title: Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles.
abstract: OBJECTIVE
  To identify risk factors for breakthrough LH surge despite GnRH antagonist (GnRH-ant) suppression in IVF cycles.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  All patients undergoing IVF from August 2004 through July 2012 in whom GnRH-ant pituitary suppression (0.25 mg/d) was used in a flexible protocol.
  
  
  METHODS
  GnRH-ant-based IVF.
  
  
  METHODS
  Breakthrough LH surges as evidenced by an increase in LH (minimum 2.5-fold increase from baseline above a threshold of 17 mIU/mL) associated with a decrease in E2, and free fluid on ultrasound.
  
  
  RESULTS
  Breakthrough LH surges despite GnRH-ant administration occurred in 37 (0.34%) of the 10,809 antagonist cycles during the study period. Compared with all patients remaining suppressed, patients with breakthrough surges were significantly older and had significantly increased FSH and decreased antral follicle counts. Compared with age-matched controls (allocation ratio, 1:50), significant differences in ovarian reserve remained evident.
  
  
  CONCLUSIONS
  The occurrence of a breakthrough LH surge despite GnRH-ant treatment is a reassuringly rare event. However, patients with diminished ovarian reserve are at risk for this outcome despite GnRH-ant down-regulation. Further studies are needed to determine whether these patients can be prospectively identified and whether they may benefit from higher doses of GnRH-ant.
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: David E
authors.initials: DE
authors.lastname: Reichman
authors.affiliation: Weill Cornell Medical College, New York, New York.
authors.forename: Lauren
authors.initials: L
authors.lastname: Zakarin
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Kenny
authors.initials: K
authors.lastname: Chao
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Laura
authors.initials: L
authors.lastname: Meyer
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Owen K
authors.initials: OK
authors.lastname: Davis
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York. Electronic address: ang2030@med.cornell.edu.
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D005298:Fertility; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005307:Fertilization in Vitro; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007246:Infertility / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007986:Luteinizing Hormone / Q000097:blood*; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors; D017211:Treatment Failure; D014463:Ultrasonography; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone
keywords: GnRH antagonist; IVF; breakthrough ovulation; cancellation; premature luteinization