O-188 Conventional in vitro fertilisation versus intracytoplasmic sperm injection in first cycle patients without severe male factor infertility (INVICSI): a randomised, controlled, open-label, multicentre trial

Abstract Study question Is the cumulative live birth rate (CLBR) after ICSI superior to conventional IVF (c-IVF) in first cycle fertility patients without severe male factor infertility? Summary answer In couples without severe male factor infertility, ICSI does not improve the CLBR compared to c-IVF after transfer of embryos from the first oocyte collection What is known already The ICSI procedure, originally developed for addressing severe male factor infertility, has seen expanded utilisation across various causes of infertility. Large retrospective studies and a recent randomised controlled trial (RCT) demonstrated comparable reproductive outcomes between ICSI and c-IVF in couples without male factor infertility. In approximately half of infertility cases, a male factor is involved, with about one-third attributed to male factor alone. Despite this, ICSI currently constitutes two-thirds of all assisted reproductive technology treatments worldwide Study design, size, duration Open-label, two-armed, multicentre RCT. A sample size of 784 women was required to detect a clinically relevant change of 10 percentage points with 80% power. Accounting for an expected 5% exclusion rate (dropouts and unexpected severely decreased quality sperm samples on the day of oocyte retrieval), 824 women were recruited from six public fertility clinics in Denmark between Nov 29, 2019, and Dec 14, 2022 Participants/materials, setting, methods Eligible participants were women aged 18-42 years and in their first treatment cycle with a partner/donor with normal or lightly to moderately decreased sperm quality. Randomisation was performed in a 1:1ratio between ICSI and c-IVF. The primary outcome was CLBR. Follow-up continued until the primary outcome was achieved or for a minimum of one year after the last participant’s inclusion.The primary outcome was assessed in an intention to treat (ITT) and a per protocol analysis Main results and the role of chance In total, 414 and 410 women were randomised to ICSI and c-IVF, respectively. Results include fresh as well as frozen-thawed embryo transfers from the first oocyte collection and are displayed as ITT. All transfers were elective single embryo transfers or single embryo transfers. The cumulative probability of achieving a live birth for couples/women undergoing ICSI was not different compared to those undergoing c-IVF (CLBR: ICSI 42.0% vs. c-IVF 46.6%, Risk ratio: 0.90, 95% CI: 0.77-1.05). The median time from inclusion to live birth did not differ between ICSI and c-IVF (309 days (IQR 268-378) vs 308 days (IQR 269-356); p = 0.12). Total fertilisation failure was seen in 4.9% of the ICSI group compared to 3.8% in the c-IVF group (Risk ratio: 1.29, 95% CI: 0.68-2.54) Limitations, reasons for caution This study was designed with 80% power to identify a 10% percentage point difference in CLBR between ICSI and c-IVF. We cannot dismiss the possibility of a smaller difference between the two methods Wider implications of the findings Our study, supported by prior research, shows that c-IVF rather than ICSI should be the first choice in initial cycles for patients without severe male factor infertility. Fertility staff should inform first cycle patients that ICSI does not increase the live birth rate for couples without severely decreased sperm quality Trial registration number NCT04128904