Empiric Medical Therapy for Idiopathic Male Infertility

Abstract

The etiology of male infertility can often be identified as either genetic, endocrine, or anatomic, and appropriately targeted therapy or alternative conception treatment options can be provided. Idiopathic male infertility is the diagnosis given to patients when no identifiable male infertility factor is found but abnormalities are still present on semen analysis, and this condition is found in 30-40% of all infertile males. Hormonal treatment is widely used for empiric treatment of idiopathic male infertility since men with idiopathic male infertility often have hormonal abnormalities not detectable on standard hormone profiles. Some of the hormonal medications used include gonadotropins, androgens, selective estrogen receptor modulators, and aromatase inhibitors. The goal in using these medications is to modify the hypothalamic-pituitary-gonadal axis in order to lead to improved semen parameters and increased pregnancy rates. Off-label use with selective estrogen receptor modulators followed by aromatase inhibitors for the treatment of idiopathic male infertility has yielded the most promising results, but large-scale, randomized controlled trials with pregnancy outcomes data are needed to provide truly convincing benefits. Increased oxidative stress leading to sperm damage is another possible cause of idiopathic male infertility. Normally excessive reactive oxygen species (ROS) are deactivated or stabilized by the body’s antioxidant system. However, when ROS production occurs unchecked, a state of oxidative stress develops which can damage spermatozoa making them susceptible to lipid peroxidation. Studies have shown that the use of antioxidant therapy to combat increased oxidative stress in patients with idiopathic male infertility can lead to improved semen parameters. However, the variable quality of study design and size, inconsistencies in antioxidant dosing, and lack of consensus on individual versus combination antioxidant therapy make it difficult to provide definitive recommendations on the benefits of antioxidants for empiric treatment of idiopathic male infertility with further large-scale, randomized controlled trials with pregnancy outcomes data needed to determine its true efficacy.