Menopur

/ Ferring Pharmaceuticals

Sterility in females. The dosage of hMG for the induction of follicle growth in normo- or hypogonadotropic woman varies according to the individual. The amount depends on ovarian reaction and should be checked by ultrasound examinations of the ovaries and measuring estradiol levels. If the hMG dosage is too high for the treated individual, multiple uni- and bilateral follicle growth can occur. hMG is administered intramuscularly or subcutaneously and in general, the therapy is begun with a daily dosage corresponding to 75 – 150 IU FSH. If the ovaries do not respond, the dosage can slowly be increased until a rise in estradiol secretion and follicle growth is evident. Treatment with the same dosage of hMG continues until pre-ovulatory estradiol serum level is attained. If the level rises too quickly, the dosage should be reduced. To induce ovulation, 5,000 or 10,000 IU hCG are injected IM to 2 days after the last hMG administration. Note: after a hMG dosage too high for corresponding individual has been administered, the following hCG administration can cause an unintentional hyperstimulation of the ovaries. Sterility in males. Initially, 3 x 1,000 to 3,000 hCG a week are administered until a normal testosterone serum level is reached. Then, an additional dose of hMG (3 x 75 to 150 IU FSH + 75 to 150 IU LH ) per week is administered IM for a few months.

Sterility in females with hypo or normogonadotropic ovarian insufficiency: stimulation of follicle growth. Sterility in males with hypo or normogonadotropic hypogonadism: In combination with hCG to stimulate spermatogenesis.

Hypersensitivity to gonadotrophins and lactose.
In females: pregnancy, enlargement of the ovaries or cysts that are not caused by polycystic ovarian syndrome, gynecological bleeding whose cause is unknown, tumors in the uterus, ovaries and breasts, tubal occlusion (unless super-ovulation is to be induced for IVF), ovarian dysgenesis, absent uterus or premature menopause.
In males: carcinoma of the prostate, tumors in the testes, dysfunction of the thyroid gland and cortex of the superarenal gland, hyperprolactinemia, tumors in the pituitary or in the hypothalamic glands.

hCG should not be administered to induce ovulation in females whose ovaries have unintentionally been hyperstimulated. When treating sterile women, ovarian activity should be checked (ultrasound and estrsdiol levels in serum) prior to hMG administration. During treatment, these tests should be carried out every one to two days until stimulation occurs. Ovarian reaction can also be measured using a cervix index. Close supervision is imperative during treatment. Treatment should be immediately discontinued if unintentional hyperstimulation occurs. The following conditions should be properly treated and excluded as the cause of infertility before menotrophin therapy is indicated: dysfunction of the thyroid gland and cortex of the suprarenal gland, hyperprolactinaemia, tumors in pituitary or hypothalamic glands. In the treatment of female infertility, ovarian activity should be checked (by ultrasound and plasma 17 β – oestradiol measurement) prior to Menopur administration. During treatment, these tests and urinary oestrogen measurement should be carried out at regular intervals, until stimulation occurs. Close supervision is imperative during treatment. If urinary oestrogen levels exceed 540 nmol (150 micrograms)/24 hours, or if plasma 17 β – oestradiol levels exceed 3000 pmol/L (800 picograms/ml), or if there is any steep rise in values, there is an increased risk of hyperstimulation and Menopur treatment should be immediately discontinued and hCG withheld. Ultrasound will reveal any excessive follicular development and unintentional hyperstimulation. In the event of hyperstimulation, the patient should be refrain from sexual intercourse until they are no longer at risk. If during ultrasound several mature follicles are visualized, hCG should not be given as there is a risk of multiple ovulation and the occurrence of hyperstimulation syndrome. Patients undergoing superovulation may be at increased risk of developing hyperstimulation in view of the excessive oestrogen response and multiple follicular development. Aspiration of all follicles, prior to ovulation, may reduce the incidence of hyperstimulation syndrome. The severe form of hyperstimulation syndrome may be life threatening and is characterized by large ovarian cysts which are prone to rupture, acute abdominal pain, ascites, very often hydrothorax and occasionally thromboembolic phenomena. Prior to treatment with Menopur, primary ovarian failure should be excluded by the determination of gonadotrophin levels.

Treatment with hMG can often lead to ovarian hyperstimulation. This, however, mostly becomes clinically relevant only after hCG has administered to induce ovulation. This can lead to the formation of large ovarian cysts that tend to rupture and can cause inraabdominal bleeding as well. In addition, ascites, hydrothorax, oliguria, hypotension and thromboembolic phenomena can occur. Treatment should be immediately discontinued when the first signs of hyperstimulation can be detected sonographically and physically felt such as pain and palpable enlargement in the lower abdomen. With pregnancy, these side effects can intensify, continue over a long period of time and be life-threatening. Unintentional multiple pregnancies occur more often during treatment with hMG. Occasionally, treatment with hMG is accompanied by nausea and vomiting. In single cases, hypersensitivity reactions and fever can occur during treatment with hMG. The administration of Menopur may lead to reactions at the injection site: reddening, pain, swelling and itching. In very rare cases, long term usage can lead to the formation of antibodies making treatment ineffectual.

Interaction with other medicdbines is unknown. HMG can be injected together with hCG when treating infertile males.

There is no indication for hMG to be used during pregnancy or to lactation period.

Treatment with hMG can lead to hyperstimulation of the ovaries. This, however, mostly becomes clinically relevant only after hCG has been administered to induce ovulation. No therapy is necessary when a slight hyperstimulation is present (Level I) accompanied by a slight enlargement of the ovaries (ovary size 5 – 7 cm), excessive steroid secretion and abdominal pain. The patient should be informed, however, and carefully watched. Clinical supervision and symptomatic treatment, and perhaps an intravenous volume replacement in case of high haemoglobin concentration is necessary if hyperstimulation (Level II) with ovarian cysts (ovary size 8 – 10 cm) is present, accompanied by abdominal symptoms, nausea and vomiting. Hospitalization is imperative when serious hyperstimulation (Level III) with large ovarian cysts (ovary size more than 10 cm) is present accompanied by ascites, hydrothorax, enlarged abdomen, abdominal pain, dyspnea, salt retention, hemoconcentration, increased blood viscosity and platelet aggregation with the danger of thromboembolisms.