Prediction of the response to controlled ovarian hyperstimulation through detection of serum microRNAs in patients undergoing in assisted reproductive procedures

Abstract

Conjugal infertility is the inability of conceiving after one year of regular sexual activities without using contraceptive methods. Assisted Human Reproduction (AHR) procedures, which include Controlled Ovarian Hyperstimulation (COH) followed by Intracytoplasmic Sperm Injection (ICSI), are the best treatment options. However, variable responses to the COH protocols are obtained, ranging from absence of response to ovarian hyperstimulation. Despite the use of serum markers predict ovarian response may optimize the COH protocols, many patients undergo cycle cancellation and clinical complications due to aberrant COH response. MicroRNAs (miRNA), small RNAs that do not code for proteins have been implicated in ovarian function, and development of Polycystic Ovary Syndrome and most recently, on the response to COH. As these molecules are reliably detected in blood serum or plasma, miRNAs emerge as promising molecular markers and disease predictors. On the other hand, its potential as response markers to COH remains poorly understood. This present project aims to evaluate the predictive potential of circulating miRNA in response to COH in serum of patients that prior to cicles of AHR. Peripheral blood will be collected from patients before COH (n=90) and then they will be classified into two groups: (1) Normoresponder (NR, n=30); (2) Hyper responder (Hiper, n=30); (3) Poor responder (n=30), according to the number of oocytes retrieved. The fraction of small RNAs will be isolated from the blood serum and subjected to the detection of miRNAs in large scale by real time quantitative PCR Arrays. Differentially expressed miRNAs will be validated posteriorly in an independent cohort of patients. We aim to identify the molecular signature of miRNAs that will be capable of predicting the response to COH. The results obtained in this study will contribute in the optimization of protocols, generating better results and more successful treatments.