From the Guidelines
Non-obstructive azoospermia (NOA) should be managed with microsurgical testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI) for fertility purposes, and hormonal therapy may be beneficial in specific cases, particularly those with hypogonadotropic hypogonadism, as recommended by the most recent guidelines 1.
Definition and Diagnosis
Non-obstructive azoospermia is characterized by the absence of sperm in the ejaculate due to severely impaired or non-existent sperm production rather than a blockage in the reproductive tract. The diagnosis is typically made after a semen analysis shows azoospermia, and the laboratory should then centrifuge the ejaculate and re-suspend the pellet in a small volume of seminal plasma and examine under wet mount microscopy for the presence of rare sperm 1.
Treatment Options
Treatment options depend on the underlying cause, but often include microTESE combined with ICSI for fertility purposes. Hormonal therapy may be beneficial in specific cases, particularly those with hypogonadotropic hypogonadism, using medications such as clomiphene citrate (25-50mg daily), human chorionic gonadotropin (hCG, 1500-2000 IU three times weekly), or follicle-stimulating hormone (FSH, 75-150 IU three times weekly) for at least 3-6 months 1.
Genetic Testing and Evaluation
Genetic testing is essential as NOA can be caused by chromosomal abnormalities like Klinefelter syndrome or Y chromosome microdeletions. Patients should undergo comprehensive evaluation including hormonal assessment (FSH, LH, testosterone), genetic testing, and possibly testicular biopsy to determine the specific cause and appropriate treatment approach 1.
Lifestyle Modifications
Lifestyle modifications including maintaining healthy weight, avoiding excessive heat exposure to testicles, limiting alcohol consumption, and quitting smoking can support overall reproductive health. Additionally, clinicians should encourage males to bank sperm, preferably multiple specimens when possible, prior to commencement of gonadotoxic therapy or other cancer treatment that may affect fertility in males 1.
Sperm Retrieval Success Rates
While sperm retrieval success rates vary (30-60% with microTESE), early intervention is crucial as sperm production may decline with age. Micro-TESE has become a mainstay in the management of the male with NOA when the azospermia is unrelated to gonadotoxic therapy, with success rates cited in the 40% to 60% range 1.
Some key points to consider in the management of NOA include:
- Comprehensive evaluation to determine the underlying cause of NOA
- MicroTESE combined with ICSI for fertility purposes
- Hormonal therapy in specific cases, particularly those with hypogonadotropic hypogonadism
- Genetic testing to identify chromosomal abnormalities
- Lifestyle modifications to support overall reproductive health
- Sperm banking prior to gonadotoxic therapy or other cancer treatment.
From the Research
Definition and Etiology of Non-Obstructive Azoospermia
- Non-obstructive azoospermia (NOA) is defined as no sperm in the ejaculate due to failure of spermatogenesis and is the most severe form of male infertility 2.
- The etiology of NOA is either intrinsic testicular impairment or inadequate gonadotropin production 2.
- Chromosomal or genetic abnormalities should be evaluated because there is a relatively high incidence compared with the normal population 2.
Treatment Options for Non-Obstructive Azoospermia
- Although rare, NOA due to inadequate gonadotropin production is a condition in which fertility can be improved by medical treatment 2.
- Testicular extraction of sperm under an operating microscope (micro-TESE) has been the first-line treatment for these patients 2, 3.
- Other treatment options include varicocelectomy for NOA patients with a palpable varicocele and orchidopexy if undescended testes are diagnosed after adulthood 2.
- Clomiphene citrate administration may result in sperm in the ejaculate of patients with nonobstructive azoospermia or the simplification of testis sperm retrieval 4, 5.
- Gonadotropins and aromatase inhibitors show promise in achieving the end point of improving the quantity and quality of sperm retrieved from the testis for in vitro fertilization 6.
Sperm Retrieval and Pregnancy Outcomes
- Using a microsurgical approach referred to as microdissection testicular sperm extraction, sperm retrieval is effective in 60% of men with nonobstructive azoospermia, including 70% of difficult cases, such as men with Klinefelter syndrome 3.
- Pregnancy is possible in 45% of couples once sperm are obtained 3.
- Sperm were noted in 54 patients (10.9%) in semen analysis after treatment in all groups at a mean concentration of 2.3 million/mL 5.
- For the 442 patients who remained azoospermic after treatment, successful sperm retrieval was significantly higher (57%) compared with the control group (33.6%) 5.