Abstract: We included six RCTs (708 women analysed) on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated cycles, and two studies compared timing of IUI and ICI. There was very low-quality evidence; the main limitations were risk of bias due to poor reporting of study methods, and serious imprecision. IUI versus ICI in natural cycles There was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95% confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality evidence). There was only one live birth in this study (in the IUI group). IUI resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2 RCTs, 76 women; I² = 48%; very low-quality evidence). No multiple pregnancies or miscarriages occurred in this study. IUI versus ICI in gonadotrophin-stimulated cycles There was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in gonadotrophin-stimulated cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality evidence). This suggested that if the chance of a live birth following ICI in gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). IUI may be associated with higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). This suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk following IUI would be between 10% and 46%. We found insufficient evidence to determine whether there was any clear difference between the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95% CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I² = 50%; very low-quality evidence). Timing of IUI and ICI We found no studies that reported on live birth rates. We found a higher clinical pregnancy rate when IUI was timed one day after a rise in blood levels of luteinising hormone (LH) compared to IUI two days after a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low-quality evidence). We found insufficient evidence to determine whether there was any clear difference in clinical pregnancy rates between ICI timed after a rise in urinary levels of LH versus a rise in basal temperature plus cervical mucus scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality evidence). Neither of these studies reported multiple pregnancy or miscarriage rates as outcomes. There was insufficient evidence to determine whether there was a clear difference in live birth rates between IUI and ICI in natural or gonadotrophin-stimulated cycles in women who started with donor sperm treatment. There was insufficient evidence available for the effect of timing of IUI or ICI on live birth rates. Very low-quality data suggested that in gonadotrophin-stimulated cycles, IUI may be associated with a higher clinical pregnancy rate than ICI, but also with a higher risk of multiple pregnancy rate. We concluded that the current evidence was too limited to choose between IUI or ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.

Plain-language summary: We found six randomised controlled trials, including 708 women. Two studies compared IUI and ICI in natural cycles. Two studies compared IUI and ICI in gonadotrophin-stimulated cycles. Two studies compared the timing of IUI and ICI. The evidence is current to December 2017. There was insufficient evidence to determine whether there was any clear difference between IUI and ICI in live birth rates, in either natural cycles or in gonadotrophin-stimulated cycles. As there was only one live birth in the small study using natural cycles, we could not make any meaningful comparison between the groups. The evidence on gonadotrophin-stimulated cycles suggested that if the live birth rate following ICI was assumed to be 30%, the chance of live birth rate following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. For IUI and ICI in natural cycles, no multiple pregnancies were reported. In gonadotrophin-stimulated cycles, IUI was associated with higher multiple pregnancy rates than ICI. The evidence suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk of multiple pregnancy following IUI would be between 10% and 46%. We concluded that the evidence was too limited to encourage or discourage either IUI or ICI, in natural cycles or with ovarian stimulation in donor sperm treatment. Following GRADE assessment, we found that the evidence for all outcomes was of very low quality. The main limitations were risk of bias, due to poor reporting of study methods, and serious imprecision, due to the limited number of studies and small study sizes.