Follicle stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic World Health Organization class 2 anovulatory subfertility

An FSH receptor polymorphism (rs6166) affects the outcome of ovulation induction in normogonadotropic anovulatory subfertility. The minor allele (680Ser) is associated with Clomiphene-resistant anovulation during treatment with clomiphene citrate.

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Olivier Valkenburg, M.D., Evert J.P. van Santbrink, Ph.D., Tamar E. König, M.D., Axel P.N. Themmen, Ph.D., André G. Uitterlinden, Ph.D., Bart C.J.M. Fauser, Ph.D., Cornelis B. Lambalk, Ph.D., Joop S.E. Laven, Ph.D.

Volume 103, Issue 4, Pages 1081-1088



To assess whether an FSH receptor polymorphism (Asn680Ser, rs6166) can affect the outcome of ovulation induction in normogonadotropic (World Health Organization class 2 [WHO2]) anovulatory subfertile women.


Prospective, longitudinal, cohort study.


University-based fertility unit.


A total of 240 consecutive women diagnosed with WHO2 anovulatory subfertility who underwent ovulation induction therapy. Results were replicated in a retrospective cohort of 185 patients with polycystic ovary syndrome (PCOS) (Rotterdam criteria).


Ovulation induction using clomiphene citrate (CC) as first-line and exogenous gonadotropins (exFSH) as second-line therapy.

Main Outcome Measure(s):

Clomiphene-resistant anovulation (CRA), clomiphene failure (CCF), and ongoing pregnancy rate.


Genotyped patients (n = 159) were similar to nongenotyped women (n = 81) regarding clinical characteristics and outcomes of ovulation induction. The 680Ser allele was associated with CRA. A pooled analysis of both cohorts showed an 89% higher chance of CRA after CC treatment (odds ratio 1.9 [95% confidence interval 1.1–3.3]) in homozygous carriers of the FSH receptor variant (680Ser/Ser). A lower chance of ongoing pregnancy (hazard ratio 0.51 [95% confidence interval 0.27–0.98]) was observed among these patients during CC treatment in the prospective cohort.


An FSH receptor polymorphism is associated with CRA during treatment with clomiphene citrate. These data ma

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