Causes and Treatment of Non-Obstructive Azoospermia: Lack of Sperm in Semen

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Azoospermia refers to a complete absence of sperm in the ejaculate. An important distinction to make is whether the absence of sperm is a result of an obstruction (obstructive azoospermia), or due to abnormal sperm production (non-obstructive azoospermia).

There are numerous causes of non-obstructive azoospermia, including:

  • Genetic abnormalities
  • Hormonal imbalances
  • Radiation and toxins
  • Medications
  • Varicocele

Causes of Non-Obstructive Azoospermia

Genetic Causes

There are several genetic causes of male infertility that may result in non-obstructive azoospermia. These include Y-chromosome microdeletions, and karyotypic abnormalities. The most common karyotypic abnormality is called Klinefelter Syndrome, and occurs when a male possesses an extra X chromosome. Up to 10 percent of patients with non-obstructive azoospermia will have detectable genetic abnormalities that result in decreased sperm production.

Hormonal Causes of Non-Obstructive Azoospermia

For the testicles to produce sperm, they must be stimulated by pituitary hormones. If there is a deficiency or absence of these hormones, sperm production cannot occur. Men who take or have taken steroids may have affected the hormones necessary for sperm production.

Radiations and Toxins

Exposure to toxic chemicals such as heavy metals, chemotherapy, and radiation therapy can all impair sperm production. Sperm banking is recommended prior to chemotherapy or radiation treatment for this reason.


Exposure to certain medications can also negatively affect sperm production. For instance, taking testosterone supplements can disrupt the normal function of the reproductive system.


Sperm production can also be affected by varicoceles, which are swollen varicose veins in the scrotum. Varicoceles cause blood pooling in the scrotum, which negatively affects sperm production.

Treatment for Non-Obstructive Azoospermia

For men with non-obstructive azoospermia, hormone therapy can be a helpful way to treat hormone deficiencies. Men who have an abnormal testosterone to estradiol ratio (T/E2) can be treated with aromatase inhibitors, which can improve sperm concentration and motility. Avoidance of toxins and adjusting medications with the help of a physician can also result in improved sperm counts.

There are conflicting data regarding whether to surgically repair varicoceles. Varicocelectomy can help reduce the swollen varicose veins by tying off the affected veins are tied off and rerouting the blood flow through healthy veins but is generally reserved for severe cases.

Pregnancy and Non-Obstructive Azoospermia

Previously, fertility doctors thought that men who have problems with sperm production could only create their family with donor sperm or through adoption. However, testis biopsies in men with non-obstructive azoospermia have often shown sperm. Testicular sperm often have lower motility, but they can be used for intracytoplasmic sperm injection (ICSI) during in vitro fertilization (IVF).

A procedure called testicular sperm extraction (TESE) with ICSI has been performed for men with non-obstructive azoospermia. Testicular sperm extraction can be performed under local or general anesthesia. Sperm retrieved through this process can be used in IVF procedures.

If a man has a diagnosis of a genetic cause for his non-obstructive azoospermia, genetic testing and counseling is recommended before IVF.

Dr. Sydney Chang is a Fellow in Reproductive Endocrinology and Infertility at the Icahn School of Medicine at Mount Sinai/Reproductive Medicine Associates of New York.  She earned her Bachelor of Arts in Human Biology at Stanford University, where she graduated with Honors and Distinction. She went on to complete her medical school education at Duke University School of Medicine. She completed her residency in Obstetrics, Gynecology, and Women’s Health at the Albert Einstein College of Medicine, where she served as an administrative chief resident.