Abstract

Women undergoing infertility treatment are routinely subjected to one or more tests of ovarian reserve. Therefore, an adequate assessment of the ovarian reserve is necessary for the treatment. In this study, we aimed to characterize the potential role of microRNAs (miRNAs) as biomarkers for women with different ovarian reserves. A total of 159 women were recruited in the study and classified according to their anti-Müllerian hormone (AMH) level into three groups: (1) low ovarian reserve (LAMH, n = 39), (2) normal ovarian reserve (NAMH, n = 80), and (3) high ovarian reserve (HAMH, n = 40). SurePrint Human miRNA array screening and reverse transcription-quantitative PCR (RT-qPCR) were respectively employed to screen and validate the miRNA abundance level in the three tested groups. Compared with NAMH, the abundance level of 34 and 98 miRNAs was found to be significantly altered in LAMH and HAMH, respectively. The abundance level of miRNAs was further validated by RT-qPCR in both, the screening samples as well as in an independent set of validation samples. The abundance levels of the validated miRNAs were significantly correlated with the AMH level. The best AUC value for the prediction of the increase and decrease in the AMH level was obtained for the miR-100-5p and miR-21-5p, respectively. The level of miRNAs abundance correlates with the level of AMH, which may serve as a tool for identifying women with a different ovarian reserve and may help to lay the ground for the development of novel diagnostic approaches.

Highlights

  • Assessment of the ovarian reserve has become essential to determine the strategy for the treatment of female infertility

  • A statistically significant difference was detected between the three groups in terms of the mean age, PRL, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Basal E2, Testosterone, Androstenedione, Dehydroepiandrosterone Sulfate (DHEA-S), and antral follicle count (AFC) (P < 0.05)

  • The difference in miRNA abundance level was determined in women with normal, low, and high ovarian reserve by miRNA microarray and reverse transcription-quantitative PCR (RT-qPCR) analyses

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Summary

Introduction

Assessment of the ovarian reserve has become essential to determine the strategy for the treatment of female infertility For this purpose, several non-invasive clinical, endocrinological, and ultrasonographic examinations, at the early follicular phase, have been applied. As miRNAs seem to be an important regulator of gene expression during follicular development and maturation, we hypothesized that circulating miRNAs in the early follicular phase could serve as potentially useful biomarkers for predicting ovarian reserve. To address this hypothesis, we characterized the abundance level of circulating miRNAs in women undergoing assisted reproductive technology (ART) using a large panel of human miRNA arrays. Data were analyzed to determine whether circulating miRNA profiles correlate

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