What is the most valid comparison treatment in trials of intrauterine insemination, timed or uninfluenced intercourse? A systematic review and meta-analysis of indirect evidence.

BACKGROUND Timed intercourse (TI), which is the usual control treatment in trials of intrauterine insemination (IUI), is not a typical coital activity and could impair fertility. This review summarizes the trials of IUI of male partner's prepared semen among subfertile couples according to whether the control group had TI or expectant management. METHODS A search of relevant databases and bibliographies until February 2008 yielded 150 citations of which 31 were potentially relevant and 11 met all criteria. The total estimates of the differences in pregnancy rates per couple were calculated with weights equal to the inverse variance. The primary analysis was a categorical meta-analysis by the type of control treatment (TI or expectant management). RESULTS In 11 trials with 13 comparisons of IUI and intercourse among 1329 couples with subfertility, the average difference in pregnancy rate between IUI and controls was 6.1% in trials with TI and 3.9% in trials with expectant management, as the control. The adjusted indirect estimate of the difference between the types of control groups was 2.8% (95% CI -6.3, 10.7). The difference by type of control treatment was not significant, neither in the 11 most relevant trials (P = 0.82), nor in a broader group of 19 trials and 2512 patients (P = 0.20). CONCLUSIONS The additional benefit accruing to IUI, where TI is the control, is not significant, but it is consistent with the possibility that pregnancy may be less likely in TI controls than in expectant management controls.