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Aspirin is no wonder drug for fertility

7 December 2015
By Richard Kennedy
President-Elect of the International Federation of Fertility Societies
Appeared in BioNews 831

Hippocrates (circa 460–377 BC), described the benefits for a range of ailments of powder made from the bark and leaves of the willow tree. We now know these preparations contained the active ingredient salicylic acid, which would later be synthesised as aspirin – a drug which, in this era, has been described as a 'wonder drug' and the 'drug of the millennium'.

In addition to its well-known anti-inflammatory properties, aspirin has proven benefits in cardiac disease and stroke, and it is increasingly thought to have a role in cancer prevention. In reproduction, it has been shown to be beneficial in the prevention of pre-eclampsia, a common and potentially serious complication of pregnancy, but its wider use in support of infertility and assisted reproduction is controversial.

Clinical trials from the 1960s to the 1980s established aspirin's efficacy as an anti-clotting agent, and it is this property that is thought to be the main reason for its benefits in a range of conditions. Of particular interest is its property of inhibiting the cyclo-oxygenase enzyme in platelets, thus preventing the synthesis of thromboxane, the most potent vasoconstricting agent in the body. Coupled with its inhibition of platelet aggregation, aspirin thereby reduces the risk of thrombosis and improves blood flow.

Aspirin's first reported use in reproductive medicine was in 1979, when it was found to reduce the incidence of pre-eclampsia. However, because of its known side effects, namely haemorrhage, its routine use has not been adopted until relatively recently. Low-dose (75mg) aspirin (LDA) retains the benefits of the drug in disease prevention but largely avoids its complications. LDA is now routinely given to pregnant women at known risk of raised blood pressure, subsequently reducing the risk of premature labour and fetal growth restriction.

It has also been suggested that the properties of aspirin that are beneficial in pregnancy may also improve the chance of conception and help prevent miscarriage. The posited mechanism of action focuses on the integrity of developing blood vessels at the site of implantation. This process is known as placentation and is a major determinant of the success of the pregnancy. Despite this promise of a breakthrough in improving implantation and overcoming one of the barriers to conception, a series of clinical trials have failed to prove this.

Aspirin has been tested in two clinical situations. First, as an adjunct to IVF. The results of several clinical trials have been analysed together to increase their collective significance, a process known as meta-analysis. In the case of aspirin and IVF, there have been several such analyses. In the first (Gelbaya, 2007) the authors conclude 'low-dose aspirin has no substantial positive effect on likelihood of pregnancy and, therefore, it should not be routinely recommended for women undergoing IVF/ICSI'. In 2011, a further analysis was published in the Cochrane Library of Systematic Reviews (Siristatidis, 2011). This included 13 clinical trials involving 2653 women and concluded: 'Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of evidence from the current trial data.'

Second, aspirin has been tested as a treatment for recurrent miscarriage. An analysis of nine studies involving 1228 women with a history of recurrent miscarriage (de Jong, 2014) concluded that 'this review does not support the use of anticoagulants, including LDA, in women with unexplained recurrent miscarriage'. They also concluded that there is not enough evidence to state whether there was any benefit in a sub-group of patients with known inherited traits that predispose them to thrombosis (thrombophilia), but this is an area for further research. Additionally, a recent large clinical trial, published in the Lancet (Schisterman, 2014), involved 1078 women with one or more prior pregnancy loss. This study found no benefit in giving LDA routinely, although they did find an improvement in live birth rates in a sub-group of patients who had one pregnancy loss at less than 20 weeks within one year of the treatment.

Taking the evidence from a large number of clinical trials and several meta-analyses, we can now conclude that the routine use of aspirin is not recommended to help couples conceive, either naturally or as an adjunct to improve the success of assisted conception. 

Unfortunately, as far as we can say at this time, the reputation of aspirin as a wonder drug does not extend to infertility.

SOURCES & REFERENCES
de Jong PG, Kaandorp S, Di Nisio M, et al. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia.
Cochrane Database Syst Rev 2014; 7:CD004734 |  22 May 2019
Gelbaya TA, Kyrgiou M, Li TC, et al. Low-dose aspirin for in vitro fertilization: a systematic review and meta-analysis.
Hum Reprod Update 2007; 13(4):357-64 |  22 May 2019
Schisterman EF, Silver RM, Lesher LL, et al. Preconception Low Dose Aspirin and Pregnancy Outcomes: Findings from the EAGeR (Effects of Aspirin in Gestation and Reproduction) Randomized Trial
Lancet 2014; 384(9937):29–36 |  22 May 2019
Siristatidis CS1, Dodd SR, Drakeley AJ. Aspirin for in vitro fertilisation.
Cochrane Database Syst Rev 2011; 10;(8):CD004832 |  22 May 2019
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