Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis

Male factor infertility affects 30%-50% of infertile couples worldwide, and there is an increasing interest in the optimal management of these patients. In studies comparing double and single intrauterine insemination (IUI), a trend towards higher pregnancy rates in couples with male factor infertility was observed. Therefore, we set out to perform a meta-analysis to examine the superiority of double versus single IUI with the male partner's sperm in couples with male factor infertility. An odds ratio (OR) of 95% confidence intervals (CIs) was calculated for the pregnancy rate. Outcomes were analysed by using the Mantel-Haesel or DerSimonian-Laird model according to the heterogeneity of the results. Overall, five trials involving 1125 IUI cycles were included in the meta-analysis. There was a two-fold increase in pregnancies after a cycle with a double IUI compared with a cycle with a single IUI (OR: 2.0; 95% CI: 1.07-3.75; P<0.03). Nevertheless, this result was mainly attributed to the presence of a large trial that weighted as almost 50% in the overall analysis. Sensitivity analysis, excluding this large trial, revealed only a trend towards higher pregnancy rates among double IUI cycles (OR: 1.58; 95% CI: 0.59-4.21), but without statistical significance (P=50.20). Our systematic review highlights that the available evidence regarding the use of double IUI in couples with male factor infertility is fragmentary and weak. Although there may be a trend towards higher pregnancy rates when the number of IUIs per cycle is increased, further large and well-designed randomized trials are needed to provide solid evidence to guide current clinical practice.