Abstract
OBJECTIVE: Ovarian follicular stimulation is a fundamental component of human IVF. Women with poor response to stimulation protocols typically have a lower probability for a successful outcome. This study investigated an association between the cumulus cell (CC) proteomic profile and ovarian response. DESIGN: Proteomic analysis of human CCs. MATERIALS AND METHODS: Infertile couples (n=20) donated CCs with informed consent, following oocyte retrieval. Mature cumulus oocyte complexes (COCs) were trimmed with ∼100 cells per single oocyte collected (n=51). CC samples were processed individually and proteomic profiles generated using surface enhanced laser desorption ionization time-of-flight mass spectrometry. The Mann-Whitney non-parametric test compared CC proteomic profiles in 2 groups: Group A=Poor responders (n=24 CCs collected from oocyte retrievals with ≤6 total COCs collected) v. Group B=Normal responders (n=27 CCs collected from oocyte retrievals with >6 total COCs collected). RESULTS: Evaluation of CC proteomic profiles <30kDa discovered protein differences according to ovarian response. Statistical analysis revealed seven proteins showing significant differential expression (P<0.001). Six proteins across the range of 3.8-5kDa demonstrated increased expression in CCs derived from normal responders compared to poor responders (P<0.001). In contrast, one small protein (2.6kDa) showed a significant increase of expression in poor responders not observed in normal responders (P<0.001). Fertilization rates following ICSI were also established to be significantly different between the two groups, Group A=71% v. Group B=88% (P<0.01). CONCLUSIONS: Women who respond poorly to ovarian stimulation protocols display significantly different CC proteomic profiles compared to normal responders. Identification studies are underway to characterize these differentially expressed CC proteins. Further understanding of the follicular environment in cycles of poor ovarian response could impact future patient management and IVF success.
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