What is the recommended dosage and treatment plan for Clomid (clomiphene citrate) for infertility?

Clomiphene Citrate (Clomid) for Infertility Treatment

Recommended Dosage and Treatment Protocol

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

Initial Treatment Approach

• Begin therapy with 50 mg daily (one tablet) for 5 consecutive days 1
• If progestin-induced bleeding is planned or spontaneous uterine bleeding occurs, start the regimen on approximately day 5 of the cycle 1
• In patients without recent uterine bleeding, therapy may be started at any time after pregnancy is excluded 1
• Time intercourse to coincide with expected ovulation, which typically occurs 5-10 days after completing the clomiphene course 1

Dose Escalation Strategy

• If ovulation does not occur after the first 50 mg course, increase to 100 mg daily (two 50 mg tablets as a single daily dose) for 5 days 1
• This second course may be started as early as 30 days after the previous one, after excluding pregnancy 1
• Increasing the dosage or duration beyond 100 mg/day for 5 days is not recommended 1
• The majority of patients who will ovulate do so after the first course of therapy 1

Treatment Duration and Stopping Rules

• 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 treatment is not recommended 1
• Long-term cyclic therapy should not exceed approximately six total cycles (including three ovulatory cycles) 1

Patient Selection Criteria

Appropriate Candidates

• Women with polycystic ovary syndrome (PCOS) 1
• Amenorrhea-galactorrhea syndrome 1
• Psychogenic amenorrhea 1
• Post-oral-contraceptive amenorrhea 1
• Secondary amenorrhea of undetermined etiology 1
• Patients with adequate endogenous estrogen levels (demonstrated by vaginal smears, endometrial biopsy, urinary estrogen assay, or bleeding response to progesterone) 1

Mandatory Exclusions Before Treatment

• Pregnancy must be excluded 1
• No ovarian cysts should be present (except in PCOS patients) 1
• Abnormal vaginal bleeding must be evaluated to exclude neoplastic lesions 1
• Normal liver function is required 1
• Primary pituitary or ovarian failure must be ruled out 1

Special Populations and Dosing Adjustments

Patients with PCOS or Suspected Gonadotropin Sensitivity

• Use particularly low dosages (50 mg or less) to minimize risk of ovarian hyperstimulation syndrome 1
• In highly sensitive patients, doses as low as 12.5 mg daily for 5 days have successfully induced ovulation 2
• For IUI with ovarian stimulation, 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 at a lower live birth rate 3

Monitoring for Multiple Pregnancy Prevention

• Withhold IUI when more than two dominant follicles >15 mm or more than five follicles >10 mm are present at time of hCG injection or LH surge 3
• Consider aspiration of excess follicles as an alternative to cycle cancellation 3

Combination Therapy Options

Clomiphene with hCG

• For patients with hyperprolactinemic amenorrhea or those who fail to ovulate with clomiphene alone, combine clomiphene (100-200 mg/day for 5 days) with two injections of 5,000 IU hCG 4
• Give first hCG injection 8-10 days after clomiphene withdrawal, and second injection 1 week later 4
• This regimen achieved 90% ovulation rate and 57% pregnancy rate in hyperprolactinemic patients 4

Sequential Clomiphene-HMG Protocol

• For patients who fail clomiphene alone: administer clomiphene 100 mg daily for 7 days, followed by HMG (two ampules daily for 4 days, then one ampule daily for 2 days), then 10,000 IU hCG after 24-hour interval 5
• This approach reduces multiple pregnancy risk and HMG costs compared to HMG alone 5

Critical Safety Considerations

Contraindications

• Avoid in patients with liver disease, especially decompensated cirrhosis 6
• Do not use in patients with ovarian enlargement (except PCOS) 1
• Contraindicated in pregnancy 1
• Avoid in patients with visual disorders 7

Monitoring Requirements

• Perform pelvic examination before the first and each subsequent treatment course to exclude ovarian enlargement or cyst formation 1
• Evaluate carefully between each cycle to exclude pregnancy 1
• Use basal body temperature charts, plasma progesterone measurements, or other appropriate tests to confirm ovulation 1
• In patients aged ≥35 years or with endometriosis risk factors, perform endometrial biopsy before initiating therapy 1

Common Pitfalls to Avoid

• Clomiphene may impair fertility through adverse effects on cervical mucus and endometrial function despite inducing ovulation 7
• The drug can alter serum lipid profiles 6
• Ovarian hyperstimulation syndrome is a potential complication, especially with multifollicular development 6
• Exercise caution in patients with uterine fibroids due to potential for further enlargement 1
• Multiple pregnancies occur but can be minimized with appropriate monitoring and cycle cancellation protocols 3, 5

Expected Outcomes

• Approximately 70% of patients ovulate with doses up to 200 mg/day 7
• About 50% of ovulating patients conceive after three ovulatory cycles 8
• This 50% conception rate after three ovulations aligns with general population fertility rates 8