O-271 The impacts of intracytoplasmic sperm injection on the neurodevelopmental disorders in offspring with male or female infertility parents: a national population cohort study in Taiwan
Authors: Lo H.W , Tsai E.M 
Published: June 2022

Abstract

Study question
This study aims to evaluate whether ICSI intervention in male or female infertility will increase the risks of neurodevelopmental disorders in offspring or not.

Summary answer
ICSI increases the risks of autism spectrum disorder and delayed developments in offspring with female infertility but has no impact on male infertility.

What is known already
Damaged sperm has been proved to change epigenetics and increase the genome instability in early embryogenesis. It might also affect the offspring’s health, such as neurodevelopmental disorders.
ICSI is the most common procedure in assisted reproductive technology. It is used not only in male infertility but also in female infertility. Several studies have advocated the potential risks of epigenetic alternation in embryos and neurodevelopmental disorders in the offspring. However, there is no conclusion to determine the risk of ICSI in the offspring’s health.
Neurodevelopmental disorders are associated with epigenetic alterations such as ASD, ADHD, DD.

Study design, size, duration
Patients were collected between January 2008 and December 2016 in the national report of the ART database and the national population database in Taiwan. The inclusion criteria were singleton, infertility parents with fresh embryos transfer, and embryos without invasion procedure except for ICSI. The exclusion criteria were donated eggs or sperms. The follow-up time started from birth to December 2018.

Participants/materials, setting, methods
In total, 1,580,267 singletons were conducted in this study. They were divided into three groups: female infertility, male infertility, and spontaneous conception. Inverse probability of treatment weighting was used to lower the bias among the study groups. The covariate factors include maternal age, obstetrics risk factors, pregnancy complications, and parental psychiatric disorders.
The offspring outcome includes ADHD, ASD, and DD. The result was analyzed with multivariate regression. The value of P &lt; 0.05 is significant.

Main results and the role of chance
Offspring with male infertility showed to increase risk of ADHD (attention deficit and hyperactivity disorder) compared to spontaneous conception (Hazard ratio 1.76, 95% CI 1.03-3.02, p = 0.0389). There was no increased risks of ADHD, ASD (autism spectrum disorder), and DD (delayed developments) in offspring with female infertility compared to spontaneous conception.
We further analyzed the impact of ICSI on offspring’s neurodevelopmental disorders. In singletons with male infertility, the risk of ADHD increased in offspring without ICSI intervention compared to spontaneous conception and male infertility with ICSI intervention (Hazard ratio 3.88, 95% CI 1.56-9.62, p = 0.0252) In newborns with female infertility, the risk of ASD and DD increased in offspring with ICSI intervention compared to spontaneous conception and female infertility without ICSI intervention. (ASD: hazard ratio 2.50, 95% CI 1.33-4.70, p = 0.0157; DD: hazard ratio 1.59, 95% CI 1.13-2.24, p = 0.0142) We also found the risks of neurodevelopmental disorders were higher in boys than girls. Preterm infants had increased risks of neurodevelopmental disorders than full-term infants.

Limitations, reasons for caution
This study had several limitations, such as the severity of sperm, the quality of embryos, and various laboratory conditions. However, we have tried to lower the potential cofactors such as maternal age, pregnancy complications, risk factors during pregnancy and labor, and psychiatric disorders in parents.

Wider implications of the findings
ICSI is widely used in female infertility to achieve pregnancy. However, our preliminary data shows that ICSI in female infertility increases the risk of neurodevelopmental disorders in offspring. This finding implies that we should pay attention on when using ICSI in female infertility couples.

Trial registration number
KMUHIRB-E(II)-20200217