School performance in children born after ICSI.

Study Question: Do children conceived after ICSI have similar school performance as children born after IVF?
Summary Answer: Children born after ICSI have similar school performance compared to children born after IVF.
What Is Known Already: Studies concerning the cognitive skills of children born after ICSI have shown diverging results.
Study Design, Size, Duration: This nationwide, register-based cohort study included all singleton children born after ICSI (n = 6953), IVF (n = 11 713) or spontaneous conception (SC) (n = 2 022 995), in Sweden between 1985 and 2006.
Participants/materials, Setting, Methods: Singleton children born after ICSI were identified in national IVF registers, cross-linked with the Medical Birth Register (MBR), the National Patient Register (NPR) and the Swedish Cause of Death Register (CDR) for characteristics and medical outcomes. Data on school performance, parental education and other parental characteristics were obtained through cross-linking to the National School Registry and to Statistics Sweden. The main control group, which consisted of children born after IVF, was identified in the national IVF registries while the second control group, consisting of children born after SC, was identified from the MBR. Simple and multivariable linear regression was used for analysis of continuous variables, and logistic regression was used for the analysis of binary outcomes. Adjustments were made for sex, year of birth, maternal smoking during pregnancy, parental age, parity, parental region of birth, parental level of education and frozen embryo transfer.
Main Results and the Role of Chance: In the adjusted analyses, there was no significant difference between ICSI and IVF children for total score (adjusted odds ratios (AORs) 1.03; 95% CI -0.22 to 2.28; P = 0.11), specific subjects, qualifying for secondary school (AOR 1.02; 95% CI 0.82-1.26; P = 0.87) or poor school performance (AOR 0.92; 95% CI 0.75-1.14; P = 0.47). In the third grade, children born after ICSI had a significantly lower chance of passing all of the subtests in Mathematics (AOR 0.89; 0.83-0.96; P = 0.002) and Swedish (AOR 0.92; 0.85-0.99; P = 0.02) compared to children born after SC. When cross-linking children with missing data on school performances (2.1% for ICSI, 2.0% for IVF and 2.3% for SC) with the Cerebral Palsy Follow-up Register (CPUP) for cerebral palsy, 2.7% of ICSI children, 5.7% of IVF children and 1.7% of SC children without registered education were found. When cross-linking children with missing data on school performances with the NPR for mental retardation, 29.9% of ICSI children, 32.6% of IVF children and 35.0% of SC children with missing data were registered under such a diagnosis.
Limitations, Reasons for Caution: The main limitation was that test scores were missing in a small percentage in both ICSI and IVF children. Although we were able to cross-link this subpopulation with the CPUP and the NPR, these diagnoses only partly explained the missing scores. Other limitations were unmeasured and unknown possible confounders, such as information about infertility diagnoses and indication for ICSI, were not available.
Wider Implications of the Findings: These findings are important to most countries where IVF and ICSI are used since there may be differences in choice of procedure. In recent years, there has been an increasing trend towards using ICSI not only for treatment of male infertility but also when the sperm quality is normal. Our results indicate that the school performance of children born after ICSI is reassuring.
Study Funding/competing Interest(s): Financial support was received through Sahlgrenska University Hospital (ALFGBG - 70 940), Hjalmar Svensson Research Foundation and Nordforsk, project number 71 450. None of the authors declare any conflict of interest.
Trial Registration Number: N/A.
(© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)