title: Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Lutherville, MD, USA. zhao1@jhmi.edu
authors.forename: Yulian
authors.initials: Y
authors.lastname: Zhao
authors.forename: Howard
authors.initials: H
authors.lastname: Zacur
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
authors.forename: Ning
authors.initials: N
authors.lastname: Ning
authors.forename: Jinshui
authors.initials: J
authors.lastname: Fan
authors.forename: Nikos F
authors.initials: NF
authors.lastname: Vlahos
mesh_terms: D000328:Adult; D003340:Corpus Luteum Maintenance / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018587:Oocyte Donation; D010062:Ovulation Induction; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D014019:Tissue Donors; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D004967:Estrogens; D006727:Hormone Antagonists; D035683:MicroRNAs; D011372:Progestins; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol