title: T-helper 2 and 3 type immunity to trophoblast in successful in vitro fertilization-embryo transfer.
abstract: OBJECTIVE
  To determine whether peripheral blood mononuclear cell (PBMC) secretion of T-helper (Th)-1 type cytokines and Th-2 and Th-3 type cytokines in women undergoing in vitro fertilization-embryo transfer (IVF-ET) is associated with therapeutic failure and success, respectively.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  One hundred one women undergoing IVF-ET and 19 fertile controls.
  
  
  METHODS
  Peripheral blood was obtained from women undergoing IVF-ET before oocyte retrieval and from 19 nonpregnant fertile controls. The PBMCs were cultured in the presence or absence of a protein extract from either a trophoblast cell line or sperm membrane.
  
  
  METHODS
  Supernatants from PBMC cultures were tested by enzyme-linked immunoabsorbent assay (ELISA) for the Th-1 type cytokines tumor necrosis factor-alpha (TNF)-alpha) and interferon-gamma (IFN)-gamma), the Th-2 type cytokines interleukin (IL)-6 and IL-10, and the Th-3 type cytokine transforming growth factor (TGF)-beta1.
  
  
  RESULTS
  Levels of IL-6 and IL-10 were significantly higher in controls than in infertile women with endometriosis, and levels of IL-10 were higher in controls than in women with unexplained infertility. No differences were found in unstimulated levels of TNF-alpha, IFN-gamma, or TGF-beta1 between infertile patients and controls. In trophoblast-stimulated PBMC cultures, levels of TGF-beta1 were significantly lower in subjects who experienced failed compared with ongoing pregnancies.
  
  
  CONCLUSIONS
  Baseline PBMC secretion of IL-6 and IL-10 is higher in fertile controls than in women with endometriosis, and IL-10 secretion is also higher than in women with unexplained infertility. Trophoblast-stimulated PBMC secretion of TGF-beta1 is positively associated with the establishment of successful pregnancy in women undergoing IVF-ET. Our study provides novel evidence to support a faciliatory role of Th-2 and Th-3 type responses to trophoblast in early pregnancy.
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. eginsburg@partners.org
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Ginsburg
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Gargiulo
authors.forename: Fu-Tsai
authors.initials: FT
authors.lastname: Kung
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Politch
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hill
mesh_terms: D000704:Analysis of Variance; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004624:Embryo Transfer / Q000706:statistics & numerical data; D005260:Female; D005307:Fertilization in Vitro / Q000706:statistics & numerical data*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D011247:Pregnancy; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology; D014327:Trophoblasts / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta