Abstract

Circulating or “extracellular” microRNAs (miRNAs) detected in biological fluids, could be used as potential diagnostic and prognostic biomarkers of several disease, such as cancer, gynecological and pregnancy disorders. However, their contributions in female infertility and in vitro fertilization (IVF) remain unknown. This study investigated the expression profiles of five circulating miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR-320a) in human follicular fluid from 91 women with normal ovarian reserve and 30 with polycystic ovary syndrome (PCOS) and their ability to predict IVF outcomes. The combination of FF miR-30a, miR-140 and let-7b expression levels discriminated between PCOS and normal ovarian reserve with a specificity of 83.8% and a sensitivity of 70% (area under the ROC curve, AUC = 0.83 [0.73–0.92]; p < 0.0001). FF samples related to low number of mature oocytes (≤2) contained significant less miR-320a levels than those related to a number of mature oocytes >2 (p = 0.04). Moreover, FF let-7b predicted the development of expanded blastocysts with 70% sensitivity and 64.3% specificity (AUC = 0.67 [0.54–0.79]; p = 0.02) and FF miR-29a potential to predict clinical pregnancy outcome reached 0.68 [0.55–0.79] with a sensitivity of 83.3% and a specificity of 53.5% (p = 0.01). Therefore, these miRNAs could provide new helpful biomarkers to facilitate personalized medical care during IVF.

Highlights

  • Development[30,31]

  • MiRNA differential expression in follicular fluid (FF) samples from women with PCOS compared to women with normal ovarian reserve

  • Comparison of the expression profiles showed that miR-30a was significantly up-regulated (p = 0.006), while miR-140 and let-7b were significantly down-regulated (p = 0.01 for both) in FF pools from patients with PCOS (n = 30) compared to women with normal ovarian reserve (n = 91) (Fig. 1A–C)

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Summary

Introduction

One recent study suggested the association between miR-320a expression in FF and embryo quality[32], the use of the expression profile of circulating miRNAs in the oocyte micro-environment as a tool to predict blastocyst development and clinical pregnancy outcomes during IVF has never been investigated. The expression profiles of five circulating miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR320a) were compared in FF samples from women with normal ovarian reserve and with PCOS, undergoing IVF/ Intra-cytoplasmic sperm injection (ICSI) procedure, with the aim of identifying new efficient biomarkers related to PCOS. Some circulating miRNAs could constitute non-invasive powerful tools for the prediction of blastulation and clinical pregnancy outcome towards the development of a personalized IVF strategy

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