Conception rates in women desiring pregnancy after levonorgestrel 52 mg intrauterine system (Liletta®) discontinuation.

OBJECTIVE: Evaluate reproductive function in nulligravid and gravid women after levonorgestrel 52 mg intrauterine system (IUS) discontinuation based on time to pregnancy. STUDY DESIGN: We evaluated women participating in the ACCESS IUS multicenter, Phase 3, open-label clinical trial of the Liletta(®) levonorgestrel 52 mg IUS who discontinued the IUS within 60 months of use and desired pregnancy. Study staff contacted participants every three months after IUS discontinuation for up to 12 months to determine whether pregnancy occurred. We excluded women who opted to stop attempting to conceive before 12 months. We evaluated 12-month conception rates in participants 16-35 years at IUS placement, comparing dichotomous outcomes using Fisher's exact test. We performed a multivariable analysis to assess the association of baseline characteristics, age at discontinuation, duration of IUS use, and positive sexually transmitted infection testing during IUS use with conception. RESULTS: Among 165 women who attempted to conceive, 142 (86.1%) did so within 12 months with a median time to conception of 92 days. The 12-month conception rates did not differ between nulligravid (66/76 [86.8%]) and gravid (76/89 [85.4%]) women (p = 0.83) and nulliparous (78/90 [86.7%]) and parous (64/75 [85.3%]) women (p = 0.83). In multivariable analysis, only obesity (aOR 0.3 [95% CI 0.1-0.8]) was associated with ability to conceive. CONCLUSIONS: After levonorgestrel 52 mg IUS discontinuation, women have rapid return of fertility in the year post-removal. Fertility rates after IUS removal do not vary based on gravidity, parity, age at discontinuation, or duration of IUS use. IMPLICATIONS: This contemporary IUS study included a large population of nulligravid and nulliparous women. IUS use over many years does not effect spontaneous fertility after IUS discontinuation, regardless of gravidity or parity. Providers and patients should have no concern about the impact of IUS use on future fertility.

Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system.

OBJECTIVE: To assess 6-year contraceptive efficacy and safety of a levonorgestrel 52 mg intrauterine system (IUS). STUDY DESIGN: We assessed pregnancy rates through 72 months in women aged 16-35 years at enrollment and safety in all participants (aged 16-45 years, n = 1751) in an ongoing 10-year phase-3 trial. RESULTS: Over six years, nine pregnancies occurred (none in year 6) for a life-table pregnancy rate of 0.87 (95% CI 0.44-1.70). Adverse event rates remain low through 6 or more years of use. Two expulsions occurred in year 6. CONCLUSION: This levonorgestrel 52 mg IUS is a highly effective and safe contraceptive over 6 years of use. IMPLICATIONS: The levonorgestrel 52 mg IUS shows high 6-year contraceptive efficacy and a low rate of adverse events through 6 or more years of use.

Ethical issues in microbicide clinical trials for HIV prevention.

Women account for half of new infections with HIV annually. Heterosexual transmission is the most common route of infection in resource limited settings (RLS). An effective microbicide would help decrease transmission of HIV and potentially enable women to have more control in sexual relationships. Research into microbicides is done predominantly in RLS. In addition, there will be different issues and challenges to consider with respect to rectal microbicide use in men. There exist several ethical issues around microbicide development and clinical research which we explore in this review. Respect for persons, including autonomy and protection of vulnerable populations, beneficence, and justice are explored as they relate to microbicide research. Improving standards of care in RLS, trial design, and informed consent are discussed in more detail. Special populations including pregnant women, adolescents, and men who have sex with men are considered in more detail. A multipronged approach to HIV prevention will be necessary to have an impact on HIV prevention. A continued discussion around ethical issues in regard to study design, interpretation of results and implementation of compounds brought to market will remain critically important.