OVULATORY DYSFUNCTION
Ovulatory dysfunction is one of the most common causes of
infertility.
Women with infrequent periods have a significantly reduced
chance for establishing a pregnancy. Ovulatory dysfunction
can be split into three categories: too much male hormone
(polycystic
ovarian disease), inadequate stimulation of the ovaries
by the brain (hypothalamic
amenorrhea), and premature
ovarian failure (premature menopause).
It has been known since the 1930s that women with infrequent
menstrual periods, infertility, and excess facial hair growth
had a difficult time getting pregnant. Frequently, these
women were overweight. This condition has been termed polycystic
ovarian disease (PCOD). Blood tests demonstrate too much
male hormone (testosterone) and luteinizing
hormone (LH). In one third of these women, the adrenal
hormone, DHEAS, is elevated as well. Women with PCOD will
have a period when given Provera
or other types of progesterone.
Pelvic ultrasound demonstrates multiple small follicles
present in both ovaries.
Over the last several years it has become clear that insulin
plays a central role in the development of PCOD. These patients
need more insulin in their bloodstream to keep their sugar
(glucose) normal. They are not diabetic. Insulin travels
through the blood stream to the ovary where it stimulates
the production of excess testosterone. Insulin also appears
to stimulate DHEAS production from the adrenal gland. Approximately
80% of PCOD women ovulate with the use of clomiphene
citrate. Yet, only half of these women will establish a
pregnancy. Some women with polycystic ovarian disease are
unable to ovulate even on high doses of clomiphene citrate.
In the past many of these women were treated with injectable
follicle
stimulating hormone (FSH) medication. Unfortunately,
the risk of twins, triplets, quadruplets and even higher
order multiple pregnancies is extremely high in this patient
group.
We have had extremely gratifying results utilizing Metformin,
an oral diabetes drug, to lower insulin levels. Remarkably,
many women who are unable to ovulate on clomiphene citrate
alone ovulate beautifully with resultant pregnancies when
Metformin is added. We like to initiate Metformin use one
month prior to adding clomiphene citrate. Metformin is continued
until pregnancy is established. Happily, multiple pregnancies
are not common using this approach. It is also far less
expensive and time consuming than using injectable FSH
therapy.
A smaller group of women are unable to ovulate because their
brain does not release FSH with subsequent ovarian stimulation.
This condition is called hypothalamic amenorrhea.These women
frequently are lean and athletic. A prior history of an
eating disorder is common. Their FSH and LH levels are almost
undetectable, and they do not have a menstrual period in
response to Provera or other forms of progesterone. Clomiphene
citrate is generally not effective in establishing ovulatory
cycles. Low dose injectable FSH therapy results in high
pregnancy rates and a modest risk of multiple gestations.
Other medical conditions can cause hypothalamic amenorrhea.
These include an overactive or underactive thyroid as well
as secretion of too much prolactin
( a hormone necessary for breast feeding). Rarely, brain
tumors can also cause hypothalamic amenorrhea.
A number of infertile women devolop a normal follicle, thicken
their endometrium,
and have appropriately rising estradiol
levels. For reasons that are still unclear, their pituitary
gland does not release an appropriate amount of LH to trigger
ovulation.
Monitoring patients with blood work for serum estradiol
and progesterone in conjunction with transvaginal ultrasonography,
can identify when a mature egg
is present. If the patient does not show signs of triggering
ovulation on her own , we will administer 10,000 IU of Human
Chorionin Gonadotropin (HCG) to cause ovulation at the appropriate
time. This has proved to be quite effective in both natural
cycles as well as clomiphene citrate cycles, in triggering
a more physiologic ovulation and in turn, establishing pregnancies.
The average age of menopause in the United Sates is fifty-two
years, and fifty years in women who smoke. Approximately
1% of women enter menopause prior to age forty. This is
termed premature ovarian failure (POF). Fortunately, POF
is an uncommon cause of ovulatory dysfunction. Several markedly
elevated FSH levels confirm this diagnosis. It is important
to screen women with POF for other hormonal problems including
abnormal thyroid function, diabetes, inadequate parathyroid
hormone production, and deficient cortisol (Addison's disease).
The use of donor
eggs is the only effective form of infertility therapy
for women with POF. Spontaneous pregnancy occurs very rarely
in women with POF.
Women with ovulatory dysfunction are worked up initially
with a thorough history and physical examination. Critical
blood tests include a pregnancy test, luteinizing hormone
(LH), follicle stimulating hormone (FSH), prolactin, thyroid
stimulating hormone (TSH), estradiol and free testosterone.
Ovulation
induction therapy is then individualized based on the
type of ovulation dysfunction present.
