Dataset Information

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

ABSTRACT: Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n = 34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures.

SUBMITTER: Butts CD

PROVIDER: S-EPMC7845532 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Butts Celeste D CD Bloom Michael S MS McGough Alexandra A Lenhart Nikolaus N Wong Rebecca R Mok-Lin Evelyn E Parsons Patrick J PJ Galusha Aubrey L AL Yucel Recai M RM Feingold Beth J BJ Browne Richard W RW Fujimoto Victor Y VY

Ecotoxicology and environmental safety 20201229

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exp ...[more]

PMID: 33385679

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Project description:Study questionAre follicular fluid (FF), arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) concentrations associated with IVF outcomes among women undergoing IVF?Summary answerThere 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 alreadyPrevious 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 durationThis 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 methodsAs, 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 chanceNon-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 cautionThe 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 findingsOverall, 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 interestsThis 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 numberN/A.

Project description:BACKGROUND: It has become increasingly clear that the follicular microenvironment of the maturing human oocyte is a determining factor for the implantation potential of an embryo deriving from that oocyte. Indeed the quality and maturity of an oocyte are influenced by the level of intrafollicular oxygen content which, in turn, is proportional to the degree of follicular vascularity. The aim of the study was to establish whether there is a relationship between follicular fluid VEGF concentrations, perifollicular vascularity and reproductive outcome in normal responders under the age of 35 undergoing IVF. MATERIALS AND METHODS: Sixty-one consecutive patients, all at their first IVF cycle, were included in the study. All patients had primary infertility due to male factor or tubal factor. At oocyte retrieval, the perifollicular vascularity of two follicles per ovary was estimated qualitatively through power Doppler blood flow, for a total of two hundred forty-four follicles. The follicular fluid from the identified follicles was centrifuged and stored until VEGF assay. The maturity and fertilization rate of the corresponding oocytes as well as embryo quality and pregnancy rate were recorded. RESULTS: In our study, we found VEGF levels to be significantly correlated with grade of perifollicular vascularity. Oocytes obtained from follicles with the higher grade of vascularization also showed a higher rate of fertilization, embryos, a better quality and higher pregnancy rates were obtained in women with highly vascularized follicles. Perifollicular blood flow doppler indices seem to predict oocyte viability and quality. Moreover, VEGF may play a potential role in the development of the perifollicular capillary network. DISCUSSION: The ability of a given follicle to express VEGF and develop an adequate vascular network may be inter-related in patients under the age of 35. An adequate blood supply may be fundamental important in the regulation of intrafollicular oxygen levels and the determination of oocyte quality.

Project description: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.

Dataset Information

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

Publications

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

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