title: Dose-finding study of daily gonadotropin-releasing hormone (GnRH) antagonist for the prevention of premature luteinizing hormone surges in IVF/ICSI patients: antide and hormone levels.
abstract: BACKGROUND
  The aim of this study was to define the minimal effective dose of antide (Iturelix) to prevent premature luteinizing hormone (LH) surges in in vitro fertilization (IVF) patients.
  
  
  METHODS
  In a prospective, single centre study, 144 IVF/ICSI patients were stimulated with r-hFSH from cycle day 2 and from cycle day 6 onwards, cotreated with daily 2 mg/2 ml (n=30), 1 mg/ml (n=30), 0.5 mg/ml (n=31), 0.5 mg/0.5 ml (n=23) and 0.25 mg/ml (n=30) GnRH antagonist (antide). Serum samples were taken three times daily during antide administration to assess antide and hormone levels. The minimal effective dose was defined as the lowest dose group with <2 LH surges (LH >12.4 IU/l and progesterone >2 ng/ml).
  
  
  RESULTS
  Serum antide levels, mean LH and E2 levels per day and their area under the curves were dose-related to antide. The bioavailability of antide almost doubled after dilution in larger volumes. Pre-injection LH levels gradually increased during GnRH antagonist treatment. LH surges occurred in the lowest dose groups 0.5 mg/ml (3.2%), 0.5 mg/0.5 ml (6.7%) and 0.25 mg/ml (13.3%). Hence, 0.5 mg/ml is considered to be the minimal effective dose. Antide was overall well tolerated and safe.
  
  
  CONCLUSIONS
  0.5 mg/ml antide is the minimal effective dose to prevent an untimely LH surge in IVF patients stimulated with r-hFSH.
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Vrije Universiteit medical centre (VUmc), Amsterdam, The Netherlands.
authors.forename: Judith A F
authors.initials: JA
authors.lastname: Huirne
authors.forename: Andre C D
authors.initials: AC
authors.lastname: van Loenen
authors.forename: Roel
authors.initials: R
authors.lastname: Schats
authors.forename: Joseph
authors.initials: J
authors.lastname: McDonnell
authors.forename: Peter G A
authors.initials: PG
authors.lastname: Hompes
authors.forename: Joop
authors.initials: J
authors.lastname: Schoemaker
authors.forename: Roy
authors.initials: R
authors.lastname: Homburg
authors.forename: Cornelis B
authors.initials: CB
authors.lastname: Lambalk
mesh_terms: D000328:Adult; D001682:Biological Availability; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000097:blood; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011374:Progesterone / Q000097:blood; D020554:Sperm Injections, Intracytoplasmic
chemical_list: D006727:Hormone Antagonists; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C057022:iturelix