CHU de Bordeaux, Endocrinology and Metabolism, Reproductive Medicine Unit, Bordeaux, France.
CHU Toulouse, Department of Reproductive Medicine, Toulouse, France.
Hum Reprod. 2019 Jan 1;34(1):92-99. doi: 10.1093/humrep/dey334.
Does endometrial scratch in women undergoing a first or second IVF/ICSI attempt improve the clinical pregnancy rate (CPR)?
Endometrial scratch (ES) in women undergoing their first or second IVF/ICSI attempt does not enhance the CPR under the technical conditions of our study.
Several studies have suggested that physical scratch of the endometrium before an IVF attempt could improve embryo implantation.
STUDY DESIGN, SIZE, DURATION: This was a randomized controlled multi-center, two-arm, parallel trial. Inclusions started in February 2010 and stopped prematurely in July 2014 after an unplanned interim analysis. At the time of study closure, 191 of the planned 358 patients had been included.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients included in the study were randomly assigned to either the ES arm or the non-ES arm. Local ES was performed between Day 20 and Day 24 of the cycle preceding ovarian stimulation using a device for endometrial biopsy. Ovarian stimulation used a combination of recombinant FSH and either an GnRH agonist protocol or a GnRH antagonist protocol without any estrogen pre-treatment. CPR was analyzed on an intent-to-treat basis. All comparisons between the two groups were done using a logistic regression model adjusted for age, BMI and infertility etiology. Differences between the two arms were considered statistically significant at P value of less than 0.0446 for the primary outcome only.
Sixty-eight embryo transfers were performed in the ES arm and sixty-four in the non-ES arm. CPR was 23.5% (16/68) in the ES arm and 35.9% (23/64) in the non-ES arm (hazard ratio (HR) = 0.43; 95% CI, 0.18-1.02; P = 0.0568). The implantation rate was 19.1% and 24.0% in the ES arm and in the non-ES arm, respectively. Two miscarriages and one ectopic pregnancy were reported in each arm. The multiple pregnancy rate was higher in the scratch arm (50.0% vs 20.0%), but the difference was not statistically significant (odds ratio (OR) = 4.54; 95% CI, 0.50-40.93; P = 0.1349). The endometrial biopsy procedure was well tolerated in most women. Of 50 patients in the ES arm having received the embryo transfer, 40 (80.0%) patients reported having felt pain during the procedure, the pain resolving quickly for 31 of them.
LIMITATIONS, REASONS FOR CAUTION: An interim analysis of the primary endpoint was conducted and an independent data monitoring committee agreed on stopping the inclusions. This analysis was prompted by the tendency towards lower pregnancy rates observed in the ES arm. Consequently, the study suffered from a lower inclusion rate and failed to reach the planned sample size.
Under the technical condition employed in this study, ES in the luteal phase of the cycle preceding the ovarian stimulation does not improve CPR in patients undergoing a first or second IVF/ICSI attempt.
STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant from Ministère de la Santé Français (Programme Hospitalier de Recherche Clinique 2009). There are no conflicts of interest.
NCT01064193.
08-Feb-2010.
DATE OF FIRST PATIENT’S ENROLMENT: 08-Feb-2010.
在接受首次或第二次体外受精/卵胞浆内单精子注射（IVF/ICSI）尝试的女性中，子宫内膜搔刮是否能提高临床妊娠率（CPR）？
在本研究的技术条件下，在接受首次或第二次 IVF/ICSI 尝试的女性中进行子宫内膜搔刮（ES）并不能提高 CPR。
几项研究表明，在 IVF 尝试前对子宫内膜进行物理搔刮可以提高胚胎着床。
研究设计、大小、持续时间：这是一项随机对照多中心、双臂、平行试验。纳入工作于 2010 年 2 月开始，并于 2014 年 7 月提前在一次计划外中期分析后停止。在研究结束时，原计划的 358 例患者中有 191 例被纳入。
参与者/材料、地点、方法：研究纳入的患者被随机分配到 ES 组或非 ES 组。在卵巢刺激前的周期第 20 至 24 天使用子宫内膜活检设备进行局部 ES。卵巢刺激使用重组 FSH 与 GnRH 激动剂方案或 GnRH 拮抗剂方案联合使用，无需任何雌激素预处理。CPR 进行意向治疗分析。仅对主要结局进行了调整年龄、BMI 和不孕病因的 logistic 回归模型比较两组间的所有比较。仅当两组间的差异具有统计学意义（P 值<0.0446）时，才认为两组间的差异具有统计学意义。
ES 组进行了 68 次胚胎移植，非 ES 组进行了 64 次。ES 组的 CPR 为 23.5%（16/68），非 ES 组为 35.9%（23/64）（风险比（HR）=0.43；95%CI，0.18-1.02；P=0.0568）。ES 组和非 ES 组的着床率分别为 19.1%和 24.0%。每组各报告 2 例流产和 1 例宫外孕。搔刮组的多胎妊娠率较高（50.0%比 20.0%），但差异无统计学意义（比值比（OR）=4.54；95%CI，0.50-40.93；P=0.1349）。大多数妇女都能很好地耐受子宫内膜活检过程。在接受胚胎移植的 50 例 ES 组患者中，40 例（80.0%）患者报告在手术过程中感到疼痛，其中 31 例疼痛很快缓解。
局限性、谨慎的原因：对主要终点进行了中期分析，独立的数据监测委员会同意停止纳入。这一分析是由 ES 组观察到的妊娠率较低的趋势引发的。因此，该研究的纳入率较低，未能达到计划的样本量。
在本研究采用的技术条件下，在卵巢刺激前的周期黄体期进行 ES 并不能提高首次或第二次 IVF/ICSI 尝试患者的 CPR。
研究资金/利益冲突：本研究由法国卫生部（2009 年医院临床研究计划）资助。无利益冲突。
NCT01064193。
2010 年 2 月 8 日。
2010 年 2 月 8 日。
