Mirna Alteration Dependent on Art Outcome in Plasma of Women at the Time of Embryo Transfer and Pregnancy Test

MIRNA ALTERATION DEPENDENT ON ART OUTCOME IN PLASMA OF WOMEN AT THE TIME OF EMBRYO TRANSFER AND PREGNANCY TEST

Alexander Freis1, Andreas Keller3, Nicole Ludwig2, Eckart Meese2, Julia Jauckus1, Thomas Strowitzki1, Ariane Germeyer1 1Department of Gynecologic Endocrinology and Fertility Disorders, Heidelberg University Women’s Hospital, Germany 2Institute of Human Genetics, Saarland University Faculty of Medicine, Germany 3Department for Clinical Bioinformatics, Saarland University, University Hospital, Germany Introduction: Molecular profiling is gaining traction in reproductive medicine. Small non-coding RNAs, so-called miRNAs, are key regulators in physiological but also pathophysiological processes that show a vast impact on fertilization. To deepen our knowledge on molecular changes following embryo transfer (ET) we examined the genome-wide miRNA profile of women undergoing ovarian hyperstimulation.

Material/Methods: Blood samples (N=12) were obtained after informed consent from women undergoing ovarian hyperstimulation to perform in vitro fertilisation by IVF or ICSI. Molecular profiling of maternal plasma of women, who implanted 100% vs. 0%, was done at the day 5 embryo transfer (ET) and pregnancy testing (PT), allowing for paired analysis and investigating the change of miRNA abundance per individual using the Human miRNA Microarray Kit Release 21.0.

Results: By comparing cases with 100% implantation vs. 0% after day 5 transfer we observed, among others, miR-4327 as the most relevant marker. Systems biology analysis of 15 most significant miRNAs between 100% and 0% implantation highlighted 331 genes that have been experimentally validated as targets of these miRNAs.

Conclusion: The presented results show a significant change in miRNA profiles dependent on the ART outcome. Our findings indicate potential downstream effects influencing pregnancies and a prospective use as biomarkers for implantation success. Among the most central miRNAs in the interaction network we found again miR-4327. The target genes of miR-4327 include MAPK1, BARX1, DCRH7, which are known to play an important role in embryonic development.