Dr Kaylen Silverberg - How is Clomid used in infertility?
Fertility Medications: Clomid for Ovarian Stimulation
CLOMIPHENE CITRATE STIMULATION
Clomiphene citrate (which goes by the brand names
Clomid™ or
Serophene™) is
used to achieve ovulation in women who either do not
ovulate at all or do not ovulate regularly. These
women have a condition called “ovulatory
dysfunction”, which is one of the most common causes
of infertility. Clomiphene citrate is also
occasionally used in the treatment of unexplained
infertility, which is discussed elsewhere on our web
site.
A small subset of women with ovulatory dysfunction
has a condition called polycystic ovarian syndrome,
which is characterized by irregular ovulation,
elevated androgen (male hormone) levels, and
occasionally resistance to insulin as well.
Clomiphene citrate is also the treatment of choice
for these patients. Clomiphene is a complicated
molecule, as it causes both estrogenic and
anti-estrogenic actions. It is in the category of
medications called SERMs (selective estrogen
receptor modulators). These medications bind to
receptors in the hypothalamus and pituitary to
increase the production of GnRH and subsequently FSH,
which are the main hormones responsible for
follicular development. Approximately 75% of women
with ovulatory dysfunction will ovulate in response
to clomiphene therapy. A conception rate of 8-12%
per cycle has been reported, with a cumulative
chance for conception approaching 60% following six
cycles of treatment.
Clomiphene is supplied from the pharmacy in 50 mg
pills. Typically, patients begin treatment with one
pill per day for five days, starting early in the
cycle. There is no clinical benefit to increasing
the dose of medication once the dose that causes
normal ovulation has been determined. Clomiphene
treatment should be limited to six ovulatory cycles
as 95% of patients who conceive on clomiphene do so
within the first six ovulatory cycles. Complications
of clomiphene citrate can include hot flashes,
ovarian enlargement with bloating and abdominal
distention, nausea, vomiting, headache, and abnormal
uterine bleeding.
Women treated with clomiphene citrate should have a
baseline ultrasound performed early in their
menstrual cycle – typically cycle days 2-5 - to
exclude the presence of a cyst. If no cyst is
present, clomiphene treatment is given for five
days, usually cycle days 3-7 or 5-9. At Texas
Fertility Center, a repeat ultrasound is performed
approximately five to seven days after the last
clomiphene tablet in order to evaluate the patient’s
response. To accomplish this, we measure the number
and size of the developing follicles as well as the
endometrial thickness. If a large
“preovulatory” follicle is present, the woman is
instructed to begin ovulation predictor testing
using a urine LH kit. If no dominant follicle has
developed, we will typically prescribe a course of
oral progesterone to induce a withdrawal bleed. We
will then increase the clomiphene dose by 50 mg in
the subsequent cycle.
Other medications that some physicians may use for
ovulation induction include the category of
medications known as aromatase inhibitors, such as
tamoxifen and letrozole. Letrozole’s trade name is
FemaraTM and it is a medication approved by the FDA
for the treatment of breast cancer. It has not been
approved for fertility treatment, and in fact, the
company that manufactures letrozole has stated that
letrozole is “not to be used” for ovulation
induction. This statement was based on the
observation that a small group of women who received
Letrozole during pregnancy exhibited an increased
risk of birth defects in their children. Based on
this information, many fertility specialists choose
to avoid this drug in favor of medications that are
approved for ovulation induction by the FDA. The
proposed advantages of letrozole over clomiphene
include a decrease in the detrimental effects on
cervical mucous and uterine lining development
sometimes seen with clomiphene; however, studies
have failed to show an increase in the pregnancy
rates with letrozole when compared to those achieved
with clomiphene.
