Male infertility

The GP’s role

Initial investigations

Reproductive history

Age of male and female partner
Previous fertility for male and female partner
Past method(s) of contraception; date ceased
Duration of attempt(s) at conceiving (e.g. regular vaginal intercourse at least twice weekly during fertile period of female cycle)

Medical history

Malignancy
Diabetes
Recent systemic illness, fever
Undescended testes
Age and progression of puberty, virilisation
Inguinal, genital or pelvic trauma (or surgery)
Genital infection (e.g. STIs, mumps)
Medication and other substance use (e.g. alcohol, tobacco, opiates, androgens)
Environmental, occupational exposures (e.g. ionising radiation, heat)
Sexual function (e.g. erectile, ejaculatory function)
General health

Physical examination

Habitus, virilisation
Scrotum (e.g. varicocele, absence of vas deferens)
Testes (e.g. size measured using orchidometer, position)
Penis (e.g. hypospadias, Peyronie’s disease)

Scrotal ultrasound is not necessary during the initial investigation of male infertility.

Laboratory investigations

Semen analysis

Semen analysis is the primary investigation used in assessment of male infertility, but it “does not reliably distinguish between fertile and infertile men”, except in the presence of confirmed azoospermia or complete sperm immotility
Men should abstain from sexual activity for between 2-7 days before sample collection
Semen analysis should be conducted in accordance with the WHO laboratory manual for the examination and processing of human semen
If initial semen analysis is abnormal, a second sample should be analysed approximately six weeks later (or longer if clinically indicated), preferably in a specialised laboratory (e.g. associated with an ART clinic)
Men with one or more abnormal semen parameters should be referred to a male reproduction specialist

Lower limits (5^th centile) of semen analysis variables for fertile men

Semen volume	1.4 ml
Sperm concentration	16 million/ml
Total sperm count per ejaculate	39 million
Total motility	42%
Progressive motility	30%
Non-progressive motility	1%
Immotile spermatozoa	20%
Vitality	54%
Normal morphology	4%

Serum analysis

Endocrine assessment should be performed for all men who:
- Have atrophic testes (e.g. volume ≤ 12 ml)
- Have sperm concentration and/or total sperm count below the lower limit of fertile men (see above)
- Have sign sand/or symptoms of androgen deficiency
Blood for endocrine assessments should be withdrawn in the morning (preferably fasting)
- The following measures are necessary for assessment of reproductive axis function in males, and should be ordered prior to referral to a fertility specialist (reference ranges vary between laboratories)
- Testosterone (T): This is the primary measure to inform management
  - Reference range: 8.6-27.9 nM (for measurements made using mass spectroscopy: immunoassays are used most commonly, and have considerable variation in reference ranges)
  - Normal T values are often present in men with abnormal semen analysis
  - A low T value with a high luteinising hormone (LH) value suggests primary androgen deficiency
  - A low T value with a low LH value suggests hypothalamic-pituitary dysfunction (e.g. secondary androgen deficiency)
- Serum hormone binding globulin (SHBG)
  - Reference range: 20-100 nM
- Luteinising hormone
  - Reference range: 1.6-8.0 IU/l
- Follicle stimulating hormone (FSH)
  - Reference range: 1.3-8.4 IU/l
  - A high FSH value suggests poor spermatogenesis
  - A normal FSH value suggests obstructive azoospermia
- Prolactin
  - Reference range: 75-410 IU/l

Management

Treatment options

Protecting and preserving fertility

Mumps vaccination, sperm cryopreservation (prior to chemotherapy, vasectomy or androgen replacement), safe sex practices, and early surgical correction of undescended testes.

Options for improving natural fertility

It may be possible to improve fertility for a minority of infertile men, including those with clinically diagnosed varicocele and abnormal semen parameters, selected cases of obstructive azoospermia, pituitary hormonal deficiency or hyperprolactinemia, genitourinary infection, erectile and psychosexual problems and through the withdrawal of drugs (especially androgenic hormones).

Assisted reproductive technology (ART)

ART options range in cost and invasiveness:

Artificial insemination with men’s sperm
Conventional IVF
Intracytoplasmic sperm injection (ICSI) for severe male factor problems. Sperm can be readily obtained by testicular needle aspiration in the setting of obstructive azoospermia. Some azoospermic men with spermatogenic failure may have sperm recovered for ICSI by microdissection testicular sperm extraction (micro-TESE)

Donor insemination

For men with complete failure of sperm production.

Specialist referral and long-term management

Warning: Never institute testosterone replacement therapy in a newly recognised androgen deficient man who is seeking fertility. The fertility issue must be addressed first as testosterone therapy has a potent contraceptive action via suppression of pituitary gonadotrophins and sperm output.

When should I refer a patient?

GPs can refer couples immediately, or after a few months during which baseline tests are performed.

Referral will depend on the associated problem

Endocrinologist (endocrine associated problems)
Urologist (undescended testes, sperm extraction, varicocele surgery)
Fertility specialist/ART clinic that offers full assessment, including examination of the male partner

Long-term management

Includes assessment for late-onset androgen deficiency, testis cancer

Fertility clinics

A list of Australian ART Clinics, accredited by the Reproductive Technology Accreditation Committee are available via the Fertility Society of Australia website.

Supporting the couple

Acknowledge both partners’ experience of infertility and encourage couple communication
Provide empathy and normalise feelings of grief and loss
Refer on to a psychologist or counsellor if the couple require further support

Clinical review

Prof Rob McLachlan AM, Medical Director, Healthy Male