Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Inflamm Bowel Dis. 2022 Jul 1;28(7):1012-1018. doi: 10.1093/ibd/izab205.
Methotrexate is widely used in inflammatory diseases during the patients' reproductive years. The effect on male fertility and sperm DNA integrity is largely unknown. We evaluated sperm DNA integrity and basic semen parameters according to the World Health Organization (WHO) in male patients with inflammatory diseases treated with methotrexate.
Semen samples from 14 patients on low-dose maintenance methotrexate were compared with samples from 40 healthy volunteers. Further, 5 patients delivered samples on and off methotrexate therapy for paired comparison. Sperm DNA fragmentation index (DFI), concentration, motility, and morphology were evaluated. Blood sex hormones and methotrexate levels were measured in blood and semen.
DNA fragmentation index in methotrexate-treated patients was comparable with that in healthy volunteers (DFI, 11.5 vs 15.0; P = .06), and DFI did not change significantly on and off methotrexate in the paired samples (DFI, 12.0 vs 14.0; P = 0.35). Sperm concentration, motility, and morphology did not differ between men treated with methotrexate and healthy volunteers. Sperm progressive motility increased off therapy compared with on therapy (65.0% vs 45.0%, P = .04), but all fluctuations in progressive motility were within the WHO reference interval. All methotrexate polyglutamates1-5 were detected in blood, but only methotrexate polyglutamate1 in semen. Serum testosterone was unaffected by methotrexate therapy.
Patients treated with low-dose methotrexate have a sperm quality comparable with that of healthy volunteers, and methotrexate treatment does not increase sperm DNA fragmentation. This study does not support cryopreservation of semen before treatment initiation nor a 3-month methotrexate-free interval prior to conception.
甲氨蝶呤在患者生育年龄广泛用于治疗炎症性疾病。但其对男性生育力和精子 DNA 完整性的影响知之甚少。我们根据世界卫生组织（WHO）的标准，评估了接受低剂量维持性甲氨蝶呤治疗的炎症性疾病男性患者的精子 DNA 完整性和基本精液参数。
将 14 名接受低剂量维持性甲氨蝶呤治疗的患者的精液样本与 40 名健康志愿者的样本进行比较。此外，对 5 名患者进行了配对比较，即在接受和停止甲氨蝶呤治疗时分别提供样本。评估精子 DNA 碎片化指数（DFI）、浓度、活力和形态。在血液和精液中测量性激素和甲氨蝶呤水平。
接受甲氨蝶呤治疗的患者的 DNA 碎片化指数与健康志愿者相似（DFI，11.5 对 15.0；P=0.06），且配对样本中 DFI 在接受和停止甲氨蝶呤治疗时无明显变化（DFI，12.0 对 14.0；P=0.35）。接受甲氨蝶呤治疗的男性与健康志愿者的精子浓度、活力和形态无差异。与治疗期间相比，治疗停止后精子前向运动能力增加（65.0% 对 45.0%，P=0.04），但所有前向运动能力的波动均在 WHO 参考区间内。所有甲氨蝶呤多聚谷氨酸 1-5 均在血液中检测到，但仅在精液中检测到甲氨蝶呤多聚谷氨酸 1。血清睾酮不受甲氨蝶呤治疗的影响。
接受低剂量甲氨蝶呤治疗的患者的精子质量与健康志愿者相似，且甲氨蝶呤治疗不会增加精子 DNA 碎片化。本研究不支持在治疗前开始冷冻精液，也不支持在受孕前 3 个月停止甲氨蝶呤治疗。
