STUDY QUESTION Does exposure to particulate matter (PM) air pollution prior to oocyte retrieval or subsequent frozen embryo transfer (FET) affect the odds of live birth? SUMMARY ANSWER Live birth rates are lower when particulate matter (PM2.5 and PM10) levels are higher prior to oocyte retrieval, regardless of the conditions at the time of embryo transfer. WHAT IS KNOWN ALREADY Exposure to air pollution is associated with adverse reproductive outcomes, including reduced fecundity and ovarian reserve, and an increased risk of infertility and pregnancy loss. It is uncertain whether the effect on ART outcomes is due to the effects of pollution on oogenesis or on early pregnancy. STUDY DESIGN, SIZE, DURATION This retrospective cohort study included 3659 FETs in 1835 patients between January 2013 and December 2021, accounting for all FETs performed at a single clinic over the study period. The primary outcome was the live birth rate per FET. Outcome data were missing for two embryo transfers which were excluded. Daily levels of PM2.5, PM10, nitric oxide, nitrogen dioxide, sulphur dioxide, ozone and carbon monoxide were collected during the study period and calculated for the day of oocyte retrieval and the day of embryo transfer, and during the preceding 2-week, 4-week, and 3-month periods. PARTICIPANTS/MATERIALS, SETTING, METHODS Clinical and embryological outcomes were analysed for their association with pollution over 24 hours, 2 weeks, 4 weeks, and 3 months, with adjustment for repeated cycles per participant, age at the time of oocyte retrieval, a quadratic age term, meteorological season, year, and co-exposure to air pollutants. Multi-pollutant models were constructed to adjust for co-exposures to other pollutants. Median concentrations in pollutant quartiles were modelled as continuous variables to test for overall linear trends; a Bonferroni correction was applied to maintain an overall alpha of 0.05 across the four exposure periods tested. MAIN RESULTS AND THE ROLE OF CHANCE Increased PM2.5 exposure in the 3 months prior to oocyte retrieval was associated with decreased odds of live birth (linear trend P = 0.011); the odds of live birth when PM2.5 concentrations were in the highest quartile were reduced by 34% (OR 0.66, 95% CI 0.47–0.92) when compared to the lowest quartile. A consistent direction of effect was seen across other exposure periods prior to oocyte retrieval, with an apparent dose-dependent relationship. Increased exposure to PM10 particulate matter in the 2 weeks prior to oocyte retrieval was associated with decreased odds of live birth (linear trend P = 0.009); the odds of live birth were decreased by 38% (OR 0.62, 95% CI 0.43–0.89, P = 0.010) when PM10 concentrations were in the highest quartile compared with the lowest quartile. Consistent trends were not seen across other exposure periods. None of the gaseous pollutants had consistent effects, prior to either oocyte retrieval or embryo transfer. LIMITATIONS, REASONS FOR CAUTION This was a retrospective cohort study, however, all FETs during the study period were included and data were missing for only two FETs. The results are based on city-level pollution exposures, and we were not able to adjust for all possible factors that may affect live birth rates. Results were not stratified based on specific patient populations, and it was not possible to calculate the cumulative live birth rate per commenced cycle. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to specifically analyse FETs to separate the effects of environmental exposures prior to oocyte retrieval from those around the time of embryo transfer. Our findings suggest that increased PM exposure prior to oocyte retrieval is associated with reduced live birth rate following FET, independent of the conditions at the time of embryo transfer. Importantly, the air quality during the study period was excellent, suggesting that even ‘acceptable’ levels of air pollution have detrimental reproductive effects during gametogenesis. At the low pollution levels in our study, exposure to gaseous pollutants did not appear to affect live birth rates. This has important implications for our understanding of the effects of pollution on reproduction, and highlights the urgent need for effective policies limiting pollution exposure to protect human health and reproduction. STUDY FUNDING/COMPETING INTEREST(S) No funding was provided for this study. S.J.L. is supported by the Jean Murray Jones Scholarship from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, has received educational sponsorship from Besins, Ferring, Merck, and Organon, honoraria from Hologic and Organon, consulting fees from Merck unrelated to the current study, and is a member of the Reproductive Technology Council of Western Australia. S.J.L. and R.J.H. are board members of Menopause Alliance Australia. C.S.R., M.W., and E.N. have no conflicts of interest to declare. R.J.H. is the Medical Director of Fertility Specialists of Western Australia, the National Medical Director of City Fertility Australia, and a shareholder in CHA SMG. He chairs the Western Australian Minister’s Expert Panel on ART and Surrogacy. R.J.H. has made presentations for and received honoraria from Merck, Merck-Serono, Origio, Igenomix, Gideon-Richter, and Ferring, and has received support for attending meetings from Merck, Organon, and Ferring. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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取卵时颗粒物空气污染与随后冷冻胚胎移植中活产几率的降低独立相关


研究问题：在取卵或随后的冷冻胚胎移植 （FET） 之前暴露于颗粒物 （PM） 空气污染中会影响活产的几率吗？摘要答案 当取卵前颗粒物（PM2.5 和 PM10）水平较高时，无论胚胎移植时的条件如何，活产率都会较低。已知的空气污染与不良的生殖结果有关，包括生育能力和卵巢储备减少，以及不孕症和流产的风险增加。目前尚不确定对 ART 结局的影响是由于污染对卵子发生的影响还是对早期妊娠的影响。研究设计、规模、持续时间 这项回顾性队列研究包括 2013 年 1 月至 2021 年 12 月期间 1835 名患者的 3659 例 FET，占研究期间在单个诊所进行的所有 FET。主要结局是每个 FET 的活产率。两项胚胎移植的结局数据缺失，这些胚胎移植被排除在外。在研究期间收集 PM2.5、PM10、一氧化氮、二氧化氮、二氧化硫、臭氧和一氧化碳的每日水平，并计算取卵当天和胚胎移植当天，以及之前的 2 周、4 周和 3 个月期间。参与者/材料、环境、方法 分析了 24 小时、2 周、4 周和 3 个月与污染的临床和胚胎学结果，并调整了每个参与者的重复周期、取卵时的年龄、二次年龄项、气象季节、年份和共同暴露于空气污染物。构建了多污染物模型以调整与其他污染物的共同暴露。 污染物四分位数的中位浓度被建模为连续变量，以测试整体线性趋势;应用 Bonferroni 校正以在测试的四个暴露期内保持 0.05 的总体 alpha。主要结果和机会的作用 取卵前 3 个月内 PM2.5 暴露增加与活产几率降低相关（线性趋势 P = 0.011）;与最低四分位数相比，当 PM2.5 浓度处于最高四分位数时，活产几率降低了 34% （OR 0.66,95% CI 0.47-0.92）。在取卵前的其他暴露期中观察到一致的效果方向，具有明显的剂量依赖性关系。取卵前 2 周内 PM10 颗粒物暴露量增加与活产几率降低相关（线性趋势 P = 0.009）;当 PM10 浓度处于最高四分位数与最低四分位数相比时，活产几率降低了 38% （OR 0.62,95% CI 0.43–0.89，P = 0.010）。在其他暴露期未见一致的趋势。在取卵或胚胎移植之前，没有一种气态污染物具有一致的效果。局限性，谨慎的原因这是一项回顾性队列研究，但是，研究期间的所有 FET 都被纳入其中，并且只有两个 FET 的数据缺失。结果基于城市层面的污染暴露，我们无法调整可能影响活产率的所有可能因素。结果没有根据特定患者群体进行分层，并且无法计算每个开始周期的累积活产率。 研究结果的更广泛影响 这是第一项专门分析 FET 的研究，以区分取卵前环境暴露的影响与胚胎移植前后的环境暴露的影响。我们的研究结果表明，取卵前颗粒物暴露的增加与 FET 后活产率降低有关，这与胚胎移植时的情况无关。重要的是，研究期间的空气质量非常好，这表明即使是“可接受”的空气污染水平也会对配子发生过程中的生殖产生不利影响。在我们研究的低污染水平下，暴露于气态污染物似乎不会影响活产率。这对我们理解污染对生殖的影响具有重要意义，并突出了迫切需要制定有效的政策来限制污染暴露，以保护人类健康和繁殖。研究资金/竞争利益 本研究没有提供资金。SJL 得到了澳大利亚和新西兰皇家妇产科学院的 Jean Murray Jones 奖学金的支持，获得了 Besins、Ferring、Merck 和 Organon 的教育赞助，Hologic 和 Organon 的酬金，默克与当前研究无关的咨询费，并且是西澳大利亚生殖技术委员会的成员。S.J.L. 和 R.J.H. 是澳大利亚更年期联盟的董事会成员。C.S.R.、M.W. 和 E.N. 没有需要申报的利益冲突。R.J.H. 是西澳大利亚州生育专家公司的医疗主任、澳大利亚城市生育协会的国家医疗主任，以及 CHA SMG 的股东。他是西澳大利亚州部长 ART 和代孕专家小组的主席。R.J.H. 为 Merck、Merck-Serono、Origio、Igenomix、Gideon-Richter 和 Ferring 做过演讲并获得酬金，并获得了 Merck、Organon 和 Ferring 的会议支持。试验注册号 N/A。