title: Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial.
abstract: OBJECTIVE
  What is the impact of initiating GnRH antagonist co-treatment for in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)?
  
  
  CONCLUSIONS
  Early initiation of GnRH antagonist does not appear to improve clinical outcomes of IVF compared with midfollicular initiation.
  
  
  BACKGROUND
  During ovarian stimulation for IVF, GnRH antagonist co-treatment is usually administered from the midfollicular phase onwards. Earlier initiation may improve the follicular phase hormonal milieu and therefore overall clinical outcomes.
  
  
  METHODS
  This open-label, multicentre randomized controlled trial was conducted between September 2009 and July 2011. A web-based program was used for randomization and 617 IVF-intracytoplasmic sperm injection (ICSI) patients were included.
  
  
  METHODS
  Recombinant FSH (150-225 IU) was administered daily from CD 2 onwards in both groups. The study group (CD2; n = 308) started GnRH antagonist co-treatment on CD 2, whereas the control group (CD6; n = 309) started on CD 6.
  
  
  RESULTS
  There were no significant differences in clinical outcomes between the two groups. A non-significant trend towards a higher LBR per started cycle and CLBR was observed in the CD6 group compared with the CD2 group (LBR: 24.0 versus 21.5%, P = 0.5; CLBR: 29.9 versus 26.7%, P = 0.6).
  
  
  CONCLUSIONS
  The study was terminated prematurely because no significant difference was observed in clinical outcomes after 617 inclusions. A much larger study population would be needed to detect a small significant difference in favour of either study arm, which raises the question of whether this would be relevant for clinical practice.
  
  
  CONCLUSIONS
  The present study shows that the additional treatment burden and costs of starting GnRH antagonist on CD 2 instead of on CD 6 are not justified, as early initiation of GnRH antagonist does not improve LBRs.
  
  
  BACKGROUND
  This study was partially supported by a grant from Merck Serono. O.H., M.J.C.E, A.V., P.A.D., R.E.B., G.J.E.O., C.A.G.H., G.C.D.M., H.J.V., P.F.M.H. and A.B. have nothing to declare. F.J.B. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gedeon Richter, Merck Serono, MSD and Roche. B.J.C. has received fees and grant support from the following companies (in alphabetic order): Ferring, Merck Serono and MSD. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, Ferring, Merck Serono and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, MSD, Merck Serono, Organon, Schering Plough and Serono. N.S.M. has received fees and grant support from the following companies (in alphabetic order): Anecova, Ferring, Merck Serono, MSD, Organon and Serono.
  
  
  BACKGROUND
  www.clinicaltrials.gov, no. NCT00866034.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: O
authors.initials: O
authors.lastname: Hamdine
authors.forename: N S
authors.initials: NS
authors.lastname: Macklon
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
authors.forename: B J
authors.initials: BJ
authors.lastname: Cohlen
authors.forename: A
authors.initials: A
authors.lastname: Verhoeff
authors.forename: P A
authors.initials: PA
authors.lastname: van Dop
authors.forename: R E
authors.initials: RE
authors.lastname: Bernardus
authors.forename: C B
authors.initials: CB
authors.lastname: Lambalk
authors.forename: G J E
authors.initials: GJ
authors.lastname: Oosterhuis
authors.forename: C A G
authors.initials: CA
authors.lastname: Holleboom
authors.forename: G C
authors.initials: GC
authors.lastname: van den Dool-Maasland
authors.forename: H J
authors.initials: HJ
authors.lastname: Verburg
authors.forename: P F M
authors.initials: PF
authors.lastname: van der Heijden
authors.forename: A
authors.initials: A
authors.lastname: Blankhart
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: F J
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D000328:Adult; D001723:Birth Rate; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005498:Follicular Phase; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods; D013997:Time Factors
chemical_list: D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix
keywords: GnRH antagonist; IVF; clinical outcomes; live birth rate