Definition – inability to conceive within twelve months of regular, unprotected intercourse.
Male factor in approximately 50 % of infertile couples – solely responsible in 20 – 30 %, co-contributor in another 20 – 30 %.
Estimated 8 – 12 % of reproductive age couples affected.
30 % male infertility idiopathic – no identifiable cause found.
Evaluation for infertility recommended after 12 months of trying to conceive, or after 6 months if maternal age > 35 or complicating male factors (conditions known to potentially affect fertility).
Normal pregnancy rates – 20 – 25 % per month; or 75 % after 6 months of trying, 85 % after 12 months, 90 % after 24 months.
Female age is the most important factor when predicting chances of conception.
Causes & risk factors
Different classifications:
- Congenital vs acquired
- Primary vs secondary (never fertile, or previously fertile)
- Pre-testicular, testicular and post-testicular
| Congenital | Acquired | Risk factors (idiopathic) |
| Anorchia
Congenital absence of vas Cryptorchidism Y chromosome microdeletion Klinefelter syndrome Kallmann syndrome Endocrinopathy Congenital obstruction |
Varicocele
Testicular trauma including inguinoscrotal surgery Testicular torsion Testicular cancer Recurrent infection Post inflammatory (epididymitis, orchitis) Excessive heat Chemotherapy Systemic conditions – cirrhosis, renal failure Antisperm antibodies Erectile dysfunction Ejaculatory dysfunction (including retrograde) Vasectomy |
Smoking
Alcohol Recreational drugs Obesity Stress Advanced paternal age Environmental toxins |
Pre-testicular:
- Essentially hormonal – hypogonadotropic hypogonadism (secondary testicular failure)
- Low testosterone, low FSH/LH
- Kallmann syndrome – X-linked defect with absent LHRH production
- High prolactin – inhibits LHRH effects (prolactinoma, antipsychotics, hypothyroidism)
- Pituitary surgery or injury, radiation etc
- LHRH agonists/antagonists
- Exogenous testosterone replacement
Testicular:
- Primary testicular failure – hypergonadotropic hypogonadism
- Low testosterone, normal FSH/LH
- Varicocele – most common finding – found in 40 % of infertile men
- Chromosomal
- Klinefelter’s 47 XXY
- Y chromosomal deletions
- Primary ciliary dyskinesia
- Germ cell aplasia – “Sertoli only” syndrome (i.e. only Sertoli cells in wall of tubules, no spermatogenesis)
- Toxins – drugs, chemotherapy, radiotherapy, heat
- Previous infections or inflammation
- Cryptorchidism
- Atrophy from any cause (infections, surgery, torsion)
- Antisperm antibodies
Post-testicular
- Congenital absence of vas deferens
- Cystic fibrosis / CFTR gene
- Ejaculatory duct obstruction
- Ejaculatory duct cysts
- Vasectomy (including iatrogenic)
- Retrograde ejaculation / ejaculatory dysfunction
- Inadequate semen deposition – penile abnormalities, spermicidal lubricants, failure of timing or technique
- Young’s syndrome – thick epididymal secretions
Assessment of an infertile male principles:
- Concurrent assessment of the female partner
- Focussed history including family history, sexual history and medical history
- Examination
- Semen analysis (preferably two)
- Hormonal analysis
- +/- karyotyping / genetic analysis
- +/- imaging / procedures
Evaluation generally takes place after 12 months of attempting pregnancy, but can take place earlier if risk factors or specific patient concerns.
History
- Confirm sexual practices, time attempting to conceive, previous fertility
- Partner factors
- Testis cancer or any cancers with chemo or radiation
- Medical history – diabetes, renal failure, neurological conditions, cancers, family history
- TICS – toxins, infections & inflammation, childhood history, sexual history
- Toxins
- Illicit drugs, alcohol, smoking, steroids
- Prescribed drugs – opioids, steroids, LHRH anologues
- Chemo, radiation
- Thermal toxicity
- Infection & Inflammation
- STIs
- Epididymitis
- Prostatitis
- Mumps orchitis
- Childhood issues
- Inguinoscrotal surgery – hernia, hydrocele, orchidopexy
- Torsion
- Cryptorchidism
- Timing of puberty
- Sexual history
- Timing and methods of determining ovulation
- Lubricants (often impair sperm motility)
- Erectile and ejaculatory dysfunction, libido
Examination
- Secondary sexual characteristics, gynaecomastia, voice,
- BMI (height, obesity)
- Scrotum – varicocele, size (orchidometer), symmetry, masses, scars, scrotal location, epididymis (engorgement, obstruction)
- < 4.6 cm or < 20 mL associated with spermatogenic impairment
- Cord and vas deferens, varicocele
- Penis – curvature, hypospadias
- Prostate if indicated
Investigations
Semen analysis as above.
Imaging
- USS scrotum – if wanting to confirm varicocele, cannot assess testis volume for whatever reason, concerns re: mass. Not used to confirm presence or absence of vas.
- USS renal – if single absent vas, may be associated with Wolffian duct abnormalities and absent kidney (esp if CFTR -ve).
- TRUS or MRI – to delineate anatomy including ejaculatory duct obstruction/cysts.
Hormones
LH, FSH, testosterone (early mane), prolactin.
Low testosterone common in subfertile men. Then check LH will differentiate central cause (low LH) or Leydig cell issue (high LH)
FSH combined with testis volume predicts obstructive vs spermatogenic dysfunction:
-
- Low FSH < 7.6 IU/L and normal testis > 4.6 cm = obstructive
- High FSH > 7.6 IU/L and small testis < 4.6 cm = spermatogenic dysfunction
- Hypogonadotropic hypogonadism – low LH/FSH, low T -> pre-testicular/Kallmann
- Hypergonadotropic hypogonadism – high LH/FSH, low/normal T -> testicular failure
- Impaired spermatogenesis – high FSH, small testis volume (?Y chromosome microdeletion)
- Hyperprolactinaemia – high prolactin, low T, high/low LH/FSH (consider MRI pituitary)
- Obstructive – normal hormonal profile and size, lower ejaculate volume
Genetics
- Indicated for non obstructive azoospermia and severe oligospermia
- Karyotyping – Klinefelter 47 XXY most commonly found abnormality
- Y chromosome microdeletions – present in 10 % azoospermia, 3-5 % severe oligospermia
- CFTR gene – if absence of vasa
Vasography largely historical or done during reconstructive procedures.
Specialised tests:
- Sperm DNA fragmentation analysis – recommended by EAU for couples with recurrent pregnancy loss or men with unexplained infertility
- Semen fructose – low or absent fructose (and low pH) suggests obstruction