目的:育龄妇女中持久性有机污染物(POPs)与卵巢储备功能降低(DOR)有关吗?
结论:在超过20%的血清样本中检测到17种POPs,只有p,p'-DDE与DOR风险增加显著相关,和β-六氯环己烷(β-HCH)与DOR风险降低显着相关,而混合物分析没有显着关联,并且没有检测到持久性有机污染物之间的任何相互作用。
背景:动物研究表明,几种POPs可以改变卵泡发育并增加卵泡消耗。然而,只有少数研究在人类中进行,样本量小,结果不一致。
方法:我们的研究包括来自AROPE病例对照研究的138例病例和151例对照。研究参与者是2016年至2020年在法国西部四个生育中心为不孕症咨询的夫妇中招募的18至40岁的女性。
方法:DOR病例定义为抗苗勒管激素(AMH)水平≤1.1ng/ml和/或窦卵泡计数(AFC)<7的女性,对照组为AMH水平在1.1至5ng/ml之间,AFC≥7,无生殖器畸形,月经周期在26至35天之间的女性。共有43种持久性有机污染物(包括15种有机氯农药,17种多氯联苯,和9个多溴联苯醚)在纳入研究时在血清中测量。我们使用有向无环图对潜在混杂因素进行了逻辑回归调整,以研究每种POP对DOR的影响作为单次暴露,并使用贝叶斯核机回归(BKMR)来测量POPs对DOR的混合效应。
结果:在43个持久性有机污染物中,在超过20%的血清样品中检测到17。在单暴露多变量逻辑回归中,p,p'-DDE(对照中的中位数165.0IQR161.0ng/l)作为连续暴露与DOR风险增加显著相关(比值比(OR)1.39,95%CI1.10-1.77),而与第二和第三部分的DOR风险增加无显著相关(分别为OR1.46,95%CI0.74-2.87和OR1.72,95%CI0.88-3.37)。当将β-HCH视为连续暴露(OR0.63,95%CI0.44-0.89)和第三时间段暴露(OR0.43,95%CI0.21-0.84)时,β-HCH(对照组中的中位数24.2IQR21.5ng/l)与DOR风险降低显着相关(OR0.77-95%0.42)。所有敏感性分析都证实了我们的结果。BKMR在单次暴露中显示出相似的关联,但在总混合效应中没有发现显着关联。此外,BKMR结果未提示POPs之间存在任何相互作用.
结论:对照是在不育夫妇中招募的,因此可能不代表所有育龄妇女。然而,它们的POP浓度与一般法国人口的浓度在相同的范围内。
结论:本研究首次探讨了血清POPs与DOR之间的关系。公认的抗雄激素特性,β-六氯环己烷的p-DDE和雌激素特性可以解释这些相反方向的关联。如果这些结果在其他地方复制,这可能对生育预防信息产生影响,并有助于了解持久性有机污染物对女性生殖系统的影响.
背景:这项研究由法国基金会(批准号2014-50537和00110196)和法国生物医学机构(2016)资助。没有任何作者有任何利益冲突声明。
背景:不适用。
Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age?
Amongst 17 POPs detected in over 20% of serum samples, only p,p\'-DDE was significantly associated with an increased risk of DOR, and β-hexachlorocyclohexane (β-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs.
Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results.
Our study included 138 cases and 151 controls from the AROPE
case-control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020.
Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) <7, and controls were women with AMH levels between 1.1 and 5 ng/ml and AFC ≥ 7, without genital malformations and with a menstrual cycle length between 26 and 35 days. A total of 43 POPs (including 15 organochlorine pesticides, 17 polychlorinated biphenyls, and 9 polybromodiphenylethers) were measured in the serum at inclusion into the study. We conducted logistic regression adjusted for potential confounders using a directed acyclic graph to study the effect of each POP on DOR as single exposures, and used Bayesian kernel machine regression (BKMR) to measure the mixture effect of POPs on DOR.
Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p\'-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10-1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74-2.87, and OR 1.72, 95% CI 0.88-3.37, respectively). β-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when β-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44-0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21-0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42-1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs.
Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population.
This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p\'-DDE and estrogenic properties of β-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system.
This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare.
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