title: Phase IV, open-label, randomized study of low-dose recombinant human follicle-stimulating hormone protocols for ovulation induction.
abstract: BACKGROUND
  This Phase IV, open-label, multicentre, randomized study (MEnTOR) compared two low-dose recombinant human follicle-stimulating hormone (r-hFSH) protocols for ovulation induction.
  
  
  METHODS
  This study was conducted in six Middle Eastern countries between March 2009 and March 2011. Eligible women (18-37 years), with World Health Organization Group II anovulatory infertility, were randomized to receive r-hFSH (starting daily dose: 75 IU) as a chronic low-dose (CLD) (37.5 IU dose increase on Day 14) or low-dose (LD) (37.5 IU dose increase on Day 7) protocol if no follicles were ≥ 10 mm. The maximum r-hFSH daily dose permitted was 225 IU/day. The total length of ovarian stimulation could not exceed 35 days, unless ultrasound assessment suggested imminent follicular growth and maturation. Patients underwent only one treatment cycle. Primary endpoint: incidence of mono-follicular development. Secondary endpoints included: stimulation duration and rates of bi-follicular development; human chorionic gonadotrophin administration rate; clinical pregnancy; and cycle cancellation (owing to inadequate response). Adverse events (AEs) were recorded. The primary efficacy analysis was performed using data from all patients who received at least one dose of correct study medication, had at least one efficacy assessment, and no protocol violations at treatment start (CLD group, n=122; LD group, n=125).
  
  
  RESULTS
  Mono-follicular development rates (primary endpoint) were similar in both groups (CLD: 56.6% [69/122] versus LD: 55.2% [69/125], p=0.93; primary efficacy analysis population). Similarly, there were no significant differences between groups in bi-follicular development, clinical pregnancy or cycle cancellation (inadequate response) rates. In patients who received human chorionic gonadotrophin injections, the mean duration of stimulation was 13.7 days in the CLD group and 12.9 days in the LD group. Clinical pregnancy rates for those patients who received an hCG injection were similar in both groups (CLD: 20.2% [19/94] versus LD: 19.8% [18/91], p=0.94; primary efficacy analysis population). Most AEs were mild in severity. Only one case of ovarian hyperstimulation syndrome was reported (mild; CLD group).
  
  
  CONCLUSIONS
  Efficacy and safety outcomes were similar for the two protocols.
authors.forename: Gamal I
authors.initials: GI
authors.lastname: Serour
authors.forename: Mohamed
authors.initials: M
authors.lastname: Aboulghar
authors.forename: Awatef
authors.initials: A
authors.lastname: Al Bahar
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Hugues
authors.affiliation: Department of Medical Affairs, Merck Serono Middle East FZ - LLC, Dubai, UAE. khaled.esmat@genzyme.com.
authors.forename: Khaled
authors.initials: K
authors.lastname: Esmat
mesh_terms: D000293:Adolescent; D000328:Adult; D000858:Anovulation / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000517:prevention & control*; D059012:Lost to Follow-Up; D008877:Middle East / Q000453:epidemiology; D006080:Ovarian Follicle / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D016471:Ovarian Hyperstimulation Syndrome / Q000517:prevention & control; D010062:Ovulation Induction; D010352:Patient Dropouts; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D005300:Fertility Agents, Female; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa