Do the children born after in vitro fertilization or intracytoplasmic sperm injection have poor intellectual performance? A prospective cohort study

BACKGROUND: Assisted reproductive technologies (ART) have been proven to be associated with the increased risk of pregnancy complications such as gestational hypertension and neonatal disorders, which may have negative effects on offspring's health. However, insufficient evidence exists to evaluate the intellectual performance of children born after ART. Thus, the aim of our study is to evaluate the intellectual performance of children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). METHODS: This prospective cohort study was performed at the Center for Reproductive Medicine, Shandong University. Children conceived by artificial insemination with donor sperm (AID) were enrolled as controls. Age and sex of children, maternal age, family income and education of parent and caregiver were used for propensity score matching in a ratio of 2:1. The total population consisted of 639 singletons aged 6-14 years old (426 in IVF/ICSI group, and 213 in AID group). Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) Questionnaire was used to evaluate the intellectual performance. Generalized estimating equation was performed to compare the WISC-IV scores between two groups. The result of sensitivity analysis from the first WISC-IV test of children remains the same. RESULTS: The WISC-IV Questionnaire scores, the verbal comprehension Index (VCI) and the perceptual reasoning Index (PRI) were all comparable between IVF/ICSI and AID groups. But scores of the block design and digit span were both lower in IVF/ICSI group [block design: 12.6 ± 4.4 vs. 13.6 ± 6.5, adjusted β (95%CI): -1.13 (-2.17, -0.08); digit span: 11.2 ± 3.5 vs. 12.2 ± 4.2, adjusted β (95%CI): -1.07 (-1.75, -0.39)]. The results of subgroup analysis showed that the scores of digit span were lower in both fresh embryo transfer (fresh ET) and frozen embryo transfer (frozen ET) groups compared with AID group [fresh ET: adjusted β (95%CI): -0.97 (-1.69, -0.24); frozen ET: -1.30 (-2.12, -0.49)], and the score of block design, matrix reasoning, coding were significantly lower in frozen ET group. The scores of digit span were lower in both IVF and ICSI groups [IVF: adjusted β (95%CI): -1.15 (-1.87, -0.43); ICSI: -0.97 (-1.83, -0.11)], and the scores of block design, matrix reasoning were significantly lower in IVF group. CONCLUSIONS: Children born after IVF/ICSI have similar FSI scores compared with offspring conceived by AID, but had a poor performance on block design and digit span. These conclusions still need to be confirmed in naturally conceived (NC) children.