Epidemiology of Male Infertility

Male infertility is the sole cause of 20% of couple infertility and contributes an additional 30% as a cause for combined couple infertility. Most men seeking infertility counseling and evaluation are referred through gynecologists or primary care physicians caring for the female partner. Thus, specialized knowledge or training about infertility is very important as is the ability to work closely with reproductive endocrinologists and gynecologic physicians. With the advancement of assisted reproductive technologies (ART) and microsurgical techniques, many men previously labeled as sterile are now capable of fathering children.

Physiology of Male Infertility

Physiologically, male fertility requires good erectile function; spermatogenesis; normal endocrine function (specifically testosterone and follicle stimulating hormone); and ejaculation. In addition, sexual intercourse timed appropriately to ovulation is an important key to conception.

Because of the anxiety and stress that is often associated with couple infertility, male patients often describe difficulty with erections. Obviously, if sexual intercourse is not occurring then conception is impossible! This information must be addressed specifically with the patient as he may not volunteer it. Erectile dysfunction secondary to various disease states including diabetes and atherosclerosis must also be elucidated. Any previous history of genitourinary cancers or pelvic surgeries that may have impaired erectile function should also be addressed.

Spermatogenesis has traditionally been described as requiring a 74 day cycle (recent studies have indicated it may actually be shorter than this time period). Any insult or intervention will usually require at least one spermatogenic cycle prior to seeing its effect.

Follicle stimulating hormone (FSH) and testosterone are imperative for normal spermiogenesis. When follicle stimulating hormone is elevated it can be an indication that the testes are not producing sperm in normal amounts related to various causes including: testicular failure; genetic abnormalities, toxic exposures (including radiation, chemotherapy, and heat). The teaching used to be if follicle stimulating hormone was elevated by at least twice the upper limit of normal, the probability of finding sperm even on testicular biopsy was almost zero. This has changed with the development of new microsurgical techniques, including microscopic testicular sperm extraction (micro TESE). Nonetheless, follicle stimulating hormone levels are useful in counseling patients on potential outcomes of the infertility evaluation. If follicle stimulating hormone is elevated (greater than twice normal) in a patient with severe oligospermia or azoospermia, the patient must be instructed that advanced reproductive techniques (ART) would most likely be required in order to have a biological child. If the patient is unwilling, financially or psychologically, to undergo ART, other options such as donor sperm insemination or adoption should be discussed. Testosterone, another crucial hormone, contributes to libido, erectile function, and sperm production. Obviously, intercourse must be timed to the periovulatory period. Sperm are able to live in the cervical mucus for an average of approximately 48 hours. Patients should be instructed to have sexual intercourse near the time of anticipated ovulation.

Differential Diagnosis of Male Infertility

Differential diagnosis of the causes of male infertility may be broken down into three categories:

Pretesticular (endocrine) causes include:

Pituitary disease: e.g., hypogonadotropic hypogonadism: low luteinizing hormone, follicle stimulating hormone and testosterone levels; Kallman syndrome (associated anosmia); isolated follicle stimulating hormone deficiency

Congenital syndromes: Prader-Willi syndrome

Elevated exogenous or endogenous androgen levels: anabolic steroid use, metabolic disorders or androgen secreting tumor

Elevated estrogen levels: hepatic dysfunction (e.g., cirrhosis), estrogen secreting tumors, morbid obesity

Elevated prolactin: pituitary prolactin secreting tumor, idiopathic hyperprolactinemia

Elevated glucocorticoids ‘ Hyperthyroidism

Testicular causes include:

Genetic/karyotypic abnormalities

Anatomic abnormalities: cryptorchidism (bilateral/unilateral); vanishing tes-tes syndrome (bilateral anorchia — XY males with impalpable testes)

Gonadotoxins: chemotherapy, radiation; cigarettes, marijuana, alcohol abuse, heavy metal exposure (lead, mercury), sulfa drugs

Varicocele. Primary laboratory characteristic is combined finding of low mo-tility and low sperm count. Increased abnormal morphology secondary to a stress pattern may be seen as well. Varicoceles can be diagnosed in approximately 35% of infertile men on physical exam only. Varicoceles diagnosed with scrotal ultrasound are defined as subclinical and there is no proven benefit to surgical repair.

Structural defects (structural sperm defects which prevent normal motility): immotile cilia syndrome; immotile viable sperm

Orchitis: Post pubertal mumps, epididymo-orchitis, syphilis, gonorrhea, and leprosy

Antisperm antibodies (testicular injury, previous vasectomy)

Testicular cancer

Idiopathic: occurs in as many as 25% of patients with abnormal semen analysis

Post-Testicular causes include:

• Ductal obstruction (CBAVD, vasectomy, scarring from sexually transmitted diseases)

• Retrograde ejaculation (multiple sclerosis, diabetes, retroperitoneal lymph node dissection)

• Anejaculation (spinal cord injury, retroperitoneal lymph node dissection, diabetes)

Evaluation of Male Infertility

Management of Male Infertility

Key Points/Summary

• Male factor infertility can be caused by pretesticular, testicular and post tes-ticular abnormalities. History, physical exam, endocrine analysis and radio-logic studies will guide diagnosis and treatment.

• A full examination for male infertility should include a complete medical and reproductive history, a physical exam by a urologist or male reproductive specialist and at least two semen analyses.

• An endocrine evaluation should be performed if there is an abnormal semen analysis, combined with impaired sexual function, and/ or physical exam findings suggestive of hormonal dysfunction.

• Men with an abnormal testicular exam should have an immediate scrotal ultrasound to look for testicular masses consistent with cancer.

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