1 Relation of Human Cumulus Granulosa Cell Hyaluronan Synthase (HAS-2) Gene expression to Oocyte Developmental Quality in Women Undergoing Intracytoplasmic Sperm Injection Khamiss OA 1 , El-Hamshary MO 2 , Mohamed AA 3 , Mohamed MM 4 1 Animal Biotechnology Department, 2 Molecular Diagnosis of Human Diseases Department Genetic Engineering and Biotechnology Research Institute (GEBRI), Minufiya University, Egypt 3, 4 Department of Obstetrics and Gynecology, Ain Shams University, Egypt Abstract Background: Our knowledge of the dialogue between the oocyte and cumulus cells during oocyte maturation is still scanty. As morphological and kinetics criteria during oocyte development provide poor prediction of both fertilization and implantation ability; study of expression of specific genes of cumulus cells (CC) before intracytoplasmic sperm injection (ICSI) may predict oocyte developmental competence and implantation potential. Objective: to evaluate Hyaluronan Synthase (HAS2) Gene expression of human cumulus cells (ccs) and its relation to oocyte developmental competence. Design: cohort observational analytical study. Methods: samples were isolated from women that participated into a standard long luteal phase down regulation protocol of ICSI technology. The samples underwent RNA extraction and cDNA synthesis. HAS-2 gene expression in cumulus cells was studied using quantitative PCR. HAS-2 gene was expressed in the melting curves for 61 patients. Expression of HAS2 was analyzed in relation to the variables by multivariable analysis. Results: Gene expression data were available from 61 oocytes with median fertilization rate 72.73%. HAS-2 relative quantification (RQ) values showed folding above the control by more than 2 folds (i.e., significant folding) in 90.2% of the studied cases. Multiple regression model for prediction of maturation rate of oocytes using: patient age, baseline FSH level, dose of HMG and RQ of HAS-2 gene expression showed significant prediction value for age and dose of HMG but insignificant prediction as regards FSH level and RQ of HAS-2 gene when single variable was used but good prediction value of R 2 = 0.065, when using the all four variables. Prediction of producing grade-one embryo using 4 variables: patient age, baseline FSH level, dose of HMG and RQ of HAS-2 gene expression showed area under the ROC curve (AUC) = 0.728 and 100% specificity which suggest a good prediction value of the variable used in this model. Multiple logistic regression model for prediction of successful pregnancy using 2 variables: patient age and RQ of HAS-2 gene expression showed area under the ROC curve (AUC) = 0.617 (95% CI, 0.484 to 0.739) and 97.4% specificity which suggest a good prediction value of the variables used in this model. Conclusion: Measurement of HAS2 levels in cumulus cells before ICSI may add an important criterion in complement of morphological evaluation of oocytes and may providing a useful tool for selecting better oocytes with greater chances to be fertilized. HAS2 gene expression can provide a novel approach to predict embryo quality and pregnancy outcome. Key words: HAS2 gene, ICSI, cumulus cells, oocyte quality.