title: Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer.
abstract: Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).
authors.affiliation: Competence Centre on Health Technologies, Tartu, Estonia; Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain. Electronic address: signealtmae@ugr.es.
authors.forename: Signe
authors.initials: S
authors.lastname: Altmäe
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors.forename: Karin
authors.initials: K
authors.lastname: Tamm-Rosenstein
authors.affiliation: Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteban
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors.forename: Jaak
authors.initials: J
authors.lastname: Simm
authors.affiliation: Institute of Computer Science, University of Tartu, Estonia.
authors.forename: Liis
authors.initials: L
authors.lastname: Kolberg
authors.affiliation: Institute of Computer Science, University of Tartu, Estonia; Quretec Ltd., Tartu, Estonia.
authors.forename: Hedi
authors.initials: H
authors.lastname: Peterson
authors.affiliation: Competence Centre on Health Technologies, Tartu, Estonia; School of Natural Sciences and Health, Tallinn University, Tallinn, Estonia.
authors.forename: Madis
authors.initials: M
authors.lastname: Metsis
authors.affiliation: Centre for Reproductive Medicine, West Tallinn Central Hospital Women's Clinic, Tallinn, Estonia.
authors.forename: Kai
authors.initials: K
authors.lastname: Haldre
authors.affiliation: Araid at I + CS, Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Horcajadas
authors.affiliation: Competence Centre on Health Technologies, Tartu, Estonia; Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Anneli
authors.initials: A
authors.lastname: Stavreus-Evers
mesh_terms: D000328:Adult; D001706:Biopsy; D016000:Cluster Analysis; D015925:Cryopreservation / Q000379:methods; D010064:Embryo Implantation / Q000502:physiology*; D004624:Embryo Transfer / Q000379:methods*; D004717:Endometrium / Q000473:pathology*; D004958:Estradiol / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006728:Hormones / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D018873:Pregnancy Rate; D025341:Principal Component Analysis; D011374:Progesterone / Q000378:metabolism; D012008:Recurrence; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D004967:Estrogens; D006728:Hormones; D011374:Progesterone; D004958:Estradiol; D020782:Matrix Metalloproteinases
keywords: artificial cycle; endometrial receptivity; frozen embryo transfer; hormone response elements; recurrent implantation failure; unexplained female infertility