Trace element concentrations in follicular fluid of small follicles differ from those in blood serum, and may represent long-term exposure

Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes

“…We also detect moderate positive correlations between concentrations of FF Hg and blood Hg, and concentrations of FF Cd and blood Cd, although no correlation for FF Pb and blood Pb. Follicular fluid is a type of blood plasma ultra-filtrate, sharing a similar yet modified chemical composition [20] and we thus anticipated positive correlations between these two compartments for all metals as reported previously [23]. However, the large component of variance attributed to analytic factors and the large relative uncertainty in values that are close to the LOD likely overshadowed any association.…”

“…The FF concentrations of Hg, Cd and Pb measured in our study are generally lower than reported in the literature [7,12,16,[21][22][23]], a comprehensive comparison of which is provided elsewhere [25]. The lower FF values measured in our study may reflect the highly sensitive ICP-MS method employed, coupled to different exposure patterns.…”

“…However, the discrepancy might also reflect non-differential exposure measurement misclassification secondary to variation in sampled follicle diameter and other sources of variability within woman, as well as analytic factors. The degree to which follicle analyte levels reflect blood levels appears to vary by analyte, and FF concentrations increasingly reflect blood concentration with increasing diameter [23]. We aspirated single follicles over 17 mm, however actual diameter was not recorded, precluding adjustment, and single oocytes/embryos were not tracked.…”

“…The constituents of FF might thereby vary from blood for some elements and might account for the independence of FF Pb and blood Pb concentrations in the study sample. Recent research indicates that FF element concentrations approach blood concentrations as a follicle grows and matures, yet concentrations may vary substantially during development [23]. Given the variability of FF metal concentrations with follicle size, use of FF from a single follicle in one ovary is likely to introduce exposure misclassification.…”

“…It is presumed that FF will provide a closer approximation to the biologically-effective dose of a toxicant to an oocyte than achieved using blood or urine measures. Several groups previously reported Hg, Cd and/or Pb concentrations measured in human FF specimens, although with little methodologic detail [7,12,15,[21][22][23]24]. To facilitate investigation of associations between toxic metals in FF and IVF outcomes, our laboratory recently developed and validated a method for the measurement of elements in FF at trace concentrations [25].…”