Male Infertility

Question 1

Goals of Evaluation

Answer 1

Male infertility can be due to a variety of conditions. Some of these conditions are identifiable and specifically treatable or reversible, such as ductal obstruction and hypogonadotropic hypogonadism. Other conditions are identifiable but not reversible, such as bilateral testicular atrophy secondary to viral orchitis.

• The goals are to identify:
• potentially correctable conditions,
• irreversible conditions that are amenable to assisted reproductive techniques (ART) using the sperm of the male partner,
• irreversible conditions that are not amenable to ART and for which donor insemination or adoption are possible options,
• life- or health-threatening conditions that may underlie the infertility and require medical attention, and
• genetic abnormalities that may affect the health of off-spring if ART is employed.

Question 2

When to do INITIAL screening and what is included

Answer 2

Perform initial screening evaluation if:

• pregnancy has not occurred within one year of unprotected intercourse.
• An earlier evaluation may be warranted if a known male or female infertility risk factor exists (e.g., cryptorchidism or female age >35 years) or if a man questions his fertility potential. Initial screening includes:
• a reproductive history (coital frequency and timing, duration of infertility, and prior fertility, childhood illnesses and developmental history, systemic medical illnesses, prior surgeries, sexual history including sexually transmitted infections, gonadotoxin exposure including heat exposure), and
• two semen analyses (Table 1).

Question 3

When to do FULL screening and what is involved

Answer 3

Perform full evaluation of male infertility if:

• the initial screening evaluation is abnormal,
• couples have unexplained infertility, and
• infertility persists following treatment of a female factor. Full evaluation includes:

• A medical history consisting of

• a reproductive history (see above),
• a complete medical and surgical history,
• a review of medications (prescription and non-prescription) and allergies, lifestyle exposures and systems, family reproductive history, and past infections such as sexually transmitted diseases and respiratory infections.
• A focused physical examination (including penis, testes, vasa, epididymes, varicocele, secondary sex characteristics, and digital rectal examination),
• at least two semen analyses,
• other procedures and tests as needed to narrow differential diagnosis or help with prognosis.

Question 4

Other procedures and tests to assess male fertility - endocrine eval - when and what is it

Answer 4

• Other procedures and tests for assessing male fertility Endocrine Evaluation (Table 2)

• Perform if:

• sperm count is <10 million/mL,
• sexual function is impaired,
• clinical findings suggest a specific endocrinopathy.

• The initial endocrine evaluation includes:

• serum follicle-stimulating-hormone (FSH),
• serum testosterone level; if low, repeat measurement of total and free (or bioavailable) testosterone and obtain serum luteinizing hormone (LH) and prolactin level.

Question 5

Other tests - post ejaculatory UA, TRUS, scrotal US

Answer 5

• Post-Ejaculatory Urinalysis (UA)

• Perform to diagnose possible retrograde ejaculation in patients with ejaculate volumes < 1.0 mL, except in patients with bilateral vasal agenesis or clinical signs of hypogonadism.

• Transrectal Ultrasonography (TRUS)

• Perform in:
• azoospermic patients with palpable vasa and low ejaculate volumes to identify ejaculatory duct obstruction.

• Scrotal Ultrasonography

• Perform if physical examination of the scrotum is difficult or inadequate or if a testicular mass is suspected.

Question 6

Specialized tests

Answer 6

Specialized Tests

• Sperm morphology by rigid (strict) criteria is not consistently predictive of fecundity; do not use in isolation to make prognostic or therapeutic decisions.
• DNA integrity testing (evaluation of degree of sperm DNA fragmentation): evidence to support routine use is insufficient.
• Reactive oxygen species (ROS) testing is not predictive of pregnancy independent of routine semen parameters nor are any therapies proven to correct an abnormal test result; data are insufficient to support the routine use of ROS testing.
• Specialized tests on semen (including leukocyte quantification, antisperm antibody testing, sperm viability, examination of sperm-cervical mucus interaction, zona-free hamster oocyte test/sperm penetration assay, human zona pellucid binding tests) are not required for routine diagnosis. May use individual tests in certain patients for identifying the etiology of specific semen parameter abnormalities or in cases of unexplained infertility or for selecting therapy.

Question 7

Genetic screening

Answer 7

• Genetic Screening
• Most common genetic factors related to male infertility:
• Cystic fibrosis gene mutations associated with congenital bilateral absence of the vas deferens (CBAVD).
• Sex chromosomal abnormalities (aneuploidy) resulting in impaired sperm production and often with impaired testosterone production.
• Y-chromosome microdeletions associated with isolated spermatogenic impairment.
• Inform patients with:
• Nonobstructive azoospermia or severe oligospermia that they might have chromosomal abnormalities or Y-chromosome microdeletions.
• Azoospermia due to CBAVD that they probably have an abnormality of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
• Offer:
• Genetic counseling and CFTR mutations testing for a patient with CBAVD and to the female partner before proceeding with treatments that utilize the sperm of a man with CBAVD.
• Include at minimum a Panel of common point mutations and the 5T allele; currently there is no consensus on the minimum number of mutations that should be tested.
• Imaging for renal abnormalities to men with unilateral vassal agenesis or CBAVD and no evidence of CFTR abnormalities.
• Gene sequencing may be considered in couples where the wife is a carrier and the husband with CBAVD tests negative on a routine Panel of CFTR mutations.
• Karyotyping and genetic counseling to patients with nonobstructive azoospermia and severe oligospermia (<5 million sperm/mL).
• Y-chromosome microdeletion analysis to men with non-obstructive azoospermia or severe oligospermia.
• There are insufficient data to recommend a minimal number of sequence tagged sites to test for in patients undergoing Y chromosome microdeletion analysis.
• Although the prognosis for sperm retrieval is poor in patients having large deletions involving AZF region a or b, the results of Y chromosome deletion analysis cannot absolutely predict the absence of sperm.

Question 8

Management of obstructive azoospermia - treatment options

Answer 8

• Surgery

• • microsurgical reconstruction of the reproductive tract
• • transurethral resection of the ejaculatory ducts (TURED)

• Sperm retrieval techniques and in vitrfertilization/intra-cytoplasmic sperm injection (IVF/ICSI) (Table 3)

• There is no evidence that either fertilization or pregnancy rates are different using either fresh or thawed cryopreserved sperm. Base the timing of sperm retrieval in relation toocyte retrieval on local preference and expertise.
• There is no evidence that the site or method of sperm retrieval affects outcome of IVF with ICSI for patients with obstructive azoospermia. Base the choice of sperm retrieval by either percutaneous or open surgery from either the testis or epididymis on local preferences and expertise.
• Open surgical testicular sperm retrieval with or without microscopic magnification is recommended for patients with nonobstructive azoospermia.
• The patient should be apprised of the associated risks of IVF/ICSI.

Question 9

Management of obstructive azoospermia - microsurgical reconstruction

Answer 9

• Microsurgical reconstruction is preferable to sperm retrieval with IVF/ICSI in men with prior vasectomy if the obstructive interval is less than 15 years and no female fertility risk factors are present.
• If epididymal obstruction is present, the decision to use either microsurgical reconstruction or sperm retrieval with IVF/ICSI should be individualized.
• Vasoepididymostomy should be performed by an expert in reproductive microsurgery.
• Sperm retrieval/ICSI is preferred to surgical treatment in cases
• of advanced female age,
• of female factors requiring I VF,
• if the chance for success with sperm retrieval/ICSI exceeds the chance for success with surgical treatment, or
• if sperm retrieval/ICSI is preferred by the couple for financial reasons.

Question 10

Semen analysis reference values

Answer 10

Question 11

Endocrine eval - relationship of T, LH, FSH, P w/ clinical condition

Answer 11

Question 12

Obstructive Azoosermia - sperm retrieval techniques

Answer 12

Question 13

Varicocele best practice statement

Answer 13