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中国一项前瞻性 IVF 队列研究:卵泡液中的全氟烷基酸与 IVF 胚胎质量。

Perfluoroalkyl Acids in Follicular Fluid and Embryo Quality during IVF: A Prospective IVF Cohort in China.

机构信息

Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Sun Yat-sen University, Guangzhou, China.

出版信息

Environ Health Perspect. 2023 Feb;131(2):27002. doi: 10.1289/EHP10857. Epub 2023 Feb 1.

Abstract

BACKGROUND

Perfluoroalkyl acids (PFAA) have been measured in ovarian follicular fluid from women using fertilization (IVF), although associations between follicular fluid PFAA and IVF outcomes have been inconsistent.

OBJECTIVES

We investigated the association between follicular fluid PFAA and embryo quality in women undergoing IVF.

METHODS

We prospectively enrolled 729 women undergoing IVF treatment in Guangxi province, China, from July 2018 to December 2018. We measured 32 PFAA, including branched isomers, in follicular fluid using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We applied restricted cubic splines, linear regression, and log-binominal regression models to investigate associations between follicular fluid PFAA and embryo quality, adjusting for confounding variables and investigated oocyte maturity as an intervening variable using causal mediation analysis. We further estimated the overall effect of the PFAA mixture on outcomes using Bayesian kernel machine regression (BKMR).

RESULTS

We detected 8 of 32 measured PFAA in of follicular fluid samples. Higher PFAA concentrations were associated with fewer high-quality embryos from IVF. The high-quality embryo rates at the 50th percentile of linear perfluoro-1-octanesulfonate acid (n-PFOS), all branched PFOS isomers (Br-PFOS) and linear perfluoro--octanoic acid (n-PFOA) were [95% confidence interval (CI): , ], (95% CI: , ) and (95% CI: , ) lower, respectively, than the high quality embryo rates at the reference 10th percentile of PFAA. Oocyte maturity mediated 11.76% (95% CI: 3.18, 31.80%) and 14.28% (95% CI: 2.95, 31.27%) of the n-PFOS and n-PFOA associations, respectively. The results of the BKMR models showed a negative association between the PFAA mixture and the probability of high-quality embryos, with branched PFOS isomers having posterior inclusion probabilities of 1 and accounting for the majority of the association.

DISCUSSION

Exposure to higher PFAA concentrations in follicular fluid was associated with poorer embryo quality during IVF. Branched PFOS isomers may have a stronger effect than linear PFOS isomers. More studies are needed to confirm these findings and to directly estimate the effects on pregnancy and live-birth outcomes. https://doi.org/10.1289/EHP10857.

摘要

背景

已有研究采用体外受精(IVF)技术检测了女性卵泡液中的全氟烷基酸(PFAA),但卵泡液 PFAA 与 IVF 结局之间的关联尚不明确。

目的

本研究旨在探讨女性 IVF 中卵泡液 PFAA 与胚胎质量之间的关系。

方法

本研究前瞻性纳入了 2018 年 7 月至 2018 年 12 月在中国广西接受 IVF 治疗的 729 名女性。采用超高效液相色谱-串联质谱法检测卵泡液中 32 种 PFAA,包括支链异构体。应用受限立方样条、线性回归和对数二项式回归模型,在调整混杂因素后,研究卵泡液 PFAA 与胚胎质量之间的关联,并通过因果中介分析探讨卵母细胞成熟度作为中介变量的作用。我们进一步使用贝叶斯核机器回归(BKMR)估计 PFAA 混合物对结局的综合影响。

结果

在 729 份卵泡液样本中,检测到 8 种 32 种测量的 PFAA 中的 8 种。较高的 PFAA 浓度与 IVF 中高质量胚胎数量减少相关。在 PFAA 第 50 百分位数线性全氟辛烷磺酸(n-PFOS)、所有支链全氟辛烷磺酸异构体(Br-PFOS)和线性全氟辛酸(n-PFOA)处,高质量胚胎的发生率分别比参考值的第 10 百分位数低 [95%置信区间(CI): , ]、 [95% CI: , ]和 [95% CI: , ]。卵母细胞成熟度分别介导了 n-PFOS 和 n-PFOA 关联的 11.76%(95% CI: 3.18,31.80%)和 14.28%(95% CI: 2.95,31.27%)。BKMR 模型的结果表明,PFAA 混合物与高质量胚胎的概率呈负相关,支链 PFOS 异构体的后验纳入概率为 1,占关联的大部分。

讨论

卵泡液中较高的 PFAA 浓度与 IVF 期间胚胎质量较差有关。支链 PFOS 异构体的影响可能比线性 PFOS 异构体更强。还需要更多的研究来证实这些发现,并直接估计对妊娠和活产结局的影响。https://doi.org/10.1289/EHP10857.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798f/9891133/d65b76929507/ehp10857_f1.jpg

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