Follicle-stimulating hormone receptor polymorphism affects theoutcome of ovulation induction innormogonadotropic (World Health Organization class 2) anovulatory subfertility

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 680Ser allele was associated with CRA. A pooled analysis of both cohorts showed an 89% higher chance ofCRA 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. 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.

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