In this study we evaluated possible differences in metabolomic profiles of spent embryo culture media (SECM) of human embryos with distinct morphology, karyotype, and implantation outcomes. A total of 153 samples from embryos of patients undergoing in vitro fertilization (IVF) programs were collected and analyzed by HPLC-MS. Metabolomic profiling and statistical analysis revealed clear clustering of day five SECM from embryos with different morphological classes and karyotype. Profiling of day five SECM from embryos with different implantation outcomes showed 241 significantly changed molecular ions in SECM of successfully implanted embryos. Separate analysis of paired SECM samples on days three and five revealed 46 and 29 molecular signatures respectively, significantly differing in culture media of embryos with a successful outcome. Pathway enrichment analysis suggests certain amino acids, vitamins, and lipid metabolic pathways to be crucial for embryo implantation. Differences between embryos with distinct implantation potential are detectable on the third and fifth day of cultivation that may allow the application of culture medium analysis in different transfer protocols for both fresh and cryopreserved embryos. A combination of traditional morphological criteria with metabolic profiling of SECM may increase implantation rates in assisted reproductive technology programs as well as improve our knowledge of the human embryo metabolism in the early stages of development.
Introduction:This research presents data about embryo capability for implantation based on the study of changes in metabolomic profile of embryo culture media, consumption of constituents of embryo culture media and anamnestic factors predisposing to aneuploid embryos. Determination of glucose and glutamate concentrations in spent media samples from embryos collected on day 5 is a new noninvasive method of assessment embryo quality to efficiency improvement of IVF outcomes.Material and methods: 96 couples underwent IVF program with preimplantation genetic testing (PGT). Spent media samples from embryos that resulted in pregnancy and delivery and samples from embryos that failed to implant were individually collected on day 5, and evaluated using mass-spectrometry.
Results:Сorrelation was identified between metabolomic profile, implantation potential of embryo and ploidy of embryos.
Conclusions:Analysis of composition of embryo culture media maid by method of metabolomic profiling can result in more specific selection of embryos for further transfer.
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