title: Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.
abstract: BACKGROUND
  Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment.
  
  
  METHODS
  Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR.
  
  
  RESULTS
  Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI.
  
  
  CONCLUSIONS
  Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.
authors: Reproductive Medicine, VU University Medical Center, Amsterdam, The Netherlands. r.homburg@vumc.nl
authors: R
authors: R
authors: Homburg
authors: M L
authors: ML
authors: Hendriks
authors: T E
authors: TE
authors: König
authors: R A
authors: RA
authors: Anderson
authors: A H
authors: AH
authors: Balen
authors: M
authors: M
authors: Brincat
authors: T
authors: T
authors: Child
authors: M
authors: M
authors: Davies
authors: T
authors: T
authors: D'Hooghe
authors: A
authors: A
authors: Martinez
authors: M
authors: M
authors: Rajkhowa
authors: R
authors: R
authors: Rueda-Saenz
authors: P
authors: P
authors: Hompes
authors: C B
authors: CB
authors: Lambalk
mesh_terms: D000328:Adult; D000858:Anovulation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002996:Clomiphene / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000627:therapeutic use; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology*; D050498:Live Birth; D010062:Ovulation Induction / Q000379:methods*; D010352:Patient Dropouts; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013020:South America / Q000453:epidemiology
chemical_list: D004965:Estrogen Antagonists; D005300:Fertility Agents, Female; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D002996:Clomiphene