II. Indications: Fertility
- Stimulate Ovulation
- Luteal Phase defect
- Unexplained Infertility
III. Contraindications
- Absolute
- Pregnancy
- Liver disease
- Ovarian Cysts
- Possible Ovarian Cancer
- Relative
- Ovarian Cyst formation
- Ovarian Hyperstimulation
- Hormonal adverse effects
- Multiple Gestation
- Visual disturbances
IV. Mechanism
- Very similar to Tamoxifen
- History
- Synthesized in 1956 as possible hormonal contraceptive
- FDA approved for Anovulation in 1967
- Two stereoisomers
- Functions as anti-Estrogen at Hypothalamus
- Competitively inhibits Estrogen receptors
- Blunts negative feedback of endogenous Estrogen on the pituitary
- Allows for unabated GnRH secretion
- Increases pituitary sensitivity to GnRH
- Enhanced Luteinizing Hormone (LH) release
- Enhanced Follicle Stimulating Hormone (FSH) release
- Affects Follicular and Luteal Phases
- Prolongs preovulatory Follicular Phase
- Preserves normal 14 day Luteal Phase and a functional corpus luteum
- Increases preovulatory follicles
- Negative effects
- Curtails uterine volume and endometrial lining
- Reduces quality and quantity of Cervical Mucus
V. Dosing: Infertility due to Ovulatory Dysfunction
- Assumes normal evaluation
- Clomid on cycle days 3 to 7
- Starting dose: 50 mg orally daily for 5 days
- If Ovulation does not occur
- Increase Clomid dose on subsequent cycles to 100 mg PO for 5 days
- Maximum dose: 150 mg daily
- If symptoms or large ovaries on 50 mg
- Decrease Clomid dose to 25 mg orally for 5 days on subsequent cycles
- Intercourse started before Ovulation (Day 10)
- Intercourse every other day at mid-cycle
- Urine LH-timed intercourse
- Confirm Ovulation
- Consider evaluation for Ovarian Hyperstimulation
- Consider Luteal Phase pelvic exam
- Consider Ultrasound monitoring
- Limit to 6 Clomid cycles
- Continue lowest ovulatory Clomid dose for 3 cycles
- If Polycystic Ovary Disease
- Metformin (Glucophage) 1500 mg daily
- Initial studies were promising and did increase Ovulation rates
- However does not increase the live birth rate
- Lord (2003) BMJ 327: 951 [PubMed]
- Sun (2013) Arch Gynecol Obstet 288(2): 423-30 [PubMed]
- Consider adding 0.5 mg Dexamethasone nightly
- Metformin (Glucophage) 1500 mg daily
- If no conception
- See Female Infertility
- Infertility specialist referral if no conception after 6 cycles
- Consider hysterosalpingogram
- Consider Transvaginal Ultrasound monitoring
VI. Dosing: Amenorrhea prior to Protocol
- Provera 10 mg orally daily for 5 days
- Cycle starts on first day of withdrawal bleeding
- Start Clomid on cycle day 3 or day 5 (see above)
VII. Adverse Effects
- Multiple Pregnancy: 7.5%
- Birth defects: 0.1 to 0.5% Incidence
- Similar rate in normal pregnancies
- Mild Ovarian Hyperstimulation: 13%
- Venous Thromboembolism
- Increased Ovarian Cancer risk (in patients remain Nulliparous)
- Other common effects
- Decreased Cervical Mucus
- Hot Flushes
- Other less common
- Pelvic Pain
- Nausea
- Mastalgia
- May exacerbtae premenstrual symptoms
VIII. Precautions
- Confirm no Male Infertility (normal semanalysis)
IX. Efficacy
- Pregnancy rate 60% in 4 months of use
X. Resources
- Clomiphene Citrate (DailyMed)
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Related Studies
| clomiphene citrate (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| CLOMIPHENE CITRATE 50 MG TAB | Generic | $0.77 each |
| clomid (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| CLOMID 50 MG TABLET | $3.76 each | |