Misoprostol for intrauterine device placement.

Rationale: Identifying effective approaches to reduce pain and improve providers' ease of intrauterine device (IUD) placement may reduce barriers to IUD access and use. The cervical softening and dilation effects of misoprostol might make IUD placement less painful for women and technically easier for providers. However, evidence suggests that misoprostol does not improve many outcomes and may only be helpful for some patients (e.g. those with a recent failed IUD placement).

Objectives: To examine the effect of misoprostol for routine IUD placement on patient and provider outcomes compared to placebo or no treatment.

Search methods: In November 2021 we searched CENTRAL, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov. We conducted update searches in July 2022 and September 2024. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in July 2025.

Eligibility criteria: We included randomized controlled trials (RCTs) of women undergoing interval IUD placement (i.e. placement outside the postabortion or postpartum period) that compared misoprostol to placebo or no treatment. We included trials that examined the placement of currently available levonorgestrel (LNG)-releasing IUDs, or any copper T IUD, for women of any age, of any parity, and for any indication.

Outcomes: Our core critical and important outcomes were pain (during tenaculum placement, during IUD placement, and after IUD placement before clinic discharge); providers' ease of placement; need for cervical dilation; placement success; patient satisfaction; misoprostol side effects (preplacement abdominal pain or cramping, and diarrhea); and adverse events (vasovagal reaction).

Risk of bias: We used the Risk of Bias 2 tool (RoB 2) to assess the risk of bias for outcomes.

Synthesis methods: We synthesized results for each outcome using meta-analysis. We calculated mean differences (MD) for continuous outcomes using inverse variance estimation and random-effects models. We calculated risk ratios (RR) for dichotomous outcomes using Mantel-Haenszel estimation and random-effects models. We used GRADE to assess the certainty of evidence for each outcome.

Included studies: We included 14 RCTs with a total of 1972 women. The trials were conducted in North America, South America, Europe and Africa, and were published between 2007 and 2022.

Synthesis of results: The results below summarize the effect of misoprostol on outcomes compared to placebo or no treatment. Pain: misoprostol results in little to no difference in pain during tenaculum placement (MD -0.73, 95% confidence interval [CI] -1.19 to -0.28; 3 RCTs, 261 women; high-certainty evidence) and after IUD placement before clinic discharge (MD -0.01, 95% CI -0.45 to 0.43; 5 RCTs, 448 women; high-certainty evidence). Misoprostol may result in little to no difference in pain during IUD placement (MD -0.47, 95% CI -1.23 to 0.29; 7 RCTs, 766 women; low-certainty evidence). Providers' ease of placement: misoprostol may result in little to no difference in a clinically meaningful effect on ease of IUD placement for providers (MD -0.89, 95% CI -1.55 to -0.22; 8 RCTs, 848 women; low-certainty evidence). Need for cervical dilation: misoprostol may result in little to no difference in need for cervical dilation for women without a recent failed placement attempt (RR 0.84, 95% CI 0.38 to 1.85; 6 RCTs, 562 women; low-certainty evidence). Misoprostol probably results in little to no difference in need for cervical dilation for women with a recent failed placement attempt (RR 0.88, 95% CI 0.56 to 1.36; 1 RCT, 90 women; moderate-certainty evidence). Placement success: misoprostol probably results in little to no difference in placement success for women without a recent failed placement attempt (RR 1.01, 95% CI 0.98 to 1.04; 12 RCTs, 1579 women; moderate-certainty evidence) but probably results in a slight increase in placement success for women with a recent failed placement attempt (RR 1.41, 95% CI 1.09 to 1.83; 1 RCT, 90 women; moderate-certainty evidence). Patient satisfaction: misoprostol may increase women's satisfaction with the IUD placement procedure, but the evidence is very uncertain (MD 2.00, 95% CI -0.05 to 4.06; 2 RCTs, 226 women; very low-certainty evidence) Misoprostol side effects before clinic discharge: misoprostol probably results in an increase in preplacement abdominal pain or cramping (RR 2.14, 95% CI 1.42 to 3.23; 7 RCTs, 781 women; moderate-certainty evidence)and probably results in a slight increase in diarrhea (RR 1.76, 95% CI 1.01 to 3.06; 9 RCTs, 940 women; moderate-certainty evidence). Adverse events before clinic discharge: misoprostol may result in little to no difference in vasovagal reaction (RR 0.94, 95% CI 0.37 to 2.37; 6 RCTs [3 RCTs had 0 events], 780 women; low-certainty evidence). We downgraded the evidence due to serious concerns about inconsistency and serious or very serious concerns about imprecision.

Authors' conclusions: Evidence from RCTs of women seeking routine IUD placement suggests that receiving misoprostol compared to placebo or no treatment makes little to no difference to pain during tenaculum placement or after IUD placement; and may make little to no difference to pain during IUD placement. Misoprostol may make little to no difference to reduced vasovagal reaction, improved providers' ease of placement, or reduced need for cervical dilation; and probably makes little to no difference to placement success, except for women with a recent failed IUD placement attempt, where misoprostol probably leads to a clinically meaningful increase in placement success. Misoprostol use probably leads to clinically important increases in harms, specifically preplacement abdominal pain or cramping and diarrhea. Misoprostol may increase patient satisfaction with the IUD placement procedure, but the evidence is very uncertain. The number of available RCTs did not support examining effect modifiers such as prior vaginal delivery status, misoprostol dose, or IUD type.

Funding: This review was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention (CDC) administered by the Oak Ridge Institute for Science and Education.

Registration: Protocol (2022): doi.org/10.1002/14651858.CD015584.