As assisted reproductive technology (ART) continues to evolve, so too has the conversation around male infertility, including azoospermia treatment and management. A comprehensive evaluation of male reproductive function and improved diagnostic tools allow for better assessment of underlying issues and potential treatments.
Most causes of male infertility can be bypassed using ART. However, treating a total absence of sperm can be challenging.
New Hope for Patients With Azoospermia
The clinical definition of azoospermia is the absence of sperm in the ejaculate. Roughly 1 percent of men have azoospermia; its incidence is approximately 10 to 15 percent in cisgender men who are known to be experiencing infertility.
Historically, men with azoospermia were encouraged to seek out a sperm donor. However, it is now established in the literature that many of the causes can be reversed by a skilled urologist or andrologist and various extraction procedures. Typically, a urologist will conduct the evaluation, diagnosis and treatment of the underlying condition, in addition to extracting the sperm from the epididymis or testicle.
Diagnosing Azoospermia
There are two types of azoospermia: obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). In OA, the testes produce enough sperm, but there is a blockage somewhere in the epididymis or vas deferens that prevents sperm from traveling out of the testes and entering the ejaculate. In NOA, a separate disorder or condition is causing a decrease or total halt in the production of sperm. NOA can be pretesticular or testicular. Differentiating these two types is necessary to properly formulate diagnostic, management and treatment plans for patients with azoospermia.
Proper semen analysis is essential for accurately diagnosing azoospermia. One global standard is the World Health Organization Manual for the Laboratory Examination and Processing of Human Semen, which was updated in July 2021.
According to a review published in Clinics, semen samples should be centrifuged at a minimum speed of 3,000 g for 15 minutes at room temperature. Then, the results are carefully examined using a high-powered microscope. The researchers recommend examining at least two samples collected more than two weeks apart.
Up to 35 percent of men thought to have NOA may have detectable sperm in their properly centrifuged specimens, the Clinics researchers report. If even minute quantities of sperm are detected, a patient could potentially undergo immediate sperm cryopreservation and their cryopreserved sperm used for intracytoplasmic sperm injection (ICSI) cycles.
Evaluating Male Fertility and Infertility
Once a patient has been diagnosed with azoospermia, they should undergo a full evaluation to differentiate between obstructive and non-obstructive azoospermia.
- Medical history: A complete medical and surgical history should be conducted to reveal any past infections, including sexually transmitted infections and childhood illnesses. Any prior radiation or chemotherapy or other gonadotoxin exposures should be assessed, as well. In some cases, male infertility may be the result of a serious systemic condition, such as hemochromatosis.
- Physical examination: The patient should be examined in a warm room in both supine and standing positions. It is important to assess for the presence of clinical varicocele. Assessment of appropriate sexual development and any androgen deficiency is important, as well as thyroid, heart and lung function.
- Endocrine evaluation: Endocrine screening is important to help determine specific diagnoses and treatment strategies. Any patients who present with suggestions of endocrinopathy should have serum testosterone and follicle-stimulating hormone (FSH) levels assessed. If testosterone is low, a more complete evaluation of hormones should be conducted to include total and free testosterone, luteinizing hormone, prolactin and estradiol levels.
- Other semen parameters: Semen volume is an important determining factor. Patients with a normal ejaculate volume may have obstruction or abnormalities in spermatogenesis, whereas those with a low semen volume and normal-sized testes may have ejaculatory dysfunction or ejaculatory duct obstruction. If patients have low or absent ejaculation, semen analysis should be repeated and followed with a post-ejaculation urine specimen.
- Testes biopsy: Biopsy is used only rarely as a diagnostic tool. But in some patients with normal testicular size, palpable vas deferens and normal serum FSH, a biopsy of the testes may help differentiate OA from disorders of spermatogenesis.
How Is Obstructive Azoospermia Treated?
Management of OA includes microsurgical reconstruction when feasible. Microsurgical reconstruction outcomes have improved in recent decades thanks in part to the increasing number of vasectomy reversals, which utilize similar surgical techniques. There are two main techniques to treat OA:
- The multilayer microdot vasovasostomy technique, in which two portions of the vas deferens are marked with microscopic ink dots and micro-stitched together.
- The longitudinal intussusception vasoepididymostomy techniques, in which the vas deferens is surgically connected to the outer wall of the epididymal tubule.
Predictors of successful surgical outcomes include the microsurgeon's experience level and the length of time the obstruction has been present (vasal obstructive interval).
According to a review published in Spermatogenesis, "Sperm retrieval and cryopreservation for future IVF/ICSI should be performed intraoperatively as an alternative solution if reconstruction proves unsuccessful." When surgical intervention is not feasible in the first place, microsurgical epididymal sperm aspiration combined with IVF/ICSI is the preferred treatment. Cryopreservation of retrieved sperm allows for flexibility in the timing of later IVF or ICSI cycles. However, research on an improved version of intussusception vasoepididymostomy published in Annals of Urology notes that successful microsurgical reconstruction is more cost-effective than either ICSI or sperm retrieval.
How Is Non-Obstructive Azoospermia Treated?
Patients with NOA may also be able to have enough sperm collected for an ICSI or IVF cycle. A technique called microdissection testicular sperm extraction (microTESE) yields sperm in roughly 47 percent of NOA cases, according to a large-scale literature review published in International Urology and Nephrology.
For hypogonadal men with NOA, there appears to be no relationship between TESE sperm retrieval outcomes and FSH levels, testosterone response to hormonal therapy, or preoperative testicular volume, according to the Spermatogenesis study. MicroTESE also shows benefits for patients with a history of NOA due to chemotherapy. Out of all cancer survivors with NOA, the best results are found for patients with previous testicular cancer; patients with a history of other cancers, particularly sarcoma, may have poorer outcomes.
For patients with varicocele and NOA, microsurgical varicocelectomy improves spermatogenesis in the testis, leading to sperm returning to the ejaculate in 22 to 55 percent of men, according to the review in Clinics. However, it is not clear whether varicocele repair increases the likelihood of successful sperm retrieval overall in men with NOA or only for certain patients. The decision to undergo the procedure should take into account the grade of varicocele and the most current clinical trial data.
Supporting Patients With Azoospermia
Given that azoospermia has historically led to a diagnosis of male infertility, healthcare practitioners should be aware that patients may automatically assume there is nothing that can help them. However, this is far from true. Whether or not a reversal is possible, azoospermic patients still have several options for building their families. Explaining available azoospermia treatment to patients and any partners may reassure them as they navigate their way forward.
