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

Objective: 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. Design: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. Setting: Multiple private IVF clinics. Patient(s): Fifty-eight patients. Samples from 55 patients underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. Intervention(s): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. Main Outcome Measure(s): Combinatorial expression of 12 genes in 101 samples from 58 patients. Result(s): 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%. Receiver operating characteristic analysis found an area under the curve of 0.763 +/- 0.079, significantly greater than 0.5 (random chance prediction). Conclusion(s): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET. (Fertil Steril (R) 2013;99:745-52. (C) 2013 by American Society for Reproductive Medicine.)