Embryo Biopsy Can Offer More Information Than Just Ploidy Status

Abstract

As a byproduct of increasing infertility cases, the use of medically assisted reproduction (MAR) has increased. As such, the need to gain information regarding the implantation potential of specific MAR preimplantation embryos prior to transfer has become increasingly critical. One potential source of this information is contained in the blastocoel fluid from day 5/6 embryos. This fluid contains cell-free DNA, proteins, RNA, metabolites, exosomes, etc., and analysis of these contents provides clinicians with an opportunity to gain more data regarding potential of each embryo. While application of preimplantation genetic testing for aneuploidies (PGT-A) may be limited to women of advanced maternal age or with recurrent pregnancy loss, the fluid taken at the time of embryo biopsy can be analyzed for any frozen embryo as well as PGT-A embryos. In both cases, blastocoel fluid analysis provides information regarding a preimplantation embryo's potential for implantation. Moreover, as remnants of apoptosis, embryonic cellfree DNA (cfDNA) and mRNA may lead clinicians to better understand and predict the extent of self-correction occurring within the preimplantation embryo. While analysis of blastocoel components are not yet viable replacements for PGT-A, their study may still reveal critical clinical information about the implantation potential for any given embryo.

Non-Invasive Preimplantation Genetic Testing for Aneuploidy and the Mystery of Genetic Material: A Review Article

“…In the first scenario, a laser cuts between TE cells extruding through zona pellucida. In the later scenario, the BF is removed to prevent ice crystal formation before cryopreservation, which is again achieved with a laser pulse between TE cells [ 35 ]. After the BF is expelled from the embryo, the blastocoel usually collapses upon itself [ 33 , 35 ].…”

The expression of pregnancy-associated plasma protein-A (PAPP-A) in human blastocoel fluid–conditioned media: a proof of concept study

“…In the search for reliable methods to karyotype preimplantation embryos in a manner which is less invasive than trophectoderm biopsy of blastocyst stage embryos, previous literature has demonstrated the presence of cell-free DNA (cfDNA) in BF and correlation with embryonic morphology has been shown as well [24]. Furthermore, cell-free nucleic acid (cfNA) content in human BF-conditioned media (BFCM) may provide additional assessment of embryo implantation potential [25].…”

Fluorescent-dependent comparative Ct method for qPCR gene expression analysis in IVF clinical pre-implantation embryonic testing

“…For human embryos generated via in vitro fertilization (IVF), the potential use of an iteration of pre-implantation embryo genetic testing that utilizes non-embryonic components to predict the embryo’s implantation potential or ploidy status represents a developing idea with the potential to increase successful implantation and pregnancy [ 1 ]. One clear target for such analysis is embryonic blastocoel fluid, the fluid within the blastocoel cavity of a developing embryo, which (i) is extruded from an embryo during biopsy, (ii) is typically discarded, and (iii) is a proven recognized source of cell-free biological macromolecules such as cell-free DNA, mRNA, and miRNA [ 2 ] . These characteristics therefore indicate blastocoel fluid as a prime fluid for predictive gene expression analysis, which can be conducted in a noninvasive manner.…”