Ovarian reserve markers after discontinuing long-term use of combined oral contraceptives

Abstract

Research question: How early do the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) normalize after discontinuation of the long-term use of combined oral contraceptives (COC). Design: This was a prospective cohort study of 68 women with a history of long-term COC use. Serum AMH concentrations, ovarian volume and AFC were measured during COC use and serially in a 4-month period after discontinuing COC: 1 and 2 weeks after discontinuation, and on cycle day 2–5 during three consecutive menstrual cycles. Changes in AMH and AFC were investigated using linear mixed models of repeated measurements adjusted for relevant covariates. Results: Mean age was 29.4 years and mean duration of COC use 8.0 years. Baseline median AMH concentrations during COC use of 13 pmol/l (interquartile range [IQR] 8.4–22 pmol/l) increased to a median of 22.5 pmol/l (IQR 11–37 mol/l) 3 months after discontinuation. The estimated average increase was 53% (95% confidence interval [CI] 1.40–1.68, P < 0.001). AFC increased from a median value of 17 (IQR 11–25) to 24 (IQR 17–34). The estimated average increase was 41% (95% CI 1.30–1.52, P < 0.001). Ovarian volume increased from 2.4 to 5.8 ml (P < 0.001). The ovarian reserve markers increased continuously from baseline measurements until 2 months after discontinuation. Thereafter a plateau was reached. Conclusion: After discontinuation of COC, AMH increased by 53% and AFC by 41%, with values returning to normal within 2 months. This study provides clinicians with the highly relevant knowledge that AMH and AFC can be measured 2 months after discontinuation of COC without having to account for their influence.