Gonadotrophins (HCG, FSH, LH)

This includes:¹

• Chorionic gonadotrophin or Choriogonadotropin alfa (both forms of Human Chorionic Gonadotrophin)²
• Follitropin alfa and beta (a recombinant form of Follicle Stimulating Hormone)^3,4
• Human menopausal gonadotrophins (a combination of follicle stimulating hormone and luteinising hormone)
• Lutropin alfa (a recombinant form of luteinising hormone)⁵

The first three are used in women with infertility due to proven hypopituitarism or infertility that does not respond to clomifene. They can also be used in superovulation during assisted conception.¹ All four of the members have no use in primary gonadal failure but may occasionally be used in hypogonadotrophic hypogonadism and associated oligospermia.¹

Human chorionic gonadotropin (hCG) is a glycopeptide that maintains the corpus luteum at ovulation if the pregnancy is viable. If there are mature ovarian follicles these can be stimulated to ovulation by hCG. In this sense the actions of hCG are similar to leutinising hormone.

In practice there are two forms of hCG: chorionic gonadotropin and choriogonadotropin alfa. The former is obtained from urine and the latter is a recombinant version of hCG.

Indications

• Chorionic gonadotropin is usually used to assist conception once clomifene alone has not worked.
• Used to aid fertility in anovulatory fertility patients who are undergoing ovulation induction.⁶
• In women undergoing assisted reproduction e.g. IVF - patients have hCG injection and then ova are harvested 36 hours later.
• In men chorionic gonadotropin enhances development of secondary sexual characteristics and spermatogenesis. Therefore, it is used in hypogonadotropic hypogonadism i.e. secondary hypogonadism to induce spermatogenesis and occasionally in cryptorchidism.
• In delayed male puberty therapeutic hCG stimulates endogenous testosterone production from leydig cells.

Cautions and contraindications

Adverse effects

Administration

Chorionic gonadotrophin can be administered as either subcutaneous or intramuscular injections and choriogonadotropin alfa only subcutaneously. They have to be given in pulses at precise intervals.

Follitropin alfa is a recombinant form of follicle stimulating hormone (FSH) and its main action is to develop ova from the ovaries.

Indications

• Women who are having difficulty in conceiving in whom the main problem lies in ovulation.
• Used in polycystic ovarian syndrome (PCOS) once clomifene and metformin have failed - this group of women tend to have excessive leutinising hormone and lack FSH.
• May be used with therapeutic hCG in women about to undergo assisted reproduction e.g. IVF.
• In men follitropin alfa will increase the number of sperm produced - they are usually pre-treated with therapeutic hCG to enhance testosterone levels which then continues until FSH therapy stops.
• Some patients will be given gonadotrophin-releasing hormone before therapeutic FSH so that the release of endogenous FSH from the pituitary is shut down. This allows accurate dosing of FSH.
• Follitropin alfa has no role in patients with primary ovarian or testicular failure.

Cautions and contraindications

Before use rule out infertility secondary to adrenal or thyroid disease and hyperprolactinaemia.

• Ovarian cysts (unless caused by PCOS)
• Malignancy involving hypothalamus, pituitary, breast, ovaries, uterus, testes or prostate
• Vaginal bleeding of unknown cause
• Pregnancy and breast feeding

Adverse effects

• Common - headache, abdominal pain (stop injections and seek advice), nausea and vomiting, ovarian hyperstimulation, injection site reactions, weight gain, acne and gynaecomastia in men.
• Less common - joint pain, fever, flu-like illness.
• Rarely - systemic allergic reactions, thromboembolism, worsening of asthma, ovarian torsion, multiple pregnancy and miscarriage.

Administration

These are usually self-administered as a subcutaneous injection (can be intramuscular). Injection sites should be rotated.

Lutropin alfa is a recombinant form of luteinising hormone. It helps patients to conceive.

Indications

Lutropin alfa is used in women who are unable to conceive and lack leutinising hormone e.g. in hypogonadal hypogonadism. It is usually given along with follitropin alfa.

Cautions and contraindications

Before use rule out infertility secondary to adrenal or thyroid disease and hyperprolactinaemia and also the presence of tumours of the pituitary and hypothalamus.

• Ovarian enlargement or cysts (unless caused by PCOS)
• Vaginal bleeding of unknown cause
• Malignancy involving uterus or breast

Adverse effects

• Common - Nausea, vomiting, abdominal and pelvic pain, headache, somnolence, injection site reactions, ovarian hyperstimulation syndrome, ovarian cyst, breast pain
• Rare - ectopic pregnancy, thromboembolism, adnexal torsion and haemoperitoneum

Administration

It is also self-administered subcutaneously and injection sites need to be rotated.

This is a combination of follicle stimulating hormone and luteinising hormone. It was discovered in the 1970s and is extracted from the urine of menopausal women.

It encourages ovulation and is usually combined with human chorionic gonadotropin. In men human menopausal gonadotropin increases testosterone and thereby, sperm production.

The cautions, contraindications, adverse effects and administration are similar as for follitropin alfa and beta (see above).

• In terms of fertility rates between recombinant versions and those derived from urine there appears to be no real difference.^7,8
• 35% of women who become pregnant after hMG or hCG will suffer a miscarriage.
• Recombinant forms are more aesthetically pleasing and associated with less immunological reactions. Unsurprisingly, urine-based gonadotrophins are less expensive.^7,8