What is the recommended dosage and usage of Clomiphene (Clomid) for a female patient of reproductive age with a history of infertility or irregular menstrual cycles?

Clomiphene 50mg Usage for Ovulation Induction

Start clomiphene citrate at 50 mg daily for 5 days beginning on cycle day 5 in women with anovulatory infertility who have adequate endogenous estrogen levels, normal liver function, and no ovarian cysts. 1

Patient Selection Criteria

Before initiating clomiphene therapy, confirm the following eligibility requirements:

• Documented ovulatory dysfunction with adequate endogenous estrogen levels (confirmed by vaginal smears, endometrial biopsy, urinary estrogen assay, or bleeding response to progesterone) 1
• Normal liver function - clomiphene is contraindicated in liver disease, especially decompensated cirrhosis 2
• Absence of pregnancy and no ovarian enlargement or cysts (except in polycystic ovary syndrome) 1
• No abnormal vaginal bleeding - neoplastic lesions must be excluded 1
• BMI ≥18.5 kg/m² if functional hypothalamic amenorrhea is present 3

Critical contraindication: Clomiphene should NOT be used in functional hypothalamic amenorrhea unless sufficient endogenous estrogen is present, as it requires adequate baseline estrogen to work effectively 3, 2

Dosing Protocol

Initial Treatment Course

• Start with 50 mg daily for 5 days 1
• Begin on approximately cycle day 5 (if progestin-induced or spontaneous bleeding occurs) 1
• If no recent bleeding, may start at any time after excluding pregnancy 1
• Ovulation typically occurs 5-10 days after completing the 5-day course 1

Dose Escalation if Needed

• If no ovulation after first course: Increase to 100 mg daily for 5 days (given as two 50 mg tablets as a single daily dose) 1
• This second course may start as early as 30 days after the previous one, after excluding pregnancy 1
• Do NOT exceed 100 mg/day for 5 days - increasing dosage or duration beyond this is not recommended 1

Treatment Duration Limits

• Maximum 3 ovulatory cycles: If ovulation occurs but pregnancy does not result after 3 ovulatory responses, discontinue treatment 1
• Maximum 6 total cycles: Long-term cyclic therapy beyond approximately 6 cycles is not recommended 1
• Discontinue after 3 failed ovulation attempts: If ovulation does not occur after 3 courses, further clomiphene treatment is not recommended and the patient requires reevaluation 1

Expected Outcomes

Approximately 80% of appropriately selected women will ovulate with clomiphene treatment, and about 50% of those who ovulate will conceive. 4, 5

• High-dose clomiphene (50-250 mg/day) increases ovulation odds ratio 6.82 (95% CI 3.92-11.85) compared to placebo 5
• Pregnancy rate per treatment cycle odds ratio 3.41 (95% CI 4.23-9.48) with clomiphene versus placebo 5
• After 3 ovulatory cycles, approximately 50% of patients conceive 6

Important limitation: Clomiphene is the first-line treatment specifically for WHO Group II anovulation (normally estrogenized anovulatory women, including PCOS), NOT for unexplained infertility in ovulatory women 4, 7

Critical Safety Monitoring

Ovarian Hyperstimulation Risk

• Perform pelvic examination before each treatment cycle to detect ovarian enlargement or cyst formation 1
• Lower doses are particularly important in women with polycystic ovary syndrome due to increased sensitivity to gonadotropins 1
• Ovarian hyperstimulation syndrome is a potential complication, especially with multifollicular development 4, 2

Multiple Pregnancy Risk

• The risk of multiple pregnancy is increased with clomiphene therapy 5
• Use the lowest effective dose to minimize multifollicular development 2

Long-term Safety Concerns

• Limit to 6 total cycles maximum - use beyond 12 cycles has been associated with a three-fold increase in ovarian cancer risk 7
• Clomiphene can alter serum lipid profiles 4, 2

Common Pitfalls to Avoid

Do not use clomiphene in functional hypothalamic amenorrhea without confirmed adequate estrogen levels - many non-randomized studies do not support its use in this indication, and it cannot be recommended as first-line treatment for FHA 3. The Endocrine Society suggests possible trial only when sufficient endogenous estrogen is present (FHA recovered) 3.

Do not use clomiphene in ovulatory women with unexplained infertility - there is no evidence of clinical benefit for live birth (OR 0.79,95% CI 0.45-1.38) or clinical pregnancy in this population 7.

Time intercourse appropriately - coitus should be timed to coincide with expected ovulation 5-10 days after completing the medication course 1. Basal body temperature charting or other ovulation detection methods should be used 1.

Exclude other impediments to pregnancy before starting treatment, including thyroid disorders, adrenal disorders, hyperprolactinemia, and male factor infertility 1.