中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (1): 111-119.doi: 10.12307/2024.137

• 细胞相关实验/试验研究Cell related experimental/trial studies • 上一篇    下一篇

基于活产建立体外受精-胚胎移植精子DNA碎片指数的参考阈值及子代短期安全性

周  超1，王淑娴2，于春梅2，庾广聿1，蒋月园1   

  1. 1广西壮族自治区南溪山医院生殖中心，广西壮族自治区桂林市   541000；2常州市妇幼保健院，江苏省常州市   213000
  • 收稿日期:2023-03-21 接受日期:2023-04-20 出版日期:2025-01-08 发布日期:2024-05-18
  • 通讯作者: 于春梅，硕士，副主任医师，常州市妇幼保健院，江苏省常州市 213000
  • 作者简介:周超，男，1992年生，广西壮族自治区灵川县人，汉族，2014年右江民族医学院毕业，主管技师，主要从事辅助生殖胚胎实验室及男科实验室工作，现主要研究方向为辅助生殖临床相关预测模型。
  • 基金资助:
    国家自然科学基金(82201757)，项目负责人：王淑娴；广西壮族自治区卫生健康委员会自筹课题(Z20211100)，项目负责人：周超

Reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth

Zhou Chao1, Wang Shuxian2, Yu Chunmei2, Yu Guangyu1, Jiang Yueyuan1   

  1. 1Reproductive Center, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541000, Guangxi Zhuang Autonomous Region, China; 2Changzhou Maternal and Child Health Area Hospital, Changzhou 213000, Jiangsu Province, China
  • Received:2023-03-21 Accepted:2023-04-20 Online:2025-01-08 Published:2024-05-18
  • Contact: Yu Chunmei, Master, Associate chief physician, Changzhou Maternal and Child Health Area Hospital, Changzhou 213000, Jiangsu Province, China
  • About author:Zhou Chao, Technician-in-charge, Reproductive Center, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541000, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 82201757 (to WSX); Self-Raised Project by the Health Commission of Guangxi Zhuang Autonomous Region, No. Z20211100 (to ZC)

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摘要：

文题释义：
精子DNA碎片指数：通过反映精子DNA单、双链断裂及碎片化程度，进而从基因层面反映男性精子核遗传物质完整性与损伤程度，现已作为一种风险分层指标，对不明原因不育、精索静脉曲张、反复妊娠丢失、危险生活及环境暴露的评估具有重要意义。
男性不育：是指育龄夫妇有规律性生活且未采取避孕措施，由男方因素导致女方在一年内未能自然受孕的状态。男性不育分为原发性不育和继发性不育。据世界卫生组织数据显示，全球育龄人口中有15%夫妇存在生育问题，其中男性因素约占所有不孕因素的50%。


背景：精子DNA碎片指数与受精、胚胎发育潜能、胚胎植入、流产及子代安全性等存在显著的相关性。然而，其临床参考值受多种因素的影响，导致临床意义极其有限，该研究以活产为结局，通过倾向评分匹配校正其他混杂因素后，构建精子DNA碎片指数与活产的最佳临床截断值，并对其进行内外部验证，具有较好的预测价值及临床应用效能。
目的：探讨基于活产建立体外受精-胚胎移植精子DNA碎片指数的参考阈值及子代短期安全性。
方法：选取2019年5月至2021年5月于常州市妇幼保健院接受体外受精-胚胎移植患者1 921例，以倾向匹配容差0.02为标准，1∶1进行倾向评分匹配，结果活产组与非活产组各成功匹配540例，以此建立模型组；通过选取同时期广西壮族自治区南溪山医院接受体外受精-胚胎移植患者135例作为外部验证组；采用受试者工作曲线探求精子DNA碎片指数对活产的临床最佳截断值，分别采用限制性立方样条曲线、标准曲线、临床决策曲线、临床影响曲线及内外部验证等方法，对该截断值的准确性及临床应用效能进行评估。
结果与结论：①非活产组精子DNA碎片指数显著高于活产组且与活产存在显著的负相关性(r=-0.444，P < 0.001)；②受试者工作曲线结果显示，DNA碎片指数对活产的最佳截断值为24.33%，曲线下面积为0.775(0.746，0.804)，特异度为72.60%，敏感度为78.90%，准确度为75.70%；③限制性立方样条曲线拟合Logistic回归结果显示，当精子DNA碎片指数大于24.57%时，临床非活产的风险呈趋势性增涨；④Logistic回归概率分析结果显示，精子DNA碎片指数为活产的危险因素[OR(95%CI)=0.916(0.904，0.928)，P < 0.001]，且当精子DNA碎片指数大于27.78%时，临床活产发生的概率将小于50%，随着精子DNA碎片指数每增高1个单位，活产的概率下降8.4%；⑤内外部对该临床截断值的验证均显示，该截点具有一定的临床预测价值及准确性；⑥临床决策曲线与临床影响曲线显示，以该临床截断值建立的预测模型在阈概率为0.22-0.73时具有临床最大净获益值，且在该阈概率范围内损失与获益的比值始终小于1，证实该预测模型具有较好的临床应用效能；⑦精子DNA碎片指数与子代短期安全性分析结果显示，精子DNA碎片指数与出生儿早产、体质量、畸形、性别差异无显著性；⑧结果表明，精子DNA碎片指数对体外受精-胚胎移植活产的最佳临床截断值为24.33%，以此建立的临床预测模型具有较好的区分度、准确度与临床应用效能，精子DNA碎片指数对子代短期安全性影响并不显著，但仍需大样本及长期的追踪评估。

https://orcid.org/0000-0001-9843-6731 (周超) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程



关键词: 精子DNA碎片指数, 活产, 体外受精-胚胎移植, 子代安全性, 最佳截断值

Abstract: BACKGROUND: There is a significant correlation between sperm DNA fragmentation index and fertilization, embryonic development potential, embryo implantation, miscarriage, and offspring safety. However, its clinical reference value is affected by many factors, resulting in extremely limited clinical significance. This study took live birth as the outcome, corrected other confounding factors through propensity score matching, constructed the best clinical cutoff value of sperm DNA fragmentation index and live birth, and conducted internal and external tests on it, which has good predictive value and clinical application efficiency.
OBJECTIVE: To investigate the reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth.
METHODS: A total of 1 921 patients who received in vitro fertilization and embryo transfer in Changzhou Maternal and Child Health Area Hospital from May 2019 to May 2021 were selected. On the basis of tendency matching tolerance of 0.02 and propensity score matching of 1:1, 540 cases were successfully matched in each live birth group and non-live birth group, and the model group was established. 135 patients who received in vitro fertilization and embryo transfer in Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the external validation group. The optimal clinical cutoff value of sperm DNA fragmentation index for live birth was investigated by the receiver operating characteristic curve. The accuracy and clinical application efficacy of the cutoff value were evaluated by restricted cubic spline curve, standard curve, clinical decision curve, clinical impact curve and internal and external validation tests. 
RESULTS AND CONCLUSION: (1) The DNA fragmentation index of sperm in the non-live birth group was significantly higher than that in the live birth group and had a significant negative correlation with live birth (r=-0.444, P < 0.001). (2) Receiver operating characteristic curve results showed that the optimal cut-off value of DNA fragmentation index for live birth was 24.33%; the area under the curve was 0.775(0.746, 0.804); the specificity was 72.60%; the sensitivity was 78.90%, and the accuracy was 75.70%. (3) Restricted cubic spline curve fitting the results of Logistic regression showed that when the sperm DNA fragmentation index was greater than 24.57%, the risk of clinical non-live birth increased. (4) The probability of Logistic regression analysis results showed that sperm DNA fragmentation index was a risk factor for live birth [OR(95%CI)=0.916(0.904, 0.928), P < 0.001], and when sperm DNA fragmentation index was greater than 27.78%, the probability of clinical live birth would be less than 50%. With the increase of sperm DNA fragmentation index by 1 unit, the probability of a live birth fell by 8.4%. (5) Internal and external to the validation of the clinical cutoff value showed that the cutoff point had certain clinical predictive value and accuracy. (6) Clinical decision curve and clinical impact curve results exhibited that the prediction model based on the clinical cut-off value had the maximum clinical net benefit value when the threshold probability was 0.22-0.73, and the ratio of loss to gain within the threshold probability range was always less than 1, which confirmed that the prediction model had good clinical application effectiveness. (7) The results of sperm DNA fragmentation index and offspring short-term security analysis showed that sperm DNA fragmentation index had no significant differences with preterm birth, body weight, deformity and sex. (8) These findings suggest that the optimal clinical cut-off value of sperm DNA fragmentation index for in vitro fertilization-embryo transfer live birth was 24.33%. The established clinical prediction model has good differentiation, accuracy and clinical application effectiveness. Sperm DNA fragmentation index has no significant impact on offspring short-term security, but large samples and long-term follow-up evaluation are still needed. 

Key words: sperm DNA fragmentation index, live birth, in vitro fertilization and embryo transfer, offspring security, optimal cutoff value

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