Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential

This study identified a 12-gene signature in human cumulus cells predictive of pregnancy across multiple clinics. The positive predictive value of our test was 81% with an area under the receiver operating characteristic of 0.763  0.079.


Amy E. Iager, M.Sc., Arif M. Kocabas, Ph.D., Hasan H. Otu, Ph.D., Patricia Ruppel, Ph.D., Anna Langerveld, Ph.D., Patricia Schnarr, B.Sc., Mariluz Suarez, M.Sc., John C. Jarrett, M.D., Joe Conaghan, Ph.D., Guilherme J.M. Rosa, Ph.D., Emilio Fernández., M.D., Richard G. Rawlins, Ph.D., Jose B. Cibelli, D.V.M., Ph.D., Javier A. Crosby, Ph.D.

Volume 99, Issue 3, Pages 745-752.e6, 1 March 2013



To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice.


Retrospective analysis of single human cumulus-oocyte-complexes using combined microarray and qRT-PCR approach.


Multiple private IVF clinics.


58 patients, 55 of which corresponded to qRT-PCR analysis and 27 of those resulted in live birth.


Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately following oocyte retrieval. Pregnancy prediction analysis employed leave-one-out cross-validation with weighted voting.

Main Outcome Measure(s):

Combinatorial expression of 12 genes in 101 samples from 58 patients.


We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78%, a sensitivity of 72%, a specificity of 84%, a positive predictive value of 81%, and a negative predictive value of 76%. ROC analysis found an area under the curve of 0.763 ± 0.079, significantly greater than 0.5 (random chance prediction).


Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET.

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