CLOMIPHENE CITRATE
Clomiphene
citrate is an oral medication commonly used for ovulation
induction. Clomiphene makes the brain sense a low estrogen
level. The brain responds by increasing the amount of follicle
stimulating hormone (FSH)
released into the blood stream, with resultant ovarian follicle
recruitment and growth. Each follicle contains an egg.
Between one and three tablets of clomiphene are taken starting
on cycle day three, four, or five and continued for five
days. Ovulation typically occurs between cycle days eleven
and seventeen.
Clomiphene citrate has two uses. One is for couples with
unexplained infertility,
to empirically raise pregnancy rates. Among couples with
two years of unexplained infertility, the likelihood of
establishing a pregnancy each month is 2-3%. The empiric
use of clomiphene citrate raises that to 8-10% per month.
Among women who do not ovulate because of polycystic
ovarian disease, approximately 80% will ovulate on clomiphene
citrate. Recent studies have shown that polycystic ovarian
disease is due to excess circulating insulin levels. Some
women with polycystic ovarian disease do not ovulate on
clomiphene citrate. Their insulin levels can be reduced
with the use of an oral diabetes drug, Metformin. The combination
of clomiphene and Metformin has resulted in many pregnancies
in our practice.
We evaluate the mid-cycle of women on clomiphene citrate
with both transvaginal ultrasoound to assess follicular
growth and blood measurements of estradiol
and progesterone.
We frequently trigger ovulation with an intramuscular
injection of hCG, which mimics the LH surge. Intrauterine
inseminations are often performed in conjunction with
clomiphene citrate ovulation induction.
Infrequent side effects of clomiphene citrate include headache,
visual changes, moodiness and hot flashes. Clomiphene can
directly thin the uterine lining, resulting in diminished
uterine
receptivity. Transvaginal ultrasonography should demonstrate
an endometrial thickness of at least 7 mm at ovulation on
clomiphene citrate therapy. Should the lining be too thin,
subsequent cycles use lower clomiphene dosing. Clomiphene
can dry up cervical mucus, a common indication for intrauterine
inseminations.
Debate exists about the use of clomiphene citrate and the
subsequent development of ovarian cancer. One study showed
that more than twelve cycles of clomiphene citrate significantly
raisee the risk of ovarian cancer. That study has not been
confirmed. We treat very few patients with clomiphene citrate
for more than six cycles. Ongoing studies through the National
Institutes of Health are underway to settle this important
question. If clomiphene citrate is associated with the development
of ovarian cancer later in life, it is one of many risk
factors including infertility, ovarian dysfunction, and
a family history of ovarian cancer.
The risk of multiple pregnancies is low with clomiphene
citrate. Approximately 7-8% of pregnancies will be twins.
Although triplet and quadruplet pregnancies have been reported
on clomiphene citrate, the incidence is extremely remote.
Ovarian cysts may result from clomiphene citrate therapy.
They typically resolve within one cycle.
Couples with unexplained infertility are usually treated
with clomiphene for three or four months before consideration
is given to a laser laparoscopy followed by injectable FSH
therapy. Women who do not spontaneously ovulate because
of polycystic ovarian disease are often treated with six
to eight ovulatory cycles of clomiphene therapy.
