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Hum. Reprod. Advance Access published online on June 24, 2004

Human Reproduction, doi:10.1093/humrep/deh373
© 2004 by European Society of Human Reproduction and Embryology
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Received February 23, 2004
Accepted May 25, 2004

Article

Changes in anti-Müllerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility

Annemarie G.M.G.J. Mulders 1, Joop S.E. Laven 1*, Marinus J.C. Eijkemans 2, Frank H. de Jong 3, Axel P.N. Themmen 3, Bart C.J.M. Fauser 4

1 Division of Reproductive Medicine, Department of Obstetrics and Gynecology, The Netherlands
2 Center for Clinical Decision Sciences, Department of Public Health, The Netherlands
3 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
4 Division of Reproductive Medicine, Department of Obstetrics and Gynecology, The Netherlands; Department of Reproductive Medicine, University Medical Center, Utrecht, The Netherlands

* To whom correspondence should be addressed. E-mail: j.laven{at}erasmusmc.nl.


   Abstract

BACKGROUND: Anti-Müllerian hormone (AMH), produced by growing pre-antral and early antral ovarian follicles, has been shown to be a useful marker for ovarian ageing. Serum AMH concentrations are elevated during reproductive life in anovulatory women, especially in those patients exhibiting polycystic ovaries (PCO). The current study was designed to investigate whether the decrease in AMH serum concentrations over time is different comparing women with normogonadotrophic anovulation [World Health Organization (WHO) group 2 (including polycystic ovary syndrome (PCOS)] and normo-ovulatory controls. METHODS and RESULTS: AMH serum levels were assessed on two occasions in 98 patients suffering from WHO 2 anovulatory infertility as well as in 41 normo-ovulatory premenopausal women. Median time interval between both visits was 2.6 years (range 0.3-9.0) for WHO 2 patients compared with 1.6 years (range 1.0-7.3) in controls. Serum AMH concentrations were significantly (P<0.0001) elevated on both occasions in WHO 2 patients (AMH1, median = 7.5 µg/l, range 0.1-35.8; and AMH2, median = 6.7 µg/l, range 0.0-30.6) compared with controls (AMH1, median = 2.1 µg/l, range 0.1-7.4; and AMH2, median = 1.3 µg/l, range 0.0-5.0). Regression analysis, corrected for age, indicated a significant relative decrease in serum AMH concentrations over time for both groups (P<0.001). However, the decline in serum AMH in WHO 2 patients was significantly less compared with controls (P=0.03). CONCLUSION: The present longitudinal study shows that serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normo-ovulatory controls. The decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. This observation may suggest retarded ovarian ageing and hence a sustained reproductive life span in these patients.

Keywords: anti-Müllerian hormone (AMH); anovulation; infertility; ovarian ageing; PCOS.
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