Noninvasive amino acid turnover predicts human embryo aneuploidy

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Abstract
Assisted reproduction technology has two significant problems: low success rates and multiple pregnancies. Because of these problems, the priority in IVF clinics is to develop a potential diagnostic test that can be used to select the embryos with the ultimate developmental competence. Aneuploidy screening as embryo selection criteria will ensure that the transferred embryos are euploid and high implantation rate. We hypothesize that aneuploidy in human preimplantation embryos could be discriminated by their amino acid metabolism profile in the spent culture media. Preimplantation genetic testing for aneuploidy results and spent embryo culture medium amino acid content were analyzed for 58 couples. The next-generation sequencing technique was used and coupled with TE biopsy. Forty euploid and 71 aneuploid blastocysts were evaluated. Embryos were cultured individually until day 5 or 6 of embryo development. Spent culture medium was collected after finishing the culture. There was no statistical difference between D3 and D5 embryo morphology between euploid and aneuploid embryos (p > .05). Eight amino acids, including SER, GLY, HIS, ARG, THR, ALA, PRO, and TYR, were detected in the culture medium from the blank control group, euploid group, and aneuploid group. Only TYR amino acid concentration was found significantly higher in the aneuploid group compared to the euploid group (p < .003). Tyrosine amino acid levels equal to and above 76.38 µmol/L could be considered aneuploid. Aneuploid embryos demonstrate altered amino acid turnover in vitro relative to euploid counterparts. A noninvasive method of amino acid profiling will be of value as a tool for routine preimplantation embryo selection among all patient groups.

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