IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial

Intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (c-IVF) are widely used fertilization techniques in assisted reproduction, but their relative effectiveness in patients without severe male factor infertility remains debated. While ICSI’s role in couples with severe male factor infertility is well established, its routine use in cases with normal or nonseverely decreased sperm quality is not evidence-based. Here we conducted the INVICSI study, an open-label, multicenter randomized controlled trial, to compare cumulative live birth rates (CLBR) as the primary outcome between ICSI and c-IVF in patients without severe male factor infertility. Between November 2019 and December 2022, 824 women undergoing their first IVF cycle were randomized to ICSI (n = 414) or c-IVF (n = 410) across six public fertility clinics in Denmark. The CLBR was 43.2% (179/414) in the ICSI group and 47.3% (193/408) in the c-IVF group, yielding a risk ratio of 0.91 (95% confidence interval, 0.79–1.06). These findings demonstrate that ICSI does not improve CLBR compared to c-IVF and support c-IVF as the preferred first-line treatment for patients with normal or nonseverely decreased sperm quality. ICSI should be reserved for severe male factor infertility. ClinicalTrials.gov registration: NCT04128904.