Systematic review of factors predictive of unfavourable vaginal bleeding in women of reproductive age using the contraceptive etonogestrel implant

Introduction: This systematic review sought predictors of unfavourable bleeding profiles in women using the etonogestrel contraceptive implant. Unfavourable bleeding is common and a leading cause of requests for removal. Methods: We included randomised controlled trials (RCTs), and prospective and retrospective cohort studies from 1998 to October 2022. Inclusion criteria were healthy women using etonogestrel for contraception. Papers not in English were excluded as were ongoing or incomplete studies. We searched Pubmed, Pubmed Central, MEDLINE (Web of Science & Ovid), Cochrane library, CINAHL Plus, WHO (HINARI), Open Grey and Greynet.org. Risk of Bias was assessed using ROB2 IRPGv9 for RCTs and ROBINS‐I for non‐RCTs. We conducted a narrative analysis. Results: We included 13 studies. Lower body mass index (BMI), younger age, parity and smoking status were statistically, significantly associated with unfavourable bleeding patterns in one or more studies. No studies reported post‐partum status having a significant association with unfavourable bleeding. The available data was too limited and too heterogeneous to perform a robust meta‐analysis. Discussion: Heterogeneity in reported outcomes and timescales limited the accuracy of synthesis. Risk of bias was moderate to serious in non‐RCTs due to baseline differences and missing or imputed data. The protective effect of higher BMI for unfavourable bleeding is in keeping with previous reviews and studies and is a clinically important finding.