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Meta-Analysis
. 2013 Aug 17;2013(8):CD009452.
doi: 10.1002/14651858.CD009452.pub2.

Heparin for assisted reproduction

Muhammad A Akhtar  1 , Shyamaly Sur, Nick Raine-Fenning, Kannamannadiar Jayaprakasan, Jim G Thornton, Siobhan Quenby
Affiliations
Meta-Analysis

Heparin for assisted reproduction

Muhammad A Akhtar et al. Cochrane Database Syst Rev. .

Abstract

Background: Heparin as an adjunct in assisted reproduction (peri-implantation heparin) is given at or after egg collection or at embryo transfer during assisted reproduction. Heparin has been advocated to improve embryo implantation and clinical outcomes. It has been proposed that heparin enhances the intra-uterine environment by improving decidualisation with an associated activation of growth factors and a cytokine expression profile in the endometrium that is favourable to pregnancy.

Objectives: To investigate whether the administration of heparin around the time of implantation (peri-implantation heparin) improves clinical outcomes in subfertile women undergoing assisted reproduction.

Search methods: A comprehensive and exhaustive search strategy was developed in consultation with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group (MDSG). The strategy was used in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). Relevant trials were identified from both electronic databases and other resources (last search 6 May 2013).

Selection criteria: All randomised controlled trials (RCTs) were included where peri-implantation heparin was given during assisted reproduction. Peri-implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or after egg collection or at embryo transfer in the included studies. Live birth rate was the primary outcome.

Data collection and analysis: Two review authors independently assessed the eligibility and quality of trials and extracted relevant data. The quality of the evidence was evaluated using GRADE methods.

Main results: Three RCTs (involving 386 women) were included in the review.Peri-implantation LMWH administration during assisted reproduction was associated with a significant improvement in live birth rate compared with placebo or no LMWH (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies, 386 women, I(2) = 51%, very low quality evidence with high heterogeneity). There was also a significant improvement in the clinical pregnancy rate with use of LMWH (OR 1.61, 95% CI 1.03 to 2.53, three studies, 386 women, I(2) = 29%, very low quality evidence with low heterogeneity).However these findings should be interpreted with extreme caution as they were dependent upon the choice of statistical method: they were no longer statistically significant when a random-effects model was used.Adverse events were poorly reported in all included studies, with no comparative data available. However, LMWH did cause adverse effects including bruising, ecchymosis, bleeding, thrombocytopenia and allergic reactions. It appeared that these adverse effects were increased if heparin therapy was used over a longer duration.

Authors' conclusions: The results of this Cochrane review of three randomised controlled trials with a total of 386 women suggested that peri-implantation LMWH in assisted reproduction treatment (ART) cycles may improve the live birth rate in women undergoing assisted reproduction. However, these results were dependent on small low quality studies with substantial heterogeneity, and were sensitive to the choice of statistical model. There were side effects reported with use of heparin, including bruising and bleeding, and no reliable data on long-term effects. The results do not justify this use of heparin outside well-conducted research trials.These findings need to be further investigated with well-designed, adequately powered, double-blind, randomised, placebo-controlled, multicentre trials. Further investigations could also focus on the effects of the local (uterine) and not systemic application of heparin during ART.

PubMed Disclaimer

Conflict of interest statement

The review authors have no commercial interest to disclose.

Figures

1
1
Study Review flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Heparin versus control, outcome: 1.1 Live Birth Rate per woman.
5
5
Forest plot of comparison: 1 Heparin versus control, outcome: 1.3 Clinical Pregnancy Rate per woman.
1.1
1.1. Analysis
Comparison 1 Heparin versus control, Outcome 1 Live Birth Rate per woman.
1.2
1.2. Analysis
Comparison 1 Heparin versus control, Outcome 2 Sens analysis Live Birth Rate (random effects).
1.3
1.3. Analysis
Comparison 1 Heparin versus control, Outcome 3 Clinical Pregnancy Rate per woman.
1.4
1.4. Analysis
Comparison 1 Heparin versus control, Outcome 4 Sens analysis Clinical Pregnancy Rate (random effects).
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009452

References

References to studies included in this review

Noci 2011 {published data only}
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