Recombinant Follicle Stimulating Hormone

• Female Infertility:
• Anovulation due to hypothalamic-pituitary dysfunction when ovulation induction with pulsatile GnRH or clomiphene citrate has failed.
• Controlled ovarian stimulation (COS) for assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
• Ovulation induction in patients with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate.
• Male Infertility:
• Treatment of hypogonadotropic hypogonadism (HH) in males with low or absent spermatogenesis to stimulate sperm production in combination with human chorionic gonadotropin (hCG).
• Off-label Uses:
• Adjunct in fertility preservation protocols.
• Combination therapy with GnRH analogs for follicular development in ART cycles.

• Adults (Female):
• Ovulation Induction:
  Initial dose typically 75 IU daily subcutaneously, adjusted based on ovarian response; dose may be increased in increments of 37.5–75 IU every 7 days. Treatment continues until adequate follicular development (usually 8–14 days).
• Controlled Ovarian Stimulation (COS):
  Starting dose ranges from 150–225 IU daily subcutaneously, adjusted per ovarian response, monitored via ultrasound and serum estradiol levels.
• Duration: Generally 7–14 days, depending on follicular response.
• Adults (Male):
• Dose varies but typically 75–150 IU subcutaneously or intramuscularly three times per week in combination with hCG for spermatogenesis.
• Duration: Several months (commonly 3–6 months) until sperm detected.
• Pediatrics:
  Not established.
• Elderly:
  Not applicable.
• Special Populations:
• No dose adjustments specifically recommended for renal or hepatic impairment.
• Careful monitoring advised.
• Administration:
• Administered via subcutaneous injection.
• Prefilled syringes or injection pens are common.
• Injection sites should be rotated to reduce local reactions.

Recombinant follicle stimulating hormone (rFSH) is a glycoprotein hormone that acts on the granulosa cells of ovarian follicles by binding to the follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor. This binding activates adenylate cyclase, increasing cyclic AMP production and triggering the synthesis of enzymes and factors essential for follicular growth, maturation, and estrogen production. In males, rFSH stimulates Sertoli cells in the testes, supporting spermatogenesis. Through this receptor-mediated mechanism, rFSH promotes follicular development in females and spermatogenic support in males, leading to improved fertility outcomes.

• Absorption:
  After subcutaneous administration, rFSH is absorbed with peak serum concentrations typically reached within 24–48 hours.
• Distribution:
  Distributed primarily to extracellular fluids; does not extensively bind plasma proteins.
• Metabolism:
  Degraded by proteolytic enzymes in the bloodstream and tissues; no involvement of CYP450 enzymes.
• Elimination:
  Primarily via renal clearance of inactive fragments.
• Half-life:
  Approximately 24–36 hours following subcutaneous injection.

• Pregnancy:
  Category X — rFSH is used as a fertility agent to induce ovulation and is not administered during pregnancy. Pregnancy should be confirmed before initiation of therapy.
• Lactation:
  Safety during breastfeeding has not been established. Due to its protein nature and rapid degradation, systemic absorption by the infant is unlikely, but caution is advised.

• Hormonal agent; gonadotropin; recombinant gonadotropin.

• Known hypersensitivity to rFSH or any excipients.
• Primary ovarian failure.
• Uncontrolled thyroid or adrenal dysfunction.
• Tumors of the hypothalamus or pituitary gland.
• Sex hormone-dependent tumors (ovarian, breast, or uterine carcinoma).
• Pregnancy or confirmed pregnancy.
• Presence of ovarian cysts or enlargement unrelated to polycystic ovary syndrome.
• Abnormal uterine bleeding of unknown origin.

• Ovarian Hyperstimulation Syndrome (OHSS):
  Risk increases with high doses or prolonged use. Monitor patients closely with ultrasound and estradiol levels. Discontinue if severe OHSS symptoms develop.
• Multiple Pregnancy:
  Increased risk due to multiple follicular development; counsel patients accordingly.
• Thromboembolism:
  Rare but reported; observe patients with history of thromboembolic disorders.
• Hypersensitivity Reactions:
  Rare anaphylactic or allergic reactions have been reported.
• Monitoring:
  Requires frequent monitoring of ovarian response by ultrasound and serum hormone levels to minimize risks.

• Common:
  Injection site reactions (pain, redness, swelling), headache, abdominal discomfort, nausea.
• Less Common:
  Ovarian hyperstimulation syndrome, pelvic pain, ovarian cyst formation.
• Rare/Serious:
  Thromboembolic events, severe allergic reactions, visual disturbances.
• Side effects generally correlate with dose and duration of therapy.

• No significant direct drug interactions reported.
• Concomitant use with GnRH analogs or hCG is common in fertility protocols; dosing should be coordinated.
• No known interactions with food or alcohol.

• Guidelines from ASRM and ESHRE endorse the use of rFSH for controlled ovarian stimulation in IVF and ovulation induction protocols.
• Recent advances include use of individualized dosing algorithms based on patient age, BMI, and ovarian reserve markers to reduce OHSS risk.
• Recombinant FSH with improved delivery devices (e.g., pen injectors) has enhanced patient convenience and compliance.
• Emerging biosimilars of rFSH approved in various countries with comparable efficacy and safety.

• Store unopened vials or cartridges refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze.
• Protect from light.
• Once reconstituted (if applicable), use immediately or store per manufacturer’s instructions (usually not exceeding 24 hours at 2°C to 8°C).
• Avoid shaking the product to prevent denaturation.