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Open Access Research

Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation

Yulian Zhao1*, Howard Zacur1, Chris Cheadle2, Ning Ning3, Jinshui Fan2 and Nikos F Vlahos4

Author Affiliations

1 Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Lutherville, MD, USA

2 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Department of Obstetrics and Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

4 2nd Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens School of Medicine, Athens, Greece

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Reproductive Biology and Endocrinology 2012, 10:72  doi:10.1186/1477-7827-10-72

Published: 6 September 2012

Abstract

Background

Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles.

Methods

The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3–5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel.

Results

A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p < 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3–5 days after retrieval. During the peri-implantation period (3–5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group.

Conclusion

Luteal support following COS has a profound influence on miRNA profiles. Up or down regulation of miRNAs after P or P + E support suggest a role(s) of luteal support in the peri-implantation uterus in IVF cycles through the regulation of associated target genes.

Keywords:
MicroRNA; Ovarian stimulation; Luteal phase support; Microarray