Abstract: The search identified 13 trials as eligible for inclusion in the review, including a total of 2653 participants with a mean age of 35 years. Ten studies used a dose of 100 mg and three used 80 mg of aspirin per day. In most of them, aspirin was commenced immediately at the start of down-regulation, while the duration of treatment varied widely. Eight studies provided a placebo for the control group. There was no evidence of a difference between the aspirin group and the group receiving no treatment or placebo in rates of live birth (RR 0.91, 95% CI 0.72 to 1.15, 3 RCTs, n = 1053, I² = 15%, moderate-quality evidence). In addition, clinical pregnancy rates were also similar for the two groups (RR 1.03, 95% CI 0.91 to 1.17, 10 RCTs, n = 2142, I² = 27%, moderate-quality evidence); sensitivity analysis, excluding studies at high risk of bias, did not change the effect estimate. There was no evidence of a difference between groups in terms of multiple pregnancy as confirmed by ultrasound (RR 0.67, 95% CI 0.37 to 1.25, 2 RCTs, n = 656, I² = 0%, low-quality evidence), miscarriage (RR 1.10, 95% CI 0.68 to 1.77, 5 RCTs, n = 1497, I² = 0%, low-quality evidence), ectopic pregnancy (RR 1.86, 95% CI 0.75 to 4.63, 3 RCTs, n = 1135, I² = 0%, very low quality evidence) or vaginal bleeding (RR 1.01, 95% CI 0.14 to 7.13, 1 RCT, n = 487, very low quality evidence). Data were lacking on other adverse effects. The overall quality of the evidence ranged from very low to moderate; limitations were poor reporting of study methods and suspected publication bias. Currently there is no evidence in favour of routine use of aspirin in order to improve pregnancy rates for a general IVF population. This is based on available data from randomised controlled trials, where there is currently no evidence of an effect of aspirin on women undergoing ART, as there is no single outcome measure demonstrating a benefit with its use. Furthermore, current evidence does not exclude the possibility of adverse effects.

Plain-language summary: We found 13 randomised controlled trials with parallel groups, comparing aspirin with placebo or no treatment in a total of 2653 women undergoing ART. Studies were conducted in the USA and a variety of countries in Europe and Asia. One of the included trials was partly funded by a pharmaceutical company relevant to the intervention. In most of the studies, groups were comparable and the mean age of participants in both groups was 32 years. An identical dose of the intervention was administered in most of the studies and most reported a similar timing of the initiation of aspirin intake. The duration of trial varied across the studies, but was sufficient to provide data on the reported outcomes as respectively investigated by each group. The evidence is current to 9 May 2016. There was no evidence of a difference between the groups in rates of live birth, clinical pregnancy, ectopic pregnancy, multiple pregnancy, miscarriage or vaginal bleeding. The number of studies was limited and the quality of the evidence ranged from very low to moderate, while data on complication rates, either during the IVF/ICSI procedure or during pregnancy and childbirth were either very limited or missing. At this second update we were not able to add new data from additional studies, as we found no new RCTs reporting on these outcomes in the prespecified comparisons. Based on the available evidence, we reached the same conclusion as the initial version of the review: no single outcome measure demonstrated a benefit with the use of aspirin. Currently, there is no evidence to support the use of aspirin treatment in order to improve pregnancy rates for a general IVF population. The evidence was of moderate quality for live birth and of very low to moderate quality for other outcomes. The main limitations of the evidence were poor reporting of study methods, publication bias and lack of studies investigating the desired outcomes.