Review question
Researchers reviewed the evidence about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) as co-treatments when applied in infertile women undergoing assisted reproduction.

Background
Assisted reproductive technologies (ART) include techniques used for treating subfertility, and in vitro fertilization (IVF) is the most common. Despite both clinical and laboratory efforts and improvements in the success of these treatments, pregnancy rates remain low. Local inflammatory response is believed to cause implantation difficulties for the embryo, through the action of prostaglandins. These substances mainly cause a differentiated local inflammatory response and uterine contractions during embryo transfer, inhibiting the embryo from implanting successfully. For this reason, clinicians usually use anti-prostaglandin agents to block this action: NSAIDs are such agents. In clinical practice, they are often offered to improve ART outcomes, but evidence is based on various types of studies. Thus because there is lack of clear evidence, their efficacy and safety still remain controversial. In this Cochrane Review we have summarised the available evidence on the use of NSAIDs in infertile women undergoing IVF, in an attempt to identify gaps and limitations in our current understanding.

Study characteristics
We performed a comprehensive literature search of the standard medical databases (from database inception to February 2019) in consultation with the Cochrane Gynaecology and Fertility Group Information Specialist, for all randomised controlled trials (studies in which participants are assigned to a treatment group using a random method) investigating the efficiency of NSAIDs compared to the use of placebo or no treatment or compared to each other in infertile women undergoing IVF. We searched for and included studies irrespective of language and country of origin. Two review authors independently selected and evaluated studies, extracted data, and attempted to contact the authors of studies for which data were missing. We found 11 studies (2384 women); data were not available in one study, so we analysed data on 1884 patients; two studies were published as abstracts in international conference reports; and we found one ongoing trial that met our inclusion requirements.

Key results
We are uncertain of an effect on ongoing pregnancy and miscarriage when NSAIDs were compared to placebo/no treatment. Results suggest that if the chance of ongoing pregnancy and miscarriage following placebo or no treatment is assumed to be 15% and 21%, respectively, the chance following the use of NSAIDs is estimated to be between 12% and 24%, and 7% and 27%, respectively. Only one study compared piroxicam with indomethacin: we are uncertain of an effect on ongoing pregnancy and on miscarriage. The evidence suggests that if the chance of ongoing pregnancy following indomethacin is assumed to be 20%, the chance following the use of piroxicam is estimated to be between 13% and 40%; while for miscarriage, the evidence suggests that if the chance following indomethacin is assumed to be 12%, the chance following the use of piroxicam is estimated to be between 5% and 27%.

Concerning the secondary outcomes, we are equally uncertain of any effect.

Currently we are uncertain of an effect of the routine use of NSAIDs as co-treatments in infertile women undergoing assisted reproduction in order to improve pregnancy rates. This is based on available data from randomised controlled trials, where no single outcome reported in the studies demonstrated a benefit with their use.

Quality of the evidence
The quality of the evidence was very low for all outcomes. This is because of several limitations including poorly reported study methods, imprecision, small study numbers and low numbers of events reported.