Objective: 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.
Design: Prospective, longitudinal, cohort study.
Setting: University-based fertility unit.
Patient(s): 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).
Intervention(s): 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.
Result(s): Genotyped patients (n = 159) were similar to nongenotyped women (n = 81) regarding clinical characteristics and outcomes of ovulation induction. The 680(Ser) 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 (680(Ser/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.
Conclusion(s): An FSH receptor polymorphism is associated with CRA during treatment with clomiphene citrate. These data may be used to design a treatment algorithm that is more efficacious and better tailored to the individual patient.
Keywords: FSHR; WHO2; ovulation induction; polymorphism; rs6166.
Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.