Conforti, Alessandro (2017) Impact of Polymorphisms of Gonadotrophins and their receptors on controlled ovarian stimulation. [Tesi di dottorato]

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Standard in vitro fertilization (IVF) protocols are characterized by the administration of exogenous follicle stimulation hormone (FSH) which is widely adopted regimen for controlled ovarian stimulation (COS) in normogonadotrophic women. In daily clinical practice, the ovarian response to these protocols are optimal in about 85% of patients, with more than 3 mature oocytes recruited. In about 12-15% of cases, however, an initial low response is seen, leading to an increase in the daily dose of FSH, resulting in a higher total FSH consumption (e.g. >2500 IU) (Alviggi et al., 2013). These observations lead to the development of the concept of “hypo-response” to COS to identify normogonadotrophic women who have normal estimated ovarian reserves but require high amounts of FSH to obtain an adequate number of oocytes retrieved (De Placido et al., 2005, Ferraretti et al., 2004, Devroey et al., 2009). These women seem to be distinct from classical poor responders because they have normal ovarian reserve, but show an unexpected sub-optimal response when stimulated with standard regimens. Conversely, specific adjustments of classical protocols seem to optimise ovarian response (De Placido et al., 2005). On the basis of the current literature, it is possible to argue that hypo-response could be related to genetic characteristics. More specifically, several lines of evidence indicate that this clinical condition may be related to polymorphisms of the genes of gonadotropins and their receptors (Alviggi et al., 2009b, Alviggi et al., 2013). Doctoral research: objectives and sessions The aim of this research project was to exploit the effects of polymorphisms of gonadotropins and their receptors on ovarian response: • The Session A, developed in the first year, is devoted to the results of retrospective analysis concerning the role of FSH-R receptor polymorphism (rs6166). This findings were recently published in a peer review journal (Alviggi et al., 2016b). • The Session B, developed in the second year, is devoted to the results of a prospective analysis in which eight polymorphism of gonadotropins and their receptors were evaluated. Our findings regarding Italian population were recently published in a peer review journal. (Conforti et al., 2017). The preliminary results about all population included were recently published as a supplement in Human Reproduction Journal (Alviggi et al., 2016c). • The Session C developed in the third year of research is devoted to a Systematic Review and Meta-analysis of available worldwide literature data regarding the effect of gonadotropin and their receptors polymorphism on COS. This analysis includes 33 studies and involves more than 4,000 observations. This systematic review was accepted for submission by Human Reproduction Update editorial board which represent the most eminent journal in Obstetrics and Gynaecology (Journal Citation Reports Thomson Reuters)

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