To assess the Pearl Index for risk of ectopic pregnancy in women using levonorgestrel-releasing intrauterine systems (LNG-IUS) with hormonal reservoirs of 13.5 mg, 19.5 mg, or 52 mg.
Methods
This was a retrospective cohort study. Women diagnosed with an ectopic pregnancy in Stockholm County, Sweden, between January 1, 2014, and December 31, 2019, were identified through the electronic medical record system. The final analysis included 2,252 cases of ectopic pregnancy. Information on age, reproductive and medical history, as well as current use of contraception was retrieved. The time of intrauterine device (IUD) insertion before ectopic pregnancy and the numbers of sold LNG-IUS during the study period were used to calculate the incidence rate for ectopic pregnancy during use per 100 woman-years (Pearl Index).
Results
Among women with an ectopic pregnancy diagnosis, 105 presented with a known type of hormonal IUD in situ, of whom 94 were included in the calculations of the Pearl Index. The estimated Pearl Index for ectopic pregnancy was 0.136 (95% CI 0.106-0.176) for the LNG-IUS 13.5-mg, 0.037 (95% CI 0.021-0.067) for the LNG-IUS 19.5-mg, and 0.009 (95% CI 0.006-0.014) for the LNG-IUS 52-mg. With the 52-mg LNG-IUS as referent, the relative risk (RR) for ectopic pregnancy was higher during the first year for LNG 13.5-mg (RR 20.59, 95% CI 12.04-35.21), and for both 13.5-mg (RR 14.49, 95% CI 9.01-23.3) and 19.5-mg (RR 4.44, 95% CI 1.64-12.00) during the total study period.
Conclusion
The absolute risk of ectopic pregnancy during the use of LNG-IUS at any doses was low. The results show that the lower the dose of the IUD, the higher the risk of an ectopic pregnancy. Higher-dose LNG-IUS should be considered when providing contraceptive counseling to a woman with known risk factors for ectopic pregnancy who are considering a hormonal IUD.
PMID 35852273 35852273 DOI 10.1097/AOG.0000000000004846 10.1097/AOG.0000000000004846 Elgemark et al. 2022, Elgemark 2022
Cite this article
Elgemark, K., Graner, S., McTaggart, J., Ramirez Löfström, J., Sörensen, D., Envall, N., & Kopp Kallner, H. (2022). The 13.5-mg, 19.5-mg, and 52-mg Levonorgestrel-Releasing Intrauterine Systems and Risk of Ectopic Pregnancy.. Obstetrics and gynecology, 140(2), 227-233. https://doi.org/10.1097/AOG.0000000000004846
Elgemark K, Graner S, McTaggart J, Ramirez Löfström J, Sörensen D, Envall N, Kopp Kallner H. The 13.5-mg, 19.5-mg, and 52-mg Levonorgestrel-Releasing Intrauterine Systems and Risk of Ectopic Pregnancy.. Obstetrics and gynecology. 2022;140(2):227-233. doi:10.1097/AOG.0000000000004846
To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma. All Finnish women aged 30-49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994-2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population. A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35-0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05-0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45-0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28-0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49-0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13-1.25; 1,542 observed compared with 1,292 expected cases). The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected incidence of breast cancer. II.
Michaelsen MP et al., 2025·BJOG: An International Journal of Obstetrics and Gynaecology
To study the association between previous use of levonorgestrel intrauterine system (LNG-IUS) and endometrial thickness (EMT) in women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Multicentre historical cohort study. Eight Danish public and private fertility clinics. 12786 women aged 18-46 years contributing with an EMT measurement from 22 464 different IVF/ICSI treatment cycles between 2000 and 2021. Exposure was previous use of LNG-IUS, combined oral contraceptive pills (OCPs), progestogen-only pills (POPs), no/other contraception or combined, cumulated use of contraception when more contraceptives had been used during the inclusion period. LNG-IUS use was categorised into 0-3 years, >3-6 years, >6-9 years and >9 years. Mixed effect logistic regression adjusted for age, BMI, smoking, educational level, total FSH dose and fertility clinic was used. EMT (< 7 mm vs >= 7 mm). Statistically significantly higher odds of EMT >= 7 mm were found for OCPs [OR 3.53 (95% CI 1.29-9.65)], POPs [OR 6.43 (95% CI 1.45-28.63)] and no/other contraception [OR 6.67 (95% CI 2.37-18.74)] relative to LNG-IUS in IVF/ICSI cycles. All duration categories of ever use of LNG-IUS were associated with significantly lower odds of EMT >= 7 mm compared to no/other contraception. Previous use of LNG-IUS was associated with decreased endometrial growth in women undergoing IVF/ICSI.
To examine trends in national reporting of broken intrauterine devices (IUDs). We enumerated IUD device "breakage" reports in the Food and Drug Administration Adverse Event Reporting System from inception (1998) until February 2022. We explored associations of breakage with IUD type (copper versus hormonal), year reported, reporter (consumer versus clinician), and patient characteristics (age and weight). We identified 4144 breakage reports for copper versus 2140 for hormonal IUDs. Among the 170,215 adverse events reported, breaks were disproportionately reported for copper (9.6%) versus hormonal (1.7%) IUDs. National pharmacovigilance data suggests disproportionate breakage in copper versus hormonal IUDs though the true prevalence of breaks cannot be calculated from this dataset.
Peebles K et al., 2021·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·
Open Access
Limited evidence suggests that the nonhormonal contraceptive copper intrauterine device (Cu-IUD) may increase bacterial vaginosis (BV) risk, possibly due to increased volume and duration of menses, a common side effect of Cu-IUD use. Although increases in bleeding typically resolve within 6-12 months following initiation, evaluations of the association between Cu-IUD and BV have not included more than 6 months of follow-up. This secondary analysis of a human immunodeficiency virus type 1 prevention trial included 2585 African women ages 18-45 followed for up to 33 months. Women reported contraceptive use each month. BV was evaluated by Nugent score in 6-monthly intervals and, if clinically indicated, by Amsel criteria. Andersen-Gill proportional hazards models were used to (1) evaluate BV risk among Cu-IUD users relative to women using no/another nonhormonal contraceptive and (2) test changes in BV frequency before, while using, and following Cu-IUD discontinuation. BV frequency was highest among Cu-IUD users at 153.6 episodes per 100 person-years (95% confidence interval [CI]: 145.2, 162.4). In adjusted models, Cu-IUD users experienced 1.28-fold (95% CI: 1.12, 1.46) higher BV risk relative to women using no/another nonhormonal contraception. Compared to the 6 months prior to initiation, BV risk was 1.52-fold (95% CI: 1.16, 2.00) higher in the first 6 months of Cu-IUD use and remained elevated over 18 months of use (P < .05). Among women who discontinued Cu-IUD, BV frequency was similar to pre-initiation rates within 1 year. Cu-IUD users experienced elevated BV risk that persisted throughout use. Women and their providers may wish to consider BV risk when discussing contraceptive options.