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Hum. Reprod. Advance Access originally published online on April 28, 2009
Human Reproduction 2009 24(8):2007-2013; doi:10.1093/humrep/dep114
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© The Author 2009. 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

Clomiphene citrate resistance in relation to follicle-stimulating hormone receptor Ser680Ser-polymorphism in polycystic ovary syndrome

A. Overbeek1,4, E.A.M. Kuijper1, M.L. Hendriks1, M.A. Blankenstein2, I.J.G. Ketel1, J.W.R. Twisk3, P.G.A. Hompes1, R. Homburg1 and C.B. Lambalk1

1 Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands 2 Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands 3 Department of Methodology and Applied Biostatistics, Institute of Health Sciences, VU University, Amsterdam, The Netherlands

4 Correspondence address. E-mail: a.overbeek{at}vumc.nl

BACKGROUND: Clomiphene citrate (CC) response in anovulatory women is difficult to predict and patient-tailored treatment would benefit patient care and time-management. The objective of this study was to evaluate the role of the follicle-stimulating hormone receptor (FSHR) Ser680Ser-polymorphism as a predictor for CC response.

METHODS: In this retrospective study, 193 patients, diagnosed with polycystic ovary syndrome (PCOS) according to Rotterdam criteria and treated with ovulation induction, were included over a 5-year period in a university hospital in the Netherlands. Data on demographics, BMI, menstrual cycle, laboratory screening (including FSHR genotyping), transvaginal ultrasonography of ovaries and ovulation parameters were collected. Main outcome measures were response to CC and FSHR genotype.

RESULTS: The frequency distribution of the 680-polymorphism was 26% (Asn/Asn), 50% (Asn/Ser) and 24% (Ser/Ser). No significant differences in basal characteristics were found. Significantly more patients with Ser/Ser-polymorphism were resistant to CC (28%) compared with Asn/Ser (14%) and Asn/Asn group (15%), with an odds ratio for ovulation of 0.44 (95% CI, 0.21–0.97). Patients with higher FSH levels, higher age and lower BMI were significantly more likely to ovulate in univariate analysis. In a multivariate logistic regression model, corrected for age, BMI, mean ovarian, volume, hyperandrogenism, and amenorrhoea, only FSHR and basal FSH levels were predictive for ovulation.

CONCLUSIONS: Chance of resistance to CC is almost double in women with PCOS harbouring the Ser/Ser genotype.

Key words: polycystic ovary syndrome/anovulation/FSH receptor/polymorphism/clomiphene citrate

Submitted on November 7, 2008; resubmitted on March 16, 2009; accepted on April 2, 2009.


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