Is a frozen embryo transfer in a programmed cycle really the best option?
Is a frozen embryo transfer in a programmed cycle really the best option?
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DOI：
10.1007/s10815-019-01449-2
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发表时间：
2019-04
影响因子：
3.1
通讯作者：
V. Baker;I. Iko;J. Segars
中科院分区：
文献类型：
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作者：
V. Baker;I. Iko;J. Segars
在美国，冷冻保存人类胚胎并随后进行冻融胚胎移植 (FET) 的比例从 2004 年胚胎移植的 7.9% 增加到 2013 年的 40.7%，全球范围内也有类似的增长 [1-3]。尽管 FET 越来越受欢迎，但新出现的数据引起了人们的关注，因为观察到 FET 后妊娠期高血压疾病的风险增加[4-12]。这些数据令人不安，因为先兆子痫对母亲和婴儿的短期和长期健康产生严重的不良后果。出现了几个问题。 FET 导致先兆子痫风险增加的原因是什么？是否可以在大型队列中观察到 FET 与妊娠期高血压疾病之间的关联？瑞典最近的一项观察性研究纳入了近 10,000 名通过 FET 实现的单胎妊娠，发现在程序化 FET 周期中高血压疾病的风险增加，但在自然或刺激的 FET 周期中则没有增加 [13]。这项瑞典研究支持了美国的前瞻性观察队列研究[14]。在后一项研究中，与改良的自然 FET 周期（存在 CL）相比，程序化周期（缺乏黄体 [CL]）与先兆子痫（12.8% vs 3.9%，P= 0.02）和具有严重特征的先兆子痫（9.6% vs 0.8%，P= 0.002）的发生率显着升高相关。回归分析包括调整未产过、年龄、既往高血压病史、体重指数、糖尿病（妊娠前和妊娠期）和多囊卵巢综合征（PCOS），证实在没有 CL 的情况下，先兆子痫的风险显着增加 [14]。因此，新出现的观察数据表明，方案选择，特别是使用不会导致 CL 形成的方案，可能至少部分解释了先兆子痫相关风险的增加。与 FET [13, 14]。 FET 通常在程序化的周期中进行，其中卵巢受到抑制，并且使用外源性雌二醇和黄体酮准备子宫内膜，部分原因是这样的方案允许最大程度地灵活安排。这些观察数据表明，缺乏 CL 会增加妊娠期高血压疾病的风险，这些数据得到了美国两个不同人群报告的母体血管生理学详细评估的支持 [14, 15]。 CL 的缺失与妊娠早期颈动脉-股动脉脉搏波速度的预期下降和颈动脉-股动脉传输时间的增加有关[14]。与存在 CL 的妊娠相比，缺乏 CL 的女性在怀孕期间平均动脉血压没有预期的下降，反应性充血指数较低，并且增强指数较高 [15]。在没有 CL 的情况下，血管生成和非血管生成循环内皮祖细胞的数量均较低 [15]。此外，与存在 CL 相比，缺乏 CL 还与妊娠早期较高的肌酐、钠和总二氧化碳水平相关[16]。
Cryopreservation of human embryos with subsequent frozenthawed embryo transfer (FET) increased from 7.9% of embryo transfers in 2004 to 40.7% of embryo transfers in 2013 in the United States (US), with similar increases globally [1–3]. Despite the increasing popularity of FET, emerging data have raised concern because of the observed increased risk of hypertensive disorders of pregnancy following FET [4–12]. These data are troubling due to preeclampsia’s associated severe adverse consequences on the short-as well as on the long-term health for mothers and infants. Several questions arise. What are the reasons for this increase in the risk of preeclampsia with FET? Would the association between FET and hypertensive disorders of pregnancy be observed in a large cohort? A recent observational study from Sweden that included nearly 10,000 singleton pregnancies achieved via FET detected an increased risk of hypertensive disorders in programmed FET cycles, but not in natural or stimulated FET cycles [13]. This Swedish study supported the prospective observational cohort study from the USA [14]. In the latter study, programmed cycles (corpus luteum [CL] absent) were associated with significantly higher rates of preeclampsia (12.8% vs 3.9%, P= 0.02) and preeclampsia with severe features (9.6% vs 0.8%, P= 0.002) compared with modified natural FET cycles (CL present). Regression analysis including adjustments for nulliparity, age, prior history of hypertension, body mass index, diabetes (pre-gestational and gestational), and polycystic ovary syndrome (PCOS) confirmed a significantly increased risk of preeclampsia in the absence of the CL [14].Thus, emerging observational data suggest that protocol choice, specifically the use of protocols that do not result in the formation of a CL may, at least in part, explain the increased risk of preeclampsia associated with FET [13, 14]. FET is commonly performed in a programmed cycle in which the ovaries are suppressed, and the endometrium is prepared using exogenous estradiol and progesterone, in part because such a protocol allows maximum flexibility in scheduling. These observational data implicating the absence of a CL with an increased risk of hypertensive disorders of pregnancy are supported by detailed assessment of maternal vascular physiology reported in two separate US populations [14, 15]. The absence of the CL was associated with attenuation of the expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester [14]. Women lacking a CL did not have the expected drop in mean arterial blood pressure in pregnancy, had a lower reactive hyperemia index, and had a higher augmentation index compared with pregnancies achieved with the CL present [15]. The number of angiogenic and non-angiogenic circulating endothelial progenitor cells were both lower in the absence of a CL [15]. Furthermore, an absent CL has also been associated with higher creatinine, sodium, and total carbon dioxide levels in early pregnancy [16], compared with the presence of the CL.