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体外受精女性的尿中邻苯二甲酸酯代谢物浓度与生殖结局:EARTH研究结果

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

作者信息

Hauser Russ, Gaskins Audrey J, Souter Irene, Smith Kristen W, Dodge Laura E, Ehrlich Shelley, Meeker John D, Calafat Antonia M, Williams Paige L

机构信息

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

出版信息

Environ Health Perspect. 2016 Jun;124(6):831-9. doi: 10.1289/ehp.1509760. Epub 2015 Nov 6.

Abstract

BACKGROUND

Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes.

OBJECTIVE

We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART).

METHODS

This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman.

RESULTS

In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites.

CONCLUSIONS

Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART.

CITATION

Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760.

摘要

背景

动物和人体研究的证据均表明,接触邻苯二甲酸盐可能与女性不良生殖结局相关。

目的

我们评估了尿中邻苯二甲酸酯代谢物浓度与辅助生殖技术(ART)结局之间的关联。

方法

本分析纳入了256名参与环境与生殖健康(EARTH)前瞻性队列研究(2004 - 2012年)的女性,她们在取卵前每个周期提供一到两份尿液样本。我们检测了11种尿中邻苯二甲酸酯代谢物[单(2 - 乙基己基)邻苯二甲酸酯(MEHP)、单(2 - 乙基 - 5 - 羟基己基)邻苯二甲酸酯(MEHHP)、单(2 - 乙基 - 5 - 氧代己基)邻苯二甲酸酯(MEOHP)、单(2 - 乙基 - 5 - 羧基戊基)邻苯二甲酸酯(MECPP)、单异丁基邻苯二甲酸酯(MiBP)、单正丁基邻苯二甲酸酯(MBP)、单苄基邻苯二甲酸酯(MBzP)、单乙基邻苯二甲酸酯(MEP)、单羧基异辛基邻苯二甲酸酯(MCOP)、单羧基异壬基邻苯二甲酸酯(MCNP)和单(3 - 羧基丙基)邻苯二甲酸酯(MCPP)]。我们使用广义线性混合模型评估尿中邻苯二甲酸酯代谢物与体外受精(IVF)结局的关联,同时考虑了每位女性的多个IVF周期。

结果

在多变量模型中,与MEHP、MEHHP、MEOHP、MECPP、ΣDEHP(MEHP + MEHHP + MEOHP + MECPP)和MCNP最低四分位数的女性相比,最高四分位数的女性卵母细胞产量较低。同样,这些相同邻苯二甲酸酯代谢物最高四分位数的女性与最低四分位数的女性相比,回收的成熟(MII)卵母细胞数量较少。ΣDEHP第四四分位数与第一四分位数的女性中,导致临床妊娠和活产的周期比例的调整差异(95%CI)分别为 - 0.19( - 0.29, - 0.08)和 - 0.19( - 0.28, - 0.08),并且个别DEHP代谢物导致临床妊娠和活产的周期比例也较低。

结论

ART后,尿中DEHP代谢物浓度与卵母细胞产量、临床妊娠和活产呈负相关。

引用

豪泽R,加斯金斯AJ,苏特I,史密斯KW,道奇LE,埃利希S,米克JD,卡拉法特AM,威廉姆斯PL,EARTH研究团队。2016年。接受体外受精女性的尿邻苯二甲酸酯代谢物浓度与生殖结局:EARTH研究结果。环境健康展望124:831 - 839;http://dx.doi.org/10.1289/ehp.1509760。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1e/4892919/ec772803ed75/ehp.1509760.g001.jpg

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