Neurodevelopmental Disorders in Offspring Conceived via In Vitro Fertilization vs Intracytoplasmic Sperm Injection

IMPORTANCE: Intracytoplasmic sperm injection (ICSI), the most common type of assisted reproductive technology (ART), might damage the sperm or embryo. The implications of male infertility and ICSI for the neurodevelopmental health of offspring remain unknown. OBJECTIVE: To analyze the risks of neurodevelopmental disorders in offspring of couples with male or female infertility with or without ICSI use. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted in Taiwan and used information collected from the national population registry data set, national birth data set, and national ART data set for all live singleton births from January 1, 2008, to December 31, 2016. The follow-up period started from the date of birth until the diagnosis of a disorder or December 31, 2018, whichever occurred first. Data were analyzed from July 1, 2021, to August 1, 2022. EXPOSURES: Male or female infertility with or without ICSI. MAIN OUTCOMES AND MEASURES: The outcome was the incidence of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and developmental delay in offspring with ART conception. Taiwan’s national population registry data set was used to identify ASD, ADHD, and developmental delay diagnosed in outpatient clinic and hospitalization records. RESULTS: The study included 1 575 971 singleton births (mean [SD] age, 5.87 [2.60] years; 819 389 boys [52.0%]), of whom 1 568 257 (99.5%) had natural conception, 2111 (0.1%) had ART conception with male infertility, and 5603 (0.4%) had ART conception with female infertility. The risks of ASD (adjusted hazard ratio, 2.49; 95% CI, 1.61-3.84; P < .001) and developmental delay (adjusted hazard ratio, 1.92; 95% CI, 1.54-2.39; P < .001) in offspring with ART conception and ICSI use were significantly higher than those in offspring with natural conception. The same results were found in offspring of couples with either male or female infertility and ICSI intervention. CONCLUSIONS AND RELEVANCE: Results of this study suggest that male infertility was not associated with an increased risk of neurodevelopmental disorders in offspring. In both male and female infertility groups, ICSI had unfavorable implications for the neurodevelopmental health of offspring in terms of increased risks of ASD and developmental delay.