title: Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, School of Public Health Rm. #157, One University Place, Rensselaer, NY 12144, USA. mbloom@albany.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bloom
authors.forename: Keewan
authors.initials: K
authors.lastname: Kim
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Kruger
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: John G
authors.initials: JG
authors.lastname: Arnason
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Steuerwald
authors.forename: Victor Y
authors.initials: VY
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000187:drug effects; D004781:Environmental Exposure; D005260:Female; D005307:Fertilization in Vitro / Q000187:drug effects*; D015571:Follicular Fluid / Q000187:drug effects*; D006801:Humans; D008670:Metals / Q000097:blood / Q000633:toxicity*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D014131:Trace Elements / Q000097:blood
chemical_list: D008670:Metals; D014131:Trace Elements