Toxic elements in follicular fluid adversely influence the likelihood of pregnancy and live birth in women undergoing IVF

Abstract

STUDY QUESTION Are follicular fluid (FF), arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) concentrations associated with IVF outcomes among women undergoing IVF? SUMMARY ANSWER There was a non-linear association between higher FF Hg concentration and a lower likelihood of biochemical pregnancy and live birth. Higher FF Pb concentration was also associated with a lower probability of live birth. WHAT IS KNOWN ALREADY Previous research suggests that toxic elements may affect fertility among couples conceiving with and without assistance. However, the results have been inconsistent, possibly related in part to exposure misclassification. Very few studies have used ovarian FF to measure toxic elements, as it requires an invasive collection procedure, yet it may offer a more accurate estimate of a biologically effective dose than blood or urine. STUDY DESIGN, SIZE, DURATION This is a prospective study of 56 women undergoing IVF, from October 2015 to June 2017. FF was collected for analysis on the day of oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS As, Cd, Hg and Pb were determined in 197 FF specimens, using inductively coupled plasma tandem mass spectrometry. FF glutathione peroxidase, glutathione reductase, total glutathione-S-transferase, superoxide dismutase, arylesterase and paraoxonase (PON1p) activities were measured using kinetic enzyme assays. MAIN RESULTS AND THE ROLE OF CHANCE Non-linear associations were detected, in which the probabilities of biochemical pregnancy (P = 0.05) and live birth (P = 0.05) were lower in association with FF Hg greater than ∼0.51 µg/l Hg, adjusted for age, race, cigarette smoking and recent seafood consumption. Higher FF Pb was also associated with a lower likelihood of live birth (relative risk (RR) = 0.68, 95% CI: 0.46, 1.00; P = 0.05). We also found a suggestive, although imprecise, antagonizing mediating effect of PON1p activity on the association between FF Pb and live birth (−28.3%; 95% CI: −358%, 270%). LIMITATIONS, REASONS FOR CAUTION The results should be interpreted judiciously given the limited sample size and difficulty accounting for correlated data in generalized additive models and mediation analyses. Additionally, women undergoing IVF are highly selected with respect to age and socioeconomic status, and so the generalizability of the results may be limited. WIDER IMPLICATIONS OF THE FINDINGS Overall, the results suggest that FF Hg was associated with a lower likelihood of biochemical pregnancy and live birth, with a potential threshold effect, and that higher FF Pb was associated with a lower probability of live birth. These results may help to guide clinical recommendations for limiting the exposure of patients to Hg and Pb and ultimately improve IVF success rates. STUDY FUNDING/COMPETING INTEREST(S) This work was funded in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1R56ES023886-01, to the University at Albany (M.S.B.), and in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1U2CES026542-01, to the Wadsworth Center (P.J.P.). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A

Heavy metals and metalloids exposure and in vitro fertilization: Critical concerns in human reproductive medicine

“…Out of 30 eligible articles included in the present systematic review, 16 articles focused on clinical studies investigating IVF outcomes ( Table 1 ) ( 16 , 21 – 35 ) while 14 articles focused on clinical studies that investigated reproductive concerns ( Table 2 ) ( 36 – 49 ).…”

“…However, it has a limitation of not being easily accessible and highly invasive, therefore, the use of other biomarkers are usually considered, especially when sampling does not pose any risk to patients, in addition to being performed at a minimal cost ( 23 ). Four studies ( 24 , 28 , 33 , 35 ) investigated the associations between heavy metals and metalloids in follicular fluid and in vitro fertilization (IVF) outcomes. A cross-sectional study by Bloom et al ( 23 ) conducted in 46 women undergoing IVF revealed an inverse association between FF Pb concentration and fertilization (RR = 0.68, p = 0.026) ( 24 ).…”

“…Their results showed lower probabilities of biochemical pregnancy ( p = 0.05) and live birth ( p = 0.05) at follicular fluid Hg concentrations greater than 0.51 µg/L Hg. In addition, higher follicular fluid Pb concentrations also correlated with a lower probability of live birth (RR = 0.68, 95% CI: 0.46–1.00; p = 0.05) ( 35 ).…”

Occupational and environmental mercury exposure and human reproductive health - a review

“…Very recently, it was reported that FF mercury level was related with a lower probability of biochemical pregnancy or live birth rate, and higher FF lead concentration was related to a lower probability of live birth. These data suggest that avoidance of exposure to mercury and lead might lead to improved IVF success rates ( 70 ). However, more data are required on this aspect.…”

Comprehensive Review Regarding Mercury Poisoning and Its Complex Involvement in Alzheimer’s Disease

“…Consumption of seafood contaminated with trace elements could be behind the positive correlation of the specific markers. Non-linear higher Hg in ovaries and a lower probability of biochemical pregnancy and live birth (p = 0.05) (weekly-60% versus annually 16%), semen parameters (50%, 46% and 31%) and reproductive outcomes in both genders using hair or urine Hg levels (0.72 ppm/0.3-0.6) suggest primary sources of exposure [137][138][139][140].…”