Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF.
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)-1beta, 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-1beta (P = 0.047) and TNF-alpha (P = 0.023) levels and clinical pregnancy. The predictive value for pregnancy of IL-1beta 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.


BACKGROUND
www.clinicaltrials.gov (nCT00264992).
Boomsma
C M
CM
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, F05.126, PO Box 85500, 3508 GA, Utrecht, The Netherlands. c.m.boomsma@umcutrecht.nl
Kavelaars
A
A
Eijkemans
M J C
MJ
Lentjes
E G
EG
Fauser
B C J M
BC
Heijnen
C J
CJ
Macklon
N S
NS
D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D010064:Embryo Implantation / Q000276:immunology; D004624:Embryo Transfer; D004717:Endometrium / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D016015:Logistic Models; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies
D015415:Biomarkers; D016207:Cytokines