What is the recommended dosing for Clomid (clomiphene citrate) for infertility treatment?

Clomiphene Citrate Dosing for Female Infertility

Start with 50 mg daily for 5 days beginning on cycle day 5, and increase to 100 mg daily for 5 days only if ovulation does not occur after the first cycle. 1

Initial Dosing Protocol

• Begin with 50 mg daily for 5 consecutive days, starting on or about the 5th day of the menstrual cycle (whether spontaneous or progestin-induced bleeding). 1
• Time intercourse to coincide with expected ovulation, which typically occurs 5-10 days after completing the clomiphene course. 1
• If the patient has had no recent uterine bleeding, therapy may be started at any time after pregnancy is excluded. 1

Dose Escalation Strategy

• If ovulation does not occur after the first 50 mg cycle, increase to 100 mg daily for 5 days (given as two 50 mg tablets as a single daily dose). 1
• This second course may be started as early as 30 days after the previous cycle, after confirming the patient is not pregnant. 1
• Do not exceed 100 mg daily for 5 days—increasing the dosage or duration beyond this is not recommended by the FDA. 1
• When ovulation occurs at 50 mg, there is no advantage to increasing the dose in subsequent cycles. 1

Treatment Duration and Stopping Rules

• Discontinue clomiphene after 3 ovulatory cycles without pregnancy—further treatment is not recommended if conception has not occurred despite three documented ovulations. 1
• Discontinue after 3 cycles if ovulation has not occurred—if the patient fails to ovulate after three treatment courses, reevaluate rather than continuing clomiphene. 1
• Long-term cyclic therapy should not exceed approximately 6 total cycles. 1

Special Populations and Considerations

Polycystic Ovary Syndrome (PCOS)

• Use particularly low doses (50 mg) or shorter treatment duration in PCOS patients due to increased sensitivity to pituitary gonadotropins and higher risk of ovarian hyperstimulation syndrome. 1
• Alternative stair-step protocols (50 mg, 100 mg, 150 mg) have been studied, though standard FDA dosing remains 50-100 mg. 2

Clomiphene-Resistant Patients

• For women who fail to ovulate at 150 mg for 5 days (off-label dosing), an extended 10-day course of 100 mg (days 3-12) may induce ovulation in approximately 47% of resistant cases, though this exceeds FDA-approved dosing. 3
• The FDA label explicitly states that doses beyond 100 mg/day for 5 days are not recommended. 1

Monitoring and Safety

• Evaluate the patient carefully between each cycle to exclude pregnancy, ovarian enlargement, or ovarian cyst formation. 1
• Use appropriate ovulation detection methods (basal body temperature, progesterone levels, or ultrasound monitoring). 1
• Cancel the cycle if more than 2 dominant follicles >15 mm or more than 5 follicles >10 mm are present to prevent high-order multiple gestations. 4

Alternative Agents

• Clomiphene citrate (100 mg per day for 5 days) is an acceptable alternative to low-dose gonadotropins with lower multiple pregnancy rates and costs, though it yields lower live birth rates than gonadotropins. 4
• For intrauterine insemulation (IUI) with ovarian stimulation, gonadotropin doses of 75 IU or lower are preferred over higher doses due to similar pregnancy rates but lower multiple pregnancy risk. 4

Common Pitfalls to Avoid

• Do not continue beyond 6 cycles total—prolonged use is not recommended and unlikely to provide additional benefit. 1
• Do not use clomiphene in patients with liver disease, especially decompensated cirrhosis, due to potential hepatotoxicity. 5
• Do not increase doses beyond 100 mg daily for 5 days as per FDA recommendations, despite some research suggesting higher doses may work in resistant cases. 1, 3
• Ensure adequate endogenous estrogen levels before initiating therapy in women with functional hypothalamic amenorrhea. 5