Toxic trace metals and human oocytes during in vitro fertilization (IVF)

Abstract

Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each μg/dL increase in blood Pb concentration (relative risk (RR) = 0.25, 95% confidence interval (CI) 0.03–2.50, P = 0.240). For 15 male IVF partners, each μg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR = 0.19, 95% CI 0.03–1.35, P = 0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses.

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

“…Sample selection and clinical protocols were previously described in detail [17,18]. Briefly, female patients underwent gonadotropininduced ovarian stimulation per clinic protocols.…”

“…Follicular fluid specimens were collected from 48 women, including 40 women with specimens from a single follicle and eight women with specimens from two follicles. Blood and urine specimens were also collected at the time of oocyte retrieval and have previously been described in detail for the overall study cohort [17,28]. Informed consent was obtained from all study participants prior to inclusion in the study.…”

“…Blood specimens were previously analyzed for Hg, Cd, and Pb, and urine specimens were previously analyzed for Cd and additional trace elements using a method optimized for a Perkin Elmer Sciex ELAN DRC II ICP-MS (PerkinElmer Life and Analytical Sciences, Shelton, CT) with dynamic reaction cell (DRC) technology [17,28]. The analytic procedures for blood [30] and urine [31] specimens have been previously described in detail.…”

“…Studies report decreased fecundity or fertility [7][8][9][10][11][12], no association [13,14], or even increased fecundity [7,15] in association with higher exposures. In our studies, we conducted preliminary evaluations of trace metal concentrations measured in blood and urine specimens collected from women undergoing in vitro fertilization (IVF), and reported associations between blood Pb and oocyte maturity [16,17], urine Cd and oocyte fertilization [17], blood Pb level and embryo cleavage [18], and blood Hg and Cd and embryo implantation [19].…”

“…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]. Here, we augment our previous dataset including blood and urine concentrations of toxic trace metals [17] with concentrations of Hg, Cd and Pb measured in single FF specimens collected from women undergoing IVF at our northern California clinic.…”