Abstract

BACKGROUND

Extended embryo culture to blastocyst stage is widely used in IVF and is the default strategy in most clinics. The last decade has witnessed a growing interest in obstetric–perinatal outcomes following blastocyst transfer. Recent studies have challenged the conclusions of systematic reviews that associate risks of preterm birth (PTB) and large for gestational age (LGA) babies with blastocyst transfer. A higher proportion of blastocysts is transferred as frozen-thawed embryos, which may also have added implications.

OBJECTIVE AND RATIONALE

The aim of this study was to conduct an updated systematic review of the obstetric–perinatal outcomes in singleton pregnancies following blastocyst-stage transfer compared to cleavage-stage transfer in IVF/ICSI cycles. Where deemed appropriate, data were combined in cumulative meta-analyses.

SEARCH METHODS

Data sources from Medline, EMBASE, CINAHL, Web of Science, the Cochrane Central Register of Clinical Trials and the International Clinical Trials Registry Platform (ICTRP) (1980–2020) were searched using combinations of relevant keywords. Searches had no language restrictions and were limited to human studies. Observational studies and randomized controlled trials comparing obstetric–perinatal outcomes between singleton pregnancies after blastocyst-stage transfer and those after cleavage-stage transfer in IVF/ICSI cycles were sought. Two independent reviewers extracted data in 2 × 2 tables and assessed the methodological quality of the relevant studies using the Critical Appraisal Skills Programme scoring. Cumulative meta-analyses were carried out with independent analysis of pregnancies after fresh and frozen embryo transfers, using the Comprehensive Meta-Analysis software. If provided by included studies, adjusted effect sizes were combined in a sensitivity analysis.

OUTCOMES

A total of 35 studies were included (n = 520 769 singleton pregnancies). Outcome data suggest singleton pregnancies following fresh blastocyst transfer were associated with higher risk of LGA (risk ratio (RR) 1.14; 95% CI 1.05–1.24) and very PTB (RR 1.17; 95% CI 1.08–1.26) compared to fresh cleavage-stage transfer. Singleton pregnancies following frozen blastocyst transfer were associated with higher risks of LGA (RR 1.17; 95% CI 1.08–1.27), PTB (RR 1.13; 95% CI 1.03–1.24) and caesarean section (RR 1.08; 95% CI 1.03–1.13) but lower risks of small for gestational age (RR 0.84, 95% CI 0.74–0.95) and perinatal mortality (RR 0.70; 95% CI 0.58–0.86). Increased risks of LGA and PTB after frozen blastocyst transfer persisted in the sensitivity analysis, which also showed a significantly increased risk of PTB after fresh blastocyst transfer. Cumulative meta-analyses revealed consistency in prevalence and magnitude of risks for a number of years. Data on other perinatal outcomes are still evolving.

WIDER IMPLICATIONS

While the available evidence is predominantly reassuring in the context of blastocyst-stage embryo transfer, observational data suggest that blastocyst transfer is associated with a higher risk of LGA. This holds true irrespective of fresh or frozen transfer. Meta-analysis of adjusted data showed an increased risk of PTB with fresh and frozen blastocyst transfer. However, the quality of available evidence ranges from low to very low. Although blastocyst-stage embryo transfer remains the default position in most centres, based on individual risk profile we may need to consider cleavage-stage embryo transfer in some to mitigate the risk of LGA/PTB.

中文翻译：

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囊胚期胚胎移植后与卵裂期胚胎移植后单胎妊娠的产科和围产期结局比较：系统评价和累积荟萃分析

摘要

背景

将胚胎培养延长至囊胚期广泛用于 IVF，并且是大多数诊所的默认策略。过去十年，人们对囊胚移植后的产科-围产期结局越来越感兴趣。最近的研究对系统评价的结论提出了挑战，系统评价将早产 (PTB) 和大于胎龄 (LGA) 婴儿的风险与囊胚移植联系起来。更高比例的囊胚以冻融胚胎的形式进行移植，这也可能产生额外的影响。

目标和理由

本研究的目的是对 IVF/ICSI 周期中囊胚期移植与卵裂期移植后单胎妊娠的产科-围产期结局进行最新的系统评价。在认为合适的情况下，将数据合并到累积荟萃分析中。

搜寻方法

使用相关关键词组合对来自 Medline、EMBASE、CINAHL、Web of Science、Cochrane 临床试验中央注册中心和国际临床试验注册平台 (ICTRP) (1980-2020) 的数据源进行搜索。搜索没有语言限制，仅限于人类研究。观察性研究和随机对照试验比较了 IVF/ICSI 周期中囊胚期移植后和卵裂期移植后单胎妊娠的产科-围产期结局。两名独立评审员提取 2 × 2 表中的数据，并使用批判性评估技能计划评分评估相关研究的方法学质量。使用综合荟萃分析软件，对新鲜和冷冻胚胎移植后的妊娠进行独立分析，进行累积荟萃分析。如果纳入的研究提供了调整后的效应大小，则将其合并到敏感性分析中。

结果

总共纳入 35 项研究（n = 520 769 例单胎妊娠）。结果数据表明，与新鲜卵裂相比，新鲜囊胚移植后的单胎妊娠与较高的 LGA 风险（风险比 (RR) 1.14；95% CI 1.05–1.24）和非常 PTB（RR 1.17；95% CI 1.08–1.26）风险相关。阶段转移。冷冻囊胚移植后的单胎妊娠与较高的 LGA (RR 1.17; 95% CI 1.08–1.27)、PTB (RR 1.13; 95% CI 1.03–1.24) 和剖腹产 (RR 1.08; 95% CI 1.03–1.13) 风险相关）但小于胎龄儿（RR 0.84，95% CI 0.74–0.95）和围产儿死亡率（RR 0.70；95% CI 0.58–0.86）的风险较低。敏感性分析中，冷冻囊胚移植后 LGA 和 PTB 的风险持续增加，这也表明新鲜囊胚移植后 PTB 的风险显着增加。累积荟萃分析揭示了多年来患病率和风险程度的一致性。其他围产期结局的数据仍在不断变化。

更广泛的影响

虽然现有证据在囊胚期胚胎移植方面主要令人放心，但观察数据表明囊胚移植与较高的 LGA 风险相关。无论新鲜还是冷冻转移，这都适用。调整数据的荟萃分析显示，新鲜和冷冻囊胚移植发生 PTB 的风险增加。然而，现有证据的质量从低到极低不等。尽管囊胚期胚胎移植仍然是大多数中心的默认位置，但根据个人风险状况，我们可能需要考虑在某些中心进行卵裂期胚胎移植，以降低 LGA/PTB 的风险。