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Hum. Reprod. Advance Access originally published online on February 19, 2009
Human Reproduction 2009 24(6):1427-1435; doi:10.1093/humrep/dep011
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF

C.M. Boomsma1,5, A. Kavelaars2, M.J.C. Eijkemans1,3, E.G. Lentjes4, B.C.J.M. Fauser1, C.J. Heijnen2 and N.S. Macklon1

1 Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, F05.126, PO Box 85500, 3508 GA, Utrecht, The Netherlands 2 Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands 3 Department of Public Health, Erasmus Medical Center Rotterdam, PO Box 1738, 3000 DR, Rotterdam, The Netherlands 4 Department of Clinical Chemistry and Hematology, Laboratory of Endocrinology, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands

5 Corresponding address. Tel: +31-88-7558627; Fax: +31-88-755-5433; E-mail: c.m.boomsma{at}umcutrecht.nl

BACKGROUND: The study of human endometrial–embryonic interactions is complicated by the disruptive impact of endometrial sample collection on the process of implantation itself. Endometrial secretion analysis is a novel technique, non-disruptive to implantation. The primary aim of this prospective cohort study was to explore whether a cytokine profile predictive of implantation and clinical pregnancy can be identified in endometrial secretions aspirated immediately prior to embryo transfer following IVF.

METHODS: Endometrial secretions, aspirated immediately prior to embryo transfer from 210 women undergoing IVF, were analyzed using a multiplex immunoassay for 17 soluble regulators of implantation, namely interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-12, IL-15, IL-17, IL-18, tumor necrosis factor (TNF)-{alpha}, interferon (IFN)-{gamma}, macrophage migration inhibitory factor, eotaxin, IFN-{gamma}-inducible 10 kDa protein (IP-10), monocyte chemo-attractant protein-1 (MCP-1), Dickkopf homolog 1, heparin-binding epidermal growth factor and vascular endothelial growth factor (VEGF). In order to detect implantation, daily urine samples were collected after embryo transfer, and human Chorionic Gonadotropin (hCG) concentrations were analyzed by an immunoassay.

RESULTS: Multivariable logistic regression analysis revealed significant associations (negative and positive association, respectively) between MCP-1 (P = 0.005) and IP-10 (P = 0.037) levels and implantation, and between IL-1β (P = 0.047) and TNF-{alpha} (P = 0.023) levels and clinical pregnancy. The predictive value for pregnancy of IL-1β and TNF-{alpha} was observed to be equivalent and additive to that of embryo quality.

CONCLUSIONS: Endometrial secretion cytokine profiling offers a novel, non-disruptive approach to study the role of the endometrium in human embryo implantation and identifies a profile which appears to be conducive to clinical pregnancy.

Clinical trial registration: www.clinicaltrials.gov (nCT00264992 [ClinicalTrials.gov] ).

Key words: cytokines/pregnancy/IVF/ ICSI outcome/endometrial receptivity/implantation

Submitted on November 12, 2008; resubmitted on December 15, 2008; accepted on December 28, 2008.


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