The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction.
Level 3 - non-randomized controlled study
Prospective observational cohort study
PubMed 38754604 · doi:10.1016/j.envres.2024.119149
What was done
Researchers evaluated 183 women undergoing in vitro fertilization (IVF) between 2005 and 2016 in the prospective Environment and Reproductive Health (EARTH) cohort. On a single day during controlled ovarian stimulation, participants provided urine to quantify 11 phthalate metabolites and serum for untargeted metabolomic profiling via liquid chromatography-high resolution mass spectrometry (C18 negative and HILIC positive columns). Multivariable generalized linear models and pathway enrichment analyses were conducted, followed by a meet-in-the-middle approach to detect overlapping metabolic features and pathways associated with both phthalate concentrations and live birth.
What was found
Metabolic pathway analysis identified 43 pathways in the C18 negative column and 32 pathways in the HILIC positive column significantly associated (p < 0.05) with at least one phthalate metabolite or the molar sum of di-2-ethylhexyl phthalate metabolites. Pathways related to lipid, amino acid, and carbohydrate metabolism were most frequently associated with phthalate exposure. Five pathways were concurrently associated with at least one phthalate metabolite and live birth: tryptophan metabolism, tyrosine metabolism, biopterin metabolism, the carnitine shuttle, and vitamin B6 metabolism. Specific effect estimates and confidence intervals were not reported in the abstract.
Why it matters
This study provides candidate biological mechanisms—specifically perturbations in amino acid, lipid, and vitamin metabolism—that may explain previously observed epidemiological links between preconception phthalate exposure and reduced fertility.
Limits
The sample size was modest (n = 183) and restricted to women undergoing assisted reproduction at a single clinical center, limiting generalizability to unassisted conception. Phthalates and serum metabolites were measured at a single time point during ovarian stimulation, and the untargeted metabolomics approach is exploratory and prone to unmeasured confounding.
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