Male Infertility: Novel Management Options for the General Urologist

Educational Objectives

The goal of this program is to improve the diagnosis and treatment of male infertility. After hearing and assimilating this program, the clinician will be better able to:

1. Evaluate a man with suspected infertility.
2. Manage a patient with azoospermia.

Summary

Evaluation: guidelines issued by American Urological Association state that minimum evaluation should include complete medical history (eg, exposures, chemotherapy, surgical interventions) and physical examination (eg, identify varicocele, determine presence or absence of vas deferens and epididymis, assess secondary sex characteristics [body habitus may suggest Klinefelter syndrome])

Semen analysis: standard evaluation should include 2 analyses; test stressful for patient, so clinician should work with sympathetic, professional laboratory or female infertility clinic familiar with performing test; home testing options may offer greater comfort for patient; clinically, morphology less important than volume, sperm count, and sperm motility; one kit for home use includes small centrifuge and enables assessment of motility and sperm count with digital tracking over time

Endocrine evaluation: measures levels of testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL); in patient with complete testicular failure, levels of FSH and LH elevated, T normal to low normal, and PRL normal; clinician may also check level of estrogen (E; often elevated in obese men and may normalize after treatment with anastrozole)

Additional testing: retrograde ejaculation — postejaculatory urinalysis optional test, but threshold that indicates retrograde ejaculation not established (sperm present in postejaculatory urine of healthy men); for alternate assessment, patient may take pseudoephedrine (eg, Sudafed) 2 or 3 times daily and observe whether volume of ejaculate increases; transrectal ultrasonography — guidelines suggest that if thickness of seminal vesicle >2 cm, ejaculatory duct obstruction may be present; imaging often not needed; scrotal ultrasonography — offers no benefit over physical examination; imaging indicated if examination abnormal or malignancy suspected

Antioxidants: many patients take vitamin supplements; although reactive oxygen species may affect fertility, currently insufficient data to support use of antioxidants to treat infertility; new office-based test measures electrical potential in ejaculate, which may correlate with oxidative stress in spermatozoa (test remains experimental)

Genetic screening: recommended for men with extremely low sperm count or azoospermia to test for cystic fibrosis (CF; can cause congenital absence of vas deferens), Klinefelter or other syndromes associated with male infertility, and Y chromosome microdeletions; commercial sources can arrange testing for patient

Azoospermia: determine whether obstructive or nonobstructive

Congenital obstructive azoospermia: for patient with unilateral vasal agenesis and negative test for CF, imaging indicated to assess for ipsilateral renal anomaly; if testicular biopsy indicated, clinician should offer cryopreservation at same time

Nonobstructive azoospermia: best treatment unknown; levels of FSH or LH usually elevated; patient may be primed with clomiphene (Clomid) or anastrozole; if FSH already markedly elevated, clomiphene (acts as anti-estrogen) ineffective; however, anastrozole may increase ratio of T to E within testicle, creating environment favorable for production of sperm; microscopic testicular sperm extraction may be performed after 6 to 9 mo of anastrozole; in animal models, spermatozoa developed from stem cells and offspring produced (such treatment controversial in humans)

Acquired obstructive azoospermia: reversal of vasectomy — first option for patients requesting reversal within 15 yr of vasectomy; vasoepididymostomy — reconstruction feasible option for man with acquired epididymal obstruction or inguinal injury to vas deferens (eg, after bilateral hernia repair); transurethral resection of ejaculatory ducts — popular in past, but long-term outcomes suboptimal; procedure should be performed under transrectal imaging after injecting seminal vesicle with dye; many patients develop retrograde ejaculation, recurrent epididymitis, and testicular pain; alternative procedures (sperm retrieval and in vitro fertilization) preferred

Oligospermia: clomiphene — recent review confirmed efficacy in patients with normal levels of FSH and LH and low sperm count; stimulates testes to produce more T and sperm; dose of 25 mg three times weekly recommended (cyclic therapy may mimic natural variations in levels of hormones; side effects uncommon at this dose); clomiphene alone can cause elevation in E (levels of E should be monitored), so addition of anastrozole can further boost T and reduce E; antioxidants — reasonable when other options unavailable; microsurgical subinguinal varicocelectomy — standard treatment for patient with varicocele and low sperm count; indications include hypogonadism, low T, testicular atrophy or pain, azoospermia, oligospermia, and low sperm motility

Readings

Chehab M et al: On-label and off-label drugs used in the treatment of male infertility. Fertil Steril 2015 Mar;103(3):595-604; Clark JY: Empiric medical and nutritional therapy for idiopathic male infertility: how good is the evidence for what works and does not? Eur Urol 2019 Jan 30 [Epub ahead of print]; Duca Y et al: Current and emerging medical therapeutic agents for idiopathic male infertility. Expert Opin Pharmacother 2018 Nov 8:1-13. Erratum in: Expert Opin Pharmacother 2018 Dec 18:1; Gudeloglu A et al: Medical management of male infertility in the absence of a specific etiology. Semin Reprod Med 2014 Jul;32(4):313-8; Shoshany O et al: Outcomes of anastrozole in oligozoospermic hypoandrogenic subfertile men. Fertil Steril 2017 Mar;107(3):589-94; Wheeler KM et al: Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2018 Dec 3 [Epub ahead of print]; Zavattaro M et al: Treating varicocele in 2018: current knowledge and treatment options. J Endocrinol Invest 2018 Dec;41(12):1365-75. Wheeler KM et al: Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2018 Dec 3 [Epub ahead of print]

Disclosures

For this program, members of the faculty and planning committees reported nothing to disclose.In his lecture, Dr. Parekattil presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Parekattil was recorded at the 70th Annual Meeting of the Florida Urological Society, presented by the Florida Urological Society, and held August 31-September 2, 2018, in Wesley Chapel, FL. For more information about upcoming CME meetings presented by the Florida Urological Society, please visit flaurological.org. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

UR420801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.