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

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.