Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.
Front Endocrinol (Lausanne). 2023 Aug 29;14:1250847. doi: 10.3389/fendo.2023.1250847. eCollection 2023.
Frozen-thawed embryo transfer (FET) has been a viable alternative to fresh embryo transfer in recent years because of the improvement in vitrification methods. Laboratory-based studies indicate that complex molecular and morphological changes in endometrium during the window of implantation after exogenous hormones with controlled ovarian stimulation may alter the interaction between the embryo and endometrium, leading to a decreased implantation potential. Based on the results obtained from randomized controlled studies, increased pregnancy rates and better perinatal outcomes have been reported following FET. Compared to fresh embryo transfer, fewer preterm deliveries, and reduced incidence of ovarian hyperstimulation syndrome were found after FETs, yet there is a trend of increased pregnancy-related hypertensive diseases in women receiving FET. Despite the increased application of FET, the search for the most optimal priming protocol for the endometrium is still undergoing. Three available FET protocols have been proposed to prepare the endometrium: i) natural cycle (true natural cycle and modified natural cycle) ii) artificial cycle (AC) or hormone replacement treatment cycle iii) mild ovarian stimulation (mild-OS) cycle. Emerging evidence suggests that the optimal timing for FET using warmed blastocyst transfer is the LH surge+6 day, hCG administration+7 day, and the progesterone administration+6 day in the true natural cycle, modified natural cycle, and AC protocol, respectively. Although still controversial, better clinical pregnancy rates and live birth rates have been reported using the natural cycle (true natural cycle/modified natural cycle) compared with the AC protocol. Additionally, a higher early pregnancy loss rate and an increased incidence of gestational hypertension have been found in FETs using the AC protocol because of the lack of a corpus luteum. Although the common clinical practice is to employ luteal phase support (LPS) in natural cycles and mild-OS cycles for FET, the requirement for LPS in these protocols remains equivocal. Recent findings obtained from RCTs do not support the routine application of endometrial receptivity testing to optimize the timing of FET. More RCTs with rigorous methodology are needed to compare different protocols to prime the endometrium for FET, focusing not only on live birth rate, but also on maternal, obstetrical, and neonatal outcomes.
冻融胚胎移植（FET）近年来已成为新鲜胚胎移植的可行替代方案，这要归功于玻璃化方法的改进。基于实验室的研究表明，在控制性卵巢刺激下外源性激素作用后种植窗期间，子宫内膜发生复杂的分子和形态变化，可能改变胚胎与子宫内膜之间的相互作用，从而降低着床潜能。基于随机对照研究的结果，FET 后报告妊娠率增加，围产期结局改善。与新鲜胚胎移植相比，FET 后早产率降低，卵巢过度刺激综合征发生率降低，但接受 FET 的女性妊娠相关高血压疾病的发生率呈上升趋势。尽管 FET 的应用增加，但寻找最佳的子宫内膜预处理方案仍在进行中。目前提出了三种 FET 方案来准备子宫内膜：i）自然周期（真正的自然周期和改良的自然周期）ii）人工周期（AC）或激素替代治疗周期 iii）轻度卵巢刺激（mild-OS）周期。新出现的证据表明，在真正的自然周期、改良的自然周期和 AC 方案中，使用解冻囊胚移植的 FET 的最佳时间分别为 LH 峰+6 天、hCG 给药+7 天和孕激素给药+6 天。尽管仍存在争议，但与 AC 方案相比，自然周期（真正的自然周期/改良的自然周期）报告的临床妊娠率和活产率更高。此外，由于缺乏黄体，AC 方案中的 FET 发现早期妊娠丢失率较高，妊娠高血压的发生率增加。尽管在自然周期和轻度 OS 周期中进行 FET 时通常采用黄体期支持（LPS），但这些方案中 LPS 的需求仍存在争议。来自 RCT 的最新发现不支持常规应用子宫内膜容受性检测来优化 FET 的时机。需要更多严格方法学的 RCT 来比较不同的方案，为 FET 准备子宫内膜，不仅关注活产率，还要关注母婴、产科和新生儿结局。
