LABERCA, Oniris, INRAE, Nantes, France; CHU Nantes, Nantes Université, Service de Médecine et Biologie de La Reproduction, Gynécologie Médicale, 38 Bd Jean Monnet, Nantes, France; Faculty of Medicine, Nantes Université, France.
CHU Nantes, Nantes Université, Service de Médecine et Biologie de La Reproduction, Gynécologie Médicale, 38 Bd Jean Monnet, Nantes, France; Faculty of Medicine, Nantes Université, France; Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000, Nantes, France.
Environ Pollut. 2022 Nov 15;313:120087. doi: 10.1016/j.envpol.2022.120087. Epub 2022 Sep 7.
The impact of persistent organic pollutants (POPs) on reproductive health is still poorly understood, even though infertility management has high associated societal and economical costs. The aims of this study were to characterize the internal levels of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and perfluoroalkylated substances (PFAS) in women undergoing in vitro fertilization (IVF); and evaluate their association with IVF outcomes, individually and as mixtures in a combined multipollutant approach. Thus, 136 women undergoing IVF treatment at Nantes University Hospital (France) were prospectively recruited between 2019 and 2020. Serum samples were analyzed using liquid chromatography with tandem-mass spectrometry for 14 PFAS. Follicular fluid was analyzed with gas chromatography coupled to high resolution mass spectrometry for 14 PCBs and 25 OCPs. Intermediate and clinical IVF outcomes were ascertained by embryologists and clinicians using standardized protocols. Multivariate Poisson regression models and Bayesian Kernel Machine Regressions (BKMR) were used to identify individual and joint associations between POPs and IVF outcomes adjusting for age, body mass index (BMI) and anti-Müllerian hormone. The results showed that most POPs were widely present in women, and globally not associated with clinically relevant IVF outcomes, like live birth rates. Nonetheless, negative associations between PCB138 and trans-nonachlor with useable blastocysts were identified, β -0.28 (95%CI [-0.52; -0.04] p = 0.02) and β -0.22 (95%CI [-0.40; -0.03] p = 0.02). Conversely, PCB28 showed positive associations with the number of useable blastocysts, pregnancy rate and live birth rate. The BKMR analysis suggested the lack of association of the mixture with intermediate and clinical outcomes. The study supports the need of conducting further studies in a larger population sample in order to ensure sufficient statistical power to identify modest effects and a robust stratification analysis to account for the large underlying disease heterogeneity.
尽管不孕不育管理带来了高昂的社会和经济成本，但持久性有机污染物（POPs）对生殖健康的影响仍知之甚少。本研究旨在描述接受体外受精（IVF）治疗的女性体内多氯联苯（PCBs）、有机氯农药（OCPs）和全氟烷基物质（PFAS）的水平，并评估它们与 IVF 结局的关联，包括个体水平和混合水平的关联。因此，2019 年至 2020 年期间，法国南特大学医院前瞻性招募了 136 名接受 IVF 治疗的女性。采用液相色谱-串联质谱法分析血清样本中 14 种 PFAS，采用气相色谱-高分辨质谱法分析卵泡液中 14 种 PCBs 和 25 种 OCPs。胚胎学家和临床医生采用标准化方案确定中间和临床 IVF 结局。多变量泊松回归模型和贝叶斯核机器回归（BKMR）用于识别 POPs 与 IVF 结局之间的个体和联合关联，同时调整年龄、体重指数（BMI）和抗苗勒管激素。结果表明，大多数 POPs 在女性中广泛存在，但与临床相关的 IVF 结局（如活产率）无关。然而，发现 PCB138 和反式-诺氯与可利用囊胚之间存在负相关，β=-0.28（95%CI[-0.52；-0.04]，p=0.02）和β=-0.22（95%CI[-0.40；-0.03]，p=0.02）。相反，PCB28 与可利用囊胚数量、妊娠率和活产率呈正相关。BKMR 分析表明，混合物与中间和临床结局之间缺乏关联。该研究支持在更大的人群样本中进一步开展研究的必要性，以确保有足够的统计效力来识别适度的影响，并进行稳健的分层分析以考虑到潜在的疾病异质性。
