognitive Development of Singletons Born After Intracytoplasmic Sperm Injection Compared With In Vitro Fertilization and Natural Conception

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Abstract
The techniques of maternal hormonal stimulation are similar for intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), and both involve fertilization in vitro. However, in contrast to IVF, ICSI involves sperm selection and oocyte penetration and thus bypasses the selection processes that occur during natural conception, raising concerns that conception by ICSI may result in altered health and development of the offspring. This prospective study compared cognitive development of 5–8-year-old singletons born after ICSI during the years 1996–1999 with matched singletons born after IVF or natural conception (NC). The observers were blinded to the mode of conception. The short form of the Revised Amsterdam Child Intelligence Test was used to measure the intelligence quotient (IQ). The unadjusted mean IQ for children conceived by ICSI (n = 83) was 3.9 points lower than that of the IVF controls (n = 82) (103 versus 107; 95% confidence interval [CI], –0.7, 8.4), and the adjusted mean IQ score was 3.6 points lower (95% CI, –0.8, 8.0). There was no difference between ICSF and IVF children in the distribution of IQ-scores (115: ICSI 24% versus IVF 32% [unadjusted: P = .268]). The unadjusted mean IQ score of children conceived by ICSI (n = 86) was 6.8 points lower than that of children conceived naturally (NC; n = 85)(XX versus XX; 95% CI, 2.0, 11.6); the adjusted mean IQ score was 5.6 points lower [95% CI, 0.9, 10.3] and was unaffected by additional adjustment for prematurity and other covariables (P < .067). Compared with NC children, the total IQ distribution among ICSI children was shifted to lower IQ scores (>115: ICSI 24% versus NC 40%; 85–115: ICSI 64% versus NC 54%; and P = .019]). This small study found that IQ scores were lower in 5–8-year-old children conceived by ICSI than in children conceived by IVF or naturally. The greatest difference was between ICSI and NC children. The clinical significance of these findings is unclear.