UNDERSTANDING INFERTILITY
DIAGNOSIS, TREATMENT AND PREGNANCY
CONSIDERATIONS FOR PATIENTS WITH POLYCYSTIC
OVARY SYNDROME
P
AUTHOR Miriam Krause, MD
COS, or polycystic ovary syndrome,
is the most common endocrine ab-
normality in young reproductive
age females, ranging up to a prev-
alence of 15%. Originally described
as “Stein-Leventhal-Syndrome” in
1935, the presentation then includ-
ed obese women with hirsutism,
amenorrhea and enlarged cystic ovaries upon surgical exploration.
By now, we know there are at least three different types of PCOS,
with diagnosis requiring a combination of clinical or laboratory ev-
idence of hyperandrogenism, oligo- or amenorrhea, and polycystic
ovaries on pelvic ultrasound (at least 12 antral follicles measuring
less than 10 mm in mean diameter on one or both ovaries, or an
ovarian volume of 10 ml or greater). The three are classic PCOS
with hyperinsulinemia, ovulatory PCOS and non-hyperandrogenic
PCOS. Different diagnostic criteria include the NIH criteria (1990),
the Rotterdam consensus criteria (2003), and the Androgen Excess
Society (2006). Using these diagnostic criteria, even thin women
with no visible hirsutism or acne can have PCOS.
Genome-wide association studies have found several genes that
may be involved in the development of PCOS: DENND-1A, THADA
and Fibrillin-3. The risk to develop PCOS is 40% if a first degree
relative has been diagnosed with the condition. Other possible
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causes include environmental factors, such as starch-based diets
or endocrine-disrupting chemicals (EDCs).
The pathophysiology of PCOS includes hypersecretion of Lu-
teinizing Hormone (LH), hyperinsulinemia, and androgen excess.
Steadily elevated LH levels do not allow for a dominant follicle to
emerge. Hyperinsulinemia leads to increased androgen production
in the ovarian theca cells, as well as to decreased SHBG (sex hormone
binding globulin) production in the liver – both result in higher free
androgen levels, which fuel increased peripheral insulin resistance
and, as a vicious circle, lead to hyperinsulinemia.
PCOS is a diagnosis of exclusion. Other conditions can present
similarly and need to be ruled out. These conditions include hypo-
thyroidism (measure TSH), hyperprolactinemia (measure prolactin
level), a testosterone-producing tumor of the ovary, a DHEAS-pro-
ducing tumor of the adrenal gland, late-onset congenital adrenal
hyperplasia (measure 17-hydroxyprogesterone), type 2 diabetes
(measure HgbA1c), primary ovarian insufficiency (measure either
Anti Mullerian Hormone level, or cycle day three FSH and estradiol),
exogenous testosterone intake (diagnosed by history), rarely Cushing
syndrome (perform 1 mg overnight dexamethasone suppression test
or 24-hour urine collection for cortisol), and acromegaly (measure
IGF-1 after 2-hour oral glucose tolerance test).
Physical exam, as always, is important. One should record weight,
BMI, waist circumference (usually greater than 35 inches), and