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Review
. 2016 Nov 3;11(11):CD004832.
doi: 10.1002/14651858.CD004832.pub4.

Aspirin for in Vitro Fertilisation

Affiliations
Free PMC article
Review

Aspirin for in Vitro Fertilisation

Charalampos S Siristatidis et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: 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.

Objectives: To evaluate the effectiveness and safety of aspirin in women undergoing ART.

Search methods: 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.

Selection criteria: Randomised controlled trials on aspirin for women undergoing ART.

Data collection and analysis: 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.

Main results: 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.

Authors' conclusions: 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.

Conflict of interest statement

Previous author V Poustie has undergone IVF treatment in the past and has previously taken low‐dose aspirin during this treatment.

Figures

Figure 1
Figure 1
Study flow diagram
Figure 2
Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 3
Figure 3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figure 4
Figure 4
Forest plot of comparison: 1 Low‐dose aspirin versus placebo or no treatment, outcome: 1.1 Live birth rate per woman or couple.
Figure 5
Figure 5
Forest plot of comparison: 1 Low‐dose aspirin versus placebo or no treatment, outcome: 1.2 Clinical pregnancy rate per woman or couple.
Analysis 1.1
Analysis 1.1
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 1 Live birth rate per woman or couple.
Analysis 1.2
Analysis 1.2
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 2 Clinical pregnancy rate per woman or couple.
Analysis 1.3
Analysis 1.3
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 3 Ongoing pregnancy rate (beyond 12 weeks).
Analysis 1.4
Analysis 1.4
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 4 Multiple pregnancy rate per woman per couple (on ultrasound).
Analysis 1.5
Analysis 1.5
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 5 Multiple pregnancy rate per woman per couple at birth.
Analysis 1.6
Analysis 1.6
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 6 Miscarriage rate per woman per couple.
Analysis 1.7
Analysis 1.7
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 7 Complications during pregnancy per woman per couple ‐ ectopic pregnancy.
Analysis 1.8
Analysis 1.8
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 8 Complications during pregnancy per woman/per couple/vaginal bleeding during pregnancy.
Analysis 1.9
Analysis 1.9
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 9 Clinical pregnancy rate ‐ subgroup analysis ‐ timing of treatment.
Analysis 1.10
Analysis 1.10
Comparison 1 Low‐dose aspirin versus placebo or no treatment, Outcome 10 Clinical pregnancy rate ‐ sensitivity analysis.

Update of

  • Aspirin for in vitro fertilisation.
    Siristatidis CS, Dodd SR, Drakeley AJ. Siristatidis CS, et al. Cochrane Database Syst Rev. 2011 Aug 10;(8):CD004832. doi: 10.1002/14651858.CD004832.pub3. Cochrane Database Syst Rev. 2011. PMID: 21833951 Updated. Review.

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