• The male partner contributes to 50% of infertility cases.
  • Causes include decreased or absent sperm production or function, or obstruction of the male genital tract.
  • Detailed history, physical examination, and repeated semen analysis are important for diagnosis and treatment.
  • Abnormal semen quality may indicate poor health or increased risk of certain health conditions.

General Considerations

Infertility, the inability of a couple to conceive a child after 1 year of sexual intercourse without contraceptive use, affects 15-20% of US couples. Approximately one-half of cases result from malefactors; therefore, evaluation of both partners is critical. Following a detailed history and physical examination, a semen analysis is essential for diagnosis and should be performed at least twice, on two separate occasions (Figure). Because spermatogenesis takes approximately 74 days, it is important to review health events and genotoxic exposures from the preceding 3 months. Male infertility is associated with a higher risk for the later development of testicular germ cell cancer; thus, these men should be counseled appropriately and taught testicular self-examination.

Clinical Findings

○ Symptoms and Signs

The history should include prior testicular insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis, sexually transmitted infections), environmental factors (excessive heat, radiation, chemotherapy, prolonged pesticide exposure), medications (testosterone, finasteride, cimetidine, selective serotonin reuptake inhibitors, and spironolactone may affect spermatogenesis; phenytoin may lower FSH; sulfasalazine and nitrofurantoin affect sperm motility; tamsulosin causes retrograde ejaculation), and other drugs (alcohol, tobacco, marijuana). Sexual function frequency and timing of intercourse, use of lubricants, and a partner’s previous fertility is important. Loss of libido, headaches, visual disturbances, or galactorrhea may indicate a pituitary tumor. The past medical or surgical history may reveal chronic disease, including thyroid or liver disease (abnormalities of spermatogenesis), diabetes mellitus (retrograde or anejaculation), or radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury).
Physical examination should pay particular attention to features of hypogonadism: underdeveloped sexual characteristics, diminished male pattern hair distribution (axillary, body, facial, pubic), body habitus, gynecomastia, and obesity. The scrotal contents should be carefully evaluated. Testicular size should be noted (normal size approximately 4.5 X 2.5 cm, volume 18 mL). Varicoceles are abnormally dilated and refluxing veins of the pampiniform plexus FNA can be identified in the standing position by gentle palpation of the spermatic cord and, on occasion, may only appreciate with the Valsalva maneuver. The vas deferens epididymis and prostate should be palpated (absence of all or part of the vas deferens may indicate the presence of a cystic fibrosis variant, congenital bilateral or unilateral absence of the vas deferens).

○ Laboratory Findings

Semen analysis should be performed after 2 to 3 days of ejaculatory abstinence. The specimen should be analyzed within 1 hour after collection. Abnormal sperm concentrations are < 15 million/mL (oligozoospermia is the presence of < 15 million sperm/ml L in the ejaculate; azoospermia iS the absence of sperm). In normal semen, the volumes range between 1.5 mL and 5 mL(volumes < 1.5 mL may result in inadequate buffering of the vaginal acidity and may be due to retrograde ejaculation, ejaculatory duct obstruction, congenital bilateral absence of the vasa deferentia, or androgen insufficiency). Normal sperm motility and morphology demonstrate> 45% motile cells and> 4% normal morphology (World Health Organization). Abnormal motility may result from varicocele, anti-sperm antibodies, infection, abnormalities of the sperm flagella, or partial ejaculatory duct obstruction. Abnormal morphology may result from a varicocele, infection, or exposure to gonadotropins (eg, tobacco smoke).
Endocrine evaluation is warranted if sperm counts are low (< 15 million/mL) or if the history and physical examination testing nation suggest an endocrinologic origin. Initial testing should include serum testosterone and FSH. Specific abnormalities in these hormones should prompt additional testing, including serum LH, prolactin, and estradiol levels. Elevated FSH and LH levels and low testosterone levels (hypogonadotropic hypogonadism) are associated with primary testicular failure. Low FSH and LH associated with low testosterone occur in secondary testicular failure (hypogonadotropic hypogonadism) and may be of hypo- thalamic or pituitary origin. Elevation of serum prolactin may indicate the presence of pituitary prolactinoma. Elevation of estradiol may impair normal gonadotropin production and impact normal spermatogenesis.

○ Genetic Testing

Men with sperm concentrations < 10 million/mL should consider testing for Y chromosome microdeletions and karyotypic abnormalities. Gene deletions from the long arm of the Y chromosome may cause azoospermia or oligozoospermia with age-related decline in spermatogenesis that is transmissible to male offspring. Karyotyping may reveal Klinefelter syndrome. The partial or complete absence of the vas deferens should prompt testing for cystic fibrosis mutations.

○ Imaging

Scrotal ultrasound can aid in characterizing the testes and may detect a subclinical varicocele. Men with low ejaculate volume and no evidence of retrograde ejaculation should undergo a transrectal ultrasound to evaluate the prostate and seminal vesicles. MRI of the sella turcica should be performed in men with markedly elevated prolactin or hypo-gonadotropic hypogonadism to evaluate the anterior pituitary gland. MRI of the pelvis and scrotum should be considered in men for whom the testes cannot be identified in the scrotum by physical examination or ultrasound. Men with unilateral absence of the vas deferens should have abdominal ultrasound or CT to exclude absence of the ipsilateral kidney, given the association of these two conditions.

○ Special Tests

Patients with low volume ejaculate should have post ejaculation urine samples centrifuged and analyzed for sperm to evaluate for retrograde ejaculation. In cases of disproportionately low motility, sperm vitality and the presence of autoantibodies should be assessed. Round cells in concentrations > 1 million/mL should prompt leukocyte esterase or peroxidase staining (immature germ cells are found normally, but inflammatory cells may require treatment).


○ General Measures

Education about the proper timing for intercourse with the woman’s ovulatory cycle as well as the avoidance of spermicidal lubricants should be discussed. In cases of gonadotoxic exposure or medication-related factors, the offending agent should be removed whenever feasible. Patients with active genitourinary tract infections should be treated with appropriate antibiotics. lifestyle habits, including a healthy diet, moderate exercise, and avoidance of gonadotropins (such as tobacco smoke, excessive alcohol, and marijuana) should be reinforced.

○ Varicocele

Varicocelectomy is performed by stopping retrograde blood flow in spermatic cord veins. Surgical ligation may be accomplished via subinguinal, inguinal, retroperitoneal, or laparoscopic approaches. Percutaneous venographic embolization of varicoceles is feasible but may have a higher recurrence rate.

○ Endocrine Therapy

Hypogonadotropic hypogonadism chorionic gonadotropin once the primary pituitary disease has been excluded or treated. Dosage is usually 2000 international units intramuscularly three times a week. If sperm counts fail to rise after 12 months, FSH therapy should be treated and initiated.

○ Ejaculatory Dysfunction Therapy

Patients with retrograde ejaculation may benefit from alpha-adrenergic agonists (pseudoephedrine, 60 mg orally three times a day) or imipramine (25 mg orally three times a day). Medical failures may require the collection of post-ejaculation urine for intrauterine insemination. Anejaculation can be treated with vibratory stimulation or electroejaculation in select cases.

○ Ductal Obstruction

Obstruction of the ejaculatory ducts may be corrected by transurethral resection of the ducts in the prostatic urethra. If obstruction of the vas deferens or epididymis is suspected, the level of obstruction must be determined via a vasogram before operative treatment, except prior vasectomy. Obstruction of the vas deferens is best managed by microsurgical vasovasostomy or vasoepididymostomy.

○ Assisted Reproductive Techniques

Intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection are alternatives for patients in whom other means of treating reduced sperm concentration, motility, or functionality has failed. Intrauterine insemination should only be performed when adequate numbers of motile sperm are noted on an ejaculate sample. With the use of intracytoplasmic sperm injection, azoospermic men can father their genetic progeny by surgical retrieval of sperm from the testicle, epididymis, or vas deferens.
When to refer couples with clinical infertility or concern about fertility potential. Men with known genital insults, genetic diagnoses, or syndromes that preclude natural fertility. Reproductive-aged men with newly diagnosed cancer or other diseases may require cytotoxic therapies with an interest in fertility preservation.


  • Eisenberg ML et al. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod. 2014 Feb;29(2):193-200. [PMID: 24306102]
  • Lopushnyan NA et al. Surgical techniques for the management of male infertility. Asian J Androl. 2012 Jan;14(1):94-102. [PMID: 22120932]
  • Walsh T et al. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med. 2009 Feb 23;169(4):351-6. [PMID: 19237718]
  • Winters BR et al. The epidemiology of male infertility. Urol Clin North Am. 2014 Feb;41(1):195-204. [PMID: 242867771]



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