Gonadotrophin therapy for male infertility

Gonadotrophin therapy is used by specialists in males with hypogonadotrophic hypogonadism to induce spermatogenesis and fertility. Before starting gonadotrophin treatment, investigate for and manage modifiable causes of hypogonadotrophic hypogonadism, including:

• pituitary tumours
• hyperprolactinaemia
• syndromes associated with iron overload (eg haemochromatosis, thalassaemia)
• use of exogenous testosterone or selective androgen receptor modulators (SARMs), which suppress pituitary function via negative feedback.

Permanent causes of hypogonadotrophic hypogonadism include congenital conditions such as Kallmann syndrome¹.

Testosterone replacement is sometimes used to treat male androgen deficiency in individuals with hypogonadotrophic hypogonadism. However, as testosterone replacement supresses spermatogenesis, it should be deferred until after fertility treatment.

Treatment with human chorionic gonadotrophin (hCG) alone may improve sperm count in males who have been through spontaneous puberty; however, some males need follicle stimulating hormone (FSH) added after a trial of hCG alone. Predictors of success include an initial testis size of more than 4 mL (measured using an orchidometer) and previous treatment with gonadotrophins.

Before starting gonadotrophins in a male, the partner may be assessed for conditions that could affect treatment success (eg anovulation, tubal obstruction).

Gonadotrophin therapy begins with hCG alone for up to 6 months. A suitable regimen is:

Response to hCG treatment is monitored by:

• trough serum testosterone concentration immediately before an injection, 3 months after starting therapy
• clinical evaluation of sexual function (eg changes in libido, erectile function) and general health
• semen analysis.

If hCG alone does not adequately improve sperm count after an adequate trial (usually 6 months), FSH is added. This is required in many gonadotrophin-deficient infertile males. A suitable regimen is:

Treatment with FSH is monitored by semen analysis every 3 months.

If the individual has not gone through spontaneous puberty, normal testis size (more than 15 mL) and normal sperm output are rarely achieved with gonadotrophin therapy. However, pregnancy may be achievable when the sperm count is still low. When the sperm count reaches a measurable concentration, the option of freezing semen for future use should be offered. Even when this sperm concentration is not achieved, gonadotrophin therapy may allow sufficient sperm to be collected (from semen or a testicular biopsy) for intracytoplasmic sperm injection (ICSI).