Department of Gynaecology & Reproductive Medicine, University Medical Centre Utrecht, Utrecht University, PO Box 85500, 3508 GA, Utrecht, the Netherlands.
Amsterdam UMC, University of Amsterdam, Center for Reproductive Medicine, Reproduction and Development, Meibergdreef 9, Amsterdam, the Netherlands.
Hum Reprod. 2021 Jan 1;36(1):87-98. doi: 10.1093/humrep/deaa268.
Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle?
In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%.
Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes.
STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%).
After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI).
LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%.
The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work.
Registered in the Netherlands Trial Register (NL5193/NTR 5342).
31 July 2015.
DATE OF FIRST PATIENT’S ENROLMENT: 26 January 2016.
在经历了一次体外受精/卵胞浆内单精子注射（IVF/ICSI）治疗失败的女性中，子宫内膜搔刮是否会影响随后新鲜 IVF/ICSI 周期的活产率？
在搔刮组中，活产率观察到增加了 4.6%，可能的置信区间范围在-0.7%至+9.9%之间。
自从首次提出子宫内膜搔刮可能改善 IVF/ICSI 中的胚胎着床以来，已经进行了许多临床试验。然而，由于样本量和研究质量的限制，仍然不清楚子宫内膜搔刮是否能改善 IVF/ICSI 的结果。
研究设计、规模、持续时间：SCRaTCH 试验是一项针对经历了一次不成功的 IVF/ICSI 周期且计划进行第二次新鲜 IVF/ICSI 治疗的女性的非盲随机对照试验，评估在随后的 IVF/ICSI 治疗中，使用子宫内膜活检导管进行单次子宫内膜搔刮是否会导致活产率高于不进行搔刮。该研究在 8 所学术医院和 24 所普通医院进行。参与者于 2016 年 1 月至 2018 年 7 月期间通过基于网络的随机化方案进行随机分组。次要结局包括累积 12 个月的持续妊娠导致活产率。
参与者/材料、设置、方法：符合条件的参与者为之前经历过一次失败的 IVF/ICSI 治疗且计划进行第二次新鲜 IVF/ICSI 治疗的女性。共有 933 名符合条件的参与者（参与率为 88%）被纳入研究。
在新鲜胚胎移植后，搔刮组的活产率比对照组观察到增加了 4.6%（分别为 110/465 与 88/461，风险比（RR）1.24[95%置信区间（CI）0.96-1.59]）。这些数据与真实差异在-0.7%至+9.9%（95%CI）之间一致，表明虽然 95%CI 的最大比例为正，但搔刮可能没有或甚至有较小的负面影响。生化妊娠丢失率和流产率在两组之间没有差异：在搔刮组中，27/153 例生化妊娠丢失和 14/126 例流产，而对照组分别为 19/130 例和 17/111 例（RR 1.21[95%CI 0.71-2.07]和 RR 0.73[95%CI 0.38-1.40]）。在 12 个月的随访后，搔刮组的活产率观察到增加了 5.1%（202/467 与 178/466），真实差异最有可能介于-1.2%至+11.4%（95%CI）之间。
局限性、谨慎的原因：本研究未设盲。对分配的了解可能是参与者分配到搔刮组的一个激励因素，使他们在可能会取消或停止治疗的情况下继续治疗。此外，本研究的目的是检测活产率的差异为 9%。
本研究结果激励了对子宫内膜搔刮的疗效和临床意义的进一步评估。如果确实存在效果，那么它可能比之前预期的要小，或者可能仅限于接受 IVF/ICSI 的特定女性群体。研究这一点需要更大的样本量，这将由正在进行的国际个体参与者数据分析（PROSPERO CRD42017079120）提供。目前，子宫内膜搔刮不应在临床试验之外进行。
研究资金/利益冲突：本研究由 ZonMW（荷兰医疗保健研究资助组织）资助。J.S.E. Laven 报告了来自 AnshLabs（得克萨斯州 Webster）、Ferring（荷兰 Hoofddorp）和卫生部（CIBG，海牙）的拨款和个人酬金，这些均来自于提交的工作之外。A.E.P. Cantineau 报告了来自 Ferring BV 的“其他”酬金、来自 Up to date Hyperthecosis 的个人酬金、来自 Theramex BV 的“其他”酬金，这些均来自于提交的工作之外。E.R. Groenewoud 报告了 Titus Health Care 在研究期间的拨款。A.M. van Heusden 报告了来自 Merck Serono、Ferring、Goodlife 的个人酬金，这些均来自于提交的工作之外。F.J.M. Broekmans 报告了来自 Ferring BV、Merck Serono、Gedeon Richter 的个人酬金、外部咨询委员会成员酬金、来自 Ferring BV 的教育活动酬金、来自 Merck Serono 的研究支持酬金、来自 Roche 的咨询和顾问工作酬金，这些均来自于提交的工作之外。C.B. Lambalk 报告了来自 Ferring、Merck、Guerbet 的拨款，这些均来自于提交的工作之外。
在荷兰试验注册中心（NL5193/NTR 5342）注册。
2015 年 7 月 31 日。
2016 年 1 月 26 日。
