Recombinant Human Follicle Stimulating Hormone

Recombinant Human Follicle Stimulating Hormone is used for: Female infertility, Assisted reproductive technologies, Ovulation Induction, Spermatogenesis induction, Polycystic Ovarian Syndrome (PCOS) In the Female: Ovulation Induction rFSH administered SC with HCG in a sequential manner, which is indicated for ovulation induction in patients who have previously received pituitary suppression. Multi-follicular Development During ART rFSH administered SC in conjunction with HCG is indicated for multiple follicular developments (controlled ovarian stimulation) during ART cycles in patients who have previously received pituitary suppression. Polycystic Ovarian Syndrome (PCOS) Used to treat Polycystic Ovarian Syndrome (PCOS) related infertility In the Male: Male infertility treatment in combination with HCG Induction of Spermatogenesis in men deficient spermatogenesis due to Hypogonadotrophic-hypogonadism.

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. Subcutaneous Ovulation Induction in Women Starting daily dose of 75 international units (IU) of rFSH is administered subcutaneously/ 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- 10,000 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. 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.

To prepare the solution, inject 1 ml water for injection into the vial of 75 IU rFSH. Do not shake, but gently swirl until the solution is clear. For patients requiring a single injection from multiple vials of rFSH up to 3 vials can be reconstituted with 1 ml water for injection. Then draw the entire contents of the first vial into a syringe and inject the contents into a second vial of lyophilized rFSH. Gently swirl the second vial, once again checking to make sure the solution is clear and free of particles. This step can be repeated with 1 additional vial for a total up to 4 vials (300 IU) of 75 IU rFSH. 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.

Tumors of the ovary, breast, uterus, pituitary or hypothalamus Pregnancy or lactation n Undiagnosed vaginal bleeding Hypersensitivity to the active substance or to any of the excipients Primary ovarian failure Fibroid tumors of the uterus incompatible with pregnancy Primary testicular failure

The presence of uncontrolled non gonodal endocrinopathies (e.g. thyroid, adrenal or pituitary disorders) should be excluded. In pregnancies occurring after induction of ovulation with gonadotrophin preparations, there is an increased risk of multiple gestations (Multiple birth). There has been no reports of hypersensitivity to Recombinant FSH, but there remains the possibility of anaphylactic responses. The first injection of Recombinant FSH should be performed under direct medical supervision. Since infertile women undergoing assisted reproduction and particularly IVF, often have tubal abnormalities the incidence of ectopic pregnancies might be increased. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important. Rates of pregnancy loss in women undergoing assisted reproduction techniques are higher than in the normal population. Unwanted ovarian hyperstimulation in the treatment of female patients, ultrasonographic assessment of follicular development, and determination of oestradiol levels should be performed prior to treatment and at regular intervals during treatment. Apart from the development of a high number of follicles, oestradiol levels may rise very rapidly, e.g. more than a daily doubling for two or three consecutive days, and possibly reaching excessively high values. The diagnosis of ovarian hyperstimulation may be confirmed by ultrasound examination. If this unwanted ovarian hyperstimulation occurs (i.e. not as part of controlled ovarian hyperstimulation in medically assisted reproduction programs), the administration of Recombinant FSH should be discontinued. In that case pregnancy should be avoided and HCG must be withheld, because it may induce in addition to multiple ovulation, the Ovarian Hyperstimulation Syndrome (OHSS). In men, semen analysis is recommended 4 to 6 months after the beginning of treatment in assessing the response.

Category: X Recombinant FSH must not be used during pregnancy and lactation

Side effects of Recombinant Human Follicle Stimulating Hormone : Recombinant FSH sometimes excites the ovaries too much. This may cause pelvic pain or breathing problems. It may also make you urinate less. In rare cases, patients with this problem have had serious lung problems, including fluid in the lungs, troublebreathing, and worsening of asthma blood clots, Severe Pelvic pain, Chest pain, or Abdominal pain, Nausea, Vomiting, Sudden weight gain, Bloating, Trouble, Breathing. Recombinant FSH may cause twins or multiple births.

Follitropin is a human follicle stimulating hormone (FSH) preparation of recombinant DNA origin, which consists of two non-covalently linked, non-identical glycoproteins designated as the alpha- and beta- subunits. The alpha- and beta- subunits have 92 and 111 amino acids. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24. Follitropin beta is produced in genetically engineered Chinese hamster cell lines (CHO). The nomenclature “beta” differentiates it from another recombinant human FSH product that was marketed earlier as follitropin alpha. Follitropin is important in the development of follicles produced by the ovaries. Given by subcutaneous injection, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. Follitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF). Numerous physio-chemical tests and bioassays indicate that follitropin beta and follitropin alpha are indistinguishable. However, a more recent study showed there is may be a slight clinical difference, with the alpha form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels. Structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (FSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural FSH. However, these small differences do not affect the bioactivity compared to natural FSH.