Micro-presentation: Management of Nonobstructive Azoospermia


Hello I'm Dr. Jeffrey Hayes the ASRM Education Specialist and the following presentation is a review of our Practice Committee Opinion on Management of Non-obstructive Azoospermia.

Healthcare providers often find themselves faced with questions that need answers regarding management of non-obstructive azoospermia. This topic is important because approximately five to ten percent of men evaluated for infertility are azoospermic with approximately 600,000 azoospermic reproductive aged US men at any time most of whom have non-obstructive azoospermia.

Non-obstructive azoospermia or NOA results from severe deficits in spermatogenesis that most commonly result from primary testicular dysfunction but that may also result from impairment of the hypothalamus or pituitary.

Men with NOA are entitled to a diagnostic evaluation that targets identification of treatable, genetically transmissible, prognostic and/or health relevant conditions. This evaluation should include a comprehensive clinical history physical examination serum testing of total testosterone and follicle stimulating hormone or FSH and further diagnostic testing in some cases based on results of the initial diagnostic evaluation. Men with NOA are also entitled to counseling regarding therapeutic alternatives to immediate sperm retrieval when appropriate.

Counseling about the advantages and disadvantages of available sperm retrieval procedures and protocols, and treatment of health relevant conditions that are discovered during their diagnostic evaluation. Detection of genetic abnormalities in men with NOA may affect prognosis for sperm retrieval and should trigger genetic counseling. Cytogenetic evaluation by karyotyping will identify cytogenetic abnormalities in approximately 5% of men with NOA. Non- mosaic Klinefelter syndrome 47 XXY is the most commonly detected cytogenetic anomaly. The diagnosis of Klinefelter syndrome informs treatment decisions about sperm retrieval and has important relevance to the health of affected men who are at increased risk for testosterone deficiency or TD, osteoporosis, metabolic syndrome, type 2 diabetes, breast cancer, and extra gonadal germ cell tumors. Other cytogenetic abnormalities detected in azoospermic men include Robertsonian translocations, reciprocal translocations, and chromosomal inversions.

Men with NOA associated with primary testicular failure should also undergo Y-chromosome micro deletion testing. Testing for Y- chromosome micro deletions is essential for counseling affected men about the risk of infertility in potential male offspring and to avoid unnecessary surgery in patients with a very poor prognosis for sperm retrieval.

Genetic testing should also be considered in NOA associated with congenital forms of hypoganadotropic hypogonadism or HH to inform patients about the risks of HH in their offspring. Testing affords clinicians the opportunity to counsel patients about the risks of HH in their offspring and empowers clinicians to screen for unaffected embryos using pre-implantation genetic testing for aneuploidy or PGT-A. Detection of any genetic abnormality during the diagnostic evaluation of NOA should prompt genetic counseling by an appropriately trained health care provider before treatment. Counseling should focus on the impact of the specifically detected genetic lesion on the patient's health and his prognosis for sperm retrieval and on the risks posed by the detected genetic lesion to the health and fertility of any potential offspring conceived using surgically retrieved sperm.

Men who harbor complete AZFa or AZFb Y-chromosome micro deletions should be counseled to consider donor sperm or adoption in conjunction with psychosocial counseling given that sperm identification is rare.

The method of sperm retrieval may also be critical in the management of NOA. Methods include percutaneous, incisional, and micro surgically assisted techniques.

Percutaneous methods such as testicular sperm aspiration or TESA involve aspiration of testicular tissue using small or large bore needles. Incisional methods are generally referred to as conventional testicular sperm extraction or cTESE. Microdissection TESE is performed by making a large testicular incision and then selectively sampling the largest diameter seminiferous tubules using optical magnification provided by an operating microscope.

Another important consideration in the management of NOA is the timing of sperm retrieval. Surgical sperm retrieval can be performed during an IVF cycle to coincide with oocyte retrieval with the intent of using fresh sperm if identified for ICSI. Alternatively sperm retrieval can be performed before ovarian stimulation with the plan for cryopreservation if sperm are identified for use in future IVF cycles.

Comprehensive management of men with NOA includes the diagnosis and treatment of associated health relevant conditions such as testosterone deficiency. In conclusion optimal care for men with NOA requires a multidisciplinary clinical team. Pre-implantation genetic testing may be helpful to minimize the risks to offspring of affected men. Men who harbor complete AZFa or AZFb Y-chromosome micro deletions should be counseled to consider donor sperm or adoption in conjunction with psychosocial counseling given that the sperm identification is rare.

Varicocelectomy should be considered in men with varicocele associated NOA prior to sperm retrieval.

Patients with NOA should be counseled about the advantages and disadvantages of available sperm retrieval techniques. Other options including donor insemination and adoption should be discussed with the patient.

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