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Serum anti-Mullerian hormone (AMH) concentration has limited prognostic value for density of primordial and primary follicles, questioning it as an accurate parameter for the ovarian reserve

  • Michael von Wolff
    Correspondence
    Corresponding author at: Women’s University Hospital, Division of Gynaecological Endocrinology and Reproductive Medicine, Friedbühlstrasse 19, 3010 Bern, Switzerland.
    Affiliations
    University Women’s Hospital, Division of Gynaecological Endocrinology and Reproductive Medicine, Inselspital, University of Berne, Berne, Switzerland
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  • Marie Roumet
    Affiliations
    CTU Berne, Institute of Social and Preventive Medicine (ISPM), University of Berne, Berne, Switzerland
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  • Petra Stute
    Affiliations
    University Women’s Hospital, Division of Gynaecological Endocrinology and Reproductive Medicine, Inselspital, University of Berne, Berne, Switzerland
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  • Jana Liebenthron
    Affiliations
    UniCareD, University Cryobank for Assisted Reproductive Medicine and Fertility Protection at UniKiD Düsseldorf, University Hospital Düsseldorf, Germany
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      Highlights

      • It was not known why the prognostic accuracy of anti-Mullerian hormone (AMH) for determining the time of menopause is limited.
      • According this study, the reason seems to be the poor correlation of the anti-Mullerian hormone concentration with the density of primordial and primary follicles.
      • Serum anti-Mullerian hormone concentrations to estimate the onset of menopause should be used with great care, as misleading interpretation could lead to psychosocial stress and negatively affect family planning.

      Abstract

      Objectives

      To evaluate the prognostic value of anti-Mullerian hormone (AMH) levels in estimating the ovarian density of primordial and primary follicles, which can be assumed to reflect the real ovarian reserve.

      Study design

      A total of 537 women, average age 30.4 years (range 8.0–43.7 years), underwent ovarian tissue cryopreservation prior to gonadotoxic therapies due to malignant diseases which do not affect ovarian reserve parameters. Standardized ovarian biopsies were obtained, and follicular density was analysed. The prognostic accuracy of serum AMH in estimating ovarian follicle density was evaluated.

      Main outcome measures

      Histologically determined follicle density, AMH serum concentration and their correlation.

      Results

      In children, follicle density was high but AMH concentration was low. AMH concentration was predicted to be maximum at the age of 15.5 years. In women aged over 15.5 years, the relationship between AMH concentration and follicle density was evaluated. Crude analysis revealed that serum AMH levels and follicular density were moderately correlated (r = 0.34, p < 0.001). From the adjusted regression model the predicted value of follicle density of women aged 20, 30 and 40 years as well as the associated 50 % and 95 % prediction intervals (50 % PI and 95 % PI, respectively) were calculated. For example, for women aged 40 years with a serum AMH level of 1 ng/ml, a follicle density of 2.3/mm3 (50 %PI: [1.1, 4.6]; 95 %PI: [0.3, 18]) was predicted. These large prediction intervals demonstrate the low predictive value of serum AMH for the ovarian follicle density.

      Conclusions

      Serum AMH levels have limited prognostic value for the follicle density and therefore for the real ovarian reserve.

      Keywords

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