Center for Reproductive Medicine, Henan Province Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450052, China.
Hum Reprod. 2021 Mar 18;36(4):1146-1156. doi: 10.1093/humrep/deaa352.
Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)?
Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC.
Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge.
STUDY DESIGN, SIZE, DURATION: This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA.
The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040-0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338-0.879), P = 0.013; and aOR: 0.357 (0.175-0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION: This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy.
To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests.
N/A.
胚胎体外培养和冷冻保存是否与流产妊娠产物(POC)中的染色体异常有关?
对于年龄≥35 岁的女性,冷冻囊胚移植与降低流产 POC 中胚胎染色体异常的频率有关;对于年龄<35 岁的女性,冷冻 ET(包括卵裂期胚胎和囊胚)与降低流产 POC 中胚胎染色体异常的频率有关。
胚胎培养和胚胎冷冻保存已被广泛应用于临床实践,并与有利的 ART 治疗结果相关。然而,据我们所知,这些胚胎操作程序与胚胎染色体异常之间的关系尚未得到评估。
研究设计、大小和持续时间:这是一项回顾性研究,共纳入 720 名接受体外受精/卵胞浆内单精子注射(IVF/ICSI)的患者,保留了流产的 POC。对所有流产胚胎进行基于单核苷酸多态性(SNP)的染色体微阵列分析(CMA)。
参与者/材料、地点和方法:本研究基于我们中心的临床生殖医学管理系统/电子病历队列数据库(CCRM/EMRCD)。共收集了 720 例接受 ART 的流产 POC(包括新鲜卵裂期 ET、新鲜囊胚移植、冷冻卵裂期 ET 和冷冻囊胚移植),通过 SNP 基 CMA 测量流产胚胎的细胞遗传学异常发生率和特征。
不同 ET 策略中 POC 的染色体异常率为 33.7%至 66.7%。在年龄≥35 岁的患者中,冷冻囊胚移植与 POC 中染色体异常发生率显著降低相关(调整优势比(aOR):0.171(95%CI:0.040-0.738);P=0.018),与新鲜囊胚移植相比。在年龄<35 岁的患者中,冷冻 ET 与新鲜 ET 相比,在卵裂期 ET 周期和囊胚转移周期中均与染色体异常发生率降低显著相关(aOR:0.545(0.338-0.879),P=0.013;aOR:0.357(0.175-0.730),P=0.005)。三体是不同 ET 策略中最常见的异常胚胎核型,其频率在不同策略之间存在显著差异(P<0.05)。
局限性、谨慎的原因:本研究为回顾性设计,我们不能从研究结果中对胚胎冷冻保存对持续妊娠的适当安全性得出任何明确结论。
据我们所知,这是第一项评估 ET 策略与胚胎染色体异常相关流产风险之间关联的研究。然而,这些关联的潜在机制尚不清楚;本研究可能会促进对 ET 策略的研究,并促进为患者提供全面的咨询和建议。
研究资金/竞争利益:本工作得到了国家自然科学基金(No.81571409)、河南省科技攻关项目(No.172102310009)和河南省医学科技攻关项目(No.201701005)的支持。作者没有竞争利益。
无。