title: The impact of ovarian stimulation with recombinant FSH in combination with GnRH antagonist on the endometrial transcriptome in the window of implantation.
abstract: The aim of this prospective paired cohort study is to elucidate the impact of ovarian stimulation with recombinant follicle-stimulating hormone in combination with gonadotropin-releasing hormone antagonist on the endometrial transcriptome. Oocyte donors underwent endometrial biopsy during the implantation window of the nonstimulated cycle and following ovarian stimulation with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonist but no luteal progesterone supplementation (n = 4). Microarray analysis showed 142 genes to be significantly upregulated and 98 significantly downregulated. Significantly upregulated genes included those sequencing for the chemokine ligand CXCL 13, the Dickkopf homolog, steroidogenic acute regulatory protein, and homeobox C6. Also upregulated were genes inhibited by progesterone, such as insulin-like growth factor binding protein 5. In conclusion, ovarian stimulation with follicle-stimulating hormone and gonadotropin-releasing hormone antagonist dysregulates the expression of many genes involved in cell adhesion, T-cell receptor signaling, and regulation of signal transduction. These data suggest that dysregulation of the endometrial transcriptome in the stimulated cycle is not fully attributable to supraphysiological sex steroid levels at the folliculo-luteal transition.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center, Utrecht, Netherlands. n.s.macklon@umcutrecht.nl
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
authors.forename: Mark H
authors.initials: MH
authors.lastname: van der Gaast
authors.forename: Amy
authors.initials: A
authors.lastname: Hamilton
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D000328:Adult; D002448:Cell Adhesion / Q000235:genetics; D054382:Chemokine CXCL13 / Q000235:genetics; D016000:Cluster Analysis; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005801:Genes, Homeobox; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008597:Menstrual Cycle / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010062:Ovulation Induction / Q000379:methods*; D010750:Phosphoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D054382:Chemokine CXCL13; C501126:DKK1 protein, human; D006727:Hormone Antagonists; D018975:Insulin-Like Growth Factor Binding Protein 5; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D007987:Gonadotropin-Releasing Hormone; D012313:RNA; D005640:Follicle Stimulating Hormone; C061018:ganirelix