The predictive value of circulating microRNAs biomarkers for the response to controlled ovarian stimulation

Abstract

Infertility problems affect 15% of couples in reproductive age. Among the currently available Assisted Reproductive Technologies (ART), the oocyte retrieval after controlled ovarian stimulation (COS) and the subsequent intra-cytoplasmic sperm injection (ICSI) presents satisfactory results. However, a variable response to stimulation is observed, ranging from absence to an exaggerated response, markedly decreasing the rate of high quality embryos retrieved. Although the serum levels of Anti-Müllerian Hormone (AMH) is currently being used for optimization of COS protocols and improvement embryo quality, eventual Ovarian Hyper Stimulation Syndrome (OHSS)-derived cycle cancelation and clinical complications are observed. Several studies have shown the abnormal expression of microRNAs (miRNAs), small non coding RNAs, in ovarian dysfunctions, such as Ovarian Premature Failure and Polycystic Ovarian Syndrome. The detection of mature miRNAs in serum and plasma opened up perspectives for the use of these molecules as molecular markers for a wide range of pathologies. This study aims to evaluate the predictive value of circulating miRNAs as serum biomarkers for COS response. Peripheral blood will be collected and serum isolated from females prior to COS for infertility treatment by ART. After the treatment, the samples will be split into three groups: Normo-responder (NR); hyperstimulated (OH) and poor-responder (PR). Small RNA fraction will be isolated from serum and submitted to large scale analysis of miRNA expression using Quantitative PCR Arrays. A set of differentially expressed miRNAs will be validated in a larger, independent cohort of samples and the predictive value will be statistically evaluated. We aim to identify a molecular signature capable of predict abnormal response to COS. The results of this study will help to pave the way towards the personalized treatment of infertility, leading to a more efficient and safer oocyte retrieval after controlled ovarian stimulation. (AU)