Higher Concentrations of Essential Trace Elements in Women Undergoing IVF May Be Associated with Poor Reproductive Outcomes Following Single Euploid Embryo Transfer

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 May 24

PMID 38786061

Authors

Roberto Gonzalez-Martin

Andrea Palomar

Silvia Perez-Deben

Stefania Salsano

Alicia Quinonero

Laura Caracena

Rocio Fernandez-Saavedra

Rodolfo Fernandez-Martinez

Estefania Conde-Vilda

Alberto J Quejido

Juan Giles

Carmen Vidal

Jose Bellver

Francisco Dominguez

Affiliations

Soon will be listed here.

Abstract

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations.

Citing Articles

Associations between Non-Essential Trace Elements in Women's Biofluids and IVF Outcomes in Euploid Single-Embryo Transfer Cycles.

Gonzalez-Martin R, Palomar A, Perez-Deben S, Salsano S, Quinonero A, Caracena L J Xenobiot. 2024; 14(3):1093-1108.

PMID: 39189177 PMC: 11348048. DOI: 10.3390/jox14030062.

References

Mirakhori F, Zeynali B, Parvaneh Tafreshi A, Shirmohammadian A . Lithium induces follicular atresia in rat ovary through a GSK-3β/β-catenin dependent mechanism. Mol Reprod Dev. 2013; 80(4):286-96. DOI: 10.1002/mrd.22163. View

Gonzalez-Martin R, Palomar A, Quinonero A, Pellicer N, Fernandez-Saavedra R, Conde-Vilda E . The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer. Int J Mol Sci. 2023; 24(13). PMC: 10341631. DOI: 10.3390/ijms241310968. View

Li D, Liang C, Cao Y, Zhu D, Shen L, Zhang Z . The associations of serum metals concentrations with the intermediate and pregnancy outcomes in women undergoing in vitro fertilization (IVF). Ecotoxicol Environ Saf. 2022; 233:113309. DOI: 10.1016/j.ecoenv.2022.113309. View

Neri C, De Luca C, Doria L, Licameli A, Nucci M, Pellegrino M . Managing fertile women under lithium treatment: the challenge of a Teratology Information Service. Minerva Ginecol. 2018; 70(3):261-267. DOI: 10.23736/S0026-4784.18.04190-4. View

Ingle M, Bloom M, Parsons P, Steuerwald A, Kruger P, Fujimoto V . Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study. J Assist Reprod Genet. 2016; 34(2):253-261. PMC: 5306414. DOI: 10.1007/s10815-016-0853-7. View

Hanson B, Kim J, Osman E, Tiegs A, Lathi R, Cheng P . Impact of paternal age on embryology and pregnancy outcomes in the setting of a euploid single-embryo transfer with ejaculated sperm: retrospective cohort study. F S Rep. 2021; 1(2):99-105. PMC: 8244285. DOI: 10.1016/j.xfre.2020.06.004. View

Castro-Barquero S, Larroya M, Crispi F, Estruch R, Nakaki A, Paules C . Diet quality and nutrient density in pregnant women according to adherence to Mediterranean diet. Front Public Health. 2023; 11:1144942. PMC: 10461001. DOI: 10.3389/fpubh.2023.1144942. View

Wu S, Wang M, Deng Y, Qiu J, Zhang X, Tan J . Associations of toxic and essential trace elements in serum, follicular fluid, and seminal plasma with In vitro fertilization outcomes. Ecotoxicol Environ Saf. 2020; 204:110965. DOI: 10.1016/j.ecoenv.2020.110965. View

Dickerson E, Sathyapalan T, Knight R, Maguiness S, Killick S, Robinson J . Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation. J Assist Reprod Genet. 2011; 28(12):1223-8. PMC: 3241832. DOI: 10.1007/s10815-011-9652-3. View

10.

de Los Santos M, Diez Juan A, Mifsud A, Mercader A, Meseguer M, Rubio C . Variables associated with mitochondrial copy number in human blastocysts: what can we learn from trophectoderm biopsies?. Fertil Steril. 2018; 109(1):110-117. DOI: 10.1016/j.fertnstert.2017.09.022. View

11.

Peacey L, Elphick M, Jones C . Roles of copper in neurokinin B and gonadotropin-releasing hormone structure and function and the endocrinology of reproduction. Gen Comp Endocrinol. 2019; 287:113342. DOI: 10.1016/j.ygcen.2019.113342. View

12.

Ozkaya M, Naziroglu M, Barak C, Berkkanoglu M . Effects of multivitamin/mineral supplementation on trace element levels in serum and follicular fluid of women undergoing in vitro fertilization (IVF). Biol Trace Elem Res. 2010; 139(1):1-9. DOI: 10.1007/s12011-010-8637-x. View

13.

Eftekhari Moghadam A, Taheri Moghadam M, Hemadi M, Saki G . Oocyte quality and aging. JBRA Assist Reprod. 2021; 26(1):105-122. PMC: 8769179. DOI: 10.5935/1518-0557.20210026. View

14.

Schmalbrock L, Weiss G, Rijntjes E, Reinschissler N, Sun Q, Schenk M . Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction. Nutrients. 2021; 13(11). PMC: 8619388. DOI: 10.3390/nu13114134. View

15.

Malavolta M, Piacenza F, Basso A, Giacconi R, Costarelli L, Mocchegiani E . Serum copper to zinc ratio: Relationship with aging and health status. Mech Ageing Dev. 2015; 151:93-100. DOI: 10.1016/j.mad.2015.01.004. View

16.

Skalnaya M, Tinkov A, Lobanova Y, Chang J, Skalny A . Serum levels of copper, iron, and manganese in women with pregnancy, miscarriage, and primary infertility. J Trace Elem Med Biol. 2019; 56:124-130. DOI: 10.1016/j.jtemb.2019.08.009. View

17.

Dodge L, Williams P, Williams M, Missmer S, Toth T, Calafat A . Paternal Urinary Concentrations of Parabens and Other Phenols in Relation to Reproductive Outcomes among Couples from a Fertility Clinic. Environ Health Perspect. 2015; 123(7):665-71. PMC: 4492268. DOI: 10.1289/ehp.1408605. View

18.

Enderle J, Klink U, di Giuseppe R, Koch M, Seidel U, Weber K . Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates. Nutrients. 2020; 12(8). PMC: 7468710. DOI: 10.3390/nu12082489. View

19.

Schrauzer G . Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 2002; 21(1):14-21. DOI: 10.1080/07315724.2002.10719188. View

20.

Rayman M, Winther K, Pastor-Barriuso R, Cold F, Thvilum M, Stranges S . Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial. Free Radic Biol Med. 2018; 127:46-54. DOI: 10.1016/j.freeradbiomed.2018.02.015. View