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25445 名男性在不孕不育诊所就诊的年龄与精子染色质结构分析(SCSA®)评估的精子 DNA 和染色质完整性之间的关系。

Relationships between the age of 25,445 men attending infertility clinics and sperm chromatin structure assay (SCSA®) defined sperm DNA and chromatin integrity.

机构信息

SCSA Diagnostics Inc., Brookings; Sanford Medical School, University of South Dakota, Sioux Falls.

Department of Mathematics and Statistics, South Dakota State University, Brookings, South Dakota.

出版信息

Fertil Steril. 2020 Aug;114(2):311-320. doi: 10.1016/j.fertnstert.2020.03.028. Epub 2020 Jul 9.

DOI:10.1016/j.fertnstert.2020.03.028
PMID:32653083
Abstract

OBJECTIVE

To determine relationships between age of men with potential male factor infertility and sperm chromatin structure assay (SCSA) measures of sperm DNA fragmentation (SDF) and high DNA stainable sperm (HDS), and to compare these data with those obtained from healthy donor men without reproductive issues.

DESIGN

Retrospective study.

SETTING

Infertility clinics and diagnostic laboratory.

PATIENTS

A total of 25,445 men attending infertility clinics. Donors were 87 men working at Lawrence Livermore National Laboratory.

INTERVENTION

None.

MAIN OUTCOME MEASURES

SCSA measures (% DNA fragmentation index (DFI), X DFI, SD DFI, and %HDS) of men aged 21-80 years.

RESULTS

In the study population, advancing paternal age was associated with increased sperm DNA fragmentation (SDF) scored as increased percentage of sperm in semen ejaculates with measurable DNA strand breaks (%DFI). The slope of increase in %DFI prior to age 41.6 years was 0.39, which increased after age 41.6 to more than double at a slope of 0.86. These changes in DNA/chromatin in more than 25,000 aging men attending infertility clinics are similar to those seen over the same age span (20-80 years) in 87 nonpatient, healthy men without reproductive issues. For the age group 20-50 years, there was no major significant difference in %DFI between patients and donor men. According to a logistic regression model, the estimated probability is that, for example, a 40-year-old and a 50-year-old man have a 20% and 40% chance, respectively, to have a pathological DFI ≥25% by age factor alone. The condensation of sperm chromatin in patients increased with age in a linear fashion, from a mean of 12.2 %HDS at age 20-25 to a mean of 7.9 %HDS at age 60-65. Patients had a greater %HDS than donors across all ages.

CONCLUSIONS

The great heterogeneity of both DFI and HDS values at a specific age prevents the automatic translation of age into an index of DNA fragmentation. However, it reinforces the idea that both DFI and HDS evaluation can play a role in detecting potential male infertility in cases that are not resolved by routine testing and in cases of multiple miscarriages. DFI and HDS data can help clinicians to predict a man's fertility potential, to consider corrective therapeutic approaches, as well as to assess the risk to the offspring's health.

摘要

目的

确定具有潜在男性因素不育症的男性年龄与精子染色质结构分析(SCSA)测量的精子 DNA 碎片化(SDF)和高 DNA 可染精子(HDS)之间的关系,并将这些数据与来自无生殖问题的健康供体男性的数据进行比较。

设计

回顾性研究。

地点

不孕诊所和诊断实验室。

患者

共有 25445 名男性在不孕诊所就诊。供体是在劳伦斯利弗莫尔国家实验室工作的 87 名男性。

干预措施

无。

主要观察指标

21-80 岁男性的 SCSA 测量值(%DNA 碎片指数(DFI)、X DFI、SD DFI 和 %HDS)。

结果

在研究人群中,随着父系年龄的增加,精子 DNA 碎片化(SDF)增加,精液中可测量 DNA 链断裂的精子百分比(%DFI)增加。41.6 岁之前 %DFI 的斜率增加 0.39,41.6 岁之后增加超过两倍,斜率为 0.86。在 25000 多名接受不孕诊所治疗的男性中,这种 DNA/染色质的变化与在同一年龄范围内(20-80 岁)在 87 名无生殖问题的健康非患者男性中看到的变化相似。对于 20-50 岁年龄组,患者和供体男性之间的 %DFI 没有显著差异。根据逻辑回归模型,估计概率是,例如,40 岁和 50 岁的男性仅因年龄因素就分别有 20%和 40%的机会出现病理性 DFI≥25%。患者精子染色质的浓缩随年龄呈线性增加,从 20-25 岁的平均 12.2%HDS 增加到 60-65 岁的平均 7.9%HDS。患者的 %HDS 高于所有年龄段的供体。

结论

特定年龄的 DFI 和 HDS 值的高度异质性阻止了将年龄自动转化为 DNA 碎片化指数。然而,这进一步证实了这样一种观点,即 DFI 和 HDS 评估都可以在通过常规检测无法解决的情况下以及在多次流产的情况下,在检测潜在男性不育症方面发挥作用。DFI 和 HDS 数据可以帮助临床医生预测男性的生育潜力,考虑纠正治疗方法,并评估对后代健康的风险。

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