Interleukin-1 receptor antagonist gene (IL-1RN) polymorphism is a predictive factor of clinical pregnancy after IVF.
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-1beta, 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.
Gremlich
S
S
Department of Gynecology and Obstetrics, CHUV Hospital/Maternity, Avenue Pierre Decker 2, 1011 Lausanne, Switzerland. sandrine.gremlich-irrausch@chuv.ch
Fratta
S
S
Rebellato
E
E
Uras
R
R
Reymondin
D
D
Damnon
F
F
Germond
M
M
Gerber
S
S
D000328:Adult; D015331:Cohort Studies; D015925:Cryopreservation; D005260:Female; D005307:Fertilization in Vitro; D005787:Gene Frequency; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D016015:Logistic Models; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D016896:Treatment Outcome
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9