Abstract

In studies of human IVF, as compared to frozen embryo transfer (ET), fresh ET is associated with smaller infants and higher risk of small for gestational age infants. Recent observations suggest that ET using vitrified embryos is associated with higher pregnancy and live birth rates compared to fresh ET, but increased rates of large for gestational age infants. The mechanisms underlying these associations are largely unknown, and available evidence suggests that the influence of IVF, vitrification and the superovulated (SO) uterine environment on placental function and fetal growth is complex. This warrants further investigation given the prevalent practice in human IVF of both fresh ET into a SO uterine environment, and vitrification with ET into a more physiologic uterine environment. Using a mouse model that closely resembles human IVF, we investigated if vitrification of IVF embryos better preserves placental function and results in better pregnancy outcomes as compared to fresh ET because of transfer into a more physiologic endometrium. We found that the SO environment, independent of vitrification status, reduced implantation rates, inhibited placental mechanistic target of rapamycin signaling and induced placental stress signaling, resulting in fetal growth restriction (1.080 ± 0.05 g estrous fresh (n = 17 litters), 1.176 ± 0.05 g estrous vitrified (n = 12), 0.771 ± 0.06 g SO fresh (n = 15), 0.895 ± 0.08 g SO vitrified (n = 10), P < 0.0001). In addition, our study suggests that vitrification impairs the developmental potential of IVF blastocysts that resulted in a significantly smaller litter size (2.6 ± 2.3 fresh estrous vs 2.5 ± 2.4 fresh SO vs 1.6 ± 1.7 estrous vitrified vs 1.7 ± 1.8 SO vitrified, P = 0.019), with no effect on fetal growth or placental function at term. Our findings suggest that vitrification may negatively impact early embryonic viability, while the SO maternal uterine environment impairs both placental development and fetal growth in IVF.

中文翻译：

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玻璃化冷冻和超排卵环境对体外受精小鼠模型中胎盘功能和胎儿生长的影响。

摘要

在人类试管婴儿的研究中，与冷冻胚胎移植 (ET) 相比，新鲜 ET 与较小的婴儿和较高的小于胎龄儿的风险有关。最近的观察表明，与新鲜 ET 相比，使用玻璃化胚胎的 ET 与更高的妊娠率和活产率相关，但增加了胎龄婴儿的大胎率。这些关联的潜在机制在很大程度上是未知的，现有证据表明 IVF、玻璃化冷冻和超排 (SO) 子宫环境对胎盘功能和胎儿生长的影响是复杂的。考虑到新鲜 ET 进入 SO 子宫环境和 ET 玻璃化进入更生理性子宫环境的人类 IVF 中的普遍做法，这值得进一步研究。使用与人类试管婴儿非常相似的小鼠模型，我们调查了与新鲜 ET 相比，IVF 胚胎的玻璃化冷冻是否能更好地保留胎盘功能并导致更好的妊娠结果，因为它会转移到更具生理性的子宫内膜中。我们发现 SO 环境与玻璃化状态无关，降低着床率，抑制雷帕霉素信号的胎盘机制目标和诱导胎盘应激信号，导致胎儿生长受限（1.080 ± 0.05 g 新鲜发情（n = 17 窝），1.176 ± 0.05 g 发情玻璃化 (n = 12), 0.771 ± 0.06 g SO 新鲜 (n = 15), 0.895 ± 0.08 g SO 玻璃化 (n = 10),P  < 0.0001)。此外，我们的研究表明，玻璃化冷冻会损害 IVF 囊胚的发育潜力，导致产仔数显着减少（2.6 ± 2.3 新鲜发情 vs 2.5 ± 2.4 新鲜 SO vs 1.6 ± 1.7 发情玻璃化 vs 1.7 ± 1.8 SO 玻璃化，P  = 0.019)，对足月胎儿生长或胎盘功能没有影响。我们的研究结果表明，玻璃化冷冻可能会对早期胚胎活力产生负面影响，而 SO 母体子宫环境会损害体外受精中的胎盘发育和胎儿生长。