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Hum. Reprod. Advance Access originally published online on March 10, 2008
Human Reproduction 2008 23(5):1200-1206; doi:10.1093/humrep/den034
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© The Author 2008. 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

Interleukin-1 receptor antagonist gene (IL-1RN) polymorphism is a predictive factor of clinical pregnancy after IVF

S. Gremlich1,3, S. Fratta2, E. Rebellato2, R. Uras2, D. Reymondin1, F. Damnon1, M. Germond2 and S. Gerber1,3

1 Department of Gynecology and Obstetrics, CHUV Hospital/Maternity, Avenue Pierre Decker 2, 1011 Lausanne, Switzerland 2 Reproductive Medicine Unit, CHUV Hospital, 1011 Lausanne, Switzerland

3 Correspondence address. E-mail: sandrine.gremlich-irrausch{at}chuv.ch; stefan.gerber{at}chuv.ch

BACKGROUND: Only 25% of IVF transfer cycles lead to a clinical pregnancy, calling for continued technical progress but also more in depth analysis of patients' individual characteristics. The interleukin-1 (IL-1) system and matrix metalloproteinases (MMPs) are strongly implicated in embryo implantation. The genes coding for IL-1Ra (gene symbol IL-1RN), IL-1β, MMP2 and MMP9 bear functional polymorphisms. We analysed the maternal genetic profile at these polymorphic sites in IVF patients, to determine possible correlations with IVF outcome.

METHODS: One hundred and sixty women undergoing an IVF cycle were enrolled and a buccal smear was obtained. The presence of IL-1RN variable number of tandem repeats and IL-1B + 3953, MMP2-1306 and MMP9-1562 single nucleotide substitutions were determined. Patients were divided into pregnancy failures (119), biochemical pregnancies (8) and clinical pregnancies (33).

RESULTS: There was a 40% decrease in IL-1RN*2 allele frequency (P = 0.024) and a 45% decrease in IL-1RN*2 carrier status in the clinical pregnancy group as compared to the pregnancy failure group (P = 0.017). This decrease was still statistically significant after a multivariate logistic regression analysis. The likelihood of a clinical pregnancy was decreased accordingly in IL-1RN*2 carriers: odds ratio = 0.349, 95% confidence interval = 0.2–0.8, P = 0.017. The IL-1B, MMP2 and MMP9 polymorphisms showed no correlation with IVF outcome.

CONCLUSIONS: IL-1RN*2 allele carriage is associated with a poor prognosis of achieving a pregnancy after IVF.

Key words: interleukin-1/receptor antagonist/polymorphism/IVF/clinical pregnancy

Submitted on October 25, 2007; resubmitted on December 20, 2007; accepted on January 22, 2008.


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