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在时间延迟系统中进行不间断胚胎培养与传统胚胎培养相比,围产期和母婴结局无显著差异。

No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

机构信息

IVIRMA Global Research Alliance, Livio Gothenburg, Gothenburg, Sweden.

Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Hum Reprod. 2023 Dec 4;38(12):2400-2411. doi: 10.1093/humrep/dead219.

Abstract

STUDY QUESTION

Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?

SUMMARY ANSWER

There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.

WHAT IS KNOWN ALREADY

Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.

STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).

PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.

MAIN RESULTS AND THE ROLE OF CHANCE

In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.

LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.

WIDER IMPLICATIONS OF THE FINDINGS

Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.

STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

与传统培养和自然受孕相比,胚胎在封闭的延时系统中培养是否会对围产期和产妇结局产生任何差异?

总结答案

与传统培养相比,延时培养和常规胚胎培养在单胎分娩的早产(<37 周)、低出生体重(>2500 克)和妊娠高血压疾病方面没有显著差异,这是本研究的主要结果。

已知情况

评估延时孵育在临床应用中的安全性的前瞻性试验证据表明,与传统孵育相比,胚胎发育率、着床率、持续妊娠率和活产率相似。很少有研究调查当与传统培养和自然受孕相比时,不间断的培养是否会改变目前与试管婴儿相关的不良围产期结局的风险。

研究设计、规模、持续时间:本研究是一项基于瑞典人群的回顾性注册研究,纳入了 2013 年至 2018 年间从选定的试管婴儿诊所进行的新鲜胚胎移植后 7379 例单胎分娩。与常规培养箱培养的胚胎相比,延时培养的胚胎所生单胎的围产期结局与延时培养箱培养的胚胎和自然受孕的 71300 例单胎进行了比较。主要围产期结局包括早产和低出生体重。主要产妇结局包括妊娠高血压疾病(妊娠高血压和子痫前期)。

参与者/材料、设置、方法:从九家试管婴儿诊所中,将 2683 例新鲜胚胎移植后在延时系统中出生的单胎与 4696 例常规培养箱中出生的单胎和 71300 例自然受孕的单胎进行了比较,这些单胎是按出生年份、产次和母亲年龄匹配的。从试管婴儿分娩中获得的患者和治疗特征与瑞典母婴登记处、出生缺陷登记处、国家患者登记处和瑞典统计局进行了交叉链接。排除了精子和卵子捐赠周期以及植入前遗传检测周期所生的婴儿。计算了比值比(OR)和调整后的 OR,并对相关混杂因素进行了调整。

主要结果及其偶然性

在调整分析中,未发现早产(调整后的 OR 1.11,95%CI 0.87-1.41)和低出生体重(调整后的 OR 0.86,95%CI 0.66-1.14)或妊娠高血压疾病的风险差异;子痫前期和高血压(调整后的 OR 0.99,95%CI 0.67-1.45 和调整后的 OR 0.98,95%CI 0.62-1.53,分别)在延时和常规培养系统之间。与自然受孕相比,延时培养所生单胎的早产(调整后的 OR 1.31,95%CI 1.08-1.60)和低出生体重(调整后的 OR 1.36,95%CI 1.08-1.72)的风险显著增加。此外,与自然受孕相比,妊娠高血压的风险降低(调整后的 OR 0.72,95%CI 0.53-0.99),但子痫前期无显著差异(调整后的 OR 0.87,95%CI 0.68-1.12)。亚组分析表明,一些风险与胚胎移植日有关,与卵裂期胚胎移植相比,囊胚期胚胎移植的不良结局更多。

局限性、谨慎的原因:本研究为回顾性设计,可能使用了不同的临床策略来选择延时与常规孵育的特定患者群体。患者数量有限,需要更大的数据集来获得更精确的估计,并调整可能的额外胚胎培养变量的影响。

更广泛的影响

与传统胚胎培养相比,胚胎在延时系统中的培养与围产期和产妇结局的主要差异无关,这表明该技术是胚胎孵育的一种可接受的替代方法。

研究资助/利益冲突:该研究由 Gedeon Richter 提供研究资助。所有作者均无利益冲突。

试验注册号码

无。

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