# Association between trace metal element concentrations in human blood plasma and early MAR embryological outcomes: a couple-based prospective cohort study

## TL;DR

This study explores how trace metal elements in blood plasma affect early embryo development in IVF treatments, finding both harmful and beneficial effects.

## Contribution

The study is the first to examine trace metal exposure in both partners and couples, identifying specific metals that influence IVF outcomes.

## Key findings

- High exposure to trace metal mixtures in couples and males was linked to fewer high-quality embryos and blastocysts.
- Metals like iron, lithium, strontium, and molybdenum positively influenced embryological outcomes, while silver and thallium had adverse effects.

## Abstract

What are the effects of plasma trace metal element exposure on early embryological outcomes of IVF in couples?

Exposure to plasma trace metal elements before treatment is associated with early embryological outcomes of IVF in couples and both partners, with both harmful and beneficial effects on embryonic development.

Trace metal element exposure is one of the strongest determinants of IVF outcomes, but existing studies have certain limitations, such as the limited range of trace metal elements considered, and most have focused only on maternal exposure, overlooking the contribution of paternal exposure. Few studies have explored the association between trace metal elements and early embryological outcomes of IVF from the couples’ perspective.

This couple-based prospective cohort study included a total of 1071 couples who underwent 1369 IVF treatment cycles between December 2020 and August 2023.

Plasma concentrations of 21 trace metal elements were measured by an inductively coupled plasma mass spectrometer. Early IVF embryological outcomes included two-pronuclear (2PN) zygote numbers, best-quality embryo numbers, fertilization rates, and blastocyst numbers. Elastic net regression was employed to identify trace metal elements associated with early IVF embryological outcomes in both partners and couples. K-medoids clustering was used to identify the exposure patterns of trace metal elements in couples and both partners. Joint effects of trace metal mixtures were evaluated using quantile-based g-computation (QGC) and group-weighted quantile sum (groupWQS), while independent effects of individual trace metal element were assessed using the generalized linear mixed model.

In our study, the mean (SD) age was 32.60 (5.22) years for females and 33.79 (5.89) for males. The detection rates for all elements, except for beryllium (Be), exceeded 90%. High exposure to trace metal element mixtures in couples and male partners was associated with decreased numbers of best-quality embryos and blastocysts. Using QGC and groupWQS, we identified both harmful and beneficial metal mixtures that influence successful embryo development. Additionally, specific plasma trace metals such as iron (Fe), lithium (Li), strontium (Sr), and molybdenum (Mo) were positively associated with embryological outcomes, while metals like silver (Ag) and thallium (Tl) had adverse effects.

We were limited by assessing plasma trace metal elements at a single time point, focusing only on fresh embryo transfer cycles, and being unable to control for unmeasured confounding factors (e.g. psychological factors and self-reported health conditions). Moreover, since our study population was couples undergoing IVF, the extrapolation of our results require caution.

These findings highlight the importance of implementing preconception trace element screening and targeted trace element interventions for couples planning to conceive, as a strategy to optimize reproductive health and IVF outcomes.

This work was supported by the National Key Research and Development Program of China (No. 2018YFC1004201), the National Natural Science Foundation of China (No. 82304159), and Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention & Henan Key Laboratory of Population Defects Prevention (No. ZD202310). All authors declare no conflict of interest.

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