Gene expression of human cumulus cells as a bio-marker of human embryo potential and pregnancy outcome: a prospective study

Abstract

OBJECTIVE: The pregnancy and live birth rates following intra cytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) attempts remain low. Subjective morphological parameters are still a primary criterion to select healthy embryos used for IVF and ICSI programs. However, such criteria do not truly predict the embryo competence. The aim of this study was to evaluate the interest genes expressed in cumulus cells surronding the oocyte used as biomarkers , to identify the a competent embryo and pregnancy outcome.DESIGN: Human cumulus cells were analyzed by microarrays and confirmed by q-RT PCR.MATERIALS AND METHODS: Cumulus cells from single oocyte provided from normal responder patients (n=43) referred for ICSI for male infertility were analyzed using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. All results were confirmed by q-RT PCR. Gene expression profiles of CC (n=152) surrounding the oocyte were compared according to morphological grade of embryos and pregnancy outcomeRESULTS: We observed that cumulus cells issued from oocytes that developed into embryos with a good morphology (grade 1-2) and or associated with ongoing pregnancy had differing gene expression profile. Among of candidate list genes, BCL2L11 (x6.9, p<0.001), PCK1 (x3.4, p=0.001) and NFIB (x0.3, p<0.001) are significantly expressed in cumulus cells and correlated with embryo potential and successful pregnancy.CONCLUSIONS: The gene expression profiling of human cumulus cells correlates with embryo potential and pregnancy outcome. Our results demonstrate a differential gene expression between human cumulus cells from oocytes resulting in different pregnancy outcome. BCL2L11, PCK1 and NFIB genes can be used as biomarkers to identify a competent embryo and predicting pregnancy. This analysis is a novel concept, offering a new potential strategy for competent embryo selection. OBJECTIVE: The pregnancy and live birth rates following intra cytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) attempts remain low. Subjective morphological parameters are still a primary criterion to select healthy embryos used for IVF and ICSI programs. However, such criteria do not truly predict the embryo competence. The aim of this study was to evaluate the interest genes expressed in cumulus cells surronding the oocyte used as biomarkers , to identify the a competent embryo and pregnancy outcome. DESIGN: Human cumulus cells were analyzed by microarrays and confirmed by q-RT PCR. MATERIALS AND METHODS: Cumulus cells from single oocyte provided from normal responder patients (n=43) referred for ICSI for male infertility were analyzed using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. All results were confirmed by q-RT PCR. Gene expression profiles of CC (n=152) surrounding the oocyte were compared according to morphological grade of embryos and pregnancy outcome RESULTS: We observed that cumulus cells issued from oocytes that developed into embryos with a good morphology (grade 1-2) and or associated with ongoing pregnancy had differing gene expression profile. Among of candidate list genes, BCL2L11 (x6.9, p<0.001), PCK1 (x3.4, p=0.001) and NFIB (x0.3, p<0.001) are significantly expressed in cumulus cells and correlated with embryo potential and successful pregnancy. CONCLUSIONS: The gene expression profiling of human cumulus cells correlates with embryo potential and pregnancy outcome. Our results demonstrate a differential gene expression between human cumulus cells from oocytes resulting in different pregnancy outcome. BCL2L11, PCK1 and NFIB genes can be used as biomarkers to identify a competent embryo and predicting pregnancy. This analysis is a novel concept, offering a new potential strategy for competent embryo selection.