The associations of urinary phthalate metabolites with the intermediate and pregnancy outcomes of women receiving IVF/ICSI treatments: A prospective single-center study
The associations of urinary phthalate metabolites with the intermediate and pregnancy outcomes of women receiving IVF/ICSI treatments: A prospective single-center study
复制标题
尿邻苯二甲酸酯代谢物与接受 IVF/ICSI 治疗的妇女的中期结局和妊娠结局的关联：一项前瞻性单中心研究
DOI：
10.1016/j.ecoenv.2019.109884
复制
发表时间：
2020-01-30
影响因子：
6.8
通讯作者：
Li, Yufeng
中科院分区：
文献类型：
--
作者：
Deng, Taoran;Du, Yaoyao;Li, Yufeng
背景：据报道，邻苯二甲酸酯暴露可诱导卵巢功能缺陷，并进一步影响胚胎发育和妊娠结局。然而，邻苯二甲酸酯与体外受精（IVF）周期的中期和妊娠结局相关的数据在中国人群中很少：共663例接受IVF/卵胞浆内单精子注射（ICSI）治疗的妇女参加了本分析。他们在取卵当天提供了一份尿液样本。我们测量了8种邻苯二甲酸酯代谢物的尿液浓度。广义线性模型被用来分析尿邻苯二甲酸酯代谢产物与卵巢反应，受精，早期胚胎发育，妊娠outcomes.Results的协会：在所有的邻苯二甲酸酯代谢产物，单正丁基邻苯二甲酸酯（MBP）有最高的尿液浓度与中位数水平为101.51微克/克肌酐（Cr）。MBP浓度与正常受精几率呈负相关（总体P趋势< 0.01）。与低浓度组相比，中浓度组中邻苯二甲酸单乙酯（MEP）与正常受精几率降低存在显著相关性（总体P趋势= 0.02）。代谢产物浓度与第3天优质胚胎或囊胚形成的几率无显著相关性，中浓度组的邻苯二甲酸单甲酯（MMP）和MEP降低了22.4%。（95% CI：0.64-0.94，总体P-趋势= 0.04）和21.9%（95% CI：0.64-0.95，总体P-趋势= 0.05）获得优质囊胚的几率。八种邻苯二甲酸酯代谢产物与临床妊娠率、活产率或早期流产率无关。在总人群中未观察到邻苯二甲酸二（2-乙基己基）酯（DEHP）代谢物与任何临床结局的显著相关性。排除男性不育后，中浓度组MEHHP的获卵率较高（总体P趋势= 0.04），而单声道与低浓度组相比，中浓度组的（2-乙基-5-氧代己基）邻苯二甲酸酯（MEOHP）与较低的正常受精几率相关（总体P趋势= 0.02）。结论：在中国IVF/ICSI女性队列中，尿MBP浓度远高于其他邻苯二甲酸酯代谢物，也高于其他国家的研究报告。MBP对施肥有不利影响。MMP和MEP可影响囊胚质量，但不影响第3天胚胎质量。DEHP代谢物未显示出与先前研究一致的生殖毒性。
Background: Phthalate exposure was reported to induce defects in ovarian function, and further influence embryo development and pregnancy outcomes. However, the data about the associations of phthalates with intermediate and pregnancy outcomes of in vitro fertilization (IVF) cycles are scarce in the Chinese population.Methods: A total of 663 women receiving IVF/intracytoplasmic sperm injection (ICSI) treatments in our center were enrolled in this analysis. They provided one urine sample on the day of oocyte retrieval. We measured urinary concentrations of eight phthalate metabolites. Generalized linear models were used to analyze the associations of urinary phthalate metabolites with ovarian response, fertilization, early embryo development, and pregnancy outcomes.Results: Among all the phthalate metabolites, mono-n-butyl phthalate (MBP) had the highest urinary concentration with a median level of 101.51 mu g/g creatinine (Cr). MBP concentration was inversely associated with normal fertilization odds (overall P-trend < 0.01). There was a significant correlation of monoethyl phthalate (MEP) with decreased odds of normal fertilization in medium-concentration group compared to low-concentration group (overall P-trend = 0.02). No significant associations of metabolite concentrations with the odds of good-quality embryos on day 3 or blastocyst formation were found. Monomethyl phthalate (MMP) and MEP in medium-concentration group reduced 22.4% (95% CI: 0.64-0.94, overall P-trend = 0.04) and 21.9% (95% CI: 0.64-0.95, overall P-trend = 0.05) of the odds to gain good-quality blastocyst compared to low-concentration group. The eight phthalate metabolites were not correlated to clinical pregnancy rate, live birth rate, or early miscarriage rate. There was no significant association of di (2-ethylhexyl) phthalate (DEHP) metabolites observed with any clinical outcomes in the total population. After excluding male infertility, mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in medium-concentration group turned to be associated with a higher number of retrieved oocytes (overall P-trend = 0.04), whereas mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) in medium-concentration group was associated with a lower odds of normal fertilization compared to low-concentration group (overall P-trend = 0.02).Conclusions: Urinary MBP concentration was much higher compared to other phthalate metabolites in this cohort of Chinese IVF/ICSI women, and also higher than it was reported by studies in other countries. MBP showed adverse impacts on fertilization. MMP and MEP could affect blastocyst quality, but not embryo quality on day 3. DEHP metabolites didn't show consistent reproductive toxicities as demonstrated in previous studies.