Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT
Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT
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DOI：
10.1093/humrep/dew156
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发表时间：
2016-10-01
影响因子：
6.1
通讯作者：
Mastenbroek, Sebastiaan
中科院分区：
文献类型：
--
作者：
Kleijkers, Sander H. M.;Mantikou, Eleni;Mastenbroek, Sebastiaan
体外受精中胚胎培养基是否影响妊娠和围产儿结局？体外受精中使用的胚胎培养基影响治疗效果和新生儿出生体重。目前存在各种各样的试管婴儿/ICSI治疗人类植入前胚胎的培养基。目前尚不清楚哪种培养基在临床效果方面最好。此外，有人认为用于胚胎体外培养的培养基会影响出生体重，但这从未被大型随机试验证明。我们进行了一项多中心双盲随机对照试验，比较了HTF和G5胚胎培养基在体外受精中的使用。2010年7月至2012年5月，共纳入836对夫妇（HTF组419对，G5组417对）。分配的培养基（1:1分配）用于一对夫妇在随机化后1年内接受的所有治疗周期，包括可能的冻融胚胎移植。主要观察指标为活产率。计划在荷兰六个参与中心之一或其附属诊所进行试管婴儿或ICSI治疗的夫妇。G5组的活产率高于HTF组(44.1% (184/417)vs 37.9%(159/419))，但差异不显著；RR: 1.2;95%置信区间（CI）： 0.99-1.37；P = 0.08)。每周期可利用胚胎数（2.8 +/- 2.3 vs 2.3 +/- 1.8, P < 0.001）、新鲜胚胎移植后的着床率（20.2 vs 15.3%, P < 0.001）和临床妊娠率（47.7 vs 40.1%, RR: 1.2; 95% CI: 1.02-1.39, P = 0.03），分配给G5的夫妇明显高于分配给HTF的夫妇。在该试验的383名活产儿童中，检索了380名儿童的出生体重数据（其中300名单胎儿童（G5: 163, HTF: 137）和80名双胞胎儿童（G5: 38, HTF: 42））。与HTF组相比，G5组出生体重显著降低，平均差异为158 g （95% CI: 42-275 g; P = 0.008）。G5组的单胎早产发生率为8.6%（14/163）比2.2%(3/137)，但经胎龄和性别调整后的单胎出生体重（z-score）也低于HTF组（-0.13 +/- 0.08比0.17 +/- 0.08,P = 0.008）。这项研究能够检测到10%的活产差异，而较小的差异仍可能具有临床相关性。其他培养基对围产期结局的影响仍有待确定。体外受精中胚胎培养基的使用不仅影响治疗效果，而且影响围产期结局。这表明，每年体外培养的数百万个人类胚胎对环境很敏感。这些发现应该会导致提高意识，机制研究和立法调整，以保护体外受精后代在他们存在的最初几天。本项目部分由The NutsOhra基金会（Grant 1203-061）和March of Dimes （Grant 6-FY13-153）资助。作者声明无利益冲突。NTR1979(荷兰审判登记处2009.9.18 2010年7月。
Does embryo culture medium influence pregnancy and perinatal outcome in IVF?Embryo culture media used in IVF affect treatment efficacy and the birthweight of newborns.A wide variety of culture media for human preimplantation embryos in IVF/ICSI treatments currently exists. It is unknown which medium is best in terms of clinical outcomes. Furthermore, it has been suggested that the culture medium used for the in vitro culture of embryos affects birthweight, but this has never been demonstrated by large randomized trials.We conducted a multicenter, double-blind RCT comparing the use of HTF and G5 embryo culture media in IVF. Between July 2010 and May 2012, 836 couples (419 in the HTF group and 417 in the G5 group) were included. The allocated medium (1:1 allocation) was used in all treatment cycles a couple received within 1 year after randomization, including possible transfers with frozen-thawed embryos. The primary outcome was live birth rate.Couples that were scheduled for an IVF or an ICSI treatment at one of the six participating centers in the Netherlands or their affiliated clinics.The live birth rate was higher, albeit nonsignificantly, in couples assigned to G5 than in couples assigned to HTF (44.1% (184/417) versus 37.9% (159/419); RR: 1.2; 95% confidence interval (CI): 0.99-1.37; P = 0.08). Number of utilizable embryos per cycle (2.8 +/- 2.3 versus 2.3 +/- 1.8; P < 0.001), implantation rate after fresh embryo transfer (20.2 versus 15.3%; P < 0.001) and clinical pregnancy rate (47.7 versus 40.1%; RR: 1.2; 95% CI: 1.02-1.39; P = 0.03) were significantly higher for couples assigned to G5 compared with those assigned to HTF. Of the 383 live born children in this trial, birthweight data from 380 children (300 singletons (G5: 163, HTF: 137) and 80 twin children (G5: 38, HTF: 42)) were retrieved. Birthweight was significantly lower in the G5 group compared with the HTF group, with a mean difference of 158 g (95% CI: 42-275 g; P = 0.008). More singletons were born preterm in the G5 group (8.6% (14/163) versus 2.2% (3/137), but singleton birthweight adjusted for gestational age and gender (z-score) was also lower in the G5 than in the HTF group (-0.13 +/- 0.08 versus 0.17 +/- 0.08; P = 0.008).This study was powered to detect a 10% difference in live births while a smaller difference could still be clinically relevant. The effect of other culture media on perinatal outcome remains to be determined.Embryo culture media used in IVF affect not only treatment efficacy but also perinatal outcome. This suggests that the millions of human embryos that are cultured in vitro each year are sensitive to their environment. These findings should lead to increased awareness, mechanistic studies and legislative adaptations to protect IVF offspring during the first few days of their existence.This project was partly funded by The NutsOhra foundation (Grant 1203-061) and March of Dimes (Grant 6-FY13-153). The authors declare no conflict of interest.NTR1979 (Netherlands Trial Registry).1 September 2009.18 July 2010.