冷冻胚胎移植后出生体重：胎儿和胎盘都更大？

近期《Human Reproduction》杂志发表了一篇题为《Birth size after embryo cryopreservation: larger by all measures?》的文章，旨在探讨冷冻胚胎移植后出生体重：胎儿和胎盘都更大吗？

本篇内容由翻译志愿者李碧颖医生翻译，蔡贺博士审校，供大家学习交流！

STUDY QUESTION

研究问题

Are the changes in birthweight after frozen and fresh embryo transfer associated with corresponding changes in other measures of foetal growth and placental efficiency?

冻胚和鲜胚移植后出生体重的变化是否与其他胎儿生长和胎盘效率指标的相应变化有关？冷冻和新鲜移植后出生体重的变化是否与衡量胎儿生长和胎盘效率的其他措施的相应变化有关？

SUMMARY ANSWER

总结答案

Although placental efficiency was reduced for both frozen and fresh embryo transfer, children born after frozen embryo transfer (frozen-ET) had symmetrically increased size at birth, whereas children born after fresh embryo transfer (fresh-ET) were asymmetrically smaller at birth, compared to naturally conceived children.

尽管冻胚移植和鲜胚移植中胎盘效率都下降，相比自然受孕后出生的婴儿，冻胚移植后出生的婴儿出生体重对称性地增大，而鲜胚移植后出生的婴儿出生体重不对称地缩小。

WHAT IS KNOWN ALREADY

目前已知

In pregnancies following frozen-ET, the risk of being born large, as measured by birthweight, is higher than after natural and fresh-ET conceptions. It is not known whether this is a result of symmetrically increased growth and increased placental efficiency.

在冻胚移植后的妊娠中，以出生体重衡量指标，胎儿出生体重大的风险高于自然妊娠和鲜胚移植后的胎儿。目前尚不清楚是否这是与胎盘效率增加相对应的改变结果。

STUDY DESIGN, SIZE, DURATION

研究设计，规模，持续时间

A Norwegian nationwide registry-based cohort study of 3093 singletons born after frozen-ET, 15 510 singletons born after fresh-ET and 1 125 366 singletons born after natural conception from 1988 to 2015 was performed. We identified 6334 sibships with at least two different conception methods.

这是一项挪威全国范围内注册的队列研究，纳入了1988年至2015年间，3092个冻胚移植后出生的单胎，15510个鲜胚移植出生的单胎和1125366个自然受孕妊娠后出生的单胎。我们还找到了至少两种不同受孕方法出生的6334个同胞兄弟姐妹。

PARTICIPANTS/MATERIALS, SETTING, METHODS

参与者/资料，环境和方法

Data were collected from the Medical Birth Registry of Norway and the Norwegian National Education Database. Main outcome measures were birth length, birthweight, head circumference, ponderal index (birthweight relative to birth length in kg/m3), placental weight, birthweight:placental weight ratio, gestational age, and birthweight z-score. We estimated mean differences between children born after frozen-ET and fresh-ET compared to natural conception, at the population level and within sibships. Adjustments were made for birth year, maternal age, parity, and education.

数据收集自挪威医学出生登记处和挪威国家教育数据库 。主要结局指标为出生长度、出生体重、头围、重量指数（Ponderal index）(出生体重/出生身长三次方，单位为 kg/m3) 、胎盘重量、出生体重：胎盘重量比 、胎龄和出生体重 z 评分 。我们评估了冻胚移植和鲜胚移植后出生的孩子与自然受孕后出生的孩子在人口水平和同胞之间的平均差异。在出生年份、母亲年龄、产次和教育水平方面进行了调整。

MAIN RESULTS AND THE ROLE OF CHANCE

主要结果和偶然性的作用

Estimates at the population level and within sibships were consistent for all outcomes, for both fresh and frozen-ET compared to natural conception. Within sibships, children born after frozen-ET had longer mean length (Δ = 0.42 cm, 95% CI 0.29 to 0.55) and head circumference (Δ = 0.32 cm, 95% CI 0.23 to 0.41) at birth, but a similar ponderal index (Δ = 0.11 kg/m3, 95% CI −0.04 to 0.26), compared to naturally conceived. Children born after fresh-ET had a shorter length (Δ = −0.22 cm, 95% CI −0.29 to −0.15) and head circumference (Δ = −0.15 cm, 95% CI −0.19 to −0.10), and lower ponderal index (Δ = −0.15 kg/m3, 95% CI −0.23 to −0.07) at birth compared to natural conception within sibships. Furthermore, mean placental weight was larger after both frozen-ET (Δ = 37 g, 95% CI 28 to 45) and fresh-ET (Δ = 7 g, 95% CI 2 to 13) compared to natural conception within sibships, whereas mean birthweight:placental weight ratio was reduced for both frozen-ET (Δ = −0.11, 95% CI −0.17 to −0.05) and fresh-ET (Δ = −0.13, 95% CI −0.16 to −0.09). A range of sensitivity analyses all gave similar conclusions as the main models, including restriction to full siblings, restriction to single embryo transfer, and adjustment for maternal BMI, height, and smoking.

与自然受孕相比，无论是冻胚还是鲜胚移植，所有的试验结果显示在人口水平和同胞的估计是一致的。在他们的同胞中，冻胚出生的婴儿有更大的出生平均身长(△ =0.42cm, 95% CI 0.29 - 0.55)和头围(△ =0.32cm, 95% CI 0.23 -0.41)，但是体重指数相似(△ =0.11kg/m3, 95% CI 0.04 - 0.26)。鲜胚移植后出生的婴儿有更短的出生平均身长，(△ =0.22cm, 95% CI 0.29- 0.15)和头围(△ =0.15cm, 95% CI 0.19 - 0.10) ， 以及更低的体重指数(△ =0.15kg/m3, 95% CI 0.23to 0.07) 。此外， 与同胞中自然受孕的相比， 冻胚移植(△ =37g, 95% CI 28-45)和鲜胚移植(△ = 7g, 95% CI 2- 13)后的平均胎盘重量均大于自然受孕，而冻胚移植(△ = 0.11, 95% CI 0. 17 至 0.05)和鲜胚移植  (△ = 0.13, 95% CI 0.16 至0.09)的平均出生体重：胎盘重量比均降低。一系列敏感性分析都得出了与主要模型相似的结论，包括限定为同胞手足、单胚胎移植、调整母亲的 BMI、身高和吸烟的情况。

LIMITATIONS, REASONS FOR CAUTION

局限性 、注意原因

Additional adjustment for maternal BMI, height, and smoking was possible only for a small sample of the study population (15%). Data on causes and duration of infertility, as well as treatment details, were limited.

仅对少数孕妇（15%的研究人群）的BMI 、身高和吸烟情况进行额外调整。关于不孕的原因和持续时间以及治疗细节的数据有限。

WIDER IMPLICATIONS OF THE FINDINGS

研究结果的更广泛意义

The increased birthweight observed in singletons after frozen-ET is associated with a symmetrically increased birth size and large placentas, also after controlling for maternal factors through sibship analyses. Identifying the responsible treatment factors and the long-term health outcomes are particularly important considering the increase in elective freezing of all embryos.

冷冻胚胎移植后观察到的单胎出生体重增加与出生大小对称增大，胎盘增大有关，通过同胞关系分析控制母体因素后结果相似。考虑到选择性冷冻所有胚胎的人数增加，明确治疗措施相关因素和长期健康结果尤为重要。

文章来源：

E Landsverk, K Westvik-Johari, L B Romundstad, S Opdahl, Birth size after embryo cryopreservation: larger by all measures?, Human Reproduction, Volume 38, Issue 7, July 2023, Pages 1379–1389, https://doi.org/10.1093/humrep/dead094