Design: Sequential multicentre randomised controlled non-inferiority trial
Population: 737 couples with unexplained infertility
Primary outcome: Cumulative live-birth rate at 7 months
Effect: 31% IUI vs 55% IVF (difference -24 points, 95% CI -31 to -16); 70% vs 71% at 20 months

The FIIX trial, published in NEJM on 27 October 2026, randomised 737 couples with unexplained infertility at several centres to up to four cycles of intrauterine insemination with ovarian stimulation or one complete IVF cycle with all embryos transferred. After seven months, couples without a pregnancy could go on to IVF.

At seven months the cumulative live-birth rate was 31% with IUI and 55% with IVF (adjusted difference -24 points, 95% CI -31 to -16), so IUI failed to show non-inferiority. By 20 months, after crossover to IVF, cumulative live-birth rates were almost identical: 70% and 71%. Serious adverse events, mostly from egg retrieval or hyperstimulation, occurred in 14 IVF couples and 6 IUI couples.

The result reframes the choice as speed against cost and intervention, rather than success against failure. Guidelines that put IUI first have not changed on one trial.

Tell couples with unexplained infertility that IVF first reached a live birth faster, but final success at 20 months was similar.
Weigh age and time pressure: faster success matters more as fertility declines.
Include cost, travel and treatment burden in the discussion; IVF costs more per cycle.
Mention the higher serious adverse event count with IVF, mostly retrieval and hyperstimulation.

Why it matters

It turns a 'which works' question into a 'how quickly, and at what cost' question that couples can weigh.

The statistics, in plain English

The seven-month difference of 24 points is large and its interval is clear of zero. The 20-month comparison has a 99% interval of -9 to 8 around zero, so the two routes end in a similar place.