Male Infertility

Preamble:
Male Infertility 101
The inability to conceive has persisted as a problem for 8-12% of couples globally, with the sole male factor contributing to approximately 20-30% of infertility cases. The burden infertility imposes on couples is substantially significant, ranging from psychological, social, and even economic burden on patients. Alarmingly, evidence suggests that sperm count has declined over time, and male infertility is strongly associated with increased mortality risk and higher incidence of cancer. As plenty of diagnostic tests are available, interpretations are often imprecise and subjective. Thus, accurate diagnosis of male infertility may be a challenge for clinicians.

Epidemiology and Challenges in Comprehensive Evaluation

Creating a successful diagnosis of male infertility remains a challenge due to the multiple organs involved in the process of conception; whereas the classification of male infertility remains unchanged (primary or secondary); follow-up assessments should be conducted the same way regardless of the differential diagnosis. Throughout the years,several parameters have differed over time, namely in semen analysis, where the recommendations by WHO (2010) have lower reference limits compared to past editions due to the evidence from statistical analysis of semen parameters in fertile men in previous years. Furthermore, hormonal evaluation is a key tool in solidifying a diagnosis.

In men with azoospermia or severe oligozoospermia, the use of karyotyping is recommended by several professional bodies; EAU even extends their recommendations to include men with a sperm count of less than 10x106/mL and those with a history of recurrent spontaneous abortions, malformations, or intellectual disabilities. Additional evaluations such as sperm DNA fragmentation (SDF) testing may add to the bigger picture in diagnosing male infertility and a more comprehensive assessment of the overall fertility status than conventional semen parameters. However, currently, professional bodies such as AUA and ASRM do not recommend the routine use of SDF.

Current and Future Avenues of Male Infertility Management

Much like the evaluation aspect of treating male infertility, today's management options have several advancements, for example, in patients with azoospermia. However,the success rate of sperm retrieval in  obstructive azoospermia is higher than in those with non-obstructive azoospermia (NOA). Finding heterogeneous patchy spermatogenesis during testicular biopsy may warrant the rationale for sperm retrieval in patients with NOA. In patients with varicoceles, the current understanding is that varicocele repair is recommended in men with clinical varicocele and abnormal semen parameters and less recommended to those who display normal semen analyses and/or subclinical varicoceles.
As for those with idiopathic male infertility, current recommendations include assisted reproductive technology or empirical medical therapy. The implementation of assisted reproductive technology has greatly facilitated couples with infertility; however, some couples still show poor outcomes despite the success of the techniques. Therefore, it should be noted that selecting the best sperm before intracytoplasmic sperm injection is of the utmost importance. Furthermore, the future in the diagnosis and management of male infertility lies with the integration of andrology and artificial intelligence; although still in its early stages, the possibilities of machine learning opening new doors in treating male infertility.

CAPSULE: Among 8–12% of infertile couples globally, a male factor contributes to approximately half of the cases. The etiology of male subfertility varies highly, ranging from congenital, acquired, or idiopathic factors which result in spermatogenesis impairment. As many health conditions can affect male fertility, a thorough assessment of patients to identify treatable or reversible lifestyle factors or medical conditions. Semen analysis remains the cornerstone for assessing male infertility. However, advanced diagnostic tests of sperm quality and function have been developed to improve accuracy. Assisted reproductive techniques have also substantially increased the ability of infertile couples to have biological children. A comprehensive overview of male infertility assessment and management, current controversies and future
directions were presented in the article.

Acknowledgment: Ponco Birowo, MD, Ph.D. is a Professor of Urology, Faculty of Medicine

Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Dr. Birowo
serves as a Guest member of the GAF Management.