Abstract
Purpose
We previously reported associations between trace concentrations of Hg, Cd and Pb in blood and urine and reproductive outcomes for women undergoing in-vitro fertilization (IVF). Here we assess measurements in single follicular fluid (FF) specimens from 46 women as a presumably more relevant marker of dose for reproductive toxicity.
Methods
FF specimens were analyzed for Hg, Cd and Pb using sector field-inductively coupled plasma-mass spectrometry (SF-ICP-MS). Variability sources were assessed by nested ANOVA. Multivariable regression was used to evaluate associations for square root transformed metals with IVF outcomes, adjusting for confounders.
Results
An inverse association is detected for FF Pb and fertilization (relative risk (RR) = 0.68, P = 0.026), although positive for Cd (RR = 9.05, P = 0.025). While no other statistically significant associations are detected, odds ratios (OR) are increased for embryo cleavage with Hg (OR = 3.83, P = 0.264) and Cd (OR = 3.18, P = 0.644), and for embryo fragmentation with Cd (OR = 4.08, P = 0.586) and Pb (OR = 2.22, P = 0.220). Positive estimates are observed for Cd with biochemical (RR = 19.02, P = 0.286) and clinical pregnancies (RR = 38.80, P = 0.212), yet with very low precision.
Conclusions
We have identified associations between trace amounts of Pb and Cd in FF from a single follicle, and oocyte fertilization. Yet, the likelihood of biological variation in trace element concentrations within and between follicles, coupled with levels that are near the limits of detection suggest that future work should examine multiple follicles using a ‘one follicle-one oocyte/embryo’ approach. A larger study is merited to assess more definitively the role that these environmental factors could play with respect to egg quality in IVF programs.
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Acknowledgments
We would like to thank Gloria Cheng from the UCSF for assistance in preparing and shipping biologic specimens, Dr. Richard W. Browne at the University at Buffalo for conducting the urine creatinine analysis and Dr. Edward Fitzgerald from the University at Albany for guidance. We extend our gratitude to the study participants whose generosity made this study possible.
Conflict of interest
The authors declare that they have no conflict of interest. This work was supported in part by institutional discretionary research funds available to Drs. Bloom and Fujimoto, and by cooperative agreement no. U38EH000464-01 from the U.S. Centers for Disease Control and Prevention (CDC) to the Wadsworth Center.
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Substantial within-woman biologic variability for the concentrations of metals measured in follicular fluid specimens necessitates a ‘one follicle-one oocyte/embryo’ approach to studies of background exposures and IVF outcomes.
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Bloom, M.S., Kim, K., Kruger, P.C. et al. Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes. J Assist Reprod Genet 29, 1369–1379 (2012). https://doi.org/10.1007/s10815-012-9882-z
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DOI: https://doi.org/10.1007/s10815-012-9882-z