Background
Misperceptions persist that intrauterine device placement is related to pelvic infections and Chlamydia and gonorrhea testing results are needed prior to placement.
Objective
We sought to evaluate the relationship of Chlamydia and gonorrhea screening to pelvic infection for up to 2 years following placement of the levonorgestrel 52-mg intrauterine system.
Study Design
A total of 1751 nulliparous and multiparous females 16 to 45 years old enrolled in a multicenter trial designed to evaluate the efficacy and safety of a new levonorgestrel intrauterine system for up to 7 years. Participants had Chlamydia screening at study entry and yearly if they were age ≤25 years. Women also had baseline gonorrhea screening if testing had not been performed since starting their current sexual relationship. Those who changed sexual partners during the trial had repeated Chlamydia and gonorrhea testing. Intrauterine system insertion could occur on the same day as screening. Participants did not receive prophylactic antibiotics for intrauterine system placement. Investigators performed pelvic examinations after 12 and 24 months and when clinically indicated during visits at 3, 6, and 18 months after placement and unscheduled visits. Pelvic infection included any clinical diagnosis of pelvic inflammatory disease or endometritis.
Results
Most participants (n = 1364, 79.6%) did not have sexually transmitted infection test results available prior to intrauterine system placement. In all, 29 (1.7%) participants had positive baseline testing for a sexually transmitted infection ( Chlamydia , n = 25; gonorrhea, n = 3; both, n = 1); 6 of these participants had known results (all with Chlamydia infection) prior to intrauterine system placement and received treatment before enrollment. The 23 participants whose results were not known at the time of intrauterine system placement received treatment without intrauterine system removal and none developed pelvic infection. The incidence of positive Chlamydia testing was similar among those with and without known test results at the time of intrauterine system placement (1.9% vs 1.5%, respectively, P = .6). Nine (0.5%) participants had a diagnosis of pelvic infection over 2 years after placement, all of whom had negative Chlamydia screening on the day of or within 1 month after intrauterine system placement. Infections were diagnosed in 3 participants within 7 days, 1 at 39 days, and 5 at ≥6 months. Seven participants received outpatient antibiotic treatment and 2 (diagnoses between 6–12 months after placement) received inpatient treatment. Two (0.1%) participants had intrauterine system removal related to infection (at 6 days and at 7 months after placement), both of whom only required outpatient treatment.
Conclusion
Conducting Chlamydia and gonorrhea testing on the same day as intrauterine system placement is associated with a low risk of pelvic infection (0.2%). Over the first 2 years of intrauterine system use, infections are infrequent and not temporally related to intrauterine system placement. Pelvic infection can be successfully treated in most women with outpatient antibiotics and typically does not require intrauterine system removal. Women without clinical evidence of active infection can have intrauterine system placement and sexually transmitted infection screening, if indicated, on the same day.
Introduction
Although the intrauterine device (IUD) is one of the most effective methods of reversible contraception, some health care providers remain concerned that IUD use increases the risk of pelvic infection. Misconceptions about IUD use and infection are entrenched in common practice throughout the world, leading some providers to believe that infection risk is high and that sexually transmitted infection (STI) screening is needed prior to IUD placement. When providers require unnecessary tests for STI and make patients wait for IUD placement, barriers to effective contraception are created.
Research over the past 2 decades has begun to clarify the relationship among pelvic infection risk, STI, and IUD placement. Pelvic infection rates are very low among a screened population, including when the IUD is placed without test results. Even when Chlamydia or gonorrhea infection is present, the risk of pelvic infection is low with IUD insertion. Despite this evidence, we lack large, rigorously conducted, prospective trials performed in the United States with direct subject evaluation to evaluate pelvic infection rates shortly after and remote from insertion. Information from such studies can further elucidate risks and perhaps remove obstacles to immediate IUD insertion.
We recently reported the initial results of a Comprehensive Contraceptive Efficacy and Safety Study (ACCESS) of an intrauterine system (IUS) for regulatory approval of Liletta (Odyssea Pharma SPRL, Liège, Belgium; an Allergan affiliate). We conducted this large prospective study with the intent of IUS placement occurring with a same-day screen and insert model, meaning that participants would not have to wait for test results to return before IUS placement occurred. This report summarizes STI prevalence and pelvic infection rates in a large cohort of US women with multiple evaluations over a 2-year period.
Materials and Methods
This report represents a planned secondary analysis of data from the ACCESS IUS multicenter, phase III, open-label clinical trial of Liletta (Medicines360, San Francisco, CA; and Allergan, Irvine, CA), a levonorgestrel (LNG) 52-mg IUS. Details on the methods of this study have been reported previously. Briefly, investigators at 29 clinical sites in the United States invited healthy, nonpregnant, sexually active, nulliparous and parous females aged 16–45 years (inclusive) with regular menstrual cycles and who desired a hormonal IUS for contraception to participate. Although only monogamous women could enroll, they could change partners during the study and continue to participate. We excluded women with a history of pelvic inflammatory disease (PID) without a subsequent intrauterine pregnancy and those with a known cervical infection (cervicitis on examination or known positive Chlamydia or gonorrhea testing) or vaginal infection (trichomoniasis and symptomatic Candida or bacterial vaginosis) unless successfully treated and considered clinically cured for at least 7 days prior to study entry. A central or local institutional review board for each center approved the study. All participants signed written informed consent before study participation. Registration is Clinicaltrials.gov number NCT00995150 .
At the screening visit, an investigator performed a pelvic examination that included determination of active vaginal, cervical, and pelvic infection. All participants had Chlamydia testing at the screening visit and those who had no gonorrhea testing since starting their current sexual relationship also had gonorrhea testing. Enrollment and IUS placement could occur on the same day as the screening procedures without Chlamydia or gonorrhea testing results. Investigators applied an antiseptic solution to the vagina and cervix prior to IUS placement. Up to 2 placement attempts could occur within 30 days of signing consent. Investigators followed up participants who had a failed insertion only if an adverse event occurred during the placement attempt.
Follow-up visits occurred at 1, 3, and 6 months after IUS placement and every 6 months thereafter to assess adverse events, changes in sexual partner, medical history, concomitant medication use, and whether the IUS was still the primary method of contraception. Investigators performed a full pelvic examination annually or at any visit for which a reported symptom warranted an examination, and an abbreviated limited examination to confirm IUS presence at all other visits. Starting at month 9, telephone contacts occurred 3 months after each clinic visit to ask the same questions as at study visits. During the trial, participants who reported a change in sexual partner had Chlamydia and gonorrhea testing in accordance with the US Centers for Disease Control and Prevention (CDC) recommendations. All STI evaluations were performed by endocervical swab, vaginal swab, or urine nucleic acid amplification testing. Investigators treated participants with a positive Chlamydia or gonorrhea test from the screening evaluation or during the study with antibiotic regimens consistent with published CDC sexually transmitted disease treatment guidelines without requirement for IUS removal.
Data are presented on infection outcomes for 2 years post-IUS placement using descriptive statistics. We also performed a survival analysis to calculate the pelvic infection rate at 2 years. We used Fisher exact testing for comparisons of proportions. Only those participants with successful IUS placement are included in all analyses. Pelvic infection included any clinical diagnosis of endometritis or PID by a study or nonstudy health care provider during clinical trial participation. Investigators at each study site assessed pelvic infection severity (mild, moderate, severe, life-threatening) in accordance with Food and Drug Administration standards for clinical trials and the relationship to the IUS or to the placement or removal procedure.
Materials and Methods
This report represents a planned secondary analysis of data from the ACCESS IUS multicenter, phase III, open-label clinical trial of Liletta (Medicines360, San Francisco, CA; and Allergan, Irvine, CA), a levonorgestrel (LNG) 52-mg IUS. Details on the methods of this study have been reported previously. Briefly, investigators at 29 clinical sites in the United States invited healthy, nonpregnant, sexually active, nulliparous and parous females aged 16–45 years (inclusive) with regular menstrual cycles and who desired a hormonal IUS for contraception to participate. Although only monogamous women could enroll, they could change partners during the study and continue to participate. We excluded women with a history of pelvic inflammatory disease (PID) without a subsequent intrauterine pregnancy and those with a known cervical infection (cervicitis on examination or known positive Chlamydia or gonorrhea testing) or vaginal infection (trichomoniasis and symptomatic Candida or bacterial vaginosis) unless successfully treated and considered clinically cured for at least 7 days prior to study entry. A central or local institutional review board for each center approved the study. All participants signed written informed consent before study participation. Registration is Clinicaltrials.gov number NCT00995150 .
At the screening visit, an investigator performed a pelvic examination that included determination of active vaginal, cervical, and pelvic infection. All participants had Chlamydia testing at the screening visit and those who had no gonorrhea testing since starting their current sexual relationship also had gonorrhea testing. Enrollment and IUS placement could occur on the same day as the screening procedures without Chlamydia or gonorrhea testing results. Investigators applied an antiseptic solution to the vagina and cervix prior to IUS placement. Up to 2 placement attempts could occur within 30 days of signing consent. Investigators followed up participants who had a failed insertion only if an adverse event occurred during the placement attempt.
Follow-up visits occurred at 1, 3, and 6 months after IUS placement and every 6 months thereafter to assess adverse events, changes in sexual partner, medical history, concomitant medication use, and whether the IUS was still the primary method of contraception. Investigators performed a full pelvic examination annually or at any visit for which a reported symptom warranted an examination, and an abbreviated limited examination to confirm IUS presence at all other visits. Starting at month 9, telephone contacts occurred 3 months after each clinic visit to ask the same questions as at study visits. During the trial, participants who reported a change in sexual partner had Chlamydia and gonorrhea testing in accordance with the US Centers for Disease Control and Prevention (CDC) recommendations. All STI evaluations were performed by endocervical swab, vaginal swab, or urine nucleic acid amplification testing. Investigators treated participants with a positive Chlamydia or gonorrhea test from the screening evaluation or during the study with antibiotic regimens consistent with published CDC sexually transmitted disease treatment guidelines without requirement for IUS removal.
Data are presented on infection outcomes for 2 years post-IUS placement using descriptive statistics. We also performed a survival analysis to calculate the pelvic infection rate at 2 years. We used Fisher exact testing for comparisons of proportions. Only those participants with successful IUS placement are included in all analyses. Pelvic infection included any clinical diagnosis of endometritis or PID by a study or nonstudy health care provider during clinical trial participation. Investigators at each study site assessed pelvic infection severity (mild, moderate, severe, life-threatening) in accordance with Food and Drug Administration standards for clinical trials and the relationship to the IUS or to the placement or removal procedure.
Results
Of the 1751 women enrolled, 1714 (97.9%) had successful placement and are included in this analysis. Demographic characteristics appear in Table 1 . Overall, 1553 (90.6%), 1401 (81.7%), and 1157 (67.3%) participants continued IUS use at 6 months, 1 year, and 2 years, respectively.
| Variable | n (%) or mean ± SD |
|---|---|
| Age, y | 27.3 ± 5.7 |
| <25 y | 621 (36.2) |
| Ethnicity | |
| Hispanic or Latina | 251 (14.6) |
| Race a | |
| American Indian or Alaska Native | 21 (1.2) |
| Asian | 67 (3.9) |
| Black or African American | 225 (13.2) |
| Native Hawaiian or other Pacific Islander | 6 (0.4) |
| White | 1342 (78.5) |
| Multiple races indicated | 49 (2.9) |
| Body mass index, kg/m 2 a | 26.9 ± 6.8 |
| Obese, ≥30.0 | 433 (25.3) |
| Partner status | |
| Lives with partner | 1003 (58.5) |
| Parity | |
| Nulliparous | 986 (57.5) |
| Marital status | |
| Never married | 1081 (63.1) |
| Married | 478 (27.9) |
| Divorced | 123 (7.2) |
| Separated | 29 (1.7) |
| Widowed | 3 (0.2) |
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