Male Infertility

Azoospermia workup, from Campbell's

Workup

Normal male ejaculation

Timing the workup

History

Medical Causes

Surgical Causes

Medication Causes

Physical Exam

Semenalysis

Labs

Diagnosing Infertility

Diagnoses (by semenalysis finding)

Semenalysis finding Further workup Interpreting findings
Azoospermia (absent sperm) Semenalysis Low volume + acidic pH indicates obstruction
Testis size Cutoff testis axis 4.6cm determines whether obstruction present
Vas deferens Absence indicates obstruction
FSH Cutoff 7.6IU/L determines whether obstruction present
Karyotype + Y Microdeletion (if elevated FSH or testicular atrophy) Kleinfelter and Y deletions are most common causes of non-obstructive azoospermia
TRUS (if normal T and vas, obstruction suspected) Confirm ejaculatory duct obstruction
Low volume History Caused by DM, SCI, RPLND
Post-ejaculate urinalysis Confirms sperm ending up in bladder
Round cells > 1mil/mL Special stains Differentiate pyospermia from germ cells
Sperm agglutination Antisperm antibody testing ICSI may be indicated for ASA instead of IUI
Poor sperm mobility Viability testing Assess whether nonmotile sperm can be used for ICSI

Adjunct Tests

Test Indication If positive:
Post-ejaculate urinalysis Low-volume ejaculate Sperm retrieval
Karyotype Nonoobstructive azoospermia microTESE (for Kleinfelter)
Repeat pregnancy loss Sperm aneuploidy - ICSI, adoption, donor sperm
Y microdeletion Nonobstructive azoospermia Adoption (AZFa/AZFb) or ICSI (AZFc)
Transrectal US Obstructive azoospermia + low volume/pH + normal T + palpable vas TURED
CFTR gene panel Absent vas deferens Test female partner
TESE
Sperm DNA fragmentation Repeat IVF failure
Repeat pregnancy loss
TESE + ICSI
Antisperm antibody testing Concern for obstruction, azoospermia, agglutination Recommend ICSI
Do not order if already planning ICSI
Scrotal US Assess for varicocele in difficult scrotum (obese, high + tight) Discuss clinical relevance of US varicocele
Abdominal imaging Assess for malignant cause of new or nonreducible large right varicocele
Renal US Assess for renal absence if vas absent unilaterally (26-75%) or bilaterally (10%)

Diagnoses (by cause):

Infertility Grouping Diagnosis Findings Treatment
Gonadotropin Dysfunction Kallman syndrome Hypogonadotropic hypogonadism
Anosmia
HCG + FSH, GnRH pump
Incomplete hypoandrogenism Increased LH
Decreased T
Clomiphene/Tamoxifen
Anostrozole/Letrozole
Pituitary tumors Elevated prolactin
MR imaging if prolactin elevated (> 50ug/L)
Bromocriptine/Cabergoline
Transsphenoidal surgery
Exogenous suppression Specific hx steroids or other drugs Stop offening agent(s)
Testicular dysfunction Kleinfelter (XXY) azoospermia (92%) + small testes + hypergonadotropins
mosaic in 10-20%
microTESE + IVF/ICSI
Leydig cell (steroidogenic) dysfunction Elevated LH
Decreased T
microTESE + IVF/ICSI
Y Microdeletions azoospermia (AZFa/AZFb) Adoption, donor sperm
oligospermia (AZFc) microTESE + IVF/ICSI
Antisperm antibodies secondary to blood/testis barrier breakdown IVF/ICSI
Varicocele Physical exam Surgical repair
DNA Fragmentation Assess after repeat IVF failure TESE + ICSI
Transportation Dysfunction Absence of Vas Deferens Physical exam findings
History renal agenesis
TESE + IVF
Congenital Bilateral Absence of the Vas Deferens (CBAVD) CFTR mutation CFTR screen panel
TESE + IVF
Hypospadias
Epispadias
Physical exam findings Intrauterine insemination
Ejaculatory duct obstruction Azoospermia + Hypovolemia
TRUS findings
TURED
Retrograde ejaculation Azoospermia + Hypovolemia
Sperm on post-ejaculate urinalysis
Sperm retrieval (alkalinize with bicarb)
Sympathomimetic agents (25% success)
Anejaculation Neurologic history
Prior RPLND
Penile vibratory device
Electroejaculation

Azoospermia

Treatments

Medications

Class Medication Dose Indication Side effects
Gonadotropin agonist Human Chorionic Gonadotropin (HCG) 1500-5000 IU 2-3x weekly
Titrate up to 10K IU/week
Titrate to T level
Hypogonadotropic hypogonadism Nausea (12%)
Breast enlargement/tenderness (1-10%)
Headache (34%)
Injection discomfort (1-10%)
Human Menopausal Gonadotropin (HMG) 75-150 IU 2-3x weekly
Selective estrogen receptor modulator Clomiphene citrate 25mg QD or 50mg EOD
Titrate to max 100mg QD
Titrate to T level
Headache (1%)
Blurred vision (2%)
Flushing (10%)
Breast discomfort (2%)
Nausea (2%)
Aromatase inhibitor Anostrozole 1mg daily Hypergonadotropic hypogonadism (Kleinfelter syndrome) Nausea (11-19%)
Headache (9-10%)
Hot flashes (12-26%)
Chest discomfort (2-12%)
Lestrozole 2.5mg daily
Dopamine agonist Cabergoline 0.25mg 2x weekly
Titrate up to 1mg
Titrate per prolactin levels
Prolactin-secreting pituitary tumor Headache (26%)
Dizziness (15-17%)
Nausea (27-29%)
Constipation (7-10%)
a-agonist Pseudoephedrine 60mg PO QID Retrograde ejaculation restlessness
Nausea/vomiting
Weakness
Headache
Nervousness
Dizziness
Palpitations

Varicoceles

Surgical treatment

Class Procedure Indications Description Side effects
Azoospermia diagnosis Testis aspiration Confirm obstructive (vs nonobstructive) azoospermia Insert biopsy needle (thru skin or skin incision) and aspirate to assess for sperm Hematoma, hematocele, spermatocele, hydrocele
Testis biopsy Incise tunica albuginea, extrude tubules and remove, close incision Low risk bleeding
Sperm retrieval Tes(TESE) Obstructive azoospermia Obtain sperm via opening testis or epididymis and removing tubules Bleeding, postop pain
microTESE Nonobstructive azoospermia Obtain sperm via assessing and extracting microtubules
Epididymal sperm extraction Obstructive azoospermia with epididymal dilation Obtain sperm via assessing and extracting microtubules
Improve sperm delivery Vas reversal Obstructive azoospermia (after vasectomy) Obtain sperm via assessing and extracting microtubules Hematoma (0.3%), granulomas (5%), delayed failure (5%), can consider TESE instead
Transurethral resection of ejaculatory ducts (TURED) Obstructive azoospermia (ejaculatory ducts) Resect ducts to remove obstruction, can transrectally inject dye to improve identification Restenosis, pain, epididymoorchitis (chemical/infectious), retention, incontinence, hematuria
Assisted reproductive technology Intrauterine insemination (IUI) Normal sperm but unable to reach egg naturally, oligospermia (5-8mil) Inject collected/concentrated sperm into uterus (via cervix) to allow natural fertilization of egg
In vitro fertilization (IVF) Sperm unable to reach egg, oligospermia (< 5mil) Sperm placed in proximity to egg, natural fertilization, embryos placed within uterus for implantation
Intracytoplasmic sperm injection (ICSI) Sperm unable to fertilize egg, oligospermia (< 5mil) Sperm directly injected into egg, embryos placed within uterus for implantation

References