STUDY QUESTION Does culture in a high relative humidity atmosphere improve clinical outcomes when using a time-lapse integrated incubator and single-step culture medium? SUMMARY ANSWER Using an integrated time-lapse system and single-step culture medium, culture in a high relative humidity atmosphere increases the likelihood of embryos, especially those subjected to preimplantation genetic testing for aneuploidies, to achieve a pregnancy compared to those cultured in dry conditions. WHAT IS KNOWN ALREADY The use of a humid atmosphere inside incubators can reduce changes in culture media osmolality, which has been reported to have a significant effect on embryo quality and morphokinetics. Studies assessing the effect of humid culture (HC) in clinical outcomes are, however, scarce and inconclusive, mostly due to a high variability in culture conditions and reduced sample size. STUDY DESIGN, SIZE, DURATION Retrospective cohort study performed over 1627 ICSI cycles performed during 3 consecutive years in which embryo cohorts were cultured in a time-lapse incubator with three dry and three humidified chambers, and using single-step culture medium. Clinical outcomes were compared between treatments in which embryo cohorts were cultured in either humid (n = 833) or dry (n = 794) conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS The study includes autologous treatments, with (N = 492) and without (N = 372) preimplantation genetic testing for aneuploidies (PGT-A) and ovum donation treatments (N = 763), performed in three university-affiliated private IVF centres. Stimulation, oocyte pickup and fertilization were performed according to the standard procedures of the clinic. All embryo cohorts were cultured in the same model of time-lapse incubator, distributed to either a dry or humidified chamber, while the rest of the culture variables remained equal. The population was weighted by the inverse probability of treatment to control for all measured confounders. The association between HC and the main outcome was assessed by logistic regression over the weighted population. The E-value was reported as a way of considering for unmeasured confounders. Differences in embryo development and other secondary outcomes between the study groups were assessed by Pearson Chi-squared test, ANOVA test and Kaplan–Meier survival analysis. MAIN RESULTS AND THE ROLE OF CHANCE An univariable logistic regression analysis, weighted by the inverse probability of treatment, determined that embryos cultured in humid conditions are more likely to achieve a clinical pregnancy than those cultured in dry conditions (odds ratio (OR) = 1.236 (95% CI 1.009–1.515), P = 0.041, E = 1.460). Through stratification, it was determined that said effect is dependent on the type of treatment: no improvement in clinical pregnancy was present in ovum donation or autologous treatments, but a statistically significant positive effect was present in treatments with preimplantation genetic testing (OR = 1.699 (95% CI 1.084–2.663), P = 0.021, E = 1.930). Said increase does not relate with an improvement in later outcomes. Differences were also found in variables related to embryo developmental morphokinetics. LIMITATIONS, REASONS FOR CAUTION The retrospective nature of the study makes it susceptible to some bias linked to the characteristics of the treatments. To lessen the effect of possible biases, cases were weighted by the inverse probability of treatment prior to the evaluation of the outcome, as means to assess for measured confounders. In addition, the E-value of the weighted OR was calculated as a sensitivity analysis for unmeasured confounders. A randomized prospective study could be performed for further assessing the effect of humid conditions in clinical outcome. WIDER IMPLICATIONS OF THE FINDINGS These results support that embryo culture under conditions of high relative humidity contributes to optimize clinical results in undisturbed culture in a time-lapse incubator with single-step medium. To our knowledge, this is the largest study on the matter and the first performing a propensity score-based analysis. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the ‘‘Centro para el Desarrollo Tecnologico Industrial’’ from the Spanish Ministry of Science, Innovation, and Universities (CDTI-20170310) and Generalitat Valenciana and European Social Fund (ACIF/2019/264). None of the authors have any competing interest to declare. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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一项基于倾向评分的比较研究，使用单步培养基评估潮湿和干燥延时孵化对胚胎发育和临床结果的影响

研究问题 当使用延时集成培养箱和单步培养基时，在高相对湿度环境中培养是否会改善临床结果？总结 答案 与在干燥条件下培养的胚胎相比，使用集成延时系统和单步培养基，在高相对湿度环境中培养会增加胚胎，尤其是那些接受非整倍体植入前基因检测的胚胎实现妊娠的可能性. 已经知道的事情 在孵化器内使用潮湿的气氛可以减少培养基渗透压的变化，据报道这对胚胎质量和形态动力学有显着影响。然而，评估湿培养 (HC) 对临床结果的影响的研究很少且尚无定论，主要是由于培养条件的高度可变性和样本量的减少。研究设计、规模、持续时间 回顾性队列研究连续 3 年进行了超过 1627 个 ICSI 周期，其中胚胎队列在具有三个干燥室和三个加湿室的延时培养箱中培养，并使用单步培养基。比较了在潮湿（n = 833）或干燥（n = 794）条件下培养胚胎队列的治疗之间的临床结果。参与者/材料、设置、方法 该研究包括自体治疗，包括（N = 492）和不包括（N = 372）非整倍体植入前基因检测（PGT-A）和卵子捐赠治疗（N = 763），在三所大学进行-附属的私人试管婴儿中心。刺激，根据诊所的标准程序进行取卵和受精。所有胚胎组均在相同的延时培养箱模型中培养，分配到干燥或加湿室中，而其余培养变量保持不变。人口由治疗的逆概率加权以控制所有测量的混杂因素。通过加权人群的逻辑回归评估 HC 与主要结果之间的关联。E 值被报告为考虑未测量的混杂因素的一种方式。通过 Pearson 卡方检验、ANOVA 检验和 Kaplan-Meier 生存分析评估研究组之间胚胎发育和其他次要结果的差异。主要结果和机会的作用单变量逻辑回归分析，由治疗的逆概率加权，确定在潮湿条件下培养的胚胎比在干燥条件下培养的胚胎更有可能实现临床妊娠（优势比 (OR) = 1.236 (95% CI 1.009–1.515)，P = 0.041， E = 1.460）。通过分层，确定所述效果取决于治疗类型：在卵子捐赠或自体治疗中临床妊娠没有改善，但在植入前基因检测治疗中存在统计学上显着的积极效果（OR = 1.699（ 95% CI 1.084–2.663），P = 0.021，E = 1.930）。所述增加与后期结果的改善无关。在与胚胎发育形态动力学相关的变量中也发现了差异。限制，谨慎的原因 该研究的回顾性使其容易受到与治疗特征相关的一些偏差的影响。为了减少可能的偏差的影响，在评估结果之前，病例按治疗的逆概率加权，作为评估测量混杂因素的手段。此外，加权 OR 的 E 值被计算为对未测量的混杂因素的敏感性分析。可以进行一项随机前瞻性研究，以进一步评估潮湿条件对临床结果的影响。研究结果的更广泛意义 这些结果支持在高相对湿度条件下的胚胎培养有助于优化在具有单步培养基的延时培养箱中不受干扰的培养的临床结果。据我们所知，这是关于此事的最大研究，也是第一次进行基于倾向得分的分析。研究资助/竞争兴趣 这项工作得到了西班牙科学、创新和大学部 (CDTI-20170310) 以及 Generalitat Valenciana 和欧洲社会基金 (ACIF/ 2019/264)。没有一个作者有任何竞争利益要声明。试用注册号 不适用。