The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial

Study questions: Does ICSI result in a higher live birth rate as compared with conventional IVF in couples with non-male factor infertility?

What is known already: ICSI is primarily indicated for severe male factor infertility. While the use of ICSI for couples with non-male factor infertility has been increasing worldwide, this is not supported by data from randomised controlled trials. Evidence from non-randomised studies suggest no benefit from ICSI compared with conventional IVF in non-male factor infertility, if not a harm.

Study design size duration: This randomised, open-label, multi-centre trial aims to compare the effectiveness of one ICSI cycle and one conventional IVF cycle in infertile couples with non-male factor infertility. A total of 1064 couples will be randomly allocated to an ICSI group and a conventional IVF group. The estimated duration of the study is 30 months.

Participants/materials setting methods: Eligible couples are those whose husbands' total sperm count and motility are normal, have undergone ≤2 previous IVF/ICSI attempts, use antagonist protocol for ovarian stimulation, agree to have ≤2 embryos transferred and are not participating in another IVF study at the same time. Women undergoing IVM cycles, using frozen semen or having a poor fertilisation (≤25%) in previous cycle will not be eligible. Couples will be randomised to undergo ICSI or conventional IVF (1:1) with ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle as the primary endpoint. All analyses will be conducted on an intention-to-treat basis. Effect sizes will be summarised as relative risk (RR), with precision evaluated by 95% CIs.

Study funding/competing interests: All authors declare having no conflict of interests with regards to this trial. This work was supported by a grant from MSD [MISP #57508].

Trial registration number: NCT03428919.

Trial registration date: 8 February 2018.

Date of first patient’s enrolment: 16 March 2018.