• Cengiz Karakaya, Ozlem Guzeloglu-Kayisli, Asli Uyar, Amanda N Kallen, Elnur Babayev, Nuray Bozkurt, Evrim Unsal, Onur Karabacak, and Emre Seli.
• Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Gazi University School of Medicine, Ankara, Turkey.
• Fertil. Steril. 2015 Jun 1;103(6):1469-76.e1-3.

ObjectiveTo analyze the association of micro-ribonucleic acid (miRNA) expression with the number of oocytes retrieved, in women undergoing in vitro fertilization (IVF).DesignExperimental study.SettingAcademic medical center.Patient(S)A total of 189 women undergoing IVF-intracytoplasmic sperm injection (ICSI).Intervention(S)Pooled cumulus cells were collected.Main Outcome Measure(S)Poor responders were identified as patients who produced fewer oocytes than the 25th percentile of their respective age group. MicroRNAs were extracted from cumulus cells, and an miRNA microarray was performed, comparing poor responders (n = 3) to non-poor responders (n = 3). Expression of miR-21-5p (active strand of miR-21) and miR-21-3p was tested in poor responders (n = 21) and non-poor responders (n = 29), using reverse transcription real-time polymerase chain reaction (qRT-PCR). Regulation of miR-21-5p and miR-21-3p, in human granulosa-like tumor (KGN) cells, by estradiol (E2), was tested in vitro.Result(S)MicroRNA microarray analysis showed up-regulation of 16 miRNAs and down-regulation of 88 miRNAs in poor responders. Notably, miR-21 was significantly up-regulated 5-fold in poor-responder samples. Analysis using qRT-PCR confirmed that miR-21-5p expression was significantly up-regulated in poor responders, whereas miR-21-3p expression was significantly lower, suggesting that elevated miR-21-5p expression in cumulus cells is not regulated at the pre-miR-21 level in poor responders. Both miR-21-5p and miR-21-3p were increased in KGN cells in response to higher doses of E2; their expression was not affected at lower E2 concentrations.Conclusion(S)We found that poor response to IVF is associated with altered miRNA expression in cumulus cells, specifically with elevated expression of miR-21-5p, and that this elevated expression is independent of lower serum E2 levels in poor responders.Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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