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Robert B. McWilliams, MD
Reproductive Endocrinology
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Clomiphene Citrate, Clomid

Clomid (Clomiphene citrate (CC)) is first line therapy for inducing ovulation. Clomid functions as an anti-estrogen within the pituitary gland allowing the serum concentrations of LH and FSH to rise, and thereby stimulates follicle development within the ovary. The effects of Clomid depend on the dose used and the estrogen status of the patient. An intact hypothalamic/pituitary/ovarian axis and a positive feedback response to estradiol are required. The drug is most effective in women who produce sufficient estrogen; i.e., have a withdrawal bleed in response to a progesterone challenge (>40 pg/ml estradiol level).

Regimen for Clomid Use

1. Clomid is initiated at the dose of 50 mg daily for 5 days, and the dose is increased if ovulation does not occur. Clomiphene is given orally, starting on cycle day 3, 4, or 5 for 5 days (cycle days 3-7; 4-8; or 5-9), where day 1 is the onset of menstrual flow. When Clomiphene therapy alone does not induce ovulation, the addition of human chorionic gonadotropin (hCG), 10,000 IU, given IM on one of cycle days 14 to 18, may compensate for a defective estrogen-positive feedback mechanism for induction of the LH surge.

2. If the patient does not ovulate on one 50 mg Clomid tablet/day, the dose is modified sequentially as follows until ovulation is confirmed: Clomid 100 mg x 5 days, Clomid 100 mg x 5 days + hCG, Clomid 150 mg x 5 days, Clomid 150 mg x 5 days + hCG, then, Clomid 200 mg x 5 days + hCG. If the patient fails to ovulate at this dose of Clomid, we declare the situation a Clomid failure.

3. The successful use of Clomid requires monitoring of induced cycles. If carefully monitored cycles indicate ovulation, the patient is instructed to use the same dosage of medication in her upcoming cycle.

4. The following are used to monitor induced cycles:

  1. Baseline ultrasound (CD 2-5) to rule out residual follicles > 15 mm
  2. Follicular monitoring with ultrasound and serum E2 levels (start 4-6 days after last pill)
  3. Post-coital test 1-3 days before ovulation: is there > 5 progressive sperm/HPF?
  4. Adequacy of LH surge (start urine LH kits 3 to 4 days after last clomiphene pill)
  5. Is luteal phase adequate? Mid-luteal progesterone >10 ng/ml (7-9 days after ovulation) and endometrial biopsy "in phase" (within 2 days of biopsy date based on upcoming menses)
  6. Three to six normal cycles for a therapeutic trial

If pregnancy does not occur after six monitor-normal Clomid cycles, we recommend ultrasound studies to exclude luteinized unruptured follicle syndrome and laparoscopy to detect asymptomatic pelvic pathology.

Patients Instructions for Clomid Use

1. Day 1 is the day of onset of menses. Once menses starts, call office to schedule a baseline ultrasound (must be obtained before starting medication). If menses begins on the weekend, please call Monday morning.

2. Starting on Day 3, 4 or 5, take pill (s) a day (50 mg/pill) for 5 days.* You are expected to ovulate between 5 to 10 days after stopping the last Clomid tablet(s).

3. You should have frequent intercourse (every other day) the week before and including the suspected day of ovulation, (cycle days 9-18). If you are using an LH detection kit, you should start testing your urine 3 to 4 days after the last Clomid tablet is taken (i.e.; if taking CC CD 4-8, start LH on CD 11) and continue until ovulation is indicated (test becomes positive.) or through day 18. If there is no spontaneous surge, a 10,000 IU intramuscular injection of hCG may be given if there is a >20 mm follicle.

4. It is recommended that you schedule an ultrasound and blood test for serum estradiol between 4 and 6 days after your last pill (i.e.; if taking CC CD 4-8, schedule U/S and E2 on CD 12 to 14).

4. Around day 21-25 (approximately 7-9 days after ovulation), come in for blood test for progesterone (this gives vital information regarding your ability to ovulate).

5. In many patients, progesterone (P4) supplementation for the luteal phase (after ovulation) will be given. Normally, this P4 supplementation (either 200 b.i.d. for suppositories or 50 IM/daily) begins within 3 days of ovulation. Pregnancy testing will then be checked if no menses begins by 14 to 16 days after ovulation.

* Clomid is supplied as 50 mg. tablets. The starting dose should be 50 mg. daily for 5 days, increasing to 100,150 or even 200 mg if ovulation does not occur. Some patients will require increased amounts of clomiphene and/or addition of other medications to clomiphene to induce regular ovulations.

Injection of human chorionic gonadotropin (hCG), given usually 7 to 9 days after the last clomiphene tablet, ensures follicular rupture and has the advantage that intercourse can be timed accurately. Ovulation normally occurs 24-36 hours after a 10,000 IU intramuscular injection of hCG is given. hCG is given based on use of ultrasound to assess follicular growth.

*The information provided here is for educational purposes only and does not apply to any particular patient situation. These are general dosage recommendations and do not apply to any particular patient. Clomid can produce serious side effects and must be administered only by a physician thoroughly trained in its use.