Background

Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes.

Methods

This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity.

Results

Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend = 0.06).

Conclusions

Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes.

中文翻译：

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接受体外受精的夫妇的父本尿中有机磷酸酯阻燃剂代谢产物的浓度，生育措施和妊娠结局

背景

在过去的十年中，随着某些溴化阻燃剂的淘汰，有机磷酸酯阻燃剂（PFR）的使用有所增加，导致人体暴露量增加。我们最近报道说，生育诊所妇女的孕妇PFR暴露增加与妊娠结局较差有关。由于先前的一项小型流行病学研究报告了男性PFR暴露与精子活动力之间呈负相关，因此我们试图检查父亲尿中PFR代谢产物浓度与伴侣的妊娠结局之间的关系。

方法

该分析包括201对参与环境与生殖健康（EARTH）前瞻性队列研究（2005-2015年）的夫妇，每个IVF周期提供一到两个尿液样本。在男性和女性伴侣中，我们测量了五种尿液PFR代谢产物[双（1,3-二氯-2-丙基）磷酸（BDCIPP），磷酸二苯酯（DPHP），异丙基苯基苯磷酸酯（ip-PPP），叔-负丁基苯基苯基磷酸酯（tb-PPP）和双（1-氯-2-丙基）磷酸酯（BCIPP）]使用负电喷雾电离液相色谱串联质谱（LC-MS / MS）。计算尿液PFR代谢产物的摩尔浓度之和。我们使用多变量广义线性混合模型来评估父本PFR代谢产物的尿液浓度与IVF结果的相关性，从而说明了每对夫妇的多个体外受精（IVF）周期。对模型进行了以下调整：IVF治疗周期的年份，原发性不孕症的诊断，母体尿中PFR的代谢产物，以及母体和母体的年龄，体重指数以及种族/民族。

结果

BDCIPP（84％），DPHP（87％）和ip-PPP（76％）的父亲尿浓度检出率高，而tb-PPP（12％）和BCIPP（0％）的检出率低。我们在调整后的模型中观察到，从雄性泌尿系统ΣPFR的第一个四分位数到第二个四分位数，受精卵母细胞的比例显着下降了12％，从雄性泌尿系统的BDCIPP的第一个四分位数到第三个四分位数中，最佳质量的胚胎数量下降了47％。与最低四分位数的尿BDCIPP浓度相比，观察到最高的受精率下降了8％（95％CI：0.01、0.12，p趋势= 0.06）。

结论

使用IVF作为研究人类生殖和妊娠结局的模型，我们发现BDCIPP的父亲尿液浓度与受精率降低有关。与先前报道的有关女性伴侣的发现相反，父亲的尿中PFR代谢产物与成功植入，临床妊娠和活产的周期比例无关。这些结果表明，父本先孕暴露于TDCIPP可能会对成功的卵子受精产生不利影响，而女性先孕暴露于ΣPFRs可能与不良妊娠结局更相关。