Investigating the impact of the timing of blastulation on implantation: management of embryo-endometrial synchrony improves outcomes
Investigating the impact of the timing of blastulation on implantation: management of embryo-endometrial synchrony improves outcomes
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DOI：
10.1093/hropen/hoy022
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发表时间：
2018-01-01
影响因子：
8.3
通讯作者：
Scott, Richard T., Jr.
中科院分区：
文献类型：
--
作者：
Franasiak, Jason M.;Forman, Eric J.;Scott, Richard T., Jr.
研究问题：胚泡发育延迟的胚胎是否具有较低的生殖潜能或较差的结局，部分原因是胚胎和子宫内膜的同步性？总结回答：在接受新鲜胚胎移植(ET)的胚泡发育延迟的胚胎中，结局降低可能归因于胚胎-子宫内膜同步性的丧失。已知的是：胚泡发育缓慢的胚胎在第5天(D5)比正常胚泡的胚胎有更低的持续着床率(SIR)。传统上，这被归因于胚胎质量下降；然而，与子宫内膜不同步也是一种可能性，尚未完全描述。这一方便的队列由实验室方案的广泛改变导致的组组成，允许评估胚胎和子宫内膜的同步性，因为它与胚泡扩张有关。研究设计、大小、持续时间：从2009年1月到2013年2月进行了一项回溯性队列分析。确定了3个队列：D5 ET、D6 ET和冷冻ET，分别为822例、763例和718例。这些队列中的每个人都已经鉴定了缓慢胚化和正常胚化的胚胎。研究了2010-2013年间所有新鲜或冷冻保存的胚胎。未经活检的胚胎在D5被分为两组：缓慢囊胚组(Morula-Gardner 1)和正常囊胚组(Gardner 2-6)。只包括单个胚胎移植或同一分类组内的两个胚胎移植。对在D5、D6或冷冻保存后进行胚胎移植的不同分类组的结果进行了比较。这评估了新鲜周期中移植时机的影响，以及在冷冻胚胎移植周期中分离纯胚胎因子的影响。持续植入定义为妊娠8周出院时超声心跳检测。SIR被定义为符合持续植入标准的移植胚胎数量除以移植胚胎总数。MAIN结果和机会的作用：总共向1966名患者移植了3391个胚胎。在D5，发育缓慢的胚胎的SIR显著降低(44%对35岁女性的%(P<；0.001))。新鲜的D6ET在D5发育缓慢的胚胎的SIR也显著较低(52%比63%=35岁(P<；0.005))，尽管继续发育到完全囊胚，并且在ET时形态相同，这表明不同步。然而，当缓慢发育的胚胎接受玻璃化冷冻和胚胎移植时，它们的SIRS与正常发育的胚胎相当(年龄=35岁时为57%比60%(P=0.3))。进行了组内相关性和根据患者年龄修正的广义估计方程，证实了这些发现。在冷冻保存的ETS中的正常化表明，在新的周期中，不同步可能是限制晚期胚泡发育的主要不利因素。限制，谨慎的理由：这是一项回溯性研究，包括从方便的样本中选择的队列，因为关于ET DAY的胚胎学实验室方案一致改变，然而，这是独立于胚胎和子宫内膜同步的管理而完成的。虽然使用了严格的超声和血清孕酮标准来统一子宫内膜容受性，但不能排除接受前和接受后子宫内膜的病理状态。研究结果的广泛意义：在接受体外受精的患者中，应该考虑围绕胚胎和子宫内膜同步性的数据，对于任何接受扩大胚胎培养的患者，都可以关注囊胚率的变化。
STUDY QUESTION: Do embryos with delayed blastulation have inferior reproductive potential or poorer outcomes due in part to embryo and endometrial synchrony?SUMMARY ANSWER: Diminished outcomes in embryos with delayed blastulation undergoing fresh embryo transfer (ET) may be attributed to a loss of embryonic-endometrial synchrony.WHAT IS KNOWN ALREADY: Embryos that blastulate slowly have lower sustained implantation rates (SIR) than those which blastulate normally on Day 5 (D5). Traditionally this has been attributed to reduced embryo quality; however, dyssynchrony with the endometrium is also a possibility and has not been fully described. This convenient cohort composed of groups that resulted from a practice wide change in laboratory protocol allows for evaluation of embryo and endometrial synchrony as it related to blastocyst expansion.STUDY DESIGN, SIZE, DURATION: A retrospective cohort analysis was carried out from January 2009 to February 2013. Three cohorts were identified: D5 ET, D6 ET and frozen ET that comprised 822 patients, 763 patients and 718 patients, respectively. Each of these cohorts had slowly blastulating and normally blastulating embryos identified.PARTICIPANTS/MATERIALS, SETTING, METHODS: The study setting was academic affiliated private practice. All first fresh or cryopreserved ETs from 2010 to 2013 were studied. Non-biopsied embryos were classified into two groups on D5: slowly blastulating (Morula-Gardner 1) or normally blastulating (Gardner 2-6). Only single ETs or transfer of two embryos within the same classification group were included. Outcomes were compared between classification groups in embryos undergoing transfer on D5, D6, or after cryopreservation. This assesses the impact of transfer timing in fresh cycles as well as isolating a pure embryonic factor in frozen ET cycles. Sustained implantation was defined as heart beat detection at discharge sonogram at 8 weeks gestation. SIR was defined as the number of embryos transferred meeting criteria for sustained implantation divided by the total number of embryos transferred.MAIN RESULTS AND THE ROLE OF CHANCE: In total, 3391 embryos were transferred to 1966 patients. On D5, SIRs were significantly lower with slowly blastulating embryos (44% versus 64% in women = 35 years of age (P < 0.001)). Fresh D6 ETs also had significantly lower SIRs for embryos that were slowly blastulating on D5 (52% versus 63% in = 35 years of age (P < 0.005)) despite continued development to full blastocysts and being morphologically equivalent at the time of ET, suggesting dyssynchrony. However, when slowly blastulating embryos underwent vitrification and then ET, they had SIRs which were equivalent to their normally blastulating counterparts (57% versus 60% in = 35 years of age (P = 0.3)). An intraclass correlation and a generalized estimating equation corrected for patient age was performed which confirmed these findings. The normalization in cryopreserved ETs indicates that dyssynchrony may be a major adverse factor limiting outcomes with late blastulating embryos in fresh cycles.LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study comprising cohorts from a convenient sample chosen due to a uniform change in embryology laboratory protocol regarding ET day, however, this was done independent of the management of embryo and endometrial synchrony. Although strict ultrasound and serum progesterone criteria were utilized to make endometrial receptivity uniform, pathologic states of pre-receptive and post-receptive endometrium cannot be ruled out.WIDER IMPLICATIONS OF THE FINDINGS: The data surrounding embryo and endometrial synchrony should be considered in patients undergoing IVF and attention to the variations in blastulation rates can be applied to any patient undergoing extended embryo culture.