title: Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility.
abstract: 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.
  
  
  METHODS
  Prospective, longitudinal, cohort study.
  
  
  METHODS
  University-based fertility unit.
  
  
  METHODS
  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).
  
  
  METHODS
  Ovulation induction using clomiphene citrate (CC) as first-line and exogenous gonadotropins (exFSH) as second-line therapy.
  
  
  METHODS
  Clomiphene-resistant anovulation (CRA), clomiphene failure (CCF), and ongoing pregnancy rate.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Electronic address: o.valkenburg@erasmusmc.nl.
authors.forename: Olivier
authors.initials: O
authors.lastname: Valkenburg
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
authors.forename: Evert J P
authors.initials: EJ
authors.lastname: van Santbrink
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam.
authors.forename: Tamar E
authors.initials: TE
authors.lastname: König
authors.affiliation: Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.affiliation: Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam.
authors.forename: Cornelis B
authors.initials: CB
authors.lastname: Lambalk
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
mesh_terms: D000328:Adult; D000858:Anovulation / Q000145:classification / Q000235:genetics* / Q000628:therapy*; D002996:Clomiphene / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000145:classification / Q000235:genetics* / Q000628:therapy*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011962:Receptors, FSH / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014944:World Health Organization; D055815:Young Adult
chemical_list: D005300:Fertility Agents, Female; D011962:Receptors, FSH; D002996:Clomiphene
keywords: FSHR; WHO2; ovulation induction; polymorphism; rs6166