Infertility affects one in six couples and assisted reproductive technologies cannot always provide a solution, especially when oocyte quality is affected. Here, we will explore two strategies to improve the developmental competence of ‘damaged’ oocytes, as can happen during vitrification, or associated with advanced maternal age. Due to similarities in the physiology of reproduction, ageing and the application of assisted reproductive technology, the horse will be used as a model for human. First, we will identify key signalling molecules supporting oocyte maturation in the natural follicular environment in human and horses: extracellular vesicles and their microRNA content. Promising candidate molecules will be supplemented to in vitro maturation medium to improve cytoplasmic quality and resistance. As a second, more radical therapy, we will perform maternal spindle transfer from lesser to superior quality oocytes, thus replacing the cytoplasm. Outcome parameters include mitochondrial activity, embryo development rates and quality in terms of morphokinetics, genomics and transcriptomics, as well as pregnancy rates in the horse model. The most promising treatments will be validated in human oocytes donated for research. This project will generate fundamental insight in the relative contribution of the nucleus and the cytoplast in oocyte quality, while providing two novel yet achievable strategies to cope with oocyte related infertility.