Objective
To examine the effects of preprocedure misoprostol on intrauterine device (IUD) placement in nulliparous women.
Study Design
In this randomized controlled double-blind trial at the University of New Mexico reproductive health clinic, nulliparous women requesting an IUD were randomized to 400 mcg of buccal misoprostol or placebo 2-8 hours before insertion. Primary outcomes included pain on a 10-cm visual analog scale and women’s perception of the value of delaying insertion for an effective medication. Provider ease of insertion and need for adjunctive insertion measures were also assessed, on a visual analog scale. Participants indicated maximum pain after IUD insertion, pain level they would tolerate to avoid delay in IUD insertion, and preference for IUD insertion without delay if an effective medication was available.
Results
Of 85 women enrolled, 3 were ineligible; 42 were randomized to misoprostol and 40 to placebo. There were no differences between groups in worst insertion pain, (5.8 ± 2.0 vs 5.9 ± 2.0, P = .94), provider ease of insertion (2.2 ± 2.2 vs 2.5 ± 2.2; P = .54) or adjunctive measures (14% vs 25%; P = .27). The groups were willing to tolerate the same mean pain (4.9 ± 2.5 vs 5.7 ± 2.4, P = .18) to avoid waiting for medication. The majority of women (85%) preferred to wait for an effective medication.
Conclusion
Misoprostol for nulliparous women did not decrease pain or improve the ease of insertion of an IUD. Most women were willing to wait for a medication that decreases pain, indicating a need to pursue alternatives for pain control with IUD insertion.
Pain with intrauterine device (IUD) insertion is a potential deterrent for nulliparous women considering an IUD and their health care providers. Many nulliparous women are adolescents or young women at high risk for unintended pregnancy who could benefit from the use of highly effective long-acting reversible contraceptive methods like the IUD. Although the majority of nulliparous women are good candidates for the IUD, many providers, including family medicine physicians, obstetrician gynecologists, and advanced practice clinicians remain reluctant to consider IUDs for adolescents or nulliparous women. Identifying an effective approach to reducing pain with IUD insertion remains elusive: trials of prophylactic ibuprofen and paracervical block have not demonstrated pain reduction. The perception that IUD insertion is difficult and causes significant pain may contribute to providers’ hesitation to offer the method or to use measures like misoprostol that have unproven success.
The IUD has a 0.2-0.3% failure rate with minimal opportunity for user error and high rates of user satisfaction. Although use of IUDs has increased among all women in the United States to 7.7% in 2009, only 2.1% of nulliparous women use the IUD. The Institute of Medicine has prioritized increasing LARC use among young women to decrease unintended pregnancies. The US Medical Eligibility Criteria and the American College of Obstetricians and Gynecologists support use of both the copper and levonorgestrel IUD in nulliparous women, including adolescents. The Contraceptive CHOICE project provided contraceptives at no cost to almost 10,000 women. In total, 41.2% of women in the CHOICE project who chose a LARC method were nulliparous.
Misoprostol, a prostaglandin E1 analogue used in gynecology for cervical ripening, has demonstrated effectiveness in decreasing pain and complications with both surgical abortion and hysteroscopy. Several studies have examined the use of misoprostol as a cervical priming agent before IUD insertion in nulliparous women with mixed results. The use of misoprostol before IUD insertion requires a time delay, which may be considered a deterrent to the nulliparous woman considering an IUD. The aim of our study is to determine whether prophylactic misoprostol use reduces pain or improves ease of insertion with IUD placement, and to determine the opportunity cost of the time delay required to administer misoprostol before IUD insertion. We sought to determine women’s perceptions of whether the possible benefit of decreased discomfort or difficulty of insertion was worth the 2- to 3-hour delay before IUD insertion and whether higher pain was a reasonable price to pay for immediate insertion.
Materials and Methods
This double-blind, randomized placebo-controlled parallel-group trial was conducted at the University of New Mexico (UNM) reproductive health clinic in Albuquerque, New Mexico, from Jan. 2010 to Jan. 2013 and was approved by the UNM Human Research Protections Office. This study will contribute data to a prospective metaanalysis coordinated by the University of Utah on the need for adjunctive measures such as mechanical cervical dilation during IUD insertion in nulliparous women.
Nulliparous women desiring a levonorgestrel intrauterine system or copper T-380A IUD for contraception were recruited for the study. Inclusion criteria included English speaking women aged 18 and over, or aged 14-17 with parental consent. Women with history of a pregnancy lasting beyond 19 6/7 weeks, any pregnancy within the last 4 weeks, active genital infection or cervicitis, undiagnosed abnormal uterine bleeding, fibroids distorting the uterine cavity, history of cervical or uterine cancer, uterine anomaly, pelvic inflammatory disease within the last 3 months, and ibuprofen or copper allergy, were excluded.
Pharmacists at the University of Utah Health Sciences Center clinical research pharmacy not directly involved in the study performed randomization and preparation of the study and placebo medications. Randomization was based on computer generated 8-block randomization sequences. The drug and placebo tablets were identical in appearance, taste and smell and packaged according to the randomization list in matching bottles labeled with consecutive numbers. These were sent to UNM and the bottles were pulled in sequential order. Participants were randomly allocated in a 1:1 ratio either to treatment with 400 mcg of misoprostol or placebo. The medication was placed buccally for 30 minutes and subjects were instructed to swallow any remaining medication. Buccal administration was chosen for its excellent bioavailability and ease of use. Participants and investigators were blinded to the assignment to treatment groups.
Participants received standard counseling for IUD insertion and signed informed consent for the procedure and for study participation. After enrollment, participants received a $20 gift card to compensate them for their time. Participants underwent IUD placement 2-8 hours after receiving the study medication. This timeframe allowed women the option of waiting in clinic or returning later the same day. Participants completed a questionnaire before IUD insertion including demographic characteristics, anticipated pain with the procedure, use of pain medication, and side effects from the study medication. Premedication with nonsteroidal antiinflammatory agents is not typically offered in our practice and was not offered to study participants. All participants were asked if they had self-medicated before the procedure.
The IUD was placed using standard technique by 1 of 5 attending physicians skilled in IUD insertion, at the UNM’s reproductive health clinic. If difficulty was encountered during insertion, the attending physicians had the option of using adjunctive measures including an os finder, a soft endometrial biopsy device, Denniston dilators, ultrasound assistance, or additional analgesia.
Patients reported pain on a 10-cm visual analog scale (VAS) with anchors at 0 = none and 10 = worst imaginable pain. Pain was evaluated at baseline when legs were positioned in stirrups, immediately after IUD insertion (after instruments were removed from the vagina), and before discharge from the clinic. Participants were provided the VAS and marked their pain on the 10 cm line accordingly. Before discharge, the research assistant also asked the participant her preference for having the IUD placed without a delay for a medication to decrease insertion pain (4-point Likert scale with anchors: 1 = strongly prefer IUD placement without the wait, 4 = strongly prefer to wait for IUD placement for medicine effect) and how much pain she was willing to tolerate to have immediate IUD placement without waiting for the medicine on a 10-cm VAS (anchors 0 = no pain, 10 = worst pain imaginable). We asked the last 2 questions after IUD insertion to allow for the possibility that the degree of insertion pain could influence the preference for a delay to await the effect of medication. If the preprocedure misoprostol reduced insertion pain, women’s preferences for delay might differ between the misoprostol and placebo groups.
Providers completed a questionnaire including perceived ease of IUD insertion on a 10-cm VAS (0 = easy and 10 = extremely difficult), and need for adjunctive measures. Participants were scheduled to return to clinic in 1-2 weeks for a standard IUD check visit at which time women reported pain since IUD insertion, complications, and satisfaction. Study investigators contacted participants unable to keep their appointment within 4 weeks of insertion and conducted a telephone interview to collect the same information.
The sample size of 80 women was determined based on our participation in the prospective metaanalysis. Before initiation of the study, we determined that this sample size, equally distributed between the misoprostol and placebo groups, would detect a 0.8 cm ± 1.25 difference between mean maximum pain with IUD insertion on the VAS with a power of 80% and α = 0.05 (2-tailed). Evidence from the family planning literature suggests a 1.5 cm difference is clinically meaningful. A sample size of 80 would also allow a 29% detectable difference between groups when 49% in 1 group prefer to wait compared with 20% in the other, with 80% power and α = 0.05 (2-tailed). To evaluate differences between groups, Fisher exact test was used for categorical and the t test was used for continuous variables. Statistical significance was set at P ≤ .05. We analyzed the data using SAS statistical software (version 9.3; SAS Institute Inc., Cary, NC).
Results
A total of 85 women were enrolled; 2 were ineligible ( Figure ). Of the 83 women randomized, 1 was ineligible, leaving 42 women randomized to misoprostol and 40 to placebo. Follow-up was completed for 40 women in each group. Two women were lost to follow-up in the misoprostol group. There were no differences in baseline characteristics between the 2 groups ( Table 1 ). Anticipated pain ( P = .11) and pain before IUD insertion ( P = .31) did not differ between groups. There was no difference in use of pain medication before IUD insertion in the 2 groups ( P = .08). An oral opioid was used by 10% and either ibuprofen or acetaminophen was used by 90% of women who self-medicated before the IUD insertion appointment; type of medication did not differ between the 2 groups ( P = .15).
| Characteristics | Misoprostol n = 42 | Placebo n= 40 | P value |
|---|---|---|---|
| Age (mean ± SD) | 24.1 ± 4.3 | 24.1 ± 4.6 | .99 |
| Race | .75 | ||
| White | 25 (59) | 22 (50) | |
| Hispanic or Latina | 12 (29) | 14 (35) | |
| Other | 5 (12) | 6 (15) | |
| Marital status | .40 | ||
| Single | 30 (71) | 33 (85) | |
| Married/Cohabitating | 10 (24) | 5 (13) | |
| Other | 1 (5) | 1 (2) | |
| Level of education | |||
| High school/GED | 1 (1) | 5 (12) | |
| Some college | 17 (41) | 15 (38) | .42 |
| Graduated from college | 17 (41) | 15 (38) | |
| Completed graduate school | 7 (17) | 5 (12) | |
| Prior miscarriage/abortion | 9 (21) | 4 (10) | .16 |
| History of STI | 8 (19) | 3 (7) | .20 |
| Type of IUD | |||
| Levonorgestrel IUS | 36 (86) | 36 (90) | .74 |
| Copper T380A | 6 (14) | 4 (10) | |
| Medication before IUD insertion | |||
| Yes | 26 (62) | 16 (40) | .08 |
| No | 16 (38) | 24 (60) |
The highest level of pain immediately after IUD insertion was similar between the misoprostol and placebo groups (5.8 ± 2.0 vs 5.9 ± 2.0, P = .94). There were no differences between groups with respect to symptoms of nausea, vomiting, or diarrhea ( Table 2 ). The amount of pain women were willing to tolerate to avoid waiting to have the IUD inserted did not differ between the groups ( P = .18). Most women in both groups (85%) reported that, if available, they would prefer to wait for a medicine to take effect to reduce pain with IUD insertion.
