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实时监测揭示了胚胎学实验室中低浓度挥发性有机化合物的影响。

Real-time monitoring reveals the effects of low concentrations of volatile organic compounds in the embryology laboratory.

作者信息

Cai Jiali, Zhou Liying, Liu Lanlan, Liu Zhenfang, Chen Jinghua, Chen Kaijie, Yang Xiaolian, Jiang Xiaoming, Ren Jianzhi

机构信息

Reproductive Medicine Centre, Ximen University Affiliated Chenggong Hospital, Xiamen, Fujian, China.

School of Medicine, Xiamen University, Xiamen, Fujian, China.

出版信息

Hum Reprod. 2025 Apr 1;40(4):601-611. doi: 10.1093/humrep/deaf008.

Abstract

STUDY QUESTION

Could real-time monitoring of volatile organic compounds (VOCs) in the embryology laboratory provide meaningful early warning for potential harm from the environment?

SUMMARY ANSWER

Even in a laboratory environment with a total VOC concentration lower than the recommendation of the Cairo Consensus, the real-time monitored VOC concentrations are associated with changes in embryo morphological parameters.

WHAT IS KNOWN ALREADY

VOCs have been considered a key environmental detriment in embryology laboratories. However, the current VOC thresholds established by the Cairo consensus were based on the practical experience of air pollution cases, and a scientifically derived threshold is lacking.

STUDY DESIGN, SIZE, DURATION: The study included 7076 oocyte collection (OPU) cycles carried out between June 2020 and December 2022 in the Center for Reproductive Medicine of the affiliated Chenggong Hospital of Xiamen University, 6306 of which resulted in at least one embryo transfer (ET) attempt during the study. VOC monitoring data were recorded every 10 min. The average and peak concentrations of total VOCs and formaldehyde during culture were associated with embryo parameters and implantation following the first ET attempt of the cycle in generalized estimating equations and generalized additive models.

MAIN RESULTS AND THE ROLE OF CHANCE

Real-time monitoring of VOCs showed a dynamic of VOC concentration in the laboratory. The concentration reached peaks during the working hours of the days and working days of the week and fell quickly at night and on weekends. The average concentrations of VOCs during the culture period were linearly associated with decreased early cleavage (OR 0.92, 95% CI: 0.85, 0.99), decreased Day 3 compaction (OR 0.51, 95% CI: 0.32, 0.83), increased asymmetry (OR 1.13, 95% CI: 1.01, 1.25), and increased grade C trophectoderm (TE) (OR 1.99, 95% CI: 1.32, 3.01). On the other hand, increased Day 3 arrest, delayed blastocyst formation, and decreased grade A TE showed a non-linear association with VOCs, suggesting a possible threshold of effect. In the first transfer attempt, negative associations were observed between maximal formaldehyde concentrations and pregnancy in both fresh transfer (RR 0.971, 95% CI: 0.94, 0.99) and freeze-all frozen-thawed ET (RR 0.959, 95% CI: 0.92, 0.99) cycles.

LIMITATIONS, REASONS FOR CAUTION: The sensitivity and specificity of the monitor are not comparable to the standard protocols, such as chromatography-mass spectroscopy. Due to the lack of ability to identify the chemical nature of the components of VOCs, the toxicity and source of the VOCs were largely unknown. The representative sampling of the laboratory air may not necessarily reflect the exposure of embryos.

WIDER IMPLICATIONS OF THE FINDINGS

While the environment of the embryology laboratory has been significantly improved, the data suggested that a low VOC level could still be a concern. Due to the dynamic of VOC concentration in the laboratory air, periodic monitoring may fail to capture the increased VOC levels and give an early alarm.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China [grant number 22176159], the Xiamen Medical Advantage subspecialty construction project [grant number 2018296], and the Wu Jieping Medical Foundation [grant number 320.6750.2024-6-14]. All authors declare no competing interests.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

胚胎学实验室中挥发性有机化合物(VOCs)的实时监测能否为环境潜在危害提供有意义的早期预警?

总结答案

即使在总VOC浓度低于开罗共识建议值的实验室环境中,实时监测的VOC浓度也与胚胎形态学参数的变化相关。

已知信息

VOCs被认为是胚胎学实验室中的关键环境危害因素。然而,开罗共识确定的当前VOC阈值是基于空气污染案例的实际经验,缺乏科学推导的阈值。

研究设计、规模、持续时间:该研究纳入了2020年6月至2022年12月在厦门大学附属成功医院生殖医学中心进行的7076个卵母细胞采集(OPU)周期,其中6306个周期在研究期间至少进行了一次胚胎移植(ET)尝试。每10分钟记录一次VOC监测数据。在广义估计方程和广义相加模型中,培养期间总VOCs和甲醛的平均浓度及峰值浓度与周期首次ET尝试后的胚胎参数和着床情况相关。

主要结果及机遇的作用

VOCs的实时监测显示了实验室中VOC浓度的动态变化。浓度在工作日的工作时间以及一周中的工作日达到峰值,在夜间和周末迅速下降。培养期间VOCs的平均浓度与早期卵裂减少(OR 0.92,95% CI:0.85,0.99)、第3天致密化减少(OR 0.51,95% CI:0.32,0.83)、不对称性增加(OR 1.13,95% CI:1.01,1.25)以及滋养外胚层(TE)C级增加(OR 1.99,95% CI:1.32,3.01)呈线性相关。另一方面,第3天停滞增加、囊胚形成延迟以及A级TE减少与VOCs呈非线性关联,表明可能存在效应阈值。在首次移植尝试中,在新鲜移植(RR 0.971,95% CI:0.94,0.99)和全冻融冻ET(RR 0.959,95% CI:0.92,0.99)周期中,均观察到最大甲醛浓度与妊娠之间存在负相关。

局限性、需谨慎的原因:该监测仪的灵敏度和特异性无法与标准方案(如色谱 - 质谱联用)相媲美。由于缺乏识别VOCs成分化学性质的能力,VOCs的毒性和来源在很大程度上未知。实验室空气的代表性采样不一定能反映胚胎的暴露情况。

研究结果的更广泛影响

虽然胚胎学实验室的环境已显著改善,但数据表明低VOC水平仍可能令人担忧。由于实验室空气中VOC浓度的动态变化,定期监测可能无法捕捉到升高的VOC水平并发出早期警报。

研究资金/利益冲突:本研究得到中国国家自然科学基金[项目编号22176159]、厦门医学优势亚专科建设项目[项目编号2018296]以及吴阶平医学基金会[项目编号320.6750.2024 - 6 - 14]的支持。所有作者均声明无利益冲突。

试验注册号

无。

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