Aspirin is one of the most widely used medicines and there are Cochrane Reviews of its effects for a wide variety of conditions. One of these reviews examines its use in in vitro fertilisation and an update was published in November 2016. Lead author, Harry Siristatidis from the Assisted Reproduction Unit at Attikon University Hospital in Athens Greece brings us up to date in this Evidence Pod.
John: Aspirin is one of the most widely used medicines and there are Cochrane Reviews of its effects for a wide variety of conditions. One of these reviews examines its use in in vitro fertilisation and an update was published in November 2016. Lead author, Harry Siristatidis from the Assisted Reproduction Unit at Attikon University Hospital in Athens Greece brings us up to date in this Evidence Pod.
Harry: Aspirin is widely used to reduce fever, pain and inflammation, as well as for treating or preventing heart disease, stroke and some cancers. Within reproductive medicine, aspirin has been used to increase the weight of newborns in pregnant women with fetal growth retardation and to improve placental and fetal blood flow in women with pre-eclampsia. For women who suffer from recurrent miscarriage, it’s suggested to those who have a condition called antiphospholipid antibody syndrome.
In in vitro fertilisation, or IVF, proposed benefits of aspirin include improvement in uterine and ovarian blood flow, prevention of blood clots in the placenta, and the production of proteins associated with pregnancy success. However, its use before conception has also been associated with an increase in miscarriage.
We have now performed a second update of this Cochrane Review, which was previously published in 2007 and 2011. The evidence on the use of low-dose aspirin for women undergoing IVF increased from 7 trials and nearly 1500 participants in 2007, to 13 trials with more than 2600 participants in 2011. But, both reviews were unable to draw firm conclusions due to the lack of enough good quality data. Unfortunately, that remains the case. The evidence is of very low to moderate quality, with the main limitations being failure to report study methods in sufficient detail and imprecision. However, it’s still important to highlight this ongoing uncertainty about a very common drug for a very common and distressing area of health care. We’ve not been able to include any further trials in this update and, in fact, the 17 trials that were newly identified and considered carefully all had to be excluded because they would not have helped to answer the fundamental questions of the review.
Looking at what is included: most studies used a dose of 100 mg of aspirin per day starting at the beginning of the IVF cycle, and lasting varying times across the studies.
Only three studies reported live birth rates, drawing on information from just over 1000 participants. We judged this research to be of moderate quality but it showed no evidence of a difference between women who took aspirin and those who didn’t. Clinical pregnancy rates were measured more often and we could use data from about 2100 participants in 10 studies, but those rates were not improved either. We also looked at several other outcomes, but were unable to detect any benefits for any of these.
In summary, therefore, there is no evidence for use of empirical aspirin for a general IVF population in order to improve pregnancy rates. Furthermore, the possibility of adverse events cannot be excluded, as data in the field remain limited. It was disappointing that only 3 studies reported on live birth rate, which we consider the most important outcome measure. Researchers in the field of reproductive medicine should use this review to construct well-designed trials of the effects on live-birth rate. Such trials are feasible. For example, to demonstrate a 10% improvement from the use of aspirin, a comparison of just 350 women on aspirin and 350 control women would be required.
Filling this evidence gap is urgent for many couples. Those undergoing IVF often feel so desperate that they are prepared to try anything that may improve their chances of conceiving. If aspirin really could improve a woman’s chances of having a baby, we need reliable and robust evidence to show this.
John: If you would like to read more about the efforts that Harry and his co-authors have put into trying to get this much needed answer from the existing evidence, and to see that evidence, you can read the full review online. Go to Cochrane library dot com and search ‘aspirin for in vitro fertilisation’.