To prevent painful injections and minimize leakage from the injection site rFSH should be slowly administered subcutaneously. The subcutaneous injection site should be alternated to prevent lipoathrophy. Any unused solution should be discarded. Subcutaneous injection of rFSH may be carried out by patient or partner, provided that proper instructions are given by the physician. Self-administration of rFSH should only be performed by patients who are well motivated, adequately trained and with access to expert advice.
Dosage in Female: There are great inter and intra-individual variations in the response of the ovaries to exogenous gonadotrophins. This makes it impossible to set an uniform dosage scheme. The dosage should, therefore, be adjusted individually depending on the ovarian response. This requires ultrasonography and monitoring of estradiol levels. There should be consideration to minimize the risk of unwanted ovarian hyperstimulation. rFSH can be given either alone, or in combination with a GnRH analogue to prevent premature luteinisation. In the latter case, especially when using a GnRH agonist, a higher total treatment dose of rFSH may be required to achieve an adequate follicular response. Clinical experience with rFSH is based on up to three treatment cycles in both indications. Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.
Ovulation Induction in Women: Starting daily dose of 75 international units (IU) of rFSH is administered subcutaneously or subcutaneous for at least the first 7 days. The dose is increased by 25 or 75 international units (IU) at weekly intervals until follicular growth and/or serum estradiol levels indicate an adequate response. When an acceptable pre-ovulatory state is achieved, final oocyte maturation is achieved with 5000 to 10,000 international units (IU) of human chorionic gonadotropin (HCG). The woman and her partner should have intercourse daily, beginning on the day prior to the administration of HCG and until ovulation becomes apparent.
Assisted Reproductive Technology (ART): In Women, Starting dose of 150 to 300 international units (IU) of rFSH is administered subcutaneous for at least the first 4 days of treatment. Subsequent doses are adjusted based upon ovarian response as determined by ultrasound evaluation of follicular growth and serum estradiol levels. Final oocyte maturation is induced with a dose of 5000-10000 international units of HCG Oocyte (egg) retrieval is performed 34 to 36 hours later.
PCOS: rFSH injections are therefore given each morning as a subcutaneous injection. It is best to start with the lowest dose of rFSH per day (using 75 IU per day). These doses are used for 4 to 6 days at a time. The ovarian response is determined by measuring estrogen levels in the blood. When the estrogen begins to rise, the rFSH is successfully growing an egg or eggs. If there is no response to a dose of rFSH in 5-6 days of injections the dose will be increased. The normal dose increments are 75 units, 100 units, 150 units and 300 units per day. Most patients respond with 75 IU to 150 IU per day. However it is very important that increments are only made cautiously.
Dosage in Male: Induction of Spermatogenesis in Men: Pre-treatment with HCG alone (2500 international units twice weekly) is required. If serum testosterone levels have not normalized after 8 weeks of HCG treatment, the dose may be increased to 5000 international units (IU) twice a week. After normalization of serum testosterone levels, administer 300 international units (IU) per week (300 international units twice weekly or 100 international units three times weekly) of rFSH subcutaneously with the same pre-treatment HCG dose used to normalize testosterone level.
rFSH administered for 7 to 12 days produces ovarian follicular growth in women who do not have primary ovarian failure. Treatment with rFSH in most instances results only in follicular growth and maturation. When sufficient follicular maturation has occurred, HCG must be given to induce ovulation.
