title: Endometrial gene expression in the early luteal phase is impacted by mode of triggering final oocyte maturation in recFSH stimulated and GnRH antagonist co-treated IVF cycles.
abstract: OBJECTIVE
  Do differences in endometrial gene expression exist after ovarian stimulation with four different regimens of triggering final oocyte maturation and luteal phase support in the same patient?
  
  
  CONCLUSIONS
  Significant differences in the expression of genes involved in receptivity and early implantation were seen between the four protocols.
  
  
  BACKGROUND
  GnRH agonist triggering is an alternative to hCG triggering in GnRH antagonist co-treated cycles, resulting in an elimination of early ovarian hyperstimulation syndrome. Whereas previous studies have revealed a low ongoing clinical pregnancy rate after GnRH agonist trigger due to a high early pregnancy loss rate, despite supplementation with the standard luteal phase support, more recent studies, employing a 'modified' luteal phase support including a bolus of 1500 IU hCG on the day of oocyte aspiration, have reported ongoing pregnancy rates similar to those seen after hCG triggering.
  
  
  METHODS
  A prospective randomized study was performed in four oocyte donors recruited from an oocyte donation program during the period 2010-2011.
  Four oocyte donors in a university IVF center each prospectively underwent four consecutive stimulation protocols, with different modes of triggering final oocyte maturation and a different luteal phase support, followed by endometrial biopsy on Day 5 after oocyte retrieval. The following protocols were used: (A) 10 000 IU hCG and standard luteal phase support, (B) GnRH agonist (triptorelin 0.2 mg), followed by 1500 IU hCG 35 h after triggering final oocyte maturation, and standard luteal phase support, (C) GnRH agonist (triptorelin 0.2 mg) and standard luteal phase support and (D) GnRH agonist (triptorelin 0.2 mg) without luteal phase support. Microarray data analysis was performed with GeneSpring GX 11.5 (RMA algorithm). Pathway and network analysis was performed with the gene ontology software Ingenuity Pathways Analysis (Ingenuity® Systems, www.ingenuity.com, Redwood City, CA, USA). Samples were grouped and background intensity values were removed (cutoff at the lowest 20th percentile). A one-way ANOVA test (P< 0.05) was performed with Benjamini-Hochberg multiple testing correction.
  
  
  RESULTS
  Significant differences were seen in endometrial gene expression, related to the type of ovulation trigger and luteal phase support. However, the endometrial gene expression after the GnRH agonist trigger and a modified luteal phase support (B) was similar to the pattern seen after the hCG trigger (A).
  
  
  CONCLUSIONS
  The study was performed in four oocyte donors only; however, it is a strength of the study that the same donor underwent four consecutive stimulation protocols within 1 year to avoid inter-individual variations.
  
  
  CONCLUSIONS
  These endometrial gene-expression findings support the clinical reports of a non-significant difference in live birth rates between the GnRH agonist trigger and the hCG trigger, when the GnRH agonist trigger is followed by a bolus of 1500 IU hCG at 35 h post trigger in addition to the standard luteal phase support.
  This study was supported by an un-restricted research grant by MSD Belgium.
  
  
  BACKGROUND
  EudraCT number 2009-009429-26, protocol number 997 (P06034).
authors.affiliation: The Fertility Clinic, Department D, Odense University Hospital, OHU, Entrance 55, Odense C 5000, Denmark. peter.humaidan@ouh.regionsyddanmark.dk
authors.forename: P
authors.initials: P
authors.lastname: Humaidan
authors.forename: I
authors.initials: I
authors.lastname: Van Vaerenbergh
authors.forename: C
authors.initials: C
authors.lastname: Bourgain
authors.forename: B
authors.initials: B
authors.lastname: Alsbjerg
authors.forename: C
authors.initials: C
authors.lastname: Blockeel
authors.forename: F
authors.initials: F
authors.lastname: Schuit
authors.forename: L
authors.initials: L
authors.lastname: Van Lommel
authors.forename: P
authors.initials: P
authors.lastname: Devroey
authors.forename: H
authors.initials: H
authors.lastname: Fatemi
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D043373:Follicle Stimulating Hormone, Human / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018587:Oocyte Donation; D054315:Oocyte Retrieval; D009866:Oogenesis / Q000187:drug effects*; D010062:Ovulation Induction; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014019:Tissue Donors; D017329:Triptorelin Pamoate / Q000494:pharmacology
chemical_list: D006063:Chorionic Gonadotropin; D043373:Follicle Stimulating Hormone, Human; D006727:Hormone Antagonists; D011994:Recombinant Proteins; C571802:follitropin beta; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C061018:ganirelix