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Evaluation of Controlled Ovarian Stimulation Protocols in Patients with Normal and Low Ovarian Reserve: Analyses of miRNAs and Selected Target Genes Involved in the Proliferation of Human Cumulus Cells and Oocyte Quality
Authors:Giulia Russo  Valentina Notarstefano  Nina Montik  Giorgia Gioacchini  Elisabetta Giorgini  Anna Rita Polidori  Fulvia Antonia Candela  Andrea Ciavattini  Maurizio Cignitti  Oliana Carnevali
Affiliation:1.Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy; (G.R.); (V.N.); (G.G.); (E.G.);2.Clinica Ostetrica Ginecologica, Università Politecnica delle Marche, Ospedale G. Salesi, Via F. Corridoni 11, 60131 Ancona, Italy; (N.M.); (A.R.P.); (F.A.C.); (A.C.); (M.C.)
Abstract:The oocyte and the surrounding cumulus cells (CCs) are deeply linked by a complex bidirectional cross-talk. In this light, the molecular analysis of the CCs is nowadays considered to be precious in providing information on oocyte quality. It is now clear that miRNAs play a key role in several ovarian functions, such as folliculogenesis, steroidogenesis, and ovulation. Thus, in this study, specific miRNAs, together with their target genes, were selected and investigated in CCs to assess the response of patients with normal (NR) and low (LR) ovarian reserve to two different controlled ovarian stimulation (COS) protocols, based on rFSH and hMG. Moreover, a Fourier transform infrared microspectroscopy (FTIRM) analysis was performed to evaluate DNA conformational changes in CCs and to relate them with the two COS protocols. The results evidenced a modulation of the expression of miRNAs and related target genes involved in CCs’ proliferation, in vasculogenesis, angiogenesis, genomic integrity, and oocyte quality, with different effects according to the ovarian reserve of patients. Moreover, the COS protocols determined differences in DNA conformation and the methylation state. In particular, the results clearly showed that treatment with rFSH is the most appropriate in NR patients with normal ovarian reserve, while treatment with hMG appears to be the most suitable in LR patients with low ovarian reserve.
Keywords:rFSH treatment  hMG treatment  oocyte quality  ovarian reserve  cumulus cells  assisted reproduction technology (ART)  DNA conformation  FTIR microspectroscopy
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