Metabolomic signatures in blastocyst spent culture medium as noninvasive predictors of live birth: a pilot study

Research Question: Can metabolomic profiling of blastocyst spent culture medium (SCM) serve as a non-invasive tool to predict live birth?
Design: This pilot study investigated the association between metabolite profiles in SCM and clinical outcomes following single blastocyst transfer. Seventy SCM samples were analyzed using untargeted liquid chromatography-mass spectrometry (LC-MS). Metabolites were identified via Human Metabolome Database (HMDB) and Compound Discoverer 3.3. Statistical analyses were performed using SPSS.
Results: Six metabolites exhibited significant differences between pregnancy and non-pregnancy groups, while ten metabolites varied between the live birth and non-live birth groups. Notably eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, decreased in pregnancy cases. In contrast 1-(4-methoxyphenyl)- 3-pentanone and (2S)-2-(6-methoxynaphthalen-2-yl) propanoic acid were consistently elevated in both pregnancy and live birth groups. Additional differential metabolites included L-glutamine, pyroglutamylglycine, alanylproline, and 15,16-dihydroxyoctadecanoic acid, potentially reflecting implantation-related metabolic activity. Logistic regression and receiver operating characteristic (ROC) curve analyses demonstrated acceptable predictive performance, with an area under curve (AUC) values of 0.788 for pregnancy and 0.834 for live birth.
Conclusions: Metabolomic profiling of SCM may offer a promising noninvasive adjunct to embryo selection strategies. While these findings suggest biological relevance of several metabolites, particularly lipids and amino acid derivatives, larger studies are needed to validate predictive value and clinical applicability.