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Study question

研究问题

What is the impact of advanced paternal age (APA) on sperm DNA fragmentation index (DFI)?

父亲高龄(APA)对精子DNA碎片指数(DFI)有什么影响？

Summary answer

概括结论

Sperm DFI levels remain relatively stable until the age of 35 and increase progressively beyond that age.

精子DFI水平在35岁之前保持相对稳定，超过这个年龄后，DFI随父亲年龄增加进行性升高。

What is known already

已知情况

APA can have a negative impact on male fertility and the health of offspring. Previous studies have shown that APA is linked to poor conventional sperm parameters, including decreased semen volume, sperm count, motility, morphology, as well as poor sperm DNA integrity. Additionally, APA has been associated with reduced natural or assisted reproduction and perinatal outcomes and a higher risk of genetic and chromosomal abnormalities in the offspring.

APA会对男性生育能力和后代的健康产生负面影响。此前的研究表明，APA与传统精子参数差有关，参数包括精液体积、精子数量、活力、形态以及精子DNA完整性。此外，APA与自然妊娠或辅助生殖技术下更差的围产期结局以及后代染色体异常的高风险有关。

Study design, size, duration

研究设计、规模、持续时间

A retrospective cohort study of 4250 consecutive semen samples from men undergoing infertility evaluation at the OVO clinic, in Montreal, Canada, between April 2016 and December 2022. Participants were stratified into seven age groups: <26 (n = 36; 0,8%), 26-30 (n = 500; 11,8%), 31-35 (n = 1269; 29,9%), 36-40 (n = 1268; 29,8%), 41-45 (n = 732; 17,2%), 46-50 (n = 304; 7,2%), >50 years (n = 141; 3,3%). The mean age was 37.4 ± 6.4 years (range 18-71 years).

这是一项回顾性队列研究，研究对象为2016年4月至2022年12月在加拿大蒙特利尔OVO诊所接受不孕症评估的4250名男性的精液样本。参与者被分为7个年龄组：<26 岁(n=36;0,8%)， 26-30岁 (n=500;11.8%)， 31-35岁 (n=1269;29,9%)， 36-40岁(n=1268;29,8%)，41-45岁(n=732;17,2%)，46-50 岁(n=304;7,2%)， >50岁(n=141;3.3%)。平均年龄为37.4±6.4岁(18-71岁)。

Participants/materials, setting, methods

研究对象/材料、设定、方法

The study was population-based and included male patients from all ages, ethnicities, and medical histories. Semen samples were collected after 2-3 days of abstinence. For patients who underwent more than one DFI testing, only the first sample was included, and any duplicates were excluded. DFI was evaluated by flow-cytometry based TUNEL assay using the APO-Direct Kit. Data were analyzed using one-way ANOVA and T3 Dunnett post-hoc multiple comparison test, as well as Pearson’s correlation coefficient.

本研究以人群为基础，包括所有年龄、种族和病史的男性患者。患者禁欲2～3天后采集精液样本。对于接受过一次以上DFI检测的患者，只保留第一个样本，并排除任何重复样本。DFI评价采用APO-Direct Kit基于流式细胞仪的TUNEL法。数据分析采用单因素方差分析和T3 Dunnett事后多重比较检验，以及Pearson相关系数检验。

Main results and the role of chance

主要结果和偏倚

The results show a significant positive correlation between %DFI and age (r = 0.19, p < 0.001). Mean %DFI levels were relatively stable in men aged <26 to 35 years (17.9%, 18.1% and 18.1% in men aged <26, 26-30 and 31-35, respectively), with %DFI increasing progressively beyond age 35 (20.7%, 22.5%, 25.7% and 27.9% in men aged 36-40, 41-45, 46-50 and >50, respectively). The mean %DFI in the 36-40 age group was significantly higher than in the 31-35 age group (p < 0,001). Our study has uncovered that %DFI follows an exponential curve starting at age 35, indicating that the %DFI accelerates significantly as men age beyond their mid-30s.

结果显示DFI与年龄显著正相关(r=0.19,p<0.001)。<26和26-35岁男性平均DFI水平相对稳定(<26岁、26-30岁和31-35岁男性的DFI分别为17.9%、18.1%和18.1%)，35岁以上男性DFI水平进行性升高(36-40岁、41-45岁、46-50岁和>50岁男性分别为20.7%、22.5%、25.7%和27.9%)。36-40岁组的平均DFI水平显著高于31-35岁组(p<0.001)。我们的研究发现，从35岁开始，DFI值遵循指数曲线变化，这表明当男性超过35岁时， DFI随着年龄增长显著增加。

Limitations, reasons for caution

局限性，需谨慎原因

This retrospective analysis has inherent limitations that may introduce confounding variables. The patient clinical background, such as medical history and lifestyle factors was not assessed. Also, the studied cohort consisted of a population under investigation for infertility and may not be representative of the general male population.

这种回顾性研究有引入混杂变量的固有局限性。本研究未评估患者的临床背景，例如病史和生活方式等因素。此外，本研究人群由正在接受不孕症调查的男性组成，可能无法代表一般男性人群。

Wider implications of the findings

研究结果的更广泛意义

The study demonstrates the age-related increase in sperm %DFI and suggests that there may be an age cut-off below which sperm %DFI is stable and beyond which sperm %DFI increases. This information may be useful to medical specialists that offer sperm DNA testing to infertile couples.

该研究表明，精子DFI的增加与年龄有关，并表明可能存在一个年龄界限，低于该年龄界限时，精子DFI保持稳定。超过该年龄界限，精子DFI百分比明显增加。这些信息可能有助于医生向不孕夫妇提供精子 DNA检测。

文章来源：

E Kadoch, A Tadevsoyan, A Zini, S Phillips, F Bissonnette, I J Kadoch, P-088 The Paternal Clock: Shedding Light on the Relationship Between Paternal Age and Sperm DNA Fragmentation, Human Reproduction, Volume 38, Issue Supplement_1, June 2023, dead093.249, https://doi.org/10.1093/humrep/dead093.249