Department of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran.
Reprod Biol Endocrinol. 2020 May 13;18(1):47. doi: 10.1186/s12958-020-00591-2.
This study investigates the effect of letrozole on hormone profiles, semen parameters, body mass index (BMI), degree of oxidative stress and sperm chromatin integrity in men with idiopathic oligo/astheno/teratozoospermia (iOAT) and T:E ratio ≤ 10.
This study is a longitudinal, prospective, interventional and open-labelled clinical trial. Semen samples were collected from 20 iOAT men with low serum testosterone (T) to estradiol (E) ratio (T:E ratio ≤ 10). The participants were treated with 2.5 mg letrozole orally per day for 3 months. Then, sperm parameters, hormone profiles, BMI, chromatin integrity and intracellular reactive oxygen species (ROS) level were assessed pre- and post- treatment. The chromatin integrity was evaluated by assessment of DNA fragmentation (with TUNEL assay) and protamine deficiency (with Chromomycin A3, CMA3). Also, the intracellular ROS levels were investigated by 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Finally, the differences between the parameters evaluated before and after letrozole treatment were analyzed with the t-test and the Wilcoxon signed-rank test.
Sperm concentration, percentage of sperm motility and its normal morphology increased significantly after letrozole treatment. Moreover, serum testosterone level increased but estradiol level decreased significantly following treatment. The mean of T:E2 ratio improved 1600%. Also, letrozole treatment significantly reduced the percentage of sperm TUNEL positivity and sperm CMA3 positivity. While no significant difference was observed between intracellular ROS levels and BMI before and after treatment. Finally, as a notable result, four spontaneous pregnancies (20%) were achieved after treatment.
Letrozole treatment can effectively increase spontaneous pregnancies by improving sperm parameters and sperm chromatin integrity in men with iOAT and T:E2 ratio ≤ 10.
Trial registration: IRCT, IRCT20191030045283N1. Registered 16 November 2019 - Retrospectively registered, https://fa.irct.ir/user/trial/43484/view.
本研究旨在探讨来曲唑对特发性少精、弱精、畸形精子症（iOAT）且睾酮（T）与雌二醇（E）比值（T:E 比≤10）的男性的激素谱、精液参数、体重指数（BMI）、氧化应激程度和精子染色质完整性的影响。
这是一项纵向、前瞻性、干预性和开放标签的临床试验。从 20 名血清睾酮（T）水平低且 T:E 比（T:E 比≤10）的 iOAT 男性中收集精液样本。这些参与者每天口服 2.5 毫克来曲唑治疗 3 个月。然后，在治疗前后评估精子参数、激素谱、BMI、染色质完整性和细胞内活性氧（ROS）水平。通过末端转移酶 dUTP 缺口末端标记法（TUNEL 测定）和鱼精蛋白缺乏（用 Chromomycin A3，CMA3）评估 DNA 碎片化来评估染色质完整性。此外，通过 2',7'-二氯二氢荧光素二乙酸酯（DCFH-DA）染色法检测细胞内 ROS 水平。最后，用 t 检验和 Wilcoxon 符号秩检验分析来曲唑治疗前后各参数的差异。
来曲唑治疗后，精子浓度、精子运动百分比和正常形态精子百分比显著增加。此外，治疗后血清睾酮水平升高，而雌二醇水平显著降低。T:E2 比值平均改善了 1600%。此外，来曲唑治疗显著降低了精子 TUNEL 阳性率和精子 CMA3 阳性率。而治疗前后细胞内 ROS 水平和 BMI 无显著差异。最后，值得注意的是，治疗后有 4 例（20%）自然妊娠。
来曲唑治疗可有效改善 iOAT 且 T:E2 比值≤10 的男性的精子参数和精子染色质完整性，从而提高自然妊娠率。
试验注册：IRCT，IRCT20191030045283N1。注册日期：2019 年 11 月 16 日-追溯性注册，https://fa.irct.ir/user/trial/43484/view。
