Intrauterine devices (IUDs) are among the most effective forms of reversible contraceptive methods. Numerous studies demonstrate their safety and efficacy.1,2 Despite this, uptake among adolescents and young women in the United States remains low.3–5 A larger proportion of this population group uses oral contraceptive pills, which are 20 times less effective than IUDs.2 This preference for less effective contraceptive methods largely explains the higher rate of unintended pregnancies among adolescents and young women compared with older women.6
A barrier to use of IUD devices among adolescents and young women is fear of pain during insertion.7–10 Among pharmacologic therapies, only amine-anesthetics, like lidocaine, have been shown to be effective at reducing pain during IUD insertion.11–13 Application of these findings to adolescents and young women in clinical practice is difficult because most studies exclude adolescents younger than age 18 years, include small numbers of women ages 18–24 years, or include only parous adolescents and young women.1,11–16 The most effective method for pain control during IUD insertion in nulliparous adolescent and young women is therefore unknown.11,15
We sought to estimate the effectiveness of a 1% lidocaine paracervical nerve block on pain during IUD insertion compared with a sham block in nulliparous adolescents and young women. We hypothesized that adolescents and young women who received the lidocaine block would report less pain compared with those receiving a sham block. Because prior studies found that pain increases with device size, we focused on pain reported during insertion of the smallest IUD available on the U.S. market.17
MATERIALS AND METHODS
This was a multisite, single-blind, sham-controlled randomized trial conducted at three clinics in Philadelphia, Pennsylvania, from March 2015 to July 2016 that involved one study visit (protocol available by request). The trial was registered with ClinicalTrials.gov (NCT# NCT02352714).
Institutional review board approval was obtained from the Children's Hospital of Philadelphia, Hospital of the University of Pennsylvania, and Thomas Jefferson University, all of which performed study visits. Approval was also obtained from AccessMatters, which funds Title X clinics in Pennsylvania, allowing flyers to be posted in Title X clinics that refer adolescents to Children’s Hospital of Philadelphia for IUD insertions. Adolescents and young women presenting to a study site requesting a hormonal IUD were asked by a clinician if they were interested in talking with research staff about the study. At nonenrolling sites, interested adolescents and young women who saw a recruitment flyer called the study coordinator who described the study and scheduled a study visit.
Eligible participants were aged 14–22 years, nulliparous, not pregnant currently or in the prior 6 weeks, interested in the Skyla IUD (13.5-mg levonorgestrel IUD), and English-speaking. The cutoff of 22 years, rather than 24 years, was chosen to minimize the number of older, young adult women.
Patients were excluded if they did not meet medical eligibility criteria for an IUD,18 had a contraindication to taking amino-amide anesthetics or nonsteroidal anti-inflammatory agents, were unwilling to be randomized, were at high risk for pregnancy based on clinical history,19 used narcotics or benzodiazepines in the prior 24 hours, previously used an IUD, or had prior unsuccessful IUD insertion. Participants could enroll at a later date if inclusion criteria were not initially met. Written informed consent was obtained from all participants, regardless of age, because adolescents 13 years and older in Pennsylvania can legally consent for reproductive services and because requiring parental permission for study participation would have compromised confidentiality.
Participants completed a questionnaire assessing demographic characteristics and medical and reproductive histories. Participants completed the four-item Patient Health Questionnaire-4, which consists of a two-item depression scale and a two-item anxiety scale. Scores greater than 3 suggest but are not diagnostic for clinical depression and anxiety, respectively.20 Participants who score high on these measures were referred to the clinician performing their IUD insertion for clinical screening and management.
Before randomization, all participants received 800 mg ibuprofen orally at least 20 minutes before the procedure to reduce postprocedure pain.12 Randomization was performed by a research coordinator in Research Electronic Data Capture software using block sizes of four with stratification by age (14–17 years or 18–22 years), race, and recruitment site after completion of the demographic questionnaire. The research coordinator informed nonresearch clinical personnel of the randomization group and the clinical personnel prepared the procedure trays, per the clinic's protocol. The clinician was informed of the group allocation once these steps were completed.
Only patients were blinded to group assignment. Research staff were not blinded because they did not enter the primary outcome data; rather, they held an iPad in front of the patient during the IUD insertion procedure to facilitate the patient entering data. Data entry was a two-step process: patients tapped the line indicating their pain level and then confirmed that the value generated was accurate before the data were sent securely to the database. Blinding of patients was ensured by having a curtain cover the instrument tray so procedure supplies could not be seen. The curtain was positioned so patients could not see around it as supplies were handed to the clinician. Blinding was also facilitated by the nature of the procedure because patients are in the dorsal lithotomy position with the supply tray at their feet making it difficult for patients to view the contents of the tray.
The lidocaine block group received 1 mL of 1% lidocaine at the tenaculum site and 4.5 mL at 4 o'clock and 8 o'clock at the cervicovaginal junction. For the sham block group, pressure was applied to these same three sites with the unbroken, wood end of a cotton-tipped applicator to depress the vaginal epithelium 1 mL. There was a 3-minute delay after administering the lidocaine and sham block before IUD insertion to allow onset of action for the lidocaine. Intrauterine device insertion followed the manufacturer's instructions and included sounding the uterus before insertion of the IUD. All devices were inserted by an experienced health care provider who was an attending physician or family planning fellow.
After IUD insertion, clinicians completed a questionnaire that assessed procedural elements including uterine size, uterine sounding depth, need for dilation, need for ultrasound guidance, and perceived benefit of the pain intervention as well as adverse events (vasovagal symptoms, prolonged cervical or tenaculum site bleeding, uterine perforation, or side effects from the lidocaine block [eg, metallic taste, tinnitus, or patient-reported cardiac arrhythmia]). One item asked whether the patient's general affect seemed “pleasant and appropriately engaging” or “anxious.” This item was used to assess health care provider–rated patient anxiety. After insertion, a postprocedure questionnaire was administered to participants by a research coordinator to rate their satisfaction with and discomfort during the procedure. Questions and response options were read by a study coordinator while the patient viewed the screen and selected an option.
Participants who completed all study activities received $50 for their time. Devices were provided free of change by the study funder. Participants' insurance was billed for the clinical procedure fee. Clinicians were not compensated for performing the IUD insertion nor for completing the questionnaire.
Participants were asked to rate their pain using a 100-mm visual analog scale (VAS) immediately after seven procedural steps: 1) baseline (after placement in the dorsal supine position but before lithotomy positioning) and immediately after placement of the 2) speculum, 3) tenaculum, 4) block, 5) uterine sound, and 6) IUD, and 7) 5 minutes after speculum removal. Participants rated their pain using an iPad by touching a line anchored from no pain (0 mm) to worst pain in my life (100 mm). All data entry was facilitated by a research coordinator at each of the three study sites with the accuracy confirmed by authors (C.S., J.F.G.-E., and A.Y.A.). The primary outcome was pain reported using the VAS at a single time point: immediately after IUD insertion (controlling for the baseline VAS score by including this variable in the unadjusted model).
An independent data and safety monitoring board periodically reviewed blinded data. The Children’s Hospital of Philadelphia Office of Compliance and Regulatory Affairs conducted a protocol assessment and adherence to Good Clinical Practice guidelines after the 10th participant was enrolled. The project coordinator conducted site visits quarterly at each recruitment site to monitor protocol compliance and assess compliance with data storage and management procedures. A deidentified data set was provided to an independent statistician from Westat Corporation, a private statistical analysis corporation, to perform data verification and query resolution. The decision to submit the manuscript for publication was made by the steering committee and was approved by the sponsor, Bayer HealthCare Pharmaceuticals Inc. The sponsor had no role in the data analysis or preparation of the manuscript.
The sample size was estimated using a two-sided test and assumed a SD of 28 mm, a 20-mm difference in VAS scores, an α of 0.05, and 90% power, which yielded a sample of 43 participants per treatment group. Prior research has shown that a 20-mm difference in VAS scores is clinically significant across various pain disorders.21,22 Because prior studies were underpowered as a result of unanticipated larger SDs, we increased our sample size to 46 per group to prevent being underpowered. The sample size was also increased in anticipation of using nonparametric testing, because the primary outcome was evaluation of a difference in medians. Recruitment continued until 95 women were enrolled because devices were shipped in five-unit boxes, meaning 95 rather than 92 devices were received. Because the devices could not be used for nonstudy patients, the additional recruitment averted the need to destroy the three remaining devices.
Between-group differences in the baseline characteristics for the treatment groups were compared using χ2 test for proportions, Fisher exact test for small numbers, and Wilcoxon rank-sum tests for data that were not normally distributed. To address the primary outcome, the median VAS score after IUD insertion with 95% CIs was calculated and compared between treatment groups, adjusting for baseline pain and baseline differences in covariates. Adjusted analysis was performed using a rank analysis of covariance model with median VAS score at IUD insertion as the dependent variable and treatment group as the independent variable. Covariates included baseline VAS score, recruitment site, demographics, and experience with gynecologic examinations.
As a secondary analysis, the median VAS score across the six assessments was compared between treatment groups using rank analysis of covariance. To examine whether VAS scores reported at each step of the procedure (dependent variable) differed between the treatment groups (independent variable), mixed-effect modeling using generalized estimation equations was used with patient included as a random effect and VAS assessment, treatment group, recruitment site, and baseline VAS score as fixed effects along with the interaction term for (VAS assessment)×(study group). An intention-to-treat analysis was performed that included all randomized women. Two-tailed P values <.05 were considered significant. Analyses were completed with SAS 9.3.
Ninety-five participants enrolled and were included in the analysis using an intention-to-treat approach. Forty-seven were randomized to the lidocaine block group and 48 to the sham block (Fig. 1). All patients had successful IUD insertion. No adverse events occurred in either group. Four women required dilation: three in the treatment group and one in the sham block group (P=.36). Three women were noted to have cervicitis on examination so their IUD insertion was postponed until after treatment. They were then reenrolled and had their IUD placed after eligibility was reconfirmed. Only data from their second, completed, visit are included.
Baseline characteristics are shown in Table 1. Almost half were white (44%) and one third were black (36%). Most were aged 18–22 years (80%), never married (96%), had some college education (67%), and were privately insured (65%). Most also reported having had sex at least once (92%) and prior contraceptive use (79%); few reported current contraceptive use (43%). Experiences with gynecologic examinations varied with 59% reporting a prior visual inspection of the vulva, 52% a bimanual examination, 44% a speculum examination, and 31% a Pap smear. Baseline characteristics were similar in both treatment groups (Table 1).
Figure 2 shows the results of our primary outcome analysis. The median VAS score immediately after IUD insertion was lower in the lidocaine block group compared with the sham block (30.0 mm [95% CI 20.0–58.0] compared with 71.5 mm [95% CI 66.0–82.0], P<.001). These between-group differences remained significant in the adjusted analyses (P<.001).
As secondary outcomes, the median VAS score averaged across the six procedural steps (controlling for the baseline VAS score) was compared between treatment groups. In addition, assessments were made to compare within-group and between-group differences in the VAS scores reported at each procedural step. Figure 2 shows between-group differences in the median VAS score at each procedural step. When comparing between the lidocaine block and sham block groups, there was no statistically significant difference in the median VAS scores at baseline or speculum placement. Visual analog scale scores were significantly higher in the sham block group compared with the lidocaine block group after tenaculum placement and remained significantly higher at all subsequent procedural steps, including 5 minutes after speculum removal. The interaction term for the interaction between the VAS assessment variable and the study group was significant (P<.001).
The within-group comparison for the sham block group showed that the median VAS scores were significantly higher at every procedural step except tenaculum placement compared with placement of the sham block (Table 2). The within-group comparison for the lidocaine block group showed that median VAS scores were significantly higher at speculum placement compared with baseline (P<.001) and at IUD placement compared with 5 minutes after the procedure was completed. The median difference between VAS scores measured at block placement as compared to at IUD placement was significantly higher in the sham block group (P<.001) compared with the lidocaine block group, but no difference was noted in the median VAS scores between these two procedural steps in the lidocaine block group (P=.31).
No covariates were significantly associated with pain after IUD insertion. Anticipated pain was positively associated with pain at IUD insertion (P<.001), but this association did not differ by treatment group (P=.33). The median pain score at IUD insertion did not differ by age. Adolescents aged 14–17 years reported a median VAS pain score of 57.8 (interquartile range 63.0) compared with 54.1 (interquartile range 50.0) among young women aged 18–22 years (P=.44). Satisfaction with the IUD insertion procedure also did not differ between the lidocaine block and sham block groups (83% compared with 71%, P=.16).
Analysis of the secondary outcomes found that the VAS scores across all six VAS assessments were lower in the lidocaine block group compared with the sham block group in the unadjusted (27.7 [95% CI 16.0–40.2] compared with 53.9 [95% CI 44.0–57.8], P<.001) and adjusted ranked analysis of covariance (P<.001).
We examined whether a 1% lidocaine paracervical nerve block reduced pain among nulliparous women aged 14–22 years during insertion of a hormonal IUD compared with a sham block involving pressure at the paracervical block sites performed with a cotton-tipped applicator. Compared with the sham block group, the lidocaine block group reported less pain with IUD insertion. The median pain reported during the entire procedure was also significantly less in the lidocaine block group compared with the sham block group. When pain reported at each step of the procedure was compared, VAS pain scores were lower in the lidocaine block group compared with the sham block group from tenaculum placement through all subsequent assessment points.
Because low rates of IUD use among young women are largely driven by concerns about pain during the procedure, this study fills an important gap in the literature.7–9 By demonstrating the effectiveness of a pain management option for young, nulliparous women that is easy to perform, our findings could reduce patient concerns about pain and increase IUD use, which is known to reduce rates of unintended pregnancies, births, and abortions in this population.23
This study overcomes some methodologic limitations of prior studies. For example, the current study was adequately powered to detect a difference between the treatment groups, included a control group, included only one IUD (rather than multiple devices of varying sizes), and had a clear procedure for randomization and blinding.11–15,24
Although women in this study who received a lidocaine block reported lower VAS scores than the sham block group, overall satisfaction with the IUD insertion procedure did not differ. This is an important finding given that when a lidocaine block is performed, IUD procedures take longer and may be associated with more side effects and higher cost.24 The risks associated with performing a lidocaine block must be carefully weighed against the potential pain reduction.
This study has several key strengths. This was an adequately powered study that focused on adolescents and young women, an understudied but important population of IUD users. The study included adolescents and young women receiving care in both adult and adolescent settings and found no differences based on site. We included only nulliparous women, who represent those at higher risk for experiencing pain during IUD insertion.25 Our findings may apply to older, nulliparous women14,24; however, additional research is needed to confirm the effect of a paracervical block in this population given the mixed findings in prior studies. These differences likely stem from differences in the control groups used and the inclusion of parous patients in prior studies.
Our sample was largely white, highly educated, insured, young adults from an urban setting with low rates of IUD use who were using the smallest IUD currently available. Given these limitations, a number of important questions regarding IUD use in adolescents and young women remains unanswered. The effectiveness of a paracervical block among adolescents specifically and among higher risk populations (eg, uninsured, homeless, or seeking confidential contraceptive services), those using larger IUDs, or from settings with higher rates of IUD use26 (and therefore more positive attitudes toward IUD use and potentially lower rates of preprocedure anxiety) deserve further exploration. Another key limitation of our study design is that research staff who facilitated collection of the primary outcome and postprocedure participant data were not blinded to group assignment.
The 1% paracervical nerve block may be useful for reducing patient-reported pain during IUD insertion, but its use must be balanced with a careful consideration of the risks associated with this nerve blockade.
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