Research question

Spontaneous pregnancy loss affects 10–15% of couples, with 1–2% suffering recurrent pregnancy loss and 50% of miscarriages remaining unexplained. Male genomic integrity is essential for healthy offspring, meaning sperm DNA quality may be important in maintaining a pregnancy. Does sperm DNA fragmentation measured by alkaline Comet assay act as a biomarker for early pregnancy loss?

Design

Sperm DNA fragmentation was measured by alkaline Comet test in 76 fertile donors and 217 men whose partners had recently experienced miscarriage. Couples were divided into five groups for analysis: one miscarriage after spontaneous conception; two or more miscarriages after spontaneous conception; one miscarriage after fertility treatment; two or more miscarriages after fertility treatment and biochemical pregnancy.

Results

Receiver operator characteristic curve analysis was used to determine ability of the average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose miscarriage and develop clinical thresholds comparing men whose partners have miscarried with men with recently proven fertility. Male partners of women who had miscarried had higher sperm DNA damage (ACS 33.32 ± 0.57%) than fertile men (ACS 14.87 ± 0.66%; P < 0.001). Average Comet score, HCS and LCS all have promise as being highly predictive of sporadic and recurrent miscarriage using clinical thresholds from comparisons with fertile men's spermatozoa: receiver operating characteristic curve AUC for ACS ≥26%, 0.965; LCS ≤70%, 0.969; HCS ≥2%, 0.883; P <0.0001.

Conclusions

Sperm DNA damage measured by the alkaline Comet has promise as a robust biomarker for sporadic and recurrent miscarriage after spontaneous or assisted conception, and may provide novel diagnoses and guidance for future fertility pathways.

中文翻译：

---

精子DNA片段化是早期流产的新生物标志物

研究问题

自发性流产影响 10-15% 的夫妇，1-2% 的夫妻反复流产，50% 的流产原因不明。男性基因组完整性对于健康的后代至关重要，这意味着精子 DNA 质量对于维持妊娠可能很重要。通过碱性彗星试验测量的精子 DNA 碎片是否可以作为早期流产的生物标志物？

设计

精子 DNA 碎片是通过碱性彗星测试在 76 名可育捐献者和 217 名其伴侣最近经历过流产的男性中测量的。夫妇分为五组进行分析：一组自然受孕后流产；自然受孕后两次或多次流产；一次生育治疗后流产；生育治疗和生化妊娠后两次或多次流产。

结果

接受者操作者特征曲线分析用于确定平均 Comet 评分 (ACS)、低 Comet 评分 (LCS) 和高 Comet 评分 (HCS) 诊断流产的能力并制定临床阈值，比较配偶流产的男性与最近证实的男性生育能力。流产女性的男性伴侣的精子 DNA 损伤 (ACS 33.32 ± 0.57%) 高于可育男性 (ACS 14.87 ± 0.66%; P < 0.001)。平均 Comet 评分、HCS 和 LCS 都有望使用与可育男性精子比较的临床阈值高度预测散发性和复发性流产：ACS ≥26% 的受试者工作特征曲线 AUC，0.965；LCS ≤70%，0.969；HCS≥2%，0.883；P <0.0001。

结论

碱性彗星测量的精子 DNA 损伤有望成为自然或辅助受孕后散发性和复发性流产的可靠生物标志物，并可能为未来的生育途径提供新的诊断和指导。