Male infertility due to testicular disorders

Abstract

Context: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.

Evidence acquisition: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail.

Evidence synthesis/results: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking.

Conclusions: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in "idiopathic" male infertility and long-term follow-up studies of babies conceived through ART.

Keywords: male infertility; semen; sperm quality; spermatogenesis; testes; testosterone.

Figure 1.

Flow diagram illustrating the assessment of an infertile male. The choice of investigations undertaken should be tailored to the clinical presentation and consider available health resources. *Typical diagnostic characteristics are provided, but some patients may have atypical characteristics. Abbreviations: CBAVD, congenital bilateral absence of vasa deferens; FSH, follicle stimulating hormone; LH, luteinizing hormone; NOA, nonobstructive azoospermia; SHBG, sex hormone binding globulin.

Figure 2.

Micro-TESE (microdissection testicular sperm extraction). Intraoperative photographs of a micro-TESE in a patient with nonobstructive azoospermia (NOA). The testis is transversely bivalved and dilated under optical magnification. Opaque tubules (circled in black) are retrieved, as these are more likely to contain seminiferous tubules with complete spermatogenesis.