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Hum. Reprod. Advance Access published online on September 30, 2005
Human Reproduction, doi:10.1093/humrep/dei317
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© The Author 2005. 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@oupjournals.org
Received March 21, 2005
Revised August 25, 2005
Accepted August 26, 2005

Article

The distribution of FSH receptor isoforms is related to basal FSH levels in subfertile women with normal menstrual cycles

C.H. de Koning 1, T. Benjamins 1, P. Harms 1, R. Homburg 1, J.M. van Montfrans 1, J. Gromoll 2, M. Simoni 2, and C.B. Lambalk 1*

1 Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Centre, P.O.Box 7057, 1007 MB Amsterdam, The Netherlands
2 Institute for Reproductive Medicine, University of Münster, Germany

* To whom correspondence should be addressed.
C.B. Lambalk, E-mail: cb.lambalk{at}vumc.nl


  Abstract

BACKGROUND: Recently a polymorphic variant of the FSH receptor in which amino acid asparagine (Asn) at position 680 is replaced by serine (Ser) was found. This is associated with higher FSH levels in the early follicular phase and an increased FSH requirement to obtain follicular response in IVF patients. The aim of our study was to test the hypothesis that this receptor isoform occurs more often in regularly menstruating subfertility patients with elevated basal FSH than in those with normal early follicular phase FSH. METHODS: A retrospective cohort study of 38 sub-fertility patients with a regular menstrual cycle and elevated FSH (>10 IU/l) compared to 40 patients with normal early follicular phase FSH was carried out. DNA was analysed to determine the FSH receptor genotype. RESULTS: The N680S variant on one or both alleles of the FSH receptor gene was significantly more prevalent in patients with elevated FSH (P < 0.05). The homozygous Asn/Asn variant at codon 680 was found in 45% of women with normal FSH and in 21% of women with elevated FSH. The homozygous Ser/Ser receptor variant was present in 12.5% of women with normal FSH and in 21% of patients with elevated FSH. Also the heterozygous combination of both variants Asn/Ser occurred more often in women with elevated FSH (58 versus 42.5%). CONCLUSIONS: The N680S sequence variation of the FSH receptor is found in >75% of the cases with elevated basal FSH and suggests a higher FSH threshold.

Keywords: basal FSH/elevated FSH/FSH receptor/FSH receptor mutations/polymorphisms.
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