Abstract: We included 33 trials with 5710 participants total; 29 were published from 2010 to 2015. Studies examined lidocaine, misoprostol, NSAIDs, and other interventions. Here we synthesize results from trials with sufficient outcome data and moderate- or high-quality evidence. For lidocaine, meta-analysis showed topical 2% gel had no effect on pain at tenaculum placement (two trials) or on pain during IUC insertion (three trials). Other formulations were effective compared with placebo in individual trials. Mean score for IUC-insertion pain was lower with lidocaine and prilocaine cream (MD -1.96, 95% CI -3.00 to -0.92). Among nulliparous women, topical 4% formulation showed lower scores for IUC-insertion pain assessed within 10 minutes (MD -15.90, 95% CI -22.77 to -9.03) and at 30 minutes later (MD -11.10, 95% CI -19.05 to -3.15). Among parous women, IUC-insertion pain was lower with 10% spray (median 1.00 versus 3.00). Compared with no intervention, pain at tenaculum placement was lower with 1% paracervical block (median 12 versus 28). For misoprostol, meta-analysis showed a higher mean score for IUC insertion compared with placebo (SMD 0.27, 95% CI 0.07 to 0.46; four studies). In meta-analysis, cramping was more likely with misoprostol (OR 2.64, 95% CI 1.46 to 4.76; four studies). A trial with nulliparous women found a higher score for IUC-insertion pain with misoprostol (median 46 versus 34). Pain before leaving the clinic was higher for misoprostol in two trials with nulliparous women (MD 7.60, 95% CI 6.48 to 8.72; medians 35.5 versus 20.5). In one trial with nulliparous women, moderate or severe pain at IUC insertion was less likely with misoprostol (OR 0.30, 95% CI 0.16 to 0.55). In the same trial, the misoprostol group was more likely to rate the experience favorably. Within two trials of misoprostol plus diclofenac, shivering, headache, or abdominal pain were more likely with misoprostol. Participants had no vaginal delivery. One trial showed the misoprostol group less likely to choose or recommend the treatment. Among multiparous women, mean score for IUC-insertion pain was lower for tramadol 50 mg versus naproxen 550 mg (MD -0.63, 95% CI -0.94 to -0.32) and for naproxen versus placebo (MD -1.94, 95% CI -2.35 to -1.53). The naproxen group was less likely than the placebo group to report the insertion experience as unpleasant and not want the medication in the future. An older trial showed repeated doses of naproxen 300 mg led to lower pain scores at one hour (MD -1.04, 95% CI -1.67 to -0.41) and two hours (MD -0.98, 95% CI -1.64 to -0.32) after insertion. Most women were nulliparous and also had lidocaine paracervical block. Nearly all trials used modern IUC. Most effectiveness evidence was of moderate quality, having come from single trials. Lidocaine 2% gel, misoprostol, and most NSAIDs did not help reduce pain. Some lidocaine formulations, tramadol, and naproxen had some effect on reducing IUC insertion-related pain in specific groups. The ineffective interventions do not need further research.

Plain-language summary: We reviewed randomized trials of reducing pain during IUC insertion through 22 June 2015. We found 33 studies with a total of 5710 women. Most were recent trials. Methods tested were nonsteroidal anti-inflammatory drugs (NSAIDs), lidocaine, misoprostol, and other treatments. Lidocaine 2% gel had no effect on pain during IUC insertion (three trials) or pain with tenaculum (type of forceps) placement (two trials). Other types of lidocaine showed some effect. Pain score for IUC insertion was lower with a lidocaine and prilocaine cream and with 10% lidocaine spray. With 4% lidocaine gel, pain scores were lower shortly after IUC insertion. With 1% lidocaine injection, pain score at tenaculum placement was lower compared with no intervention. With four misoprostol trials, the pain score with IUC insertion was higher for misoprostol versus placebo ('dummy' treatment). Two other trials showed higher pain scores with misoprostol versus placebo either at IUC insertion or after. However, another study showed the misoprostol group had less serious IUC-insertion pain. Also, the misoprostol group rated the insertion more favorably. In analysis of four trials, cramping was more likely with misoprostol versus placebo. Within two other trials, the misoprostol group was more likely to have shivering, headache, or abdominal pain. In one study, the misoprostol group was less likely to choose the treatment again or recommend it. Pain score during IUC insertion was lower for the opioid tramadol versus naproxen. In the same trial, pain was lower for naproxen versus placebo. The naproxen group was less likely than the placebo group to rate the experience as unpleasant and not want the treatment in the future. In another trial, women with several naproxen doses had lower pain scores after IUC insertion than the placebo group. Overall, the effectiveness results were of moderate quality, having come from single studies. Trials of lidocaine, tramadol and naproxen showed some effect on reducing pain from IUC insertion.