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Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy

Division of Reproduction and Developmental Science, Queen's Medical Research Institute, Centre for Reproductive Biology, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK¹ Assisted Conception Unit, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, UK² MRC Human Reproductive Sciences Unit, Edinburgh, UK³ Scottish Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4SA, UK

Correspondence should be addressed to R A Anderson; Email: richard.anderson{at}ed.ac.uk

The close relationship between cumulus cell function and oocyte developmental competence indicates that analysis of cumulus gene expression is a potential non-invasive method to aid embryo selection and IVF outcome. Cumulus was isolated from 674 oocytes from 75 women undergoing ICSI and gene expression analysed by quantitative RT-PCR. Cumulus expression of cyclooxygenase 2 (PTGS2) was higher with mature oocytes, whereas brain-derived neurotrophic factor (BDNF) was lower when fertilisation was normal. Expression levels of gremlin (GREM1) and BDNF were weak positive and negative predictors of embryo quality respectively. Ranking of GREM1 expression within cohorts of oocytes showed that oocytes associated with the highest GREM1 expression were more likely to be transferred or cryopreserved than discarded (49 vs 33%, P<0.02), although the clinical pregnancy rate was not significantly different. This study demonstrates both the feasibility and difficulties of this method of analysis in the largest such group studied thus far. Novel relationships between BDNF expression and fertilisation were identified, and the potential value of GREM1 expression as a marker of embryo quality supports the further assessment of GREM1 analysis in the context of embryo selection.