II. Indications: Fertility

III. 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

IV. History

  1. Synthesized in 1956 as possible hormonal contraceptive
  2. FDA approved for Anovulation in 1967

V. 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

VI. 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

VII. Precautions

  1. Confirm no Male Infertility (normal semanalysis)

VIII. Efficacy

  1. Pregnancy rate 60% in 4 months of use

IX. Dosing: Infertility due to Ovulatory Dysfunction

  1. Assumes normal evaluation
  2. Clomid on cycle days 3 to 7
    1. Starting dose: 50 mg orally daily for 5 days
    2. If Ovulation does not occur
      1. Increase Clomid dose on subsequent cycles 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 orally for 5 days on subsequent cycles
  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. Metformin (Glucophage) 1500 mg daily
      1. Initial studies were promising and did increase Ovulation rates
      2. However does not increase the live birth rate
      3. Lord (2003) BMJ 327: 951 [PubMed]
      4. Sun (2013) Arch Gynecol Obstet 288(2): 423-30 [PubMed]
    2. Consider adding 0.5 mg Dexamethasone nightly
  8. If no conception
    1. See Female Infertility
    2. Infertility specialist referral if no conception after 6 cycles
    3. Consider hysterosalpingogram
    4. Consider Transvaginal Ultrasound monitoring

X. Dosing: Amenorrhea prior to Protocol

  1. Provera 10 mg orally daily for 5 days
  2. Cycle starts on first day of withdrawal bleeding
  3. Start Clomid on cycle day 3 or day 5 (see above)

XI. 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%
  4. Venous Thromboembolism
  5. Increased Ovarian Cancer risk (in patients remain nulliparous)
    1. Trabert (2013) Fertil Steril 100(6): 1660-6 [PubMed]

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Cost: Medications

clomiphene citrate (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
CLOMIPHENE CITRATE 50 MG TAB Generic $0.94 each

Ontology: Clomid (C0591268)

Definition (CHV) brand name of a fertility drug
Definition (CHV) brand name of a fertility drug
Definition (CHV) brand name of a fertility drug
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002996
English Clomide, clomid, clomid [brand name], clomide, Clomid