Diagnosis and Treatment of Infertility in Men

Publication Date: October 1, 2020
Last Updated: March 14, 2022

Guideline Statements

Assessment

1. For initial infertility evaluation, both male and female partners should undergo concurrent assessment. (Expert Opinion)
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2. Initial evaluation of the male for fertility should include a reproductive history. (Clinical Principle) Initial
evaluation of the male should also include one or more semen analyses (SAs). (Strong Recommendation; Evidence Level: Grade B)
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3. Men with one or more abnormal semen parameters or presumed male infertility should be evaluated by a male reproductive expert for complete history and physical examination as well as other directed tests when indicated. (Expert Opinion)
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4. In couples with failed ART cycles or recurrent pregnancy losses (RPL) (two or more losses), evaluation of the male should be considered. (Expert Opinion)
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Lifestyle Factors and Relationships Between Infertility and General Health

5. Clinicians should counsel infertile men or men with abnormal semen parameters of the health risks associated with abnormal sperm production. (Moderate Recommendation; Evidence Level: Grade B)
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6. Infertile men with specific, identifiable causes of male infertility should be informed of relevant, associated health conditions. (Moderate Recommendation; Evidence Level: Grade B)
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7. Clinicians should advise couples with advanced paternal age (≥40) that there is an increased risk of adverse health outcomes for their offspring. (Expert Opinion)
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8. Clinicians may discuss risk factors (i.e., lifestyle, medication usage, environmental exposures) associated with male infertility, and patients should be counseled that the current data on the majority of risk factors are limited. (Conditional Recommendation; Evidence Level: Grade C)
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Diagnosis/Assessment/Evaluation

9. The results from the SA should be used to guide management of the patient. In general, results are of greatest clinical significance when multiple abnormalities are present. (Expert Opinion)
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10. Clinicians should obtain hormonal evaluation including follicle-stimulating hormone (FSH) and testosterone for infertile men with impaired libido, erectile dysfunction, oligozoospermia or azoospermia, atrophic testes, or evidence of hormonal abnormality on physical evaluation. (Expert Opinion)
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11. Azoospermic men should be initially evaluated with semen volume, physical exam, and FSH levels to differentiate genital tract obstruction from impaired sperm production. (Expert Opinion)
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12. Karyotype and Y-chromosome microdeletion analysis should be recommended for men with primary infertility and azoospermia or severe oligozoospermia (<5 million sperm/mL) with elevated FSH or testicular atrophy or a presumed diagnosis of impaired sperm production as the cause of azoospermia. (Expert Opinion)
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13. Clinicians should recommend Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation carrier testing (including assessment of the 5T allele) in men with vasal agenesis or idiopathic obstructive azoospermia. (Expert Opinion)
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14. For men who harbor a CFTR mutation, genetic evaluation of the female partner should be recommended. (Expert Opinion)
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15. Sperm DNA fragmentation analysis is not recommended in the initial evaluation of the infertile couple. (Moderate Recommendation; Evidence Level: Grade C)
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16. Men with increased round cells on SA (>1million/mL) should be evaluated further to differentiate white blood cells (pyospermia) from germ cells. (Expert Opinion)
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17. Patients with pyospermia should be evaluated for the presence of infection. (Clinical Principle)
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18. Antisperm antibody (ASA) testing should not be done in the initial evaluation of male infertility. (Expert Opinion)
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19. For couples with RPL, men should be evaluated with karyotype (Expert Opinion) and sperm DNA fragmentation. (Moderate Recommendation; Evidence Level: Grade C)
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20. Diagnostic testicular biopsy should not routinely be performed to differentiate between obstructive azoospermia and non-obstructive azoospermia (NOA). (Expert Opinion)
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Imaging

21. Scrotal ultrasound should not be routinely performed in the initial evaluation of the infertile male. (Expert Opinion)
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22. Transrectal ultrasonography (TRUS) should not be performed as part of the initial evaluation. Clinicians should recommend TRUS in men with SA suggestive of ejaculatory duct obstruction (EDO) (i.e., acidic, azoospermic, semen volume <1.5mL, with normal serum T, palpable vas deferens). (Expert Opinion)
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23. Clinicians should not routinely perform abdominal imaging for the sole indication of an isolated small or moderate right varicocele. (Expert Opinion)
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24. Clinicians should recommend renal ultrasonography for patients with vasal agenesis to evaluate for renal abnormalities. (Expert Opinion)
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Treatment

Varicocele Repair/Varicocelectomy

25. Surgical varicocelectomy should be considered in men attempting to conceive who have palpable varicocele(s), infertility, and abnormal semen parameters, except for azoospermic men. (Moderate Recommendation; Evidence Level: Grade B)
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26. Clinicians should not recommend varicocelectomy for men with non-palpable varicoceles detected solely by imaging. (Strong Recommendation; Evidence Level: Grade C)
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27. For men with clinical varicocele and NOA, couples should be informed of the absence of definitive evidence supporting varicocele repair prior to ART. (Expert Opinion)
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Sperm Retrieval

28. For men with NOA undergoing sperm retrieval, microdissection testicular sperm extraction (TESE) should be performed. (Moderate Recommendation; Evidence Level: Grade C)
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29. In men undergoing surgical sperm retrieval, either fresh or cryopreserved sperm may be used for ICSI. (Moderate Recommendation; Evidence Level: Grade C)
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30. In men with azoospermia due to obstruction undergoing surgical sperm retrieval, sperm may be extracted from either the testis or the epididymis. (Moderate Recommendation; Evidence Level: Grade C)
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31. For men with aspermia, surgical sperm extraction or induced ejaculation (sympathomimetics, vibratory stimulation or electroejaculation) may be performed depending on the patient’s condition and clinician’s experience. (Expert Opinion)
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32. Infertility associated with retrograde ejaculation (RE) may be treated with sympathomimetics and alkalinization of urine with or without urethral catheterization, induced ejaculation, or surgical sperm retrieval. (Expert Opinion)
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Obstructive Azoospermia, Including Post-Vasectomy Infertility

33. Couples desiring conception after vasectomy should be counseled that surgical reconstruction, surgical sperm retrieval, or both reconstruction and simultaneous sperm retrieval for cryopreservation are viable options. (Moderate Recommendation; Evidence Level: Grade C)
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34. Clinicians should counsel men with vasal or epididymal obstructive azoospermia that microsurgical reconstruction may be successful in returning sperm to the ejaculate. (Expert Opinion)
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35. For infertile men with azoospermia and EDO, the clinician may consider transurethral resection of ejaculatory ducts (TURED) or surgical sperm extraction. (Expert Opinion)
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Medical & Nutraceutical Interventions for fertility

36. Male infertility may be managed with ART. (Expert Opinion)
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37. A clinician may advise an infertile couple with a low total motile sperm count on repeated SA that IUI success rates may be reduced, and treatment with ART (IVF/ICSI) may be considered. (Expert Opinion)
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38. The patient presenting with hypogonadotropic hypogonadism (HH) should be evaluated to determine the etiology of the disorder and treated based on diagnosis. (Clinical Principle)
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39. Clinicians may use aromatase inhibitors (AIs), hCG, selective estrogen receptor modulators (SERMs), or a combination thereof for infertile men with low serum testosterone. (Conditional Recommendation; Evidence Level: Grade C)
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40. For the male interested in current or future fertility, testosterone monotherapy should not be prescribed. (Clinical Principle)
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41. The infertile male with hyperprolactinemia should be evaluated for the etiology and treated accordingly. (Expert Opinion)
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42. Clinicians should inform the man with idiopathic infertility that the use of SERMs has limited benefits relative to results of ART. (Expert Opinion)
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43. Clinicians should counsel patients that the benefits of supplements (e.g., antioxidants, vitamins) are of questionable clinical utility in treating male infertility. Existing data are inadequate to provide recommendation for specific agents to use for this purpose. (Conditional Recommendation; Evidence Level: Grade B)
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44. For men with idiopathic infertility, a clinician may consider treatment using an FSH analogue with the aim of improving sperm concentration, pregnancy rate, and live birth rate. (Conditional Recommendation; Evidence Level: Grade B)
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45. Patients with NOA should be informed of the limited data supporting pharmacologic manipulation with SERMs, AIs, and gonadotropins prior to surgical intervention. (Conditional Recommendation; Evidence Level: Grade C)
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Gonadotoxic Therapies and Fertility Preservation

46. Clinicians should discuss the effects of gonadotoxic therapies and other cancer treatments on sperm production with patients prior to commencement of therapy. (Moderate Recommendation: Evidence Level: Grade C)
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47. Clinicians should inform patients undergoing chemotherapy and/or radiation therapy to avoid pregnancy for a period of at least 12 months after completion of treatment. (Expert Opinion)
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48. Clinicians should encourage men to bank sperm, preferably multiple specimens when possible, prior to commencement of gonadotoxic therapy or other cancer treatment that may affect fertility in men. (Expert Opinion)
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49. Clinicians should consider informing patients that a SA performed after gonadotoxic therapies should be done at least 12 months (and preferably 24 months) after treatment completion. (Conditional Recommendation; Evidence Level: Grade C)
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50. Clinicians should inform patients undergoing a retroperitoneal lymph node dissection (RPLND) of the risk of aspermia. (Clinical Principle)
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51. Clinicians should obtain a post-orgasmic urinalysis for men with aspermia after RPLND who are interested in fertility. (Clinical Principle)
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52. Clinicians should inform men seeking paternity who are persistently azoospermic after gonadotoxic therapies that TESE is a treatment option. (Strong Recommendation; Evidence Level: Grade B)
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Recommendation Grading

Overview

Title

Diagnosis and Treatment of Infertility in Men

Authoring Organizations

Publication Month/Year

October 1, 2020

Last Updated Month/Year

March 18, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Male, Adult

Health Care Settings

Outpatient

Intended Users

Physician, nurse, nurse practitioner, physician assistant

Scope

Diagnosis, Treatment

Diseases/Conditions (MeSH)

D007248 - Infertility, Male

Keywords

infertility, Clinical guildeline

Source Citation

Schlegel PN, Sigman M, Collura B, De Jonge CJ, Eisenberg ML, Lamb DJ, Mulhall JP, Niederberger C, Sandlow JI, Sokol RZ, Spandorfer SD, Tanrikut C, Treadwell JR, Oristaglio JT, Zini A. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I. Fertil Steril. 2021 Jan;115(1):54-61. doi: 10.1016/j.fertnstert.2020.11.015. Epub 2020 Dec 9. PMID: 33309062. AND Schlegel PN, Sigman M, Collura B, De Jonge CJ, Eisenberg ML, Lamb DJ, Mulhall JP, Niederberger C, Sandlow JI, Sokol RZ, Spandorfer SD, Tanrikut C, Treadwell JR, Oristaglio JT, Zini A. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II. J Urol. 2021 Jan;205(1):44-51. doi: 10.1097/JU.0000000000001520. Epub 2020 Dec 9. PMID: 33295258.

Methodology

Number of Source Documents
320
Literature Search Start Date
January 1, 2000
Literature Search End Date
May 1, 2019