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体外受精和胞浆内单精子注射受孕的单胎儿的胚胎形态质量与代谢和认知发育的关系:一项匹配队列研究。

Embryo morphologic quality in relation to the metabolic and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection: a matched cohort study.

机构信息

Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

出版信息

Am J Obstet Gynecol. 2022 Sep;227(3):479.e1-479.e23. doi: 10.1016/j.ajog.2022.05.019. Epub 2022 May 11.

Abstract

BACKGROUND

Embryos with higher morphologic quality grading may have a greater potential to achieve clinical pregnancy that leads to a live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of the offspring.

OBJECTIVE

This pilot study aimed to examine the associations between embryo morphologic quality and the physical, metabolic, and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection at preschool age.

STUDY DESIGN

This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of the Women's Hospital, School of Medicine, Zhejiang University. A total of 144 children, aged 4 to 6 years, participated in the follow-up assessment from 2020 to 2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched with singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children's age (±1 year). We measured the offspring's height, weight, body mass index, blood pressure, thyroid hormone levels, and metabolic indicators. Neurodevelopmental assessments were performed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Adaptive Behavior Assessment System, Second Edition. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphologic quality and offspring health outcomes.

RESULTS

A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function, and metabolic indicators were comparable between the 2 groups. After adjustment for potential risk factors by linear regression model 1 and model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than offspring of good-quality embryo transfers (beta, 0.22; 95% confidence interval, 0.09-0.90; beta, 0.22; 95% confidence interval, 0.09-0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessments, there was no difference in the full-scale intelligence quotient based on the Wechsler Preschool and Primary Scale of Intelligence (109.96±12.42 vs 109.60±14.46; P=.88) or the general adaptive index based on the Adaptive Behavior Assessment System (108.26±11.70 vs 108.08±13.44; P=.94) between the 2 groups. The subindices of the 2 tests were also comparable. These findings remained after linear regression analysis.

CONCLUSION

At 4 to 6 years of age, singletons born from poor-quality embryo transfers have comparable metabolic and cognitive development as those born from good-quality embryo transfers using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and end in live birth are likely to have a developmental potential comparable to that of good-quality embryos.

摘要

背景

形态学质量评级较高的胚胎可能具有更大的临床妊娠潜力,从而导致活产,无论其为卵裂期胚胎还是囊胚。很少有研究调查胚胎分级对后代长期健康的影响。

目的

本初步研究旨在检查体外受精和卵胞浆内单精子注射形成的胚胎形态质量与学龄前单胎的身体、代谢和认知发育之间的关系。

研究设计

本匹配队列研究纳入了 2014 年至 2016 年期间在浙江大学医学院附属妇产科医院生殖中心进行新鲜卵裂期胚胎移植周期的不孕夫妇所生育的单胎。共有 144 名 4 至 6 岁的儿童参加了 2020 年至 2021 年的随访评估,不良胚胎组的随访率为 39%。优质胚胎组的单胎与不良胚胎组的单胎按受精方式和儿童年龄(±1 岁)以 2:1 的比例进行匹配。我们测量了后代的身高、体重、体重指数、血压、甲状腺激素水平和代谢指标。使用韦氏学前和小学智力量表第四版和适应行为评估系统第二版对神经发育进行评估。我们还从病历中收集了数据。线性回归模型用于分析胚胎形态质量与后代健康结果之间的关系。

结果

最终分析纳入了 48 名接受不良胚胎移植的单胎和 96 名接受优质胚胎移植的匹配单胎。两组的年龄、性别、身高、体重、体重指数、血压、甲状腺功能和代谢指标无差异。经线性回归模型 1 和模型 2 调整潜在风险因素后,不良胚胎组的游离甲状腺素水平较优质胚胎组有升高趋势(β,0.22;95%置信区间,0.09-0.90;β,0.22;95%置信区间,0.09-0.91),但无临床意义。在神经发育评估方面,基于韦氏学前和小学智力量表的总智商(109.96±12.42 与 109.60±14.46;P=.88)或基于适应行为评估系统的一般适应指数(108.26±11.70 与 108.08±13.44;P=.94)在两组之间无差异。两个测试的子指标也相似。这些发现在进行线性回归分析后仍然存在。

结论

在 4 至 6 岁时,来自不良胚胎移植的单胎在代谢和认知发育方面与来自新鲜卵裂期胚胎的优质胚胎移植的单胎相当。本初步研究结果表明,能够存活并最终导致活产的不良胚胎可能具有与优质胚胎相当的发育潜力。

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