Delayed pregnancy detection and return to fertility with extended levonorgestrel-containing oral contraceptives: A real world setting cohort study

Purpose: As part of the European risk management plan of a 91-day extended levonorgestrel-containing combined oral contraceptive (COC_LNG ), a study was performed to assess its safety. This analysis was conducted to examine delayed pregnancy detection and return to fertility with extended combined oral contraceptives (COC).

Methods: We conducted a retrospective cohort study in new users of 91-day COC_LNG or 28-day COC_LNG within a US-based healthcare claims database from 2006 to 2017. Delayed pregnancy detection during current COC_LNG exposure was defined as the time between estimated pregnancy start and first prenatal care encounter. Additionally, the time between estimated pregnancy start and COC_LNG discontinuation was measured. To measure return to fertility, pregnancy rates were estimated among females who discontinued treatment. 91-day COC_LNG users were propensity score-matched to 28-day COC_LNG users. Hazard ratio for pregnancy was calculated using Cox proportional hazards models.

Results: The 91-day and 28-day COC_LNG users had 25 593 and 76 586 treatment episodes, respectively. The median time to pregnancy detection was 64.5 and 61.0 days (p = 0.24) in users of 91-day COC_LNG and 28-day COC_LNG . The median exposure time to treatment after estimated pregnancy start was 54.0 and 38.0 days (p < 0.01). In the fertility analysis, pregnancy rates were 54.82 (95% CI, 50.05-59.93) and 69.30 (95% CI, 64.98-73.82) per 1000 person-years in extended COC_LNG discontinuers and 28-day COC_LNG discontinuers. The adjusted hazard ratio of pregnancy was 0.77 (95% CI, 0.69-0.85).

Conclusions: Small differences were observed for pregnancy rates and delayed pregnancy detection between 91-day extended COC_LNG and 28-day COC_LNG , which may be related to the longer days' supply of extended COC_LNG . Differences in the fertility analysis may be related to unmeasured residual confounding.