Multi-center clinical evaluation of the Access AMH assay to determine AMH levels in reproductive age women during normal menstrual cycles

  • Clarisa R. Gracia
  • Sanghyuk S. Shin
  • Maureen Prewitt
  • Janna S. Chamberlin
  • Lori R. Lofaro
  • Kristin L. Jones
  • Marta Clendenin
  • Katherine E. Manzanera
  • Dennis L. Broyles
Reproductive Physiology and Disease



AMH is widely used for assessing ovarian reserve, and it is particularly convenient, because it is thought to have minimal variability throughout the menstrual cycle. However, studies assessing the stability of AMH over the menstrual cycle have been conflicting.


The purpose of this study is to determine whether AMH levels vary across the normal menstrual cycle.


A multi-center, prospective cohort study conducted at three US centers.


Fifty females with regular menstrual cycles aged 18–45 underwent serial venipuncture every 3–5 days starting in the early follicular phase and lasting up to 10 collections. AMH was tested using the Access 2 immunoassay system.


Age-adjusted mixed-effect models utilizing data from 384 samples from 50 subjects demonstrated a within subject standard deviation of 0.81 (95% CI 0.75–0.88) with a coefficient of variation of 23.8% across the menstrual cycle and between subject standard deviation of 2.56 (95% CI 2.13–3.21) with a coefficient of variation of 75.1%. Intra-class correlation (ICC) of AMH across the menstrual cycle was 0.91.


Overall, AMH levels, using the automated Access AMH assay, appear to be relatively stable across the menstrual cycle. Fluctuations, if any, appear to be small, and therefore, clinicians may advise patients to have AMH levels drawn at any time in the cycle.


Ovarian reserve AMH Menstrual cycle Intra-cycle variability Anti-Mullerian hormone Endocrinology Access AMH 



Kerrie Rossow and Thong Her, Beckman Coulter, Chaska, for their help with specimen testing, and Kim Doeden and Yang Bai, Beckman Coulter, Carlsbad, for their assistance with study management and data analyses, respectively.

Compliance with ethical standards

IRB approval was obtained at each site, and informed consent was obtained from all participants prior to enrollment.


  1. 1.
    Anderson RA, Nelson SM, Wallace WH. Measuring anti-Müllerian hormone for the assessment of ovarian reserve: when and for whom is it indicated? Maturitas. 2012;71(1):28–33. Scholar
  2. 2.
    Sowers M, McConnell D, Gast K, Zheng H, Nan B, McCarthy JD, et al. Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles. Fertil Steril. 2010;94(4):1482–6. Scholar
  3. 3.
    van Rooij IA, Tonkelaar I, Broekmans FJ, Looman CW, Scheffer GJ, de Jong FH, et al. Anti-müllerian hormone is a promising predictor for the occurrence of the menopausal transition. Menopause. 2004;11(6 Pt 1):601–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Sowers MR, Eyvazzadeh AD, McConnell D, Yosef M, Jannausch ML, Zhang D, et al. Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition. J Clin Endocrinol Metab. 2008;93(9):3478–83. Scholar
  5. 5.
    Robertson DM, Kumar A, Kalra B, Shah S, Pruysers E, Vanden Brink H, et al. Detection of serum antimüllerian hormone in women approaching menopause using sensitive antimüllerian hormone enzyme-linked immunosorbent assays. Menopause. 2014;21(12):1277–86.CrossRefPubMedGoogle Scholar
  6. 6.
    Freeman EW, Sammel MD, Lin H, Gracia CR. Anti-mullerian hormone as a predictor of time to menopause in late reproductive age women. J Clin Endocrinol Metab. 2012;97(5):1673–80. Scholar
  7. 7.
    Freeman EW, Sammel MD, Lin H, Boorman DW, Gracia CR. Contribution of the rate of change of antimüllerian hormone in estimating time to menopause for late reproductive-age women. Fertil Steril. 2012;98(5):1254–9.e1-2. Scholar
  8. 8.
    Broer SL, Mol BW, Hendriks D, Broekmans FJ. The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril. 2009;91(3):705–14. Scholar
  9. 9.
    Nelson SM, Klein BM, Arce JC. Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials. Fertil Steril. 2015;103(4):923–30.e1. Scholar
  10. 10.
    Fraissinet A, Robin G, Pigny P, Lefebvre T, Catteau-Jonard S, Dewailly D. Use of the serum anti-Müllerian hormone assay as a surrogate for polycystic ovarian morphology: impact on diagnosis and phenotypic classification of polycystic ovary syndrome. Hum Reprod. 2017;32(8):1716–22. Scholar
  11. 11.
    Demirdjian G, Bord S, Lejeune C, Masica R, Riviere D, Nicouleau L, et al. Performance characteristics of the Access AMH assay for the quantitative determination of anti-Mullerian hormone (AMH) levels on the Access* family of automated immunoassay systems. Clin Biochem. 2016;49:1267–73.CrossRefPubMedGoogle Scholar
  12. 12.
    La Marca A, Stabile G, Artenisio AC, Volpe A. Serum anti-Mullerian hormone throughout the human menstrual cycle. Hum Reprod. 2006;21(12):3103–7. Scholar
  13. 13.
    Tsepelidis S, Devreker F, Demeestere I, Flahaut A, Gervy C, Englert Y. Stable serum levels of anti-Müllerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women. Hum Reprod. 2007;22(7):1837–40. Scholar
  14. 14.
    Robertson DM, Hale GE, Fraser IS, Hughes CL, Burger HG. Changes in serum antimüllerian hormone levels across the ovulatory menstrual cycle in late reproductive age. Menopause. 2011;18(5):521–4. Scholar
  15. 15.
    Overbeek A, Broekmans FJ, Hehenkamp WJ, Wijdeveld ME, van Disseldorp J, van Dulmen-den Broeder E, et al. Intra-cycle fluctuations of anti-Müllerian hormone in normal women with a regular cycle: a re-analysis. Reprod BioMed Online. 2012;24(6):664–9. Scholar
  16. 16.
    Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, Te Velde ER, Broekmans FJ. Anti-Müllerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab. 2006;91(10):4057–63. Scholar
  17. 17.
    Cook CL, Siow Y, Taylor S, Fallat ME. Serum müllerian-inhibiting substance levels during normal menstrual cycles. Fertil Steril. 2000;73(4):859–61.CrossRefPubMedGoogle Scholar
  18. 18.
    Wunder DM, Bersinger NA, Yared M, Kretschmer R, Birkhäuser MH. Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women. Fertil Steril. 2008;89(4):927–33. Scholar
  19. 19.
    Hadlow N, Longhurst K, McClements A, Natalwala J, Brown SJ, Matson PL. Variation in antimüllerian hormone concentration during the menstrual cycle may change the clinical classification of the ovarian response. Fertil Steril. 2013;99(6):1791–7. Scholar
  20. 20.
    Randolph JF, Harlow SD, Helmuth ME, Zheng H, McConnell DS. Updated assays for inhibin B and AMH provide evidence for regular episodic secretion of inhibin B but not AMH in the follicular phase of the normal menstrual cycle. Hum Reprod. 2014;29(3):592–600. Scholar
  21. 21.
    KissellKA, DanaherMR, SchistermanEF, Wactawski-WendeJ, AhrensKA, SchliepK, et al. Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women. Hum Reprod 2014.
  22. 22.
    Streuli I, Fraisse T, Chapron C, Bijaoui G, Bischof P, de Ziegler D. Clinical uses of anti-Müllerian hormone assays: pitfalls and promises. Fertil Steril. 2009;91(1):226–30. Scholar
  23. 23.
    Broer SL, Dólleman M, van Disseldorp J, Broeze KA, Opmeer BC, Bossuyt PM, et al. Prediction of an excessive response in in vitro fertilization from patient characteristics and ovarian reserve tests and comparison in subgroups: an individual patient data meta-analysis. Fertil Steril. 2013;100(2):420–9.e7. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Clarisa R. Gracia
    • 1
    • 2
  • Sanghyuk S. Shin
    • 3
  • Maureen Prewitt
    • 1
  • Janna S. Chamberlin
    • 3
  • Lori R. Lofaro
    • 3
  • Kristin L. Jones
    • 4
  • Marta Clendenin
    • 3
  • Katherine E. Manzanera
    • 3
  • Dennis L. Broyles
    • 3
  1. 1.Department of Obstetrics and GynecologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Reproductive EndocrinologyUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Beckman Coulter, Inc.CarlsbadUSA
  4. 4.Beckman Coulter, Inc.ChaskaUSA

Personalised recommendations