胚胎培养期间氧浓度对产科和新生儿结局的影响：一项随机对照试验的二次分析。

STUDY QUESTION

Does oxygen concentration during 3-day embryo culture affect obstetric and neonatal outcomes?

SUMMARY ANSWER

Oxygen concentration during 3-day embryo culture does not seem to affect the obstetric and neonatal outcomes measured.

WHAT IS KNOWN ALREADY

Atmospheric oxygen appears to be harmful during extended embryo culture. Embryo culture conditions might therefore be a potential risk factor for subsequent fetal development and the health of future children. No data are available concerning the obstetrics and neonatal outcomes after Day 3 transfer of embryos cultured under reduced and atmospheric oxygen tensions.

STUDY DESIGN, SIZE, DURATION: A secondary analysis of a previous randomized controlled trial assessing clinical pregnancy outcomes was carried out. This analysis included 1125 consecutive oocyte donation cycles utilizing ICSI or IVF and Day 3 embryo transfers between November 2009 and April 2012. The whole cohort of donated oocytes from patients who agreed to participate in the study were randomly allocated (1:1 ratio) to a reduced O2 tension group (6% O2) or an air-exposed group (20% O2) based on a computer-generated randomization list. Fresh and vitrified oocytes were used for oocyte donation. Only those pregnancies with a live birth at or beyond 24 weeks of gestation were included.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Day 3 embryos were cultured in an atmosphere of 5.5% CO2, 6% O2, 88.5% N2 versus a dual gas system in air.

MAIN RESULTS AND THE ROLE OF CHANCE

From the eligible 1125 cycles, 564 were allocated to the 6% O2 group and 561 cycles to the 20% O2 group. However, 50 and 62 cycles did not reach embryo transfer in the 6% and 20% O2 groups, respectively. No differences were found between 6% O2 and atmospheric O2 tension in the number of livebirths per embryo transfer (mean ± SD, 0.5 ± 0.7 versus 0.5 ± 0.7), pregnancy complications or neonatal outcomes. Both groups (6% and atmospheric O2) had similar single and twin delivery rates (40.8% versus 38.1% and 10.7% versus 12.3%, respectively). Preterm delivery rates and very preterm delivery rates (10.80% versus 13.24% and 1.25% versus 2.94%, respectively), birthweight (3229 ± 561 g versus 3154 ± 731 g), low birthweight (2.92% versus 2.45%), birth height (50.18 ± 2.41 cm versus 49.7 ± 3.59 cm), head circumference (34.16 ± 1.87 cm versus 33.09 ± 1.85 cm) and 1 min Apgar scores (8.96 ± 0.87 versus 8.89 ± 0.96) were also similar between 6% and atmospheric O2 groups, respectively.

LIMITATIONS, REASONS FOR CAUTION: The number of liveborns finally analyzed is still small and not all obstetric and neonatal variables could be evaluated. Furthermore, a small proportion of the obstetric and neonatal data was obtained through a questionnaire filled out by the patients themselves. One reason for the lack of effect of oxygen concentration on pregnancy outcome could be the absence of trophectoderm cells at cleavage stage, which may make Day 3 embryos less susceptible to hypoxic conditions.

WIDER IMPLICATIONS OF THE FINDINGS

Nowadays many IVF laboratories use a more physiological oxygen concentration for embryo culture. However, the benefits of using low oxygen concentration on both laboratory and clinical outcomes during embryo culture are still under debate. Furthermore, long-term studies investigating the effect of using atmospheric O2 are also needed. Gathering these type of clinical data is indeed, quite relevant from the safety perspective. The present data show that, at least in egg donation cycles undergoing Day 3 embryo transfers, culturing embryos under atmospheric oxygen concentration seems not to affect perinatal outcomes.

STUDY FUNDING/COMPETING INTEREST(S): The present project was supported by the R + D program of the Regional Valencian Government, Spain (IMPIVA IMDTF/2011/214). The authors declare that they have no conflict of interest with respect to the content of this manuscript.

TRIAL REGISTRATION NUMBER

NCT01532193.

研究问题

胚胎培养 3 天时的氧浓度是否会影响产科和新生儿结局？

总结答案

胚胎培养 3 天时的氧浓度似乎不会影响测量的产科和新生儿结局。

已知情况

大气氧似乎在胚胎的长时间培养中是有害的。因此，胚胎培养条件可能是随后胎儿发育和未来儿童健康的潜在风险因素。关于在 20%氧气张力下培养的胚胎转移到第 3 天后的产科和新生儿结局尚无数据。

研究设计、大小和持续时间：这是一项先前随机对照试验评估临床妊娠结局的二次分析。该分析包括 2009 年 11 月至 2012 年 4 月期间使用 ICSI 或 IVF 进行的 1125 个连续卵母细胞捐赠周期和第 3 天胚胎转移。根据计算机生成的随机分组列表，同意参加研究的患者的所有捐赠卵母细胞被随机分配（1:1 比例）到低氧张力组（6% O2）或空气暴露组（20% O2）。新鲜和冷冻的卵母细胞用于卵母细胞捐赠。仅包括 24 周以上的活产妊娠。

参与者/材料、设置、方法：第 3 天的胚胎在 5.5% CO2、6% O2、88.5% N2 的大气中培养，而在空气的双气体系统中培养。

主要结果和机会的作用

从合格的 1125 个周期中，有 564 个周期被分配到 6% O2 组，561 个周期被分配到 20% O2 组。然而，在 6%和 20% O2 组中，分别有 50 个和 62 个周期未达到胚胎转移。在胚胎转移的活产数（平均值±标准差，0.5±0.7 与 0.5±0.7）、妊娠并发症或新生儿结局方面，6% O2 和大气氧张力之间没有差异。两组（6%和大气 O2）的单胎和双胎分娩率相似（40.8%与 38.1%和 10.7%与 12.3%）。早产率和极早产率（10.80%与 13.24%和 1.25%与 2.94%）、出生体重（3229±561g 与 3154±731g）、低出生体重（2.92%与 2.45%）、出生身高（50.18±2.41cm 与 49.7±3.59cm）、头围（34.16±1.87cm 与 33.09±1.85cm）和 1 分钟 Apgar 评分（8.96±0.87 与 8.89±0.96）在 6%和大气 O2 组之间也相似。

局限性、谨慎的原因：最终分析的活产数仍然较小，并非所有产科和新生儿变量都可以评估。此外，一部分产科和新生儿数据是通过患者自己填写的问卷获得的。氧浓度对妊娠结局没有影响的一个原因可能是胚胎在卵裂期时没有滋养外胚层细胞，这可能使第 3 天的胚胎对低氧条件不太敏感。

研究结果的更广泛意义

如今，许多 IVF 实验室使用更生理的氧浓度进行胚胎培养。然而，在胚胎培养过程中使用低氧浓度对实验室和临床结果的益处仍存在争议。此外，还需要进行长期研究以调查使用大气氧的影响。从安全角度来看，收集这类临床数据确实非常重要。目前的数据表明，至少在接受第 3 天胚胎移植的卵母细胞捐赠周期中，在大气氧浓度下培养胚胎似乎不会影响围产期结局。

研究资金/利益冲突：本项目由西班牙瓦伦西亚地区政府的 R&D 计划（IMPIVA IMDTF/2011/214）资助。作者声明他们与本文内容没有利益冲突。

试验注册编号

NCT01532193。

The influence of oxygen concentration during embryo culture on obstetric and neonatal outcomes: a secondary analysis of a randomized controlled trial.

机构信息

出版信息