Effect of Letrozole on sperm parameters, chromatin status and ROS level in idiopathic Oligo/Astheno/Teratozoospermia

Abstract

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.

Letrozole, an aromatase inhibitor, improves seminal parameters and hormonal profile in aged endangered Markhoz bucks

“…Therefore, it seems that letrozole administration modifies the serum hormonal profile In the present study, significantly higher semen index, semen volume, sperm concentration, total sperm per ejaculate, sperm viability, motility, and progressive motility were observed in letrozole-injected aged bucks. This is consistent with many previous studies [6,[10][11][12] which have demonstrated that aromatase inhibitors improved the sperm parameters in ejaculates of men with infertility problems by increasing the testosterone/estradiol ratio. In similar study, Turner et al [24] asserted that spermatogenesis efficiency increased by treating the adult rats with anastrozole, as an aromatase inhibitor.…”

“…Kooshesh et al [11] indicated that letrozole administration acts as a fertility agent in idiopathic infertile men, reducing protamine deficiency and DNA fragmentation affected by chromatin packaging and apoptosis pathways by stimulating FSH levels.…”

The Efficacy and Safety of Letrozole or Anastrozole in The Treatment of Specific Male Infertility Patients: Meta-Analysis and Systematic Review

“…The PICO of 25 studies that did not conform to Table 1 were excluded, and four studies were excluded due to unavailable experimental data. Finally, 10 articles [19][20][21][22][23][24][25][26][27][28] met the inclusion criteria for inclusion analysis (Figure 1), including 3 articles in Chinese [19][20][21] and 7 articles in English [22][23][24][25][26][27][28] .…”

“…In data reports, most of them adopt the mode of mean and standard deviation, except that Li et al 21 and Tian et al 20 adopt the form of interquartile rang when reporting semen concentration and total sperm count. Adverse reactions were reported in six studies 20,21,[23][24][25]28 . Two studies 19,25 reported pregnancy rates.…”

Letrozole Protects Against Cadmium-induced Inhibition of Spermatogenesis via LHCGR and Hsd3b6 to Activate Testosterone Synthesis in Mice

“…Letrozole is a reversible type 2 aromatase inhibitor that attaches to cytochrome P-450 and inhibits the conversion of testosterone to estradiol and androstenedione to estrone [10]. Therefore, it can increase levels of testosterone and stimulate spermatogenesis [11]. Few scienti c studies also seem to support the therapeutic potential of letrozole in male reproductive health [12].…”