Department of Obstetrics and Gynecology, Assisted Reproduction Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, 3# Qingchun East Road, Hangzhou 310016, PR China.
Department of Obstetrics & Gynecology, Chinese University of Hong Kong, Shatin, Hong Kong, PR China.
Hum Reprod. 2017 Dec 1;32(12):2394-2403. doi: 10.1093/humrep/dex312.
Is pinopode measurement of any prognostic value?
Pinopode expression was significantly associated with the occurrence of pregnancy after frozen embryo transfer.
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.
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.
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.
STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the grants from the general project of medicine and health in Zhejiang Province of China (2015KYA142; 2018KY106), the Key Research and Development Program of Zhejiang Province (2017C03022) and the National Natural Science Foundation of China (81701514).The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare.
ISRCTN26300668.
种植突的测量是否具有任何预后价值？
种植突的表达与冷冻胚胎移植后妊娠的发生显著相关。
种植突在着床期出现在子宫内膜中。种植突的测量已被提出作为子宫内膜容受性的标志物。
研究设计、大小和持续时间：这项前瞻性队列研究于 2014 年至 2016 年在浙江杭州浙江大学医学院附属妇产科医院生殖医学中心进行，招募了 172 名患有不孕症并接受体外受精治疗后进行冷冻胚胎移植的女性。在 172 名参与者中，46 名女性参与了第一项研究，以量化在激素替代周期中孕酮治疗开始后 3-7 天种植突的日变化模式，其余 126 名患有不孕症的女性参与了一项研究，以检查激素替代周期中冷冻胚胎移植后种植突计数与妊娠结局之间的关系。
参与者/材料、设置、方法：参与者的平均年龄为 29 岁。所有参与者均接受了能够支持成功着床的人工激素替代方案。46 名女性在孕酮治疗开始后第 3、4、5、6 和 7 天（P+3，n=6；P+4，n=6；P+5，n=11；P+6，n=13；P+7，n=10）分别获得子宫内膜活检。另外 126 份子宫内膜活检在孕酮治疗开始后第 6 天获得。扫描电子显微镜用于捕获种植突图像，然后使用图像 J 程序对种植突的数量和亚型进行量化。
我们发现，至少需要 60 个显微镜视野才能获得可重复的结果。一项观察者内变异性研究表明，关于发育中的种植突（DP）亚型（r=0.95）和完全发育的种植突（FDP）亚型（r=0.86），两次测量之间的一致性良好，但对于退化的种植突（RP）亚型（r=0.39）则不一致。从第 P+4 天到第 P+6 天，DP/总种植突（TP）的比例迅速下降。FDP/TP 的百分比从第 P+4 天迅速增加，在第 P+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，怀孕的参与者在第 P+6 天的 FDP/TP 百分比显著（P=0.011）更高，而在同一天的 DP/TP 百分比显著（P=0.005）更低。使用包含 DP 和 FDP 百分比的评分系统，发现高种植突评分（82.3%；63.0%）的女性的妊娠率和胚胎着床率显著（P=0.001；P=0.046）高于低种植突评分（53.3%；46.7%）的女性。仍然有可能是由于偶然因素导致了这些观察结果。
局限性、谨慎的原因：本研究检查了激素替代周期中的种植突计数和亚型，尚不确定相同的观察结果是否适用于自然周期。
多年来，种植突一直被质疑为子宫内膜容受性的潜在标志物。我们的结果表明，种植突测量可能对预测妊娠有价值。
研究资助/利益冲突：该研究得到了中国浙江省医学和健康一般项目（2015KYA142；2018KY106）、浙江省重点研发计划（2017C03022）和国家自然科学基金（81701514）的资助。资助者在研究设计、数据收集和分析、出版决定或手稿准备方面没有作用。我们没有竞争利益要申报。
ISRCTN26300668。
