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:
-
Baseline ultrasound (CD 2-5) to rule out residual follicles >
15 mm
-
Follicular monitoring with ultrasound and serum E2 levels (start
4-6 days after last pill)
- Post-coital
test 1-3 days before ovulation: is there > 5 progressive sperm/HPF?
- Adequacy
of LH surge (start urine LH kits 3 to 4 days after last clomiphene
pill)
-
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)
- 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.
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