What is the protocol for prescribing ovulation induction, including medication dosage and timing of baseline and follow-up tests, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen levels, and ultrasound monitoring?

Ovulation Induction Protocol: Medication Dosing and Monitoring Schedule

First-Line Treatment: Clomiphene Citrate

Start clomiphene citrate at 50 mg daily for 5 days, beginning on cycle day 3-5 after spontaneous or progestin-induced withdrawal bleeding. 1

Baseline Testing Requirements

Before initiating ovulation induction, minimal testing is required:

• No routine hormonal testing (FSH, LH, estrogen) is mandatory before starting clomiphene citrate in healthy women 1
• Pregnancy must be excluded between each treatment cycle 1
• Baseline weight and BMI should be documented, as higher body weight predicts need for higher clomiphene doses and lower response rates 2, 3
• Free androgen index (FAI), mean ovarian volume, and cycle history (oligomenorrhea vs amenorrhea) are the strongest predictors of clomiphene response, though not required before initiating treatment 2

Timing of Medication Administration

The standard protocol is to start clomiphene citrate on cycle day 3-5 after either spontaneous menses or progestin-induced withdrawal bleeding 1. However, one study suggests that starting clomiphene citrate immediately after completing medroxyprogesterone acetate (before withdrawal bleeding) may result in more follicular growth and greater endometrial thickness 4.

Monitoring During Treatment Cycle

• Ovulation typically occurs 5-10 days after completing the 5-day clomiphene course 1
• Time intercourse to coincide with expected ovulation (approximately cycle days 12-19) 1
• Appropriate ovulation detection tests should be used, though the FDA label does not specify which tests 1
• Ultrasound monitoring is not mandatory but can be helpful for assessing follicular development and endometrial thickness 4
• Routine hormonal monitoring during the cycle is not required for standard clomiphene citrate protocols 1

Dose Escalation Protocol

If ovulation does not occur after the first cycle at 50 mg:

• Increase to 100 mg daily for 5 days in the next cycle 1
• This second course may be started as early as 30 days after the previous cycle, after excluding pregnancy 1
• Do not exceed 100 mg daily for 5 days—doses beyond this are not recommended 1

Special consideration for PCOS patients: Women with polycystic ovary syndrome may be particularly sensitive to clomiphene and are at risk for ovarian hyperstimulation, so starting with 50 mg or even lower doses (12.5-25 mg) may be appropriate 1, 5.

Treatment Duration and Stopping Rules

• If ovulation does not occur after 3 cycles (including dose escalation), discontinue clomiphene citrate and reevaluate the patient 1
• If 3 ovulatory cycles occur without pregnancy, further clomiphene treatment is not recommended 1
• Total treatment should not exceed approximately 6 cycles 1
• Approximately 50% of patients who ovulate with clomiphene will conceive after 3 ovulatory cycles 6

Post-Cycle Assessment

• If menses does not occur after an ovulatory response, reevaluate the patient (likely for pregnancy) 1
• Exclude pregnancy, ovarian enlargement, or ovarian cyst formation before starting each new treatment cycle 1

Alternative for Clomiphene Failure

For women with PCOS who fail clomiphene citrate, low-dose gonadotropin therapy is recommended over high-dose protocols to induce monofollicular development and reduce ovarian hyperstimulation risk 7. This requires more intensive monitoring with serial ultrasounds and estradiol levels, though specific day-by-day protocols vary by institution.

Common Pitfalls to Avoid

• Do not routinely order baseline FSH, LH, or estrogen levels—these are not required for healthy women starting clomiphene 1
• Do not continue clomiphene beyond 100 mg daily—higher doses are not more effective 1
• Do not skip pregnancy testing between cycles—this is essential before each new treatment cycle 1
• Do not ignore body weight—heavier patients are less likely to respond and may need earlier transition to alternative therapies 2, 3