Warwick Medical School, University of Warwick, Coventry, UK.
Department of Reproductive Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Cochrane Database Syst Rev. 2021 Mar 17;3(3):CD001894. doi: 10.1002/14651858.CD001894.pub6.
Failure of implantation and conception may result from inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation.
To determine effects of assisted hatching (AH) of embryos derived from assisted conception on live birth and multiple pregnancy rates. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register (until May 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; until May 2020), in the Cochrane Library; MEDLINE (1966 to May 2020); and Embase (1980 to May 2020). We also searched trial registers for ongoing and registered trials (http://www.clinicaltrials.gov - a service of the US National Institutes of Health; http://www.who.int/trialsearch/Default.aspx - The World Health Organization International Trials Registry Platform search portal) (May 2020).
Two review authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical, or laser disruption of the zona pellucida before embryo replacement) versus no AH that reported live birth or clinical pregnancy data.
We used standard methodological procedures recommended by Cochrane. Two review authors independently performed quality assessments and data extraction.
We included 39 RCTs (7249 women). All reported clinical pregnancy data, including 2486 clinical pregnancies. Only 14 studies reported live birth data, with 834 live birth events. The quality of evidence ranged from very low to low. The main limitations were serious risk of bias associated with poor reporting of study methods, inconsistency, imprecision, and publication bias. Five trials are currently ongoing. We are uncertain whether assisted hatching improved live birth rates compared to no assisted hatching (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.92 to 1.29; 14 RCTs, N = 2849; I² = 20%; low-quality evidence). This analysis suggests that if the live birth rate in women not using assisted hatching is about 28%, the rate in those using assisted hatching will be between 27% and 34%. Analysis of multiple pregnancy rates per woman showed that in women who were randomised to AH compared with women randomised to no AH, there may have been a slight increase in multiple pregnancy rates (OR 1.38, 95% CI 1.13 to 1.68; 18 RCTs, N = 4308; I² = 48%; low-quality evidence). This suggests that if the multiple pregnancy rate in women not using assisted hatching is about 9%, the rate in those using assisted hatching will be between 10% and 14%. When all of the included studies (39) are pooled, the clinical pregnancy rate in women who underwent AH may improve slightly in comparison to no AH (OR 1.20, 95% CI 1.09 to 1.33; 39 RCTs, N = 7249; I² = 55%; low-quality evidence). However, when a random-effects model is used due to high heterogeneity, there may be little to no difference in clinical pregnancy rate (P = 0.04). All 14 RCTs that reported live birth rates also reported clinical pregnancy rates, and analysis of these studies illustrates that AH may make little to no difference in clinical pregnancy rates when compared to no AH (OR 1.07, 95% CI 0.92 to 1.25; 14 RCTs, N = 2848; I² = 45%). We are uncertain about whether AH affects miscarriage rates due to the quality of the evidence (OR 1.13, 95% CI 0.82 to 1.56; 17 RCTs, N = 2810; I² = 0%; very low-quality evidence).
AUTHORS' CONCLUSIONS: This update suggests that we are uncertain of the effects of assisted hatching (AH) on live birth rates. AH may lead to increased risk of multiple pregnancy. The risks of complications associated with multiple pregnancy may be increased without evidence to demonstrate an increase in live birth rate, warranting careful consideration of the routine use of AH for couples undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). AH may offer a slightly increased chance of achieving a clinical pregnancy, but data quality was of low grade. We are uncertain about whether AH influences miscarriage rates.
胚胎着床和受孕失败可能是由于囊胚无法从其外层（即透明带）中逸出所致。人为破坏这层外壳称为辅助孵化，被提议作为一种通过促进胚胎着床来提高辅助受孕成功率的方法。
确定辅助孵化（AH）对辅助受孕胚胎的活产率和多胎妊娠率的影响。
我们检索了 Cochrane 妇科和生殖医学组专业注册库（截至 2020 年 5 月）、Cochrane 中央对照试验注册库（CENTRAL；截至 2020 年 5 月）、Cochrane 图书馆；MEDLINE（1966 年至 2020 年 5 月）；以及 Embase（1980 年至 2020 年 5 月）。我们还检索了试验注册处正在进行和已注册的试验（http://www.clinicaltrials.gov - 美国国立卫生研究院的一项服务；http://www.who.int/trialsearch/Default.aspx - 世界卫生组织国际试验注册平台搜索门户）（2020 年 5 月）。
两名综述作者确定并独立筛选了试验。我们纳入了随机对照试验（RCT），这些试验比较了辅助孵化（机械、化学或激光破坏透明带之前进行胚胎移植）与不进行辅助孵化的活产率或临床妊娠率数据。
我们使用了 Cochrane 推荐的标准方法学程序。两名综述作者独立进行了质量评估和数据提取。
我们纳入了 39 项 RCT（7249 名女性）。所有研究均报告了临床妊娠数据，包括 2486 例临床妊娠。只有 14 项研究报告了活产数据，有 834 例活产事件。证据质量从极低到低不等。主要限制是研究方法报告不充分导致严重的偏倚风险、不一致性、不精确性和发表偏倚。目前有 5 项试验正在进行中。我们不确定辅助孵化是否能提高活产率，与不进行辅助孵化相比（比值比（OR）1.09，95%置信区间（CI）0.92 至 1.29；14 项 RCT，N = 2849；I² = 20%；低质量证据）。该分析表明，如果不使用辅助孵化的女性活产率约为 28%，那么使用辅助孵化的女性活产率将在 27%至 34%之间。对每个女性的多胎妊娠率的分析表明，与随机分配到辅助孵化的女性相比，随机分配到不进行辅助孵化的女性的多胎妊娠率可能略有增加（OR 1.38，95%CI 1.13 至 1.68；18 项 RCT，N = 4308；I² = 48%；低质量证据）。这表明，如果不使用辅助孵化的女性多胎妊娠率约为 9%，那么使用辅助孵化的女性多胎妊娠率将在 10%至 14%之间。当纳入的所有研究（39 项）汇总时，与不进行辅助孵化相比，进行辅助孵化的女性的临床妊娠率可能略有提高（OR 1.20，95%CI 1.09 至 1.33；39 项 RCT，N = 7249；I² = 55%；低质量证据）。然而，由于高度异质性，当使用随机效应模型时，临床妊娠率可能几乎没有差异（P = 0.04）。所有报告活产率的 14 项 RCT 也报告了临床妊娠率，对这些研究的分析表明，与不进行辅助孵化相比，辅助孵化对临床妊娠率的影响可能很小（OR 1.07，95%CI 0.92 至 1.25；14 项 RCT，N = 2848；I² = 45%）。我们不确定辅助孵化是否会影响流产率，因为证据质量较差（OR 1.13，95%CI 0.82 至 1.56；17 项 RCT，N = 2810；I² = 0%；极低质量证据）。
本更新表明，我们不确定辅助孵化（AH）对活产率的影响。AH 可能会增加多胎妊娠的风险。与多胎妊娠相关的并发症风险可能会增加，而没有证据表明活产率会增加，这需要仔细考虑在接受体外受精（IVF）或胞浆内精子注射（ICSI）的夫妇中常规使用 AH。AH 可能会稍微增加实现临床妊娠的机会，但数据质量为低等级。我们不确定 AH 是否会影响流产率。
