Secreted MicroRNA to Predict Embryo Implantation Outcome: From Research to Clinical Diagnostic Application

Abstract

Embryo implantation failure is considered a leading cause of infertility and a significant bottleneck for in vitro fertilization (IVF) treatment. Confirmed factors that lead to implantation failure involve unhealthy embryos, unreceptive endometrium, and asynchronous development and communication between the two. The quality of embryos is further dependent on sperm parameters, oocyte quality, and early embryo development after fertilization. The extensive involvement of such different factors contributes to the variability of implantation potential across different menstrual cycles. An ideal approach to predict the implantation outcome should not compromise embryo implantation. The use of clinical material, including follicular fluid, cumulus cells, sperm, seminal exosomes, spent blastocyst culture medium, blood, and uterine fluid, that can be collected relatively non-invasively without compromising embryo implantation in a transfer cycle opens new perspectives for the diagnosis of embryo implantation potential. Compositional comparison of these samples between fertile women and women or couples with implantation failure has identified both quantitative and qualitative differences in the expression of microRNAs (miRs) that hold diagnostic potential for implantation failure. Here, we review current findings of secreted miRs that have been identified to potentially be useful in predicting implantation outcome using material that can be collected relatively non-invasively. Developing non-invasive biomarkers of implantation potential would have a major impact on implantation failure and infertility.

MicroRNAs in the Regulation of Endometrial Receptivity for Embryo Implantation

“…The endometrium can also be influenced by the implanting embryo. Several studies identified miRNAs that are expressed by embryos and present in embryo secretions [ 116 , 117 , 118 , 119 , 120 ]. Due to the increasingly common use of IVF techniques, blastocyst spent media have been analysed for miRNA and other biomarkers [ 116 , 117 , 118 , 119 , 120 ].…”

“…Several studies identified miRNAs that are expressed by embryos and present in embryo secretions [ 116 , 117 , 118 , 119 , 120 ]. Due to the increasingly common use of IVF techniques, blastocyst spent media have been analysed for miRNA and other biomarkers [ 116 , 117 , 118 , 119 , 120 ]. A few previous reviews discussed miRNAs and embryos, often regarding embryo development but also implantation [ 116 , 117 , 118 , 119 , 120 ].…”

“…Due to the increasingly common use of IVF techniques, blastocyst spent media have been analysed for miRNA and other biomarkers [ 116 , 117 , 118 , 119 , 120 ]. A few previous reviews discussed miRNAs and embryos, often regarding embryo development but also implantation [ 116 , 117 , 118 , 119 , 120 ]. Other previous reviews deliberated the miRNAs secreted by preimplantation blastocysts in facilitating the embryo–endometrium crosstalk to promote implantation [ 118 , 120 ].…”

“…A few previous reviews discussed miRNAs and embryos, often regarding embryo development but also implantation [ 116 , 117 , 118 , 119 , 120 ]. Other previous reviews deliberated the miRNAs secreted by preimplantation blastocysts in facilitating the embryo–endometrium crosstalk to promote implantation [ 118 , 120 ]. Hence, no extensive discussion on this topic is made here.…”

The Emerging Roles and Therapeutic Potential of Extracellular Vesicles in Infertility

“…It was demonstrated that the sperm RNAs involved in the regulation during the process of fertilization and further embryo development (5), and the extracellular vesicles microRNAs derived from human follicular fluid are involved in critically important pathways (including WNT, MAPK, ErbB, and TGFb signaling pathway) for follicle growth and oocyte maturation, which also explaining the correlation between the lack of extracellular vesicle-delivered RNAs and poorer outcomes among azoospermic men after successful microscopic testicular sperm extraction. Also, these results could represent noninvasive biomarkers of oocyte quality or sperm quality in assisted reproductive technology (75).…”