title: An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF.
abstract: The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Yvonne E M
authors.initials: YE
authors.lastname: Koot
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sander R
authors.initials: SR
authors.lastname: van Hooff
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Carolien M
authors.initials: CM
authors.lastname: Boomsma
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Dik
authors.initials: D
authors.lastname: van Leenen
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marian J A
authors.initials: MJ
authors.lastname: Groot Koerkamp
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mariëtte
authors.initials: M
authors.lastname: Goddijn
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.|Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
mesh_terms: D000328:Adult; D001706:Biopsy; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D011247:Pregnancy; D012008:Recurrence; D015203:Reproducibility of Results