Variability of essential and non-essential trace elements in the follicular fluid of women undergoing in vitro fertilization (IVF)

Butts, Celeste D.; Bloom, Michael S.; McGough, Alexandra; Lenhart, Nikolaus; Wong, Rebecca S. Y.; Mok-Lin, Evelyn; Parsons, Patrick J.; Galusha, Aubrey L.; Yucel, Recai; Feingold, Beth J.; Browne, Richard W.; Fujimoto, Victor Y.

doi:10.1016/j.ecoenv.2020.111733

Cited by 17 publications

(29 citation statements)

References 65 publications

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“…To our surprise, the TE concentrations differed strongly between the FF from the same woman, even more intensively than among all the serum samples from the 40 women analyzed in this study. This result is in some agreement with a recent report on essential and non-essential TE in FF from the United States, where the differences were associated with demographic and clinical parameters, such as age, race, or BMI [51]. Unfortunately, data from matched serum samples of these U.S. American women are currently not available.…”

Section: Discussionsupporting

confidence: 90%

Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction

Schmalbrock

Weiss²,

Rijntjes

et al. 2021

Nutrients

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Female subfertility is a growing concern, especially in view of an increasing prevalence of polycystic ovary syndrome (PCOS). Assisted reproductive technologies (ART) offer a perspective for pregnancy, but the outcome rate is still suboptimal. The trace elements (TE), copper (Cu), selenium (Se), and zinc (Zn) are essential for fertility and development. We hypothesized that TE concentrations are related to oocyte quality and growth and affect pregnancy outcomes in women undergoing ART. Concentrations of TE were measured by total reflection X-ray fluorescence. Extracellular glutathione peroxidase 3 (GPX3) and selenoprotein P (SELENOP) were determined as additional Se biomarkers. Corresponding serum and follicular fluid (FF) samples were available from women with (n = 20) and without (n = 20) PCOS diagnosis undergoing hormone treatment within the ART procedure, respectively, and FF samples were classified into five groups based on morphological assessment. Serum showed higher TE concentrations than FF, and TE levels correlated positively between both matrices. Individual FF from the same women showed surprisingly high variability in TE concentration, and follicles without oocytes displayed the lowest TE concentrations. Both Se biomarkers GPX3 and SELENOP were present in FF and correlated positively to Se concentrations. Some notable relationships were observed between morphokinetic parameters, TE concentrations, and GPX3 activity. A slightly depressed serum Zn concentration was observed in PCOS. Our results indicate a direct relationship between TE in serum and FF, positive correlations between the three Se biomarkers in FF, and high variability between the FF from the same woman with the lowest TE concentrations in the follicles with the poorest quality. The differences observed in relation to PCOS diagnoses appear relatively minor. Collectively, the data support the notion that TE assessment of follicles may contribute to optimal oocyte selection and subsequently influence ART success.

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Section: Discussionsupporting

confidence: 90%

Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction

Schmalbrock

Weiss²,

Rijntjes

et al. 2021

Nutrients

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“…Median FF concentrations were 0.34 µg/l for As, 0.34 µg/l for Hg, 18.1 ng/L for Cd and 0.06 µg/l for Pb. As summarized in Supplementary Table SI , we previously reported that the majority of FF As, Hg and Cd variability was attributed to sources between women, while most FF Pb variability was attributed to sources between follicles ( Butts et al , 2021 ).…”

Section: Resultsmentioning

confidence: 97%

“…Although we simultaneously modelled toxic elements as predictors of IVF outcomes, we did not account for their potential interactions and so a larger future investigation will be necessary to more definitively assess the simultaneous impact of FF toxic elements. However, our FF exposure biomarker may allow for a closer approximation of a biologically effective dose than blood and urine, and our collection of up to four individual follicles offers an advantage over the more frequently employed pooled follicle approach, which may be subject to exposure measurement error ( Butts et al , 2021 ). We also adjusted for seafood consumption, to reduce residual confounding by diet, the primary non-occupational exposure source for Hg.…”

Section: Discussionmentioning

confidence: 99%

“…Ovarian FF surrounds the oocyte, directly reflecting its developmental microenvironment ( Gosden et al , 1988 ). Hence, concentrations of toxic elements in FF may provide more accurate indicators of the biologically effective doses that influence reproductive outcomes, in comparison to blood or urine ( Butts et al , 2021 ). Additionally, toxic elements may have non-monotonic or threshold-type effects on IVF outcomes ( Zhu et al , 2020 ), which have been under-investigated.…”

Section: Introductionmentioning

confidence: 99%

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

Butts

Bloom

McGough

et al. 2021

Human Reproduction Open

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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

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“…FF is composed of the secretions of granulosa and theca cells combined with plasma exudates. The determination of metabolites in FF is often regarded as a reliable method for the evaluation of exposure to factors affecting reproductive outcomes [ 3 , 4 ]. A recent study on oxidative lipid metabolomics of FF pointed out that fifteen oxidative lipid metabolites closely related to the arachidonic acid metabolic pathway in patients with decreased ovarian reserve were significantly lower than those in the normal ovarian reserve group, indicating that dysfunction of oxidative lipid metabolism was closely related to ovarian reserve function [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of nicotinamide on follicular development and the quality of oocytes

Yang

Feng

et al. 2022

Reprod Biol Endocrinol

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Background Nicotinamide (NAM) is an important antioxidant, which is closely related to female fertility, but its role has not been clearly elucidated. The purpose of the present study was to investigate the effects of NAM on follicular development at different stages and the quality of oocytes. Methods The concentration of NAM in follicular fluid (FF) of 236 women undergoing in vitro fertilization (IVF) was ascertained by enzyme-linked immunosorbent assay (ELISA), and the correlation between NAM and clinical indexes was analyzed. During the in vitro maturation (IVM) of mice cumulus-oocyte complexes (COCs), different concentrations of NAM were added to check the maturation rate and fertilization rate. The reactive oxygen species (ROS) levels in the oocytes treated with different hydrogen peroxide (H2O2) and NAM were assessed. Immunofluorescence staining was performed to measure the proportion of abnormal spindles. Results The level of NAM in large follicles was significantly higher than that in small follicles. In mature FF, the NAM concentration was positively correlated with the rates of oocyte maturation and fertilization. Five mM NAM treatment during IVM increased maturation rate and fertilization rate in the oxidative stress model, and significantly reduced the increase of ROS levels induced by H2O2 in mice oocytes. Conclusions Higher levels of NAM in FF are associated with larger follicle development. The supplement of 5 mM NAM during IVM may improve mice oocyte quality, reducing damage caused by oxidative stress.

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Variability of essential and non-essential trace elements in the follicular fluid of women undergoing in vitro fertilization (IVF)

Cited by 17 publications

References 65 publications

Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction

Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction

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

Effects of nicotinamide on follicular development and the quality of oocytes

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