Clomid

1. Indications: Fertility
   1. Stimulate Ovulation
      1. Anovulatory Bleeding (Metrorrhagia)
      2. Oligo-Ovulation
   2. Luteal Phase defect
   3. Unexplained Infertility
2. Contraindications
   1. Absolute
      1. Pregnancy
      2. Liver disease
      3. Ovarian Cysts
      4. Possible Ovarian Cancer
   2. Relative
      1. Ovarian Cyst formation
      2. Ovarian hyperstimulation
      3. Hormonal adverse effects
      4. Multiple Gestation
      5. Visual disturbances
3. History
   1. Synthesized in 1956 as possible hormonal contraceptive
   2. FDA approved for Anovulation in 1967
4. Mechanism
   1. Very similar to Tamoxifen
   2. Two stereoisomers
      1. Enclomiphene (62%): Anti-Estrogen (trans form)
      2. Zuclomiphene (38%): Estrogen agonist (cis form)
   3. Functions as anti-Estrogen at Hypothalamus
      1. Competitively inhibits Estrogen receptors
      2. Blunts negative feedback of endogenous Estrogen
      3. Allows for unabated GnRH secretion
      4. Increases pituitary sensitivity to GnRH
         1. Enhanced Luteinizing hormone (LH) release
         2. Enhanced Follicle Stimulating Hormone (FSH) release
   4. Affects Follicular and Luteal Phases
      1. Prolongs preovulatory Follicular Phase
      2. Preserves normal 14 day Luteal Phase
      3. Increases preovulatory follicles
   5. Negative effects
      1. Curtails uterine volume and endometrial lining
      2. Reduces quality and quantity of Cervical Mucus
5. Adverse Effects
   1. Common
      1. Decreased Cervical Mucus
      2. Hot Flushes
   2. Less common
      1. Pelvic Pain
      2. Nausea
      3. Mastalgia
      4. May exacerbtae premenstrual symptoms
6. Precautions
   1. Confirm no Male Infertility (normal semanalysis)
7. Efficacy
   1. Pregnancy rate 60% in 4 months of use
8. Dosing
   1. Infertility due to Ovulatory Dysfunction
      1. Assumes normal evaluation
      2. Clomid on cycle days 3 to 7
         1. Starting dose: 50 mg orally daily
         2. If Ovulation does not occur
            1. Increase Clomid dose to 100 mg PO for 5 days
            2. Maximum dose: 150 mg daily
         3. If symptoms or large ovaries on 50 mg
            1. Decrease Clomid dose to 25 mg PO for 5 days
      3. Intercourse started before Ovulation (Day 10)
         1. Intercourse every other day at mid-cycle
         2. Urine LH-timed intercourse
      4. Confirm Ovulation
      5. Consider evaluation for ovarian hyperstimulation
         1. Consider Luteal Phase pelvic exam
         2. Consider Ultrasound monitoring
      6. Limit to 6 Clomid cycles
         1. Continue lowest ovulatory Clomid dose for 3 cycles
      7. If Polycystic Ovary Disease
         1. Consider in combination with Methotrexate if PCOS is present to improve efficacy in stimulating Ovulation
            1. Lord (2003) BMJ 327: 951
         2. Consider adding 0.5 mg Dexamethasone nightly
      8. If no conception
         1. Perform hysterosalpingogram
         2. Consider Ultrasound monitoring
   2. Amenorrhea prior to Protocol
      1. Provera 10 mg PO qd for 5 days
      2. Cycle starts on first day of withdrawal bleeding
      3. Start Clomid on cycle day 3 or day 5 (see above)
9. Complications
   1. Multiple pregnancy: 7.5%
   2. Birth defects: 0.1 to 0.5% Incidence
      1. Similar rate in normal pregnancies
   3. Mild ovarian hyperstimulation: 13%