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Hum. Reprod. Advance Access published online on March 1, 2008
Human Reproduction, doi:10.1093/humrep/den050
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Anti-Mullerian hormone indicates early ovarian decline in fragile X mental retardation (FMR1) premutation carriers: a preliminary study

J. Rohr1, E.G. Allen1,3, K. Charen1, J. Giles1, W. He1, C. Dominguez2 and S.L. Sherman1,3

1 Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Whitehead Building, Atlanta, GA, 30322, USA 2 Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, USA

3 Correspondence address. E-mail: egraves{at}genetics.emory.edu (E.G.A.); ssherman{at}genetics.emory.edu (S.L.S.)

BACKGROUND: Women who carry the fragile X mental retardation (FMR1) premutation are at risk for fragile X-associated primary ovarian insufficiency. Past studies have shown that carriers who are still cycling have increased levels FSH compared with non-carriers. As anti-Mullerian hormone (AMH) has been shown as an excellent marker of ovarian decline, we examined AMH levels among premutation carriers to characterize their ovarian function.

METHODS: We determined the level of FSH and AMH in serum samples collected during early follicular phase from women who carried longer FMR1 repeat alleles (defined as ≥70 repeats, n = 40) and those with shorter repeat alleles (<70 repeats, n = 75), identified by DNA analysis. Comparisons were made stratified by age and carrier status.

RESULTS: For all age groups, AMH levels were significantly lower among longer repeat allele carriers compared to shorter repeat allele carriers (P = 0.002, 0.006 and 0.020 for women ages 18–30, 31–40 and 41–50 years, respectively). In contrast, increased FSH indicative of early ovarian decline was only evident for longer repeat allele carriers aged 31–40 years (P = 0.089, 0.001 and 0.261 for women ages 18–30, 31–40 and 41–50 years, respectively).

CONCLUSIONS: These preliminary data suggest that AMH levels indicate early ovarian decline among women with longer FMR1 repeat alleles; moreover, AMH appears to be a better marker than FSH in identifying this early decline.

Key words: Mullerian inhibiting substance/fragile X/premature ovarian failure/FSH/menopause

Submitted on September 3, 2007; resubmitted on January 23, 2008; accepted on January 31, 2008.


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