Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes

Abstract

Background: Anti-Müllerian hormone (AMH) is a widely used marker for estimating ovarian reserve, and it may predict response to ovarian stimulation. While AMH is considered a stable, cycle-independent marker, studies have shown it can exhibit significant fluctuations based on factors like age, reproductive stage, and menstrual cycle phase. The fluctuations in AMH levels can make it challenging to predict individual responses accurately, particularly when the AMH is not measured in the COS cycle. The aim of this study was to assess the inter-cycle variability of serum AMH levels in two consecutive menstrual cycles and their correlation with response to controlled ovarian stimulation outcome in the latter.

Methods: In this single-centre retrospective cohort study, data of normal and low responder patients who underwent intracytoplasmic sperm injection following a GnRH antagonist cycle at a university hospital infertility clinic between January 2022 and December 2023 were reviewed. Serum AMH levels were measured in the early follicular phase of two consecutive menstrual cycles with Elecsys-AMH Roche^® system (Roche Diagnostics, Meylan, France). Correlations between AMH levels and controlled ovarian stimulation outcomes, including total oocyte and mature oocyte (MII) counts, were assessed. The study included normal and poor responder women to maintain data integrity.

Results: A total of 79 patients were included in the final analyses. Significant cycle-to-cycle variation in serum AMH levels was observed, with a median variation of 44.3%. Normal responders exhibited a mean change of 0.60 ± 0.46 ng/ml, while poor responders had a mean change of 0.28 ± 0.28 ng/ml. Approximately 20% of patients were reclassified between normal and poor responder categories based on the second AMH measurement. The controlled ovarian stimulation cycle AMH levels showed a stronger correlation with both total oocyte count (r = 0.871, P < 0.001) and MII oocyte count (r = 0.820, P < 0.001) compared to preceding cycle AMH levels.

Conclusion: AMH levels can exhibit significant variations between consecutive cycles, potentially leading to misclassification of patients. Measuring AMH in the early follicular phase of the COS cycle provides a more accurate prediction of the numbers of total and MII oocytes collected. Consistent and repeated AMH measurements can help clinical decision-making.

Keywords: Anti-Müllerian hormone; Infertility; Inter-cycle variation; Ovarian reserve test.

Fig. 1

Individual variation of AMH between two consecutive cycles. The blue-shaded area shows the range of first AMH measurement of patients who were reclassified in terms of ovarian response after the second measurement

Fig. 2

Correlations between the total number of oocytes retrieved and serum AMH levels. Blue: Estimated linear regression line for the correlation between preceding cycle AMH and number of total oocytes retrieved. Area between dotted blue lines: 95% prediction interval for the blue line. Red: Estimated linear regression line for the correlation between COS cycle AMH and number of total oocytes retrieved. Area between dotted red lines: 95% prediction interval for the red line. The R² values for preceding and COS cycles are 0.555 and 0.759, respectively

Fig. 3

Correlations between the number of MII oocytes retrieved and serum AMH levels. Blue: Estimated linear regression line for the correlation between preceding cycle AMH and number of MII oocytes retrieved. Area between dotted blue lines: 95% prediction interval for the blue line. Red: Estimated linear regression line for the correlation between COS cycle AMH and number of MII oocytes retrieved. Area between dotted red lines: 95% prediction interval for the red line. The R² values for preceding and COS cycles are 0.424 and 0.672, respectively