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. 2022 Feb 28;23(5):2706.
doi: 10.3390/ijms23052706.

LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes

Chupalav Eldarov  1 , Alina Gamisonia  1 , Vitaliy Chagovets  1 , Luiza Ibragimova  1 , Svetlana Yarigina  1 , Veronika Smolnikova  1 , Elena Kalinina  1 , Nataliya Makarova  1 , Victor Zgoda  2 , Gennady Sukhikh  1   3 , Mikhail Bobrov  1
Affiliations

LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes

Chupalav Eldarov et al. Int J Mol Sci. .

Abstract

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.

Keywords: LC-MS; aneuploidy; exometabolomics; human embryo; implantation; metabolomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Score plot of intergroup PLS-DA of day 5 culture medium samples from embryos of different morphological classes.
Figure 2
Figure 2
Score plot of intragroup comparison of metabolite profiles of day 5 culture medium samples from the class 1 embryos by PLS-DA. Samples are grouped according to morphological classification for day 5 embryos.
Figure 3
Figure 3
Score plot of OPLS-DA comparative analysis of metabolomic profiles of day 5 culture media samples from the 1st class embryos with euploid and aneuploid karyotypes.
Figure 4
Figure 4
Score plot of OPLS-DA comparative multivariate statistical analysis of metabolomic profiles of day 5 culture media samples from embryos of the first morphological class with successful and unsuccessful implantation.
Figure 5
Figure 5
Mass spectra of MSn analysis for L-Phenylalanine and L-tryptophan.
Figure 6
Figure 6
Score plot of OPLS-DA of metabolomic profiles of day 3 (A) and day 5 (B) culture media samples from euploid embryos of 1st morphological class with successful and unsuccessful implantation.
See this image and copyright information in PMC

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