Levels of Environmental Contaminants in Human Follicular Fluid, Serum, and Seminal Plasma of Couples Undergoing In Vitro Fertilization

Abstract

Environmental chemicals are thought to adversely affect human reproductive function, however there are no studies that have explored the association between failed fertilization and exposure of both partners to environmental contaminants. Therefore, we collected blood and follicular fluid from the female partner and seminal plasma from the male partner of 21 couples attending an in vitro fertilization (IVF) program, in order to determine the extent of the existence of environmental chemicals in these fluids. Any relationship to the outcome of IVF was also considered. Sera and fluids were analysed for a variety of contaminants, including polychlorinated biphenyls, pesticides, cotinine, and the steroids progesterone and estradiol. Of the couples examined, 18 had fertilizations, three of whom became pregnant. There were no fertilizations in three other couples. The contaminants most frequently found in follicular fluid, more than 50% of the samples tested, were p,p'-DDE, mirex, hexachloroethane, 1,2,4-trichlorobenzene, PCB 49, PCB 153, and PCB 180. Cadmium was detected in eight of 21 (38.1%) samples of follicular fluid whereas cotinine was detected in 18 (85.7%). Residue levels of p,p'-DDE, endosulfan I, PCB 99, PCB 138, PCB 153, PCB 180 were quantified in more than 50% of the sera samples examined. Seminal plasma was relatively free of pollutants with mirex being the most frequently detected contaminant found in seven of 21 (33.3%) samples. Mirex could not be detected in the seminal plasma of the husbands whose partner's oocytes failed to fertilize whereas significant levels of mirex were found in the seminal plasma of all couples who had a pregnancy. Cadmium was also found in the follicular fluid of these pregnant subjects. No relationship was found between follicular fluid cotinine in pregnant and non-pregnant subjects. Where identical contaminants were found in both sera and follicular fluids, the levels were about twofold higher in serum and were positively correlated in both fluids. Fertilization was negatively correlated with serum and follicular fluid p,p'-DDE whereas pregnancy was positively correlated with follicular fluid PCB 49. These data reveal that more than 50% of the population of women attending a fertility program have had exposure to environmental chemicals sufficient to produce detectable concentrations in their serum and ovarian follicular fluid. Of the chemical contaminants detected in the serum and follicular fluid of these women, p,p'-DDE was the most frequently detected, had the highest residue levels, and was associated with failed fertilization.

Determination of polybrominated diphenyl ethers in human semen

“…There are several reports regarding the presence of some POPs, such as dioxins, dibenzofurans, and the dioxin-like PCBs, organochlorinated pesticides, in semen or seminal plasma (Kumar et al, 2000;Pant et al, 2007;Schecter et al, 1996;Younglai et al, 2002). In the present study, we found for the first time the presence of PBDEs in human semen and demonstrated that PBDEs could enter human semen like other POPs.…”

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

“…A prior investigation of 619 Saudi Arabian IVF patients reported a positive yet nonsignificant association between FF Pb and oocyte fertilization (OR0 1.45, 95%CI 0.69-3.02), with a 'borderline-significant' positive association for FF Cd (OR01.87, 95%CI 0.91-3.82) in the same logistic regression model including 19 covariates [7]. An earlier, and smaller study reported significantly higher FF Cd concentrations for three Canadian IVF patients who achieved pregnancy, compared to three IVF patients with no fertilized oocytes [15]. Our FF Cd results are consistent with prior publications reporting a positive association with fertilization, yet our FF Pb results are inconsistent with the single prior study reporting an association.…”

“…However, the aforementioned Saudi Arabian IVF study reports an inverse association between blood Cd and the number of 'poor embryos' (r0−0.09, P00.04), yet no association was found for FF Hg, Cd or Pb [7]. In addition, the earlier Canadian IVF study reported no association between measured FF Cd and embryo quality [15]. Embryotoxic effects have been reported following embryo treatment in vitro with low levels of Cd and Pb in the experimental literature [44,45].…”

“…Yet, the results from studies assessing reproductive toxicity associated with trace exposures to Hg, Cd and Pb in women have been inconsistent. 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].…”

“…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].…”