What is the recommended dosing of Clomid (clomiphene citrate) for a female patient of reproductive age with polycystic ovary syndrome (PCOS), ovulatory dysfunction, or unexplained infertility?

Clomid Dosing for Fertility Treatment

Start clomiphene citrate at 50 mg daily for 5 days (cycle days 3-7) as first-line ovulation induction therapy for women with PCOS, ovulatory dysfunction, or unexplained infertility, escalating to 100 mg then 150 mg in subsequent cycles only if ovulation does not occur. 1

Standard Dosing Protocol

Initial Treatment Cycle

• Begin with 50 mg daily for 5 consecutive days, starting on cycle day 5 (or days 3-7 of the menstrual cycle) 1
• If the patient has had no recent uterine bleeding, induce withdrawal bleeding with progestin first, then start clomiphene on day 5 of the induced cycle 1
• In patients with infrequent menses and confirmed non-pregnancy, treatment may be started at any time with additional contraceptive protection for 7 days 1
• No backup contraception is needed if started within the first 5 days of menstrual bleeding 1

Dose Escalation Strategy

• If ovulation does not occur after the first 50 mg cycle, increase to 100 mg daily for 5 days in the second cycle 1
• If ovulation still does not occur, increase to 150 mg daily for 5 days in the third cycle 1
• Do not increase the dose if ovulation occurs at 50 mg, even if pregnancy is not achieved—there is no advantage to higher doses once ovulation is established 1
• Doses beyond 150 mg daily or treatment duration beyond 5 days are not recommended 1

Treatment Duration Limits

• The majority of patients who will ovulate do so after the first treatment course 1
• If ovulation does not occur after three courses of therapy, discontinue clomiphene and reevaluate the patient 1
• If three ovulatory responses occur without pregnancy, further clomiphene treatment is not recommended 1
• Long-term cyclic therapy should not exceed approximately six total cycles (including three ovulatory cycles) 1

Monitoring and Timing

Ovulation Timing

• Ovulation most often occurs 5-10 days after completing a 5-day clomiphene course 1
• Time intercourse to coincide with expected ovulation 1
• Use basal body temperature charting or other ovulation detection methods to confirm ovulation 1

Cycle Spacing

• The next treatment cycle may be started as early as 30 days after the previous one, after confirming non-pregnancy 1
• If menses does not occur after an ovulatory response, reevaluate the patient before proceeding 1

Special Considerations for PCOS Patients

Lower Initial Dosing

• A low dosage or shorter duration is particularly recommended for PCOS patients due to increased sensitivity to pituitary gonadotropins and higher risk of ovarian hyperstimulation syndrome 1
• The 50 mg starting dose avoids side effects while maintaining similar efficacy to 100 mg doses 2
• PCOS patients are the most likely to achieve success with clomiphene therapy 1

Expected Outcomes

• Approximately 80% of PCOS patients ovulate with clomiphene, and 50% of those who ovulate will conceive 3, 2
• The American College of Obstetricians and Gynecologists recommends clomiphene as first-line ovulation induction for PCOS based on good and consistent scientific evidence 3

Efficacy Across Indications

PCOS and Ovulatory Dysfunction

• Clomiphene normalizes the luteal phase in stimulated patients and is effective for anovulation due to hypothalamic or pituitary dysfunction 2
• Pregnancy rates per woman reach 44% with clomiphene in PCOS patients 4

Unexplained Infertility

• Clomiphene increases pregnancy rates in unexplained subfertility with an odds ratio of 2.38 (95% CI 1.22-4.62) per patient compared to placebo 5
• The odds ratio for pregnancy per cycle is 2.5 (95% CI 1.35-4.62) 5

Common Pitfalls to Avoid

Dosing Errors

• Do not exceed 150 mg daily or extend treatment beyond 5 days per cycle—this does not improve outcomes 1
• Do not increase the dose in patients who ovulate at 50 mg, as higher doses provide no additional benefit and may impair endometrial receptivity 1
• Do not continue clomiphene beyond six total cycles due to diminishing returns and potential adverse effects 1

Patient Selection Errors

• Do not use clomiphene in patients with ovarian cysts (except PCOS), pregnancy, abnormal vaginal bleeding, or liver dysfunction 1
• Perform pelvic examination before each treatment course to exclude ovarian enlargement 1
• Ensure adequate endogenous estrogen levels before initiating therapy 1

Monitoring Failures

• Do not proceed to the next cycle without confirming non-pregnancy, as clomiphene is contraindicated in pregnancy 1
• Evaluate for endometrial biopsy in older patients before starting therapy due to increased risk of endometrial carcinoma with age 1

Alternative Considerations

When Clomiphene Fails

• Low-dose gonadotropin therapy is preferred over high-dose protocols for clomiphene-resistant PCOS patients 3
• Letrozole demonstrates superior live birth rates compared to clomiphene in some studies, though clomiphene remains guideline-recommended first-line therapy 3, 6

Adjunctive Therapy

• Metformin improves ovulation frequency and should be used as adjunct to clomiphene, not as primary fertility treatment 6
• Weight loss of even 5% improves ovulation and pregnancy rates in PCOS patients 6