Single versus double intrauterine insemination (IUI) for pregnancy: A systematic review and meta-analysis

This study is focused in appraising the current evidence comparing double and single IUI for achieving a pregnancy. The primary outcomes were live birth and ectopic pregnancy per women randomized. Secondary outcomes included clinical pregnancy and miscarriage. The evaluation of the risk of bias within each study was structured using the Cochrane risk of bias and the overall quality of the body of evidence was assessed through the GRADE criteria. Electronic searches were run in 4 databases and resulted in 15 studies included encompassing 3795 women. The subgroup 'mild male infertility' included 1246 women whilst the subgroup 'normal semen quality' included 1188 women. Clinical pregnancy was reported by all studies, and there is no evidence of a difference between single and double IUI (RR 1.22, CI 0.97 to 1.54, 15 RCTs, 3795 women, I2 = 45%). In the subgroup analysis, we could not identify a particular group that could benefit from the intervention. No conclusion can be drawn regarding live birth, ectopic pregnancy, and miscarriage because they were reported by too few studies and the estimates were too imprecise. Currently, there is no evidence to support the use of double IUI in clinical practice. It requires a second appointment and insemination, thus making the treatment more complex and expensive, without a clear evidence of a benefit. Nevertheless, evidence is still of low quality and our confidence in the effect estimate is limited: the true effect may be substantially different from the hereby demonstrated.