Objective:  To compare a strategy of two cycles of intrauterine insemination with controlled ovarian hyperstimulation (IUI/COH) vs one in vitro fertilisation (IVF) treatment programme (one fresh plus associated frozen embryo cycles) in couples presenting with unexplained, mild male or mild female subfertility.
Methods:  A retrospective cohort design was used and analysed according to intention‐to‐treat principles. A total of 272 couples underwent an intended course of two cycles of IUI/COH and 176 couples underwent one IVF treatment programme.
Results:  The cumulative live birth rate (CLBR) per couple for the IUI/COH group was 27.6% compared to 39.2% for the IVF group (P = 0.01). The mean time to pregnancy was 69 days in the IUI/COH group compared to 44 days in the IVF group (P = 0.02). The IVF programme was costlier, with an incremental cost‐effectiveness ratio for an additional live birth in the range of $39 637–$46 325. The multiple delivery rate was 13.3% in the IUI/COH group compared to 10.1% in the IVF group (P = 0.55). One set of triplets and one set of quadruplets followed IUI/COH treatment.
Conclusions:  One IVF treatment programme was more effective, but costlier than an intended course of two cycles of IUI/COH. With consistently higher success rates, shorter times to pregnancy and a trend to less higher order multiple pregnancies, this study supports the view that IVF is now potentially safer and more clinically effective than IUI/COH as a first‐line therapy for subfertility.