T-helper 2 and 3 type immunity to trophoblast in successful in vitro fertilization-embryo transfer.
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.
Ginsburg
Elizabeth S
ES
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. eginsburg@partners.org
Xiao
Ling
L
Gargiulo
Antonio R
AR
Kung
Fu-Tsai
FT
Politch
Joseph A
JA
Schust
Danny J
DJ
Hill
Joseph A
JA
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
D016207:Cytokines; D016212:Transforming Growth Factor beta