title: Predictive biomarkers of preterm delivery in women with ongoing IVF pregnancies.
abstract: In vitro fertilization (IVF) pregnancies potentially have a higher rate of preterm delivery (PTD) than do spontaneously conceived gestations, and differences persist following adjustment for multiple gestation, maternal age, and parity. The reasons for this increased susceptibility to PTD remain incompletely elucidated. To identify potential biomarkers predictive of PTD in IVF subjects, we performed a retrospective analysis of multiple markers in sera obtained during early gestation that have been suggested to be associated with peri-implantation events. Sera from 35 women with a preterm birth and 68 women with a term delivery, obtained between 9 and 11 days after embryo transfer, were tested blindly for concentrations of interleukin (IL)-1β, IL-6, IL-13, IL-17, human epididymal protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (BP)-1, and interferon-γ. Concentrations of HE4 (p=0.001) and IL-13 (p=0.029) were reduced, and levels of IGF-II (p=0.023) and SLPI (p=0.043) were increased, in women who subsequently delivered preterm. By receiver operator curve analysis, the combination of HE4 and IL-13 levels best predicted the outcome preterm birth. The association between deficiencies in circulating HE4 and IL-13 levels during early pregnancy and subsequent PTD suggest that factors contributing to sub-optimal embryo implantation influence length of gestation in women undergoing IVF.
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Tomi T
authors.initials: TT
authors.lastname: Kanninen
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sisti
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Ilana
authors.initials: I
authors.lastname: Ramer
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Goldschlag
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Witkin
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA. Electronic address: sdspando@med.cornell.edu.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Spandorfer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000276:immunology; D007752:Obstetric Labor, Premature / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D015415:Biomarkers; D016207:Cytokines; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: Human epididymal protein 4; In vitro fertilization; Interleukin-13; Preterm birth