荷兰阿姆斯特丹自由大学D C Kieslinger等研究人员发现，体外培养胚胎的延时拍摄监测没有改善临床结果。相关论文于2023年3月30日在线发表于国际学术期刊《柳叶刀》。

研究人员表示，延时拍摄监测越来越多地被用于生育实验室，用于培养和选择胚胎进行移植。这种方法被提供给夫妇，有望提高怀孕的机会，尽管目前没有足够的证据表明有优越的临床效果。研究人员旨在评估延时拍摄监测的潜在改善是由基于延时的胚胎选择方法本身，还是作为该系统一部分的不间断培养环境造成的。

在这项三臂、多中心、双盲、随机对照试验中，接受体外受精或卵胞浆内单精子注射的夫妇从荷兰的15家生育诊所招募，并使用基于网络的计算机化随机服务随机分配到三组中的一组。夫妻双方和医生都被掩盖了治疗组，但胚胎学家和实验室技术人员不能被掩盖。延时拍摄早期胚胎活力评估（EEVA; TLE）组接受基于EEVA延时选择方法的胚胎选择和不间断培养。延时拍摄常规（TLR）组接受常规胚胎选择和不间断培养。对照组接受常规胚胎选择和中断培养。共同主要终点是所有妇女在12个月内的累计持续妊娠率和预后良好人群的新鲜单胚胎移植后的持续妊娠率。分析是通过意向性治疗进行的。该试验已在ICTRP搜索门户注册，编号为NTR5423，目前不接受新的参与者。

1731对夫妇在2017年6月15日至2020年3月31日期间被随机分配（577人进入TLE组，579人进入TLR组，以及575人进入对照组）。12个月的累积持续妊娠率在三组之间没有显著差异：TLE组为50-8%（577人中的293人），TLR组为50-9%（579人中的295人），对照组为49-4%（575人中的284人）（P=0-85）。在预后良好的人群中，新鲜单胚胎移植后的持续妊娠率，TLE组为38-2%（327例中的125例），TLR组为36-8%（323例中的119例），而对照组为37-8%（325例中的123例）（P=0-90）。报告了10例严重的不良事件（5例TLE，4例TLR，对照组1例），这些事件与研究程序无关。

结果表明，与常规方法相比，使用EEVA测试的基于延时拍摄的胚胎选择和延时拍摄孵化器中的不间断培养条件都没有改善临床结果。在承诺改善结果的情况下，广泛地将延时拍摄监测应用于生育治疗，应该受到质疑。

附：英文原文

Title: Clinical outcomes of uninterrupted embryo culture with or without time-lapse-based embryo selection versus interrupted standard culture (SelecTIMO): a three-armed, multicentre, double-blind, randomised controlled trial

Author: D C Kieslinger, C G Vergouw, L Ramos, B Arends, M H J M Curfs, E Slappendel, E H Kostelijk, M H E C Pieters, D Consten, M O Verhoeven, D E Besselink, F Broekmans, B J Cohlen, J M J Smeenk, S Mastenbroek, C H de Koning, Y M van Kasteren, E Moll, J van Disseldorp, E A Brinkhuis, E A M Kuijper, W M van Baal, H G I van Weering, P J Q van der Linden, M H Gerards, P M Bossuyt, M van Wely, C B Lambalk

Issue&Volume: 2023-03-30

Abstract: Background

Time-lapse monitoring is increasingly used in fertility laboratories to culture and select embryos for transfer. This method is offered to couples with the promise of improving pregnancy chances, even though there is currently insufficient evidence for superior clinical results. We aimed to evaluate whether a potential improvement by time-lapse monitoring is caused by the time-lapse-based embryo selection method itself or the uninterrupted culture environment that is part of the system.

Methods

In this three-armed, multicentre, double-blind, randomised controlled trial, couples undergoing in-vitro fertilisation or intracytoplasmic sperm injection were recruited from 15 fertility clinics in the Netherlands and randomly assigned using a web-based, computerised randomisation service to one of three groups. Couples and physicians were masked to treatment group, but embryologists and laboratory technicians could not be. The time-lapse early embryo viability assessment (EEVA; TLE) group received embryo selection based on the EEVA time-lapse selection method and uninterrupted culture. The time-lapse routine (TLR) group received routine embryo selection and uninterrupted culture. The control group received routine embryo selection and interrupted culture. The co-primary endpoints were the cumulative ongoing pregnancy rate within 12 months in all women and the ongoing pregnancy rate after fresh single embryo transfer in a good prognosis population. Analysis was by intention to treat. This trial is registered on the ICTRP Search Portal, NTR5423, and is closed to new participants.

Findings

1731 couples were randomly assigned between June 15, 2017, and March 31, 2020 (577 to the TLE group, 579 to the TLR group, and 575 to the control group). The 12-month cumulative ongoing pregnancy rate did not differ significantly between the three groups: 50·8% (293 of 577) in the TLE group, 50·9% (295 of 579) in the TLR group, and 49·4% (284 of 575) in the control group (p=0·85). The ongoing pregnancy rates after fresh single embryo transfer in a good prognosis population were 38·2% (125 of 327) in the TLE group, 36·8% (119 of 323) in the TLR group, and 37·8% (123 of 325) in the control group (p=0·90). Ten serious adverse events were reported (five TLE, four TLR, and one in the control group), which were not related to study procedures.

Interpretation

Neither time-lapse-based embryo selection using the EEVA test nor uninterrupted culture conditions in a time-lapse incubator improved clinical outcomes compared with routine methods. Widespread application of time-lapse monitoring for fertility treatments with the promise of improved results should be questioned.

DOI: 10.1016/S0140-6736(23)00168-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00168-X/fulltext