Clomiphene Citrate a First Step to Improve Idiopathic Male Infertility: A Retrospective Analysis

Background. Infertility in men is a common and worldwide problem with limited registered treatment options and licensed therapies. Clomiphene citrate (CC) is an empirical off-label therapy. CC is a selective estrogen receptor modulator that may improve testicular function, including sperm quality, by stimulating steroidogenesis and spermatogenesis. However, there is a lack of evidence regarding the efficacy of CC as therapy for male infertility. Objectives. To assess the improvement of CC on sperm parameters, pregnancy, hypogonadism, and measurement of safety. Methods. In this retrospective study, 52 men treated with CC for idiopathic nonobstructive infertility were analyzed. Data of sperm parameters, pregnancy rate, hormonal values, side effects, improvement in hypogonadal symptoms, and potential predictors of treatment response were collected. Results. A total of 52 infertile men underwent CC treatment. An increase in sperm concentration was observed in 19 patients (37%). An upgrade in sperm concentration classification according to the WHO criteria was noted in 21% of the patients receiving CC therapy. Additionally, 15% of initially ineligible patients for intrauterine insemination became eligible during CC. In total, 33% of couples achieved pregnancy, either spontaneously or with assisted reproductive techniques (ART). Low-normal follicle-stimulating hormone and larger testis volume before CC treatment were predictors for better semen concentration during treatment. The retrieval rate was 75% for azoospermic patients who underwent testicular sperm extraction or percutaneous epididymal sperm aspiration, enough for intracytoplasmic sperm injection. With CC, testosterone levels increased and hypogonadal symptoms improved. Mild side effects were reported by 8% of patients. Conclusion. The results of this study contribute to the existing evidence that CC is a safe and noninvasive therapy for idiopathic infertile males. It could be considered as a step-up therapy before initiating more invasive ART procedures.