Review question
Cochrane researchers reviewed the evidence about the effectiveness and safety of aspirin used with the aim of increasing the chance of live birth in women undergoing assisted reproductive technology (ART).
Background
Aspirin has been commonly used in an attempt to increase the chance of live birth in women undergoing ART. However, there is contradictory evidence on the effectiveness of this treatment and on the appropriate time to commence treatment and its duration. Although physiologically aspirin exerts a beneficial effect on some aspects required for a successful pregnancy, aspirin intake has been also associated with miscarriage and vaginal bleeding. It was, therefore, important to evaluate current evidence on the effectiveness of this treatment.
Study characteristics
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.
Key results
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.
Quality of the evidence
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.
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.
Aspirin is used with the aim of optimising the chance of live birth in women undergoing assisted reproductive technology (ART), despite inconsistent evidence of its efficacy and safety (in terms of intraoperative bleeding during oocyte retrieval and risk of miscarriage). The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is the second update of the review first published in 2007.
To evaluate the effectiveness and safety of aspirin in women undergoing ART.
We searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4) in the Cochrane Library (searched 9 May 2016); the databases MEDLINE (1946 to 9 May 2016) and Embase (1974 to 9 May 2016); and trial registers (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform search portal). We also examined the reference lists of all known primary studies and review articles, citation lists of relevant publications and abstracts of major scientific meetings, combined with the Cochrane Gynaecology and Fertility Group's search strategy.
Randomised controlled trials on aspirin for women undergoing ART.
Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcome was live birth. Secondary outcomes included clinical pregnancy, ongoing pregnancy, multiple pregnancy, miscarriage, and other complications associated with IVF/ICSI or with pregnancy and birth. We combined data to calculate risk ratios (RRs) (for dichotomous data) and mean differences (MDs) (for continuous data) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
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.