title: Prospective assessment of midsecretory endometrial leukemia inhibitor factor expression versus ανβ3 testing in women with unexplained infertility.
abstract: OBJECTIVE
  To evaluate endometrial leukemia inhibitor factor (LIF) expression as a marker of endometrial receptivity in women with unexplained infertility (UI).
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  University-associated infertility clinics.
  
  
  METHODS
  Women with UI for more than 1 year and healthy control women.
  
  
  METHODS
  Endometrial biopsy.
  
  
  METHODS
  Time to pregnancy was compared between patients with UI who were evaluated for endometrial LIF protein as well as ανβ3 integrin expression. Endometrium was evaluated using immunohistochemistry (IHC) and messenger RNA by real time reverse transcriptase-polymerase chain reaction (PCR) (quantitative real-time reverse transcriptase-PCR) in samples from women with UI as well as healthy control women.
  
  
  RESULTS
  Leukemia inhibitor factor was expressed in epithelial cells in a cyclic fashion in controls, and overall expression in the secretory phase was similar between controls and women with UI, whereas ανβ3 integrin expression was reduced. However, using quantitative real-time PCR, LIF messenger RNA abundance was 4.4-fold lower in women with low levels of ανβ3 integrin expression compared with samples with normal integrins. By immunohistochemistry, ανβ3 integrin expression was always lacking when the histology was out of phase, whereas LIF expression was only negative in a subset of those samples. Reduced endometrial LIF expression was strongly associated with poor reproductive outcomes.
  
  
  CONCLUSIONS
  Endometrial LIF expression peaks in the midsecretory phase and is reduced in some women with UI. The use of LIF in combination with ανβ3 integrin as biomarkers appears to be superior to integrin testing alone when evaluating endometrial receptivity, primarily because of its earlier pattern of expression during the secretory phase.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology and Reproductive Science, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Franasiak
authors.affiliation: Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Holoch
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Lingwen
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Pathology Associates, Greenville Hospital System, Greenville, South Carolina.
authors.forename: David P
authors.initials: DP
authors.lastname: Schammel
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
authors.affiliation: Department of Obstetrics and Gynecology, University of South Carolina School of Medicine, Greenville, Greenville, South Carolina. Electronic address: blessey@ghs.org.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005298:Fertility; D005786:Gene Expression Regulation; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism*; D008183:Luteal Phase / Q000378:metabolism*; D011247:Pregnancy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D013997:Time Factors; D061685:Time-to-Pregnancy; D055815:Young Adult
chemical_list: D015415:Biomarkers; C061248:ITGB3 protein, human; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger
keywords: Implantation; LIF; endometriosis; endometrium; leukemia inhibitory factor