By Alexandra Morell, MD
Synopsis: In a randomized clinical trial of 151 women, intrauterine instillation of mepivacaine significantly reduced pain with intrauterine device insertion on visual analog scales both before (53.9 mm vs. 67.2 mm, respectively; P < 0.001) and after adjustment for individual provider variability (55.2 mm vs. 77.4 mm, respectively; P < 0.001), compared to placebo.
Source: Envall N, Elgemark K, Kopp Kallner H. Mepivacaine instillation for pain reduction during intrauterine device placement in nulliparous women: A double-blinded randomized trial. Am J Obstet Gynecol. 2024;231(5):524.e1-524.e7.
Long-acting reversible contraceptives, including intrauterine devices (IUDs) and etonogestrel implants, are extremely effective methods of contraception.1 In particular, the levonorgestrel IUD and copper IUD both have an efficacy rate of greater than 99%. The copper IUD works by inhibiting sperm migration and viability, ultimately affecting successful fertilization. In contrast, the levonorgestrel IUD inhibits fertilization by changing the composition of cervical mucus to limit sperm penetration. The levonorgestrel IUD is approved by the U.S. Food and Drug Administration (FDA) for three to eight years, depending on the hormonal dosage, and the copper IUD is approved for up to 10 years. Despite the advantages pertaining to efficacy and long-term use, one barrier to IUD uptake is fear of pain and anxiety at the time of insertion.1,2
This was a randomized, placebo-controlled trial involving 12 centers in Sweden. The main objective of the trial was establishing mepivacaine superiority for pain reduction at the time of IUD placement compared to placebo. Inclusion criteria for the study were nulliparous women between ages 18 and 31 years desiring a 52-mg levonorgestrel IUD for contraception, who had the ability to understand an English or Swedish consent. A negative pregnancy test was required prior to enrollment.
Participants were excluded if they currently were using an IUD with a plan for replacement or had a history of cervical conization or known cervical stenosis, a body weight less than 40 kg, clinical symptoms of an active pelvic infection, known uterine abnormality, unexplained abnormal uterine bleeding, medical conditions associated with increased bleeding risk at the time of placement, inability to receive local anesthesia, or use of pain medications outside of oral analgesics prior to placement.
Participant charts were reviewed for demographic and prior obstetric history. Participants rated their current pain level and typical pain level associated with menstrual cramping using a 100-mm visual analog scale (VAS), with 0 indicating “no pain” and 100 mm indicating “worst pain imaginable” prior to the procedure. Either 10 mL of 20-mg/mL mepivacaine or 10 mL of 9-mg/mL sodium chloride (placebo) were introduced into the uterus via a 1.6-mm hydrosonography catheter at the time of IUD placement. Providers waited two minutes prior to proceeding with the remainder of the insertion in the typical manufacturer-instructed fashion. VAS scores also were obtained after intrauterine instillation, IUD insertion, and 10 minutes after conclusion of the procedure. In addition, 10 minutes after the procedure, participants also answered a questionnaire with additional questions about their experience.
For statistics, Student’s t-test was used to compare VAS pain scores between the intervention and placebo arms. A pilot study from the authors was used to determine the sample size required to detect a 20% reduction in mean VAS pain scores or absolute reduction of 13 mm for a 90% power with significance level 0.05. Based on this, each group required 71 participants, so the authors aimed to include 75 participants in each group.
A total of 151 women enrolled in the study between May 2021 and August 2021. Participants were randomized in a 1:1 fashion, resulting in 76 participants in the mepivacaine group and 75 in the placebo group. In the intention-to-treat analysis, the mean VAS score in the mepivacaine group at the time of IUD insertion was 53.9 mm (standard deviation [SD], 22.8 mm) vs. 67.2 mm (SD, 22.4 mm) in the placebo group, resulting in an absolute difference of 13.3 mm (95% confidence interval [CI], 5.75-20.87; P < 0.001). After adjusting for differences between individual providers, the mean VAS score in the mepivacaine group was 55.2 mm (SD, 26.5 mm) vs. 67.4 mm (SD, 25.6 mm) in the control group, with an absolute difference of 12.2 mm (95% CI, 4.85-19.62; P < 0.001). There was no difference in VAS pain scores 10 minutes post-IUD placement (37.3 mm; SD, 24.2 mm intervention vs. 42.4 mm; SD, 25.7 mm placebo).
In the post-procedure questionnaire, 93.3% (n = 70) of participants in the intervention group reported the placement pain as tolerated compared with 80.3% (n = 53) in the placebo group (P = 0.02). In addition, 86.5% (n = 64) in the mepivacaine group would choose an IUD again for contraception compared with 68.8% (n = 44) in the placebo group (P = 0.01). Lastly, 77% (n = 57) would recommend the method for pain relief in the mepivacaine group vs. 60.9% (n = 39) in the placebo group (P = 0.04).
Commentary
The results from this multicenter, double-blind, randomized controlled trial demonstrated that intrauterine instillation of mepivacaine improved patient pain scores compared to placebo, reducing pain by 13 mm on the 100 mm VAS. In addition, a post-procedure questionnaire also demonstrated that a higher percentage of participants receiving intrauterine mepivacaine compared to placebo reported the placement as tolerable and recommended this method of pain relief.
Intrauterine instillation of local anesthetic currently is not part of the standard of care in the United States.1,3 Several prior studies examining intrauterine instillation have not shown a significant difference in pain scores. In a randomized controlled trial of 86 women, intrauterine instillation of 10 mL of 1% mepivacaine compared with placebo resulted in no difference in VAS scores measured on a 10-cm scale.4
A randomized controlled trial published by Miles et al investigated the combination of 5 mL 2% lidocaine intrauterine instillation with oral naproxen compared with placebo and did not find a significant difference in mean pain scores on a 10-cm scale.5 An additional randomized controlled trial investigating intrauterine instillation of lidocaine found no difference in pain scores using a 0- to 9-point scale when comparing 1.2 mL 2% lidocaine vs. placebo.6
The method of measuring pain scores was different between these studies (two used the 10-cm VAS scale and another used a 0- to 9-point scale) compared with the current study, which used a 100-mm VAS scale. However, the discrepancy between studies highlights the ongoing need for evaluating whether intrauterine instillation of either mepivacaine or lidocaine may be an effective pain relief option. It also can be debated whether a 13-mm reduction is a clinically significant reduction in pain for patients. One downside of this technique is that most clinics do not stock hydrosonography catheters on a routine basis.
The 2024 practice guideline from the Centers for Disease Control and Prevention (CDC) does have modified recommendations pertaining to pain control at the time of IUD insertion.3 The CDC recommends a patient-centered discussion regarding pain expectations and management options. Currently, a paracervical block with lidocaine and topical lidocaine are proposed in the recommendations as potential pain management strategies by the CDC, although previous studies have shown mixed results.
As with any procedure, the consent process prior to an IUD insertion is extremely important. This process also can involve a discussion about pain expectations and pain relief options, which likely will differ between offices. A detailed discussion will allow for shared decision-making between the patient and provider about if an IUD is a good option. Ongoing studies are needed to know if intrauterine instillation of analgesics also should be discussed and offered at the time of IUD insertion.
Alexandra Morell, MD, is Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
References
1. Committee on Practice Bulletins – Gynecology, Long-Acting Reversible Contraception Work Group. Practice Bulletin No. 186: Long-acting reversible contraception: Implants and intrauterine devices. Obstet Gynecol. 2017;130(5):e251-e269.
2. Nguyen L, Lamarche L, Lennox R, et al. Strategies to mitigate anxiety and pain in intrauterine device insertion: A systematic review. J Obstet Gynaecol Can. 2020;42(9):1138-1146.e2.
3. Curtis KM, Nguyen AT, Tepper NK, et al. U.S. selected practice recommendations for contraceptive use, 2024. MMWR Recomm Rep. 2024;73(3):1-77.
4. Envall N, Lagercrantz HG, Sunesson J, Kopp Kallner H. Intrauterine mepivacaine instillation for pain relief during intrauterine device insertion in nulliparous women: A double-blind, randomized, controlled trial. Contraception. 2019;99(6):335-339.
5. Miles SM, Shvartsman K, Dunlow S. Intrauterine lidocaine and naproxen for analgesia during intrauterine device insertion: Randomized controlled trial. Contracept Reprod Med. 2019;4:13.
6. Nelson AL, Fong JK. Intrauterine infusion of lidocaine does not reduce pain scores during IUD insertion. Contraception. 2013;88(1):37-40.
In a randomized clinical trial of 151 women, intrauterine instillation of mepivacaine significantly reduced pain with intrauterine device insertion on visual analog scales both before (53.9 mm vs. 67.2 mm, respectively; P < 0.001) and after adjustment for individual provider variability (55.2 mm vs. 77.4 mm, respectively; P < 0.001), compared to placebo.
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