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重新考虑人类卵母细胞冷冻保存的安全性和有效性。

Reconsideration of the safety and effectiveness of human oocyte cryopreservation.

机构信息

Department of Research and Development, KSRS, San Francisco, CA, USA.

Department of Sciences, Mathematics and Biotechnology, University of California, Berkeley Extension, Berkeley, CA, USA.

出版信息

Reprod Biol Endocrinol. 2023 Feb 27;21(1):22. doi: 10.1186/s12958-023-01071-z.

Abstract

Mature oocyte cryopreservation (OC) has become increasingly common since the American Society for Reproductive Medicine declared OC to no longer be experimental. Utilization of the open vitrification protocol has led to a marked improvement in the efficacy of oocyte cryopreservation. However, the safety and effectiveness of this cryopreservation method remain controversial. A previous report stated that among all initiated recipient cycles, the live-birth rate among recipients of all ages was significantly higher when using fresh donor oocytes (FDOs) rather than cryopreserved donor oocytes (CDOs). Confounding patient characteristics were noted as possible causes. OC stands as an acceptable elective medical intervention for preserving fertility in women. To further understand the effects of OC on the live birth rate resulting from fresh versus cryopreserved donor oocytes, reported data from the Society for Assisted Reproductive Technology from 2013 to 2020 were analyzed. The mean of the mean live-birth rate in all ages resulting from FDOs was 49.0% (44.6-53.3%) versus 41.0% (39.1-43.2%) for CDOs (difference, 8.0% [95% confidence interval, 5.35-10.57%], p value < 0.001). The lower live-birth rate observed for CDOs versus FDOs has been consistent throughout past decades. While there has been no reported increase in the aneuploidy rate for CDOs compared to FDOs, differences in the nondisjunction separation rate among different chromosomes were described in a recent report. Open vitrification culture medium usually contains high concentrations of cryoprotectants, such as 15% dimethyl sulfoxide (DMSO) and 15% ethylene glycol (EG). Recent studies showed that tissue culture with 0.1% DMSO or 10% EG resulted in deregulation of gene expression, disruption of epigenetic imprints, and accumulation of reactive oxygen species. The addition of melatonin, which can remove reactive oxygen species from vitrification medium, was shown to improve CDOs qualities and functions to conditions similar to those of FDOs; however, there were insufficient data to conclude that melatonin could improve the lower live-birth rate. These factors that affect live birth rates, birth defects, birth weights and developmental health cannot be ignored and perhaps need to be studied again and followed when evaluating the true effectiveness of human oocyte cryopreservation.

摘要

成熟卵母细胞冷冻保存(OC)自美国生殖医学学会宣布 OC 不再是实验性的以来,已变得越来越普遍。开放玻璃化方案的应用导致卵母细胞冷冻保存的效果显著提高。然而,这种冷冻保存方法的安全性和有效性仍然存在争议。先前的一份报告指出,在所有启动的受者周期中,所有年龄段的受者使用新鲜供体卵母细胞(FDO)而非冷冻保存供体卵母细胞(CDO)的活产率显著更高。注意到混杂的患者特征可能是原因。OC 是一种可接受的选择医学干预措施,用于保留女性的生育能力。为了进一步了解新鲜供体卵母细胞与冷冻保存供体卵母细胞对活产率的影响,分析了 2013 年至 2020 年来自辅助生殖技术协会的报告数据。所有年龄段 FDO 产生的平均活产率为 49.0%(44.6-53.3%),而 CDO 为 41.0%(39.1-43.2%)(差异为 8.0%[95%置信区间,5.35-10.57%],p 值<0.001)。与 FDO 相比,CDO 观察到的活产率较低,这一情况在过去几十年中一直存在。虽然没有报道称 CDO 的非整倍体率与 FDO 相比有所增加,但最近的一份报告描述了不同染色体间非分离分离率的差异。开放玻璃化培养物通常含有高浓度的冷冻保护剂,如 15%二甲基亚砜(DMSO)和 15%乙二醇(EG)。最近的研究表明,用 0.1%DMSO 或 10%EG 进行组织培养会导致基因表达失调、表观遗传印记破坏和活性氧物质积累。添加褪黑素,它可以从玻璃化介质中去除活性氧物质,显示出改善 CDO 质量和功能,使其条件类似于 FDO;然而,没有足够的数据表明褪黑素可以提高较低的活产率。这些影响活产率、出生缺陷、出生体重和发育健康的因素不容忽视,在评估人类卵母细胞冷冻保存的真正有效性时,可能需要重新研究和监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a3c/9969709/2430fc788005/12958_2023_1071_Fig1_HTML.jpg

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