Despite the large number of babies born worldwide following ICSI, concerns about the procedure’s safety still exist due to the use of suboptimal spermatozoa. Thus, follow-up of ICSI children is highly recommended. We propose the use of parent-administered questionnaires to monitor ICSI offspring development.
To determine whether male infertility treatment affects offspring development.
We compared obstetrical and neonatal outcomes, as well as physical and psychological development between IVF and ICSI toddlers. Once newborns reached 3 years of age, participating patients were sent a set of parent-administered questionnaires including the Ages & Stages Questionnaires (ASQ), Prescreening Developmental Questionnaire 2 (PDQ-II), Peabody Developmental Motor Scales (PDMS-2), Social Skills Rating System (SSRS), Parenting Stress Index (PSI-3), and Child Behavior Checklist (CBCL/2-3). Child development was measured by the ASQ, PDQ-II, and PDMS-2 questionnaires, while SSRS, PSI-3, and CBCL/2-3 were used to measure child behavior. The child’s developmental or behavioral outcome was considered “abnormal” when he or she scored below average in ≥2 questionnaires from the respective category. We also carried out subanalyses to assess the effects of male genomic integrity, DNA fragmentation, chemical exposure, utilization of surgically retrieved spermatozoa, and extended embryo culture on ICSI child development.
A total of 12,306 couples met the inclusion criteria for this study; 1,914 of 7,433 (25.8%) ICSI and 451 of 4,873 (9.3%) IVF patients returned questionnaires. Our comparison of obstetrical outcomes between the two groups did not reveal any significant differences in the mode of delivery distribution, with the majority of mothers having uncomplicated vaginal deliveries. Furthermore, gender distribution, gestational ages and birthweights were also comparable between the ICSI and IVF children. However, IVF children displayed impaired developmental characteristics when compared to the ICSI-conceived cohort (P=0.0004) (aOR=0.72, 95% CI=0.5-0.9). There was no difference in child behavior. Three cases of autism were reported, 1 IVF and 2 ICSI children, all generated from couples with an older male partner. ASQ questionnaire outcomes were also compared for the IVF and ICSI offspring by gender, however, no significant differences were observed.Five separate subanalyses were then carried out exclusively for the ICSI-conceived group. Levels of spermatogenic failure, DNA fragmentation, and chemical exposure did not significantly affect offspring development. Interestingly, while length of embryo culture did not appear to influence child development, the abnormal behavior rate was significantly higher in children from the day-3 embryo transfer cohort (P=0.04) (aOR=0.4, 95% CI=0.05-0.34). ICSI children conceived from ejaculated spermatozoa displayed impaired developmental and behavioral characteristics when compared to toddlers conceived from surgically retrieved specimens (P=0.05) (aOR=4.9, 95% CI=1.2-20.7).
The majority of ICSI and IVF children are developing well without significant delays. Although ICSI child development was not affected by most of the variables assessed, those generated from surgically retrieved spermatozoa were at a significantly lower risk for abnormal developmental, as well as behavioral, characteristics than offspring generated from ejaculated specimens. However, given small numbers of respondents available for many subgroups of interest, further studies of outcomes of children born from fathers with severe male factor infertility is warranted.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.