Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles
Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles
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植入时的 Pinopode 评分可预测激素替代周期中冷冻胚胎移植后的成功植入
DOI：
10.1093/humrep/dex312
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发表时间：
2017-12-01
影响因子：
6.1
通讯作者：
Zhang, S. Y.
中科院分区：
文献类型：
--
作者：
Jin, X. Y.;Zhao, L. J.;Zhang, S. Y.
研究问题：pinopode测量有任何预后价值吗？回答：Pinopode的表达与冷冻胚胎移植后妊娠的发生显著相关。已知情况：pinopode在着床期间在子宫内膜中表达。Pinopode测量被认为是子宫内膜容受性的标志。研究设计、规模、持续时间：2014年至2016年，邵逸夫医院生殖医学中心进行了一项前瞻性队列研究，招募了172名不孕症妇女，在体外受精治疗后接受冷冻胚胎移植。在172名参与者中，46名妇女参加了第一项研究，以量化激素替代周期中黄体酮治疗开始后3-7天内pinopodes的每日变化模式，其余126名不孕妇女参加了一项研究，以检查激素替代周期中冷冻胚胎移植后pinopodes计数与妊娠结局之间的关系。参与者/材料、环境、方法：参与者的平均年龄为29岁。所有参与者都接受了能够支持成功植入的人工激素替代方案。46例妇女在黄体酮治疗开始后3、4、5、6、7天分别行子宫内膜活检（P + 3, n = 6; P + 4, n = 6; P + 5, n = 11; P + 6, n = 13; P + 7, n = 10）。另外126例子宫内膜活检在黄体酮启动后6天进行。利用扫描电子显微镜捕获足跖虫图像，然后使用image J程序对足跖虫的数量和亚型进行量化。主要结果和偶然性的作用：我们发现至少需要60个显微场才能获得可重复的结果。一项观察者内变异性研究显示，关于发育中的pinopode （DP）亚型（r = 0.95）和完全发育的pinopode （FDP）亚型（r = 0.86），两种测量结果之间的一致性很好，但对于回归（RP） pinopode亚型（r = 0.39）则不一致。DP/总pinopotes （TP）的比例从P + 4 d迅速下降至P + 6 d的最低点。从第4天开始，FDP/TP的比例迅速上升，在第6天达到峰值。另一方面，RP/TP的百分比在第P + 7天达到峰值。与未怀孕的参与者相比，怀孕的参与者在P + 6天的FDP/TP百分比显着（P = 0.011）较高，同一天的DP/TP百分比显着（P = 0.005）较低。采用结合DP和FDP百分比的评分系统，发现pinopode评分高的妇女的妊娠率和胚胎着床率为82.3%；阳性率为63.0% (P = 0.001; P = 0.046)，显著高于低评分组（53.3%;46.7%）。仍然有一种可能性是，这些观察结果可能是偶然出现的。局限性和谨慎的原因：本研究检查了激素替代疗法周期中的蛲虫数量和亚型，尚不确定同样的观察结果是否适用于自然周期。研究结果的更广泛意义：足趾作为子宫内膜容受性的潜在标记物多年来一直受到质疑。我们的研究结果表明，pinopode测量可能在预测妊娠方面有价值。
STUDY QUESTION: Is pinopode measurement of any prognostic value?SUMMARY ANSWER: Pinopode expression was significantly associated with the occurrence of pregnancy after frozen embryo transfer.WHAT IS KNOWN ALREADY: Pinopodes are expressed in the endometrium during the implantation period. Pinopode measurement has been proposed as a marker of endometrial receptivity.STUDY DESIGN, SIZE, DURATION: A prospective cohort study was conducted at the Center of Reproductive Medicine, Sir Run Run Shaw Hospital, between 2014 and 2016, recruiting 172 women with infertility and undergoing frozen embryo transfer following IVF treatment. Among 172 participants, 46 women took part in the first study to quantify the daily changing pattern of pinopodes 3-7 days after the initiation of progesterone therapy in the hormone replacement cycles and the remaining 126 women with infertility participated in a study to examine the relationship between pinopode count and pregnancy outcome following frozen embryo transfer in hormone replacement cycles.PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean age of participants was 29 years old. All participants received an artificial hormone replacement protocol capable of supporting successful implantation. Endometrial biopsies from 46 women were obtained 3, 4, 5, 6 and 7 days after the initiation of progesterone therapy (P + 3, n = 6; P + 4, n = 6; P + 5, n = 11; P + 6, n = 13; P + 7, n = 10, respectively). Another 126 endometrial biopsies were obtained precisely 6 days after the initiation of progesterone. Scanning electron microscopy was used to capture the pinopode images, followed by use of the image J program to quantify the count and subtype of the pinopodes.MAIN RESULTS AND THE ROLE OF CHANCE: We found that at least 60 microscopic fields were necessary to achieve a reproducible result. An intra-observer variability study showed good agreement between two measurements regarding the developing pinopode (DP) subtype (r = 0.95) and the fully developed pinopode (FDP) subtype (r = 0.86) but not for the regressing (RP) pinopode subtype (r = 0.39). The proportion of DP/total pinopodes (TP) declined rapidly form day P + 4 to a minimum on day P + 6. The percentage of FDP/TP increased rapidly from day P + 4 to reach a peak on day P + 6. On the other hand, the percentage of RP/TP reached a peak on day P + 7. Participants who conceived had a significantly (P = 0.011) higher percentage of FDP/TP on day P + 6 and significantly (P = 0.005) lower percentage of DP/TP on the same day compared with participants who did not become pregnant. Using a scoring system incorporating the percentages of DP and FDP, it was found that the pregnancy rate and the embryo implantation rate of women with a high pinopode score 82.3%; 63.0%) was significantly (P = 0.001; P = 0.046) higher than that of women with a low pinopode score (53.3%; 46.7%), respectively. There remains a possibility that the observations could have arisen due to chance.LIMITATIONS, REASONS FOR CAUTION: This study examined pinopode count and subtype in the HRT cycles, and it is uncertain whether the same observations apply to in natural cycles.WIDER IMPLICATIONS OF THE FNDINGS: Pinopodes have been questioned as a potential marker of endometrial receptivity for many years. Our results suggested that pinopode measurement may be of value in predicting pregnancy.