Background: 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 2 ratio ≤ 10. Materials and methods: 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 2) ratio (T:E 2 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. Results: 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. Conclusions: Letrozole treatment can effectively increase spontaneous pregnancies by improving sperm parameters and sperm chromatin integrity in men with iOAT and T:E2 ratio ≤ 10.

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L-carnitine, through its antioxidant potential, plays a significant role in reducing ROS production in male genital tract; therefore, fundamental improvements in spermatogenesis process and sperm structural and functional parameters in seminal plasma can be observed by treatment with L-carnitine. A literature search was performed using PubMed (including Medline) from the database earliest inception to 2021. Eligibility criteria included studies on protective effects of L-carnitine against damages to the male reproductive system. Based on the findings of the current study, L-carnitine has an effective potential to protect testis and improve conventional and functional sperm parameters against ROS-induced damages by sperm cryopreservation, busulfan treatment, and radiation