Merapur

Treatment of female and male infertility in the following groups of patients:

- Anovulatory women: Merapur can be used to stimulate follicle development in amenorrhoeic patients. Clomiphene (or a similar ovulation inducing agent which influences steroid feed-back mechanisms) is the preferred treatment for women with a variety of menstrual cycle disturbances, including luteal phase insufficiency with anovulatory cycles and with normal prolactin, and also amenorrhoeic patients with evidence of endogenous oestrogen production but normal prolactin and normal gonadotrophin levels. Non-responders may then be selected for menotrophin therapy.

- Women undergoing superovulation within a medically assisted fertilisation programme: Merapur can be used to induce multiple follicular development in patients undergoing an assisted conception technique such as in-vitro fertilisation (IVF).

- Hypogonadotrophic hypogonadism in men: Merapur may be given in combination with human chorionic gonadotrophin (e.g. Choragon) for the stimulation of spermatogenesis. Patients with primary testicular failure are usually unresponsive.

Anovulatory infertility:

Menotrophin is administered to induce follicular maturation and is followed by treatment with chorionic gonadotrophin to stimulate ovulation and corpus luteum formation.

The dosage and schedule of treatment must be determined according to the needs of each patient. Response is monitored by studying the patient's urinary oestrogen excretion or by ultrasound visualisation of follicles. Menotrophin may be given daily by either intramuscular or subcutaneous injection to provide a dose of 75 to 150 units of FSH and 75 to 150 units of LH, and gradually adjusted if necessary until an adequate response is achieved, followed after 1 or 2 days by chorionic gonadotrophin. In menstruating patients, treatment should be started within the first 7 days of the menstrual cycle. The treatment course should be abandoned if no response is seen in 3 weeks. This treatment cycle may be repeated at least twice more if necessary. Alternatively, three equal doses of menotrophin, each providing 225 to 375 units of FSH with 225 to 375 units of LH, may be given on alternate days followed by chorionic gonadotrophin one week after the first dose.

In the daily therapy schedule, the dose is gradually increased until oestrogen levels start to rise. The effective dose is then maintained until adequate pre-ovulatory oestrogen levels are reached. If oestrogen levels rise too rapidly, the dose should be decreased.

As a measure of follicle maturity the following values can be taken:

- total urinary oestrogen: 75 - 150 micrograms (270 - 540 nmol)/24 hours

- plasma 17 beta-oestradiol: 400 - 800 picograms/ml (1500 - 3000 pmol/L).

When adequate pre-ovulatory oestrogen levels have been reached, administration of Merapur is stopped, and ovulation may then be induced by administering human chorionic gonadotrophin at a dose of 5000 - 10000 IU.

Women undergoing superovulation in IVF or other assisted conception techniques:

In in-vitro fertilisation procedures or other assisted conception techniques menotrophin is used in conjunction with chorionic gonadotrophin and sometimes also clomiphene citrate or a gonadorelin agonist. Stimulation of follicular growth is produced by menotrophin in a dose providing 75 to 300 units of FSH with 75 to 300 units of LH daily. Treatment with menotrophin, either alone or in conjunction with clomiphene or a gonadorelin agonist, is continued until an adequate response is obtained and the final injection of menotrophin is followed 1 or 2 days later with up to 10000 units of chorionic gonadotrophin.

Maturation of follicles is monitored by measurement of oestrogen levels, ultrasound and/or clinical evaluation of oestrogen activity. It is recommended there should be at least 3 follicles greater than 17mm in diameter with 17 beta-oestradiol levels of at least 3500 pmol/L (920 picograms/ml). Egg maturation occurs by administration of human chorionic gonadotrophin in a dose of 5000-10000 IU, 30 - 40 hours after the last Merapur injection. Human chorionic gonadotrophin should not be administered if these criteria have not been met. Egg retrieval is carried out 32 - 36 hours after the human chorionic gonadotrophin injection.

Male infertility:

Spermatogenesis is stimulated with chorionic gonadotrophin (1000 - 2000 IU two to three times a week) and then menotrophin is given in a dose of 75 or 150 units of FSH with 75 or 150 units of LH two or three times weekly. Treatment should be continued for at least 3 or 4 months.

Children:

Not recommended for use in children.

Elderly:

Not recommended for use in the elderly.

Method of Administration:

By intramuscular or subcutaneous use.

Men and Women

Merapur is contraindicated in men and women with:

- Tumours of the pituitary or hypothalamic glands

- Hypersensitivity to the active substance or any of the excipients used in the formulation

Men

- Tumours in the testes

- Prostate carcinoma

Women

- Ovarian, uterine or mammary carcinoma

- Pregnancy and lactation

- Gynaecological haemorrhage of unknown aetiology

- Ovarian cysts or enlarged ovaries not due to polycystic ovarian disease.

In the following situations treatment outcome is unlikely to be favourable, and therefore Merapur should not be administered:

- Primary ovarian failure

- Malformation of sexual organs incompatible with pregnancy

- Fibroid tumours of the uterus incompatible with pregnancy

- Structural abnormalities in which a satisfactory outcome cannot be expected, for example, tubal occlusion (unless superovulation is to be induced for IVF), ovarian dysgenesis, absent uterus or premature menopause.