Medical Management of Male Infertility: Now and Future

Grace Chen; Martin Kathrins; Samuel Ohlander; Craig Niederberger


Curr Opin Urol. 2023;33(1):10/15/2022 

In This Article

Abstract and Introduction


Purpose of Review: Medical therapy for idiopathic male infertility has historically been empiric and based on small observational studies rather than larger well designed clinical trials. This review is timely and relevant because of the recent publication of several studies that are less susceptible to bias because of being placebo-controlled and more highly powered.

Recent Findings: The largest proportion of recent publications covered antioxidants, with eight randomized controlled trials (RCTs) included in this review. The Males, Antioxidants, and Infertility (MOXI) trial is of particular interest, being a large multicenter RCT, which demonstrated no improvement in semen parameters or live-birth rates with antioxidant use. In addition, phosphodiesterase-5 inhibitors (PDE5i) have been shown to improve semen parameters, while duloxetine use was not associated with any adverse effects on sperm. Progress was also made in the realm of regenerative medicine, with the realization of the first successful primate model of sperm production from pluripotent stem cells.

Summary: It may be time to stop recommending antioxidants for idiopathic male infertility given recent studies suggesting lack of efficacy, but given their relative safety, it is reasonable to continue their use until the evidence is overwhelming. Otherwise, stem cell therapy is another anticipated area of research interest.


Male factor infertility has many potential causes, but is frequently multifactorial or idiopathic. If the cause is known, pharmacologic treatments tend to be well established. However, up to a quarter of male infertility cases are idiopathic. For these cases, treatment options are empiric and have less definitive outcome data to support use of these agents.

In this review, we summarize the most recent developments in the medical management of male infertility and speculate on developing therapies to look forward to. Most recent publications build upon existing treatment options, which are mainly drugs targeting the hypothalamic–pituitary–gonadal (HPG) axis. A large proportion of these studies focus on the effect of antioxidant use on semen parameters, as it has long been posited that increased oxidative stress may play a factor in idiopathic male infertility. An update on this topic is much needed, as previous data came from uncontrolled studies with variable designs. One experimental treatment under investigation that will also be given attention in this chapter is the use of stem cells to restore spermatogenesis in nonfunctioning testes.