Recombinant Gonadotropin

Aka: Recombinant Gonadotropin, Synthetic Pituitary Gonadotropin, Recombinant Follicle Stimulating Hormone, Synthetic FSH, Recombinant Luteinizing Hormone, Synthetic LH, Menotropin, Human Menopausal Gonadotropin, Urofollitropin, Pergonal, Menopur, Follitropin Alfa, Gonal-f, Follitropin Beta, Follistim AQ

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II. Indications

  1. Ovulation Induction (Female Infertility due to Anovulation)
    1. Follitropin Alfa (FSH, Gonal-f)
    2. Follitropin Beta (FSH, Follistim AQ)
  2. Spermatogenesis induction (Male Infertility)
    1. Follitropin Alfa (FSH, Gonal-f)
    2. Follitropin Beta (FSH, Follistim AQ)

III. Mechanism

  1. Gonadotropin-Releasing Hormone (GnRH)
    1. GnRH is generated within hypothalamic Neurons (infundibular nucleus, arcuate nucleus)
    2. GnRH is released typically in pulses in men and women
      1. GnRH is also released in a surge before Ovulation
    3. GnRH binds receptors on the Pituitary Gland triggering release of gonadotropins (LH and FSH)
  2. Pituitary Gonadotropins
    1. Gonadotropins are glyoproteins secreted by Basophil cells in the anterior Pituitary Gland
    2. Gonadotropins (LH, FSH) stimulate release of sex Hormones (e.g. Estrogen, Testosterone)
      1. Luteinizing Hormone (LH)
      2. Follicle Stimulating Hormone (FSH)
    3. Stimulation (releasing factors)
      1. Hypothalamic Gonadotrophic Releasing Hormone (GnRH)
    4. Inhibition (negative feedback loop to Hypothalamus and Pituitary Gland)
      1. Testosterone (Males)
      2. Estrogen
      3. Progesterone
      4. Inhibin (from corpus luteum in women, spermatogenesis in men)
  3. Follicle Stimulating Hormone (FSH)
    1. Follicle Stimulating Hormone (FSH) effects in women
      1. Stimulates ovarian follicle growth
        1. Ovarian follicle then secretes Estradiol
      2. Functions in concert with LH which stimulates ovarian follicles to ovulate and mature into a corpus luteum
        1. Corpus luteum in turn secretes Estrogen and Progesterone
    2. Follicle Stimulating Hormone (FSH) effects in men
      1. Stimulates spermatogenesis and sperm maturation within Sertoli Cells
      2. Functions in concert with LH which stimulates Leydig Cells within Testes to produce Testosterone
  4. Luteinizing Hormone (LH)
    1. Luteinizing Hormone (LH) effects in women
      1. Stimulates ovarian follicles to ovulate and mature into a corpus luteum
      2. Corpus luteum in turn secretes Estrogen and Progesterone
      3. Functions in concert with FSH which stimulates ovarian follicle growth and Estradiol secretion
    2. Luteinizing Hormone (LH) effects in men
      1. Stimulates Leydig Cells within Testes to produce Testosterone
      2. Functions in concert with FSH which stimulates spermatogenesis and maturation within Sertoli Cells
  5. Images
    1. hypothalamusPituitaryHormones.png

IV. Medications: Recombinant Gonadotropins

  1. Follitropin Alfa (FSH, Gonal-f)
    1. Available in multidose vials and prefilled multi-dose pens: 300, 450, 900, 1050 IU Follicle Stimulating Hormone (FSH)
    2. Administered as Subcutaneous Injections in lower Abdomen
  2. Follitropin Beta (FSH, Follistim AQ)
    1. Available in with cartridge for use in pen: 300, 600, 900 IU Follicle Stimulating Hormone (FSH)
    2. Administered as Subcutaneous Injections in lower Abdomen

V. Medications: Human Gonadotropin Urine Extracts

  1. Urine extracts have largely been replaced in U.S. by Recombinant Gonadotropins (see above)
  2. Menotropin (e.g. Pergonol, Menopur, Human Menopausal Gonadotropin, Pergonal)
    1. Purified urine samples of postmenopausal women that contain high concentrations of FSH and LH
    2. Used in Female Infertility as IM Injections (for 10 days), followed by HCG to stimulate Ovulation
  3. Urofollitropin (FSH, Bravelle)
    1. Discontinued in U.S.
    2. Follicle Stimulating Hormone (FSH) extracted from purified urine of postmenopausal women
      1. Was available as powder fo injection, containing 75 IU of FSH activity
    3. Luteinizing Hormone (LH) has been removed from the Menotropin sample
    4. Administered as Subcutaneous Injections in lower Abdomen

VI. Dosing

  1. See other references for specific Infertility regimens
  2. Use is typically limited to Infertility specialists

VII. Adverse Effects

  1. Multiple Pregnancy
  2. Ectopic Pregnancy
  3. Ovarian Hyperstimulation Syndrome
  4. Hypercoagulable state
  5. Ovarian Torsion
  6. Ovarian Cysts
  7. Ovarian Enlargement
  8. Ovarian Neoplasm

VIII. Safety

  1. Avoid in Lactation
  2. Contraindicated in pregnancy
    1. Associated with congenital abnormalities when used AFTER pregnancy is established
    2. No known increased risk of congenital abnormalities when used to induce Ovulation for Infertility

IX. Resources

  1. Follitropin Alfa (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae85b9c3-e7eb-4981-a5d9-346050e8f189
  2. Follitropin Beta (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=96f11b5d-cc7b-48aa-830a-a28e1962d871
  3. Menotropin - Menopur
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22c8db95-c3db-1770-8086-31356fbabe35

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