title: Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis.
abstract: OBJECTIVE
  To assess the impact of elevated early follicular progesterone (P) levels in gonadotropin-releasing hormone (GnRH) antagonist cycles on clinical outcome using prospective data in combination with a systematic review and meta-analysis.
  
  
  METHODS
  Nested study within a multicenter randomized controlled trial and a systematic review and meta-analysis.
  
  
  METHODS
  Reproductive medicine center in an university hospital.
  
  
  METHODS
  158 in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) patients.
  
  
  METHODS
  Recombinant follicle-stimulating hormone (FSH) (150-225 IU) administered daily from cycle day 2 onward; GnRH antagonist treatment randomly started on cycle day 2 or 6; assignment into two groups according to P level on cycle day 2: normal or elevated (>4.77 nmol/L or >1.5 ng/mL, respectively).
  
  
  METHODS
  Ongoing pregnancy rate (OPR) per started cycle.
  
  
  RESULTS
  The incidence of elevated P was 13.3%. A non-statistically-significant difference in OPR was present between the normal and elevated P groups (27.0% vs. 19.0%). No differential impact of early or late GnRH antagonist initiation on the effect of elevated or normal P on OPR was observed. A systematic search of Medline and EMBASE from 1972-2013 was performed to identify studies analyzing elevated early P levels in GnRH antagonists. The meta-analysis (n=1,052) demonstrated that elevated P levels statistically significantly decreased the OPR with 15% (95% CI -23, -7 %). Heterogeneity across the studies, presumably based on varying protocols, may have modulated the effect of elevated P.
  
  
  CONCLUSIONS
  From the present meta-analysis it appears that early elevated P levels are associated with a lower OPR in GnRH antagonists. The incidence of such a condition, however, is low.
  
  
  BACKGROUND
  NCT00866034.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands. Electronic address: O.Hamdine@umcutrecht.nl.
authors.forename: Ouijdane
authors.initials: O
authors.lastname: Hamdine
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands; Academic Unit of Human Development and Health, Princess Anne Hospital, University of Southampton, Southampton, United Kingdom.
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.affiliation: Division of Reproductive Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.affiliation: Department of Gynecology and Fertility, Isala Clinics, Zwolle, the Netherlands.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Cohlen
authors.affiliation: Department of Gynecology and Fertility, Maasstad Hospital, Rotterdam, the Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: Verhoeff
authors.affiliation: Department of Gynecology and Fertility, Catharina Hospital, Eindhoven, the Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Dop
authors.affiliation: Department of Gynecology and Fertility, Tergooi Hospital, Blaricum, the Netherlands.
authors.forename: Rob E
authors.initials: RE
authors.lastname: Bernardus
authors.affiliation: Division of Reproductive Medicine, VU University Medical Centre, Amsterdam, the Netherlands; Department of Gynaecology-Obstetrics, Centre for Reproductive Medicine of the University Hospital of Ghent, Ghent, Belgium.
authors.forename: Cornelis B
authors.initials: CB
authors.lastname: Lambalk
authors.affiliation: Department of Gynecology and Fertility, Medisch Spectrum Twente Hospital Group, Enschede, the Netherlands.
authors.forename: Gerrit J E
authors.initials: GJ
authors.lastname: Oosterhuis
authors.affiliation: Department of Gynecology and Fertility, Bronovo Hospital, the Hague, the Netherlands.
authors.forename: Caspar A G
authors.initials: CA
authors.lastname: Holleboom
authors.affiliation: Department of Gynecology and Fertility, Albert Schweitzer Hospital, Zwijndrecht, the Netherlands.
authors.forename: Grada C
authors.initials: GC
authors.lastname: van den Dool-Maasland
authors.affiliation: Department of Gynecology and Fertility, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Harjo J
authors.initials: HJ
authors.lastname: Verburg
authors.affiliation: Department of Gynecology and Fertility, ZGT Almelo, Almelo, the Netherlands.
authors.forename: Petrus F M
authors.initials: PF
authors.lastname: van der Heijden
authors.affiliation: Department of Gynecology and Fertility, St. Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Blankhart
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D006727:Hormone Antagonists / Q000008:administration & dosage; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009426:Netherlands; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D010062:Ovulation Induction / Q000009:adverse effects / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D011374:Progesterone / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage; D020554:Sperm Injections, Intracytoplasmic; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D005640:Follicle Stimulating Hormone
keywords: Clinical outcome; GnRH antagonist; IVF; progesterone levels