Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility.

Study Question: In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)?

Summary Answer: In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples.

What Is Known Already: ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples.

Study Design, Size, Duration: This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919).

Participants/materials, Setting, Methods: In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire.

Main Results And The Role Of Chance: The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively).

Limitations, Reasons For Caution: Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons.

Wider Implications Of The Findings: The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions.

Study Funding/competing Interest(s): No external funding was received for this study, and no authors reported conflicting interests.

Trial Registration Number: NCT04866524 (clinicaltrials.gov).