No. 34. Management of Infertility Caused by Ovulatory Dysfunction

ACOG
PRACTICE
BULLETIN
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 34, FEBRUARY 2002
This Practice Bulletin was

developed by the ACOG Committee on Practice Bulletins
Gynecology with the assistance
of Robert Barbieri, MD. The
information is designed to aid
practitioners in making decisions about appropriate obstetric and gynecologic care. These
guidelines should not be construed as dictating an exclusive
course of treatment or procedure. Variations in practice may
be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
VOL. 99, NO.2, FEBRUARY 2002
Management of
Infertility Caused by
Ovulatory Dysfunction
Approximately 20% of infertile women have ovulatory disorders (1, 2). In infertile women with ovulatory disorders, the cause of anovulation will guide the
selection of an appropriate treatment plan. Advances in reproductive
endocrinology allow the generalist obstetriciangynecologist to provide treatment that results in successful ovulatory stimulation and pregnancy in most
women with ovulatory disorders.
Background
Etiology
Ovulatory dysfunction is likely to be present in women with polymenorrhea or
oligomenorrhea and is almost always present in women with amenorrhea
(except in patients with uterine disease, such as uterine synechiae or
Ashermans syndrome). Regular menstrual cycles, with a cycle length between
22 and 35 days, and the presence of premenstrual bloating, dysmenorrhea, and
breast tenderness suggest the presence of ovulatory cycles.
Laboratory methods for determining ovulation include the basal body temperature chart, urine testing for the luteinizing hormone (LH) surge, properly
timed measurement of serum progesterone, and endometrial biopsy. Serial
pelvic ultrasonography also may be able to identify the growth and rupture of
a follicle, suggesting that ovulation has occurred. Basal body temperature
charts are inexpensive but may be a burden to the patient to complete and only
document ovulation retrospectively. The pulsatile ovarian secretion of progesterone in the luteal phase may decrease the sensitivity of a single measurement
of progesterone, but a serum progesterone level higher than 3 ng/mL is highly
specific for detecting ovulation. (These tests also can detect ovulation in
induced cycles.)
ACOG Practice Bulletin No. 34 Management of Infertility

Caused by Ovulatory Dysfunction
347
If anovulation or clinically significant oligo-ovulation has been documented, a complete physical examination and selected laboratory testing are important to
identify the etiology of the ovulatory dysfunction.
The most common causes of ovulatory dysfunction are
1) polycystic ovary syndrome (PCOS) (approximately
70% of cases of ovulatory dysfunction) (3), 2) hypothalamic amenorrhea, also known as hypogonadotropic
hypogonadism (approximately 10% of cases), 3) hyperprolactinemia (approximately 10% of cases), and 4) premature ovarian failure, also known as hypergonadotropic
hypoestrogenic anovulation (approximately 10% of
cases) (4).
During the physical examination, the practitioner
should note the presence of galactorrhea, thyromegaly or
other evidence of hypothyroidism or hyperthyroidism,
acanthosis nigricans, hirsutism, acne, or signs of virilization. In addition, the patients body mass index (BMI)
should be calculated. A BMI less than 20 may indicate
hypothalamic ovulatory dysfunction (low gonadotropinreleasing hormone [GnRH] secretion, low LH and
follicle-stimulating hormone [FSH] secretion, low
endogenous estrogen secretion) (5). The combination of
amenorrhea and galactorrhea strongly correlates with
hyperprolactinemia. The presence of acanthosis nigricans
suggests the patient has a marked degree of insulin
resistance.
In general, clinicians should first recommend the
least resource-intensive ovulation induction regimens
that are appropriate for each cause of ovulatory dysfunction. For example, for women with hypogonadotropic
hypogonadism and a BMI less than 20, weight gain may
be associated with the resumption of normal menses.
Polycystic Ovary Syndrome

Polycystic ovary syndrome is defined as the presence of
oligomenorrhea or amenorrhea and hyperandrogenism in
the absence of other hyperandrogenic disorders, such as
androgen-secreting tumors or nonclassical adrenal hyperplasia. Clinical evidence of hyperandrogenism includes
hirsutism and acne. Laboratory evidence of hyperandrogenism includes an elevated total, bioavailable, or free
testosterone concentration. Elevated serum dehydroepiandrosterone sulfate (DHEAS) or androstenedione
levels also are evidence of hyperandrogenism. The morphologic characteristics of polycystic ovaries as
demonstrated on pelvic ultrasonography are not essential
for the diagnosis of PCOS but support the diagnosis. In
women of reproductive age, the prevalence of PCOS is
approximately 5%, making it one of the most common
reproductive disorders (3). Among women with ovulatory dysfunction, about 70% have PCOS (3).
348

In women with PCOS, many therapies are available

to treat anovulatory infertility, including weight loss,
clomiphene, clomiphene plus metformin, clomiphene
plus glucocorticoid, gonadotropin injections, ovarian surgery, and in vitro fertilization-embryo transfer (IVF-ET).
Using the principle of progressing from the least
resource-intensive treatments to the most resource-intensive treatments, one potential strategy for organizing the
care of women with PCOS is presented in the box.
Hypothalamic Anovulation
Hypothalamic anovulation (hypogonadotropic hypogonadism) usually is associated with low levels of GnRH
secretion, low or normal levels of LH and FSH secretion,
and low levels of endogenous estrogen secretion.
Diseases associated with hypothalamic anovulation
include anorexia nervosa, Kallmanns syndrome, and
hypothalamic tumors and cysts. Factors associated with
hypogonadotropic hypogonadism include a low BMI
(<20); high-intensity exercise; certain dietary patterns,
including high-fiber, low-fat diets; and excessive stress.
One approach to treating this condition is to reverse the
lifestyle factors that contribute to the anovulation. For
example, in one study of 26 underweight women who
practiced strict dieting and were infertile, the subjects
were counseled by a dietitian and given physician-directed advice to increase their BMI (5). After the intervention, the women gained a mean 3.7 kg, and 73% of the
women became pregnant. Decreasing the intensity of
A Step-by-Step Approach to Ovulation Induction

in Women with PCOS
The least resource-intensive interventions are recommended in the early steps in the protocol, while the
most resource-intensive interventions are reserved for
later treatment.
Step 1. If the BMI is higher than 30, recommend
weight loss of at least 10% of body weight.
Step 2. Prescribe clomiphene to induce ovulation.
Step 3. If DHEAS is higher than 2 g/mL, consider
combining clomiphene with a glucocorticoid to
induce ovulation.
Step 4. If clomiphene does not result in ovulation,
consider a combination of metformin plus
clomiphene.
Step 5. Initiate low-dose FSH injections.
Step 6. Initiate low-dose FSH injections plus metformin.
Step 7. Consider laparoscopic ovarian surgery or in vitro
fertilization.
OBSTETRICS & GYNECOLOGY
exercise and stress also may help improve the rate of

ovulation in some of these women. However, no welldesigned clinical trials testing these recommendations
have been reported.
In the past, one option for ovulation induction for
hypogonadotropic hypogonadism was the parenteral
administration of GnRH in pulses using a portable programmable pump. It was associated with monofollicular
ovulation and a high rate of singleton pregnancy but the
pump is not commercially available in the United States
(6, 7).
Hyperprolactinemia
The most common causes of hyperprolactinemia are a
prolactin-secreting pituitary gland tumor and the use of
psychiatric medications. The presence of hyperprolactinemia should be confirmed if there is any question
about the timing of the blood test or the quality of the
assay; blood should be drawn after the patient has fasted
and preferably not after a breast examination or breast
stimulation (8). All women with hyperprolactinemia
should be tested for hypothyroidism (a thyroid-stimulating hormone screening or additional thyroid hormone
testing as clinically indicated) and pregnancy (9). An
imaging study (magnetic resonance imaging or computed tomography) of the central nervous system and the
pituitary gland should be obtained in all women with
hyperprolactinemia unless there is an obvious cause,
such as hypothyroidism, that makes a pituitary gland
tumor unlikely (10). If the imaging study reveals a
macroadenoma of the pituitary gland (tumor diameter
10 mm), the patient should be referred to a physician
with expertise in endocrinology or pituitary gland disease for consultation. Induction of ovulation in women
with large pituitary gland tumors is associated with a
high risk of neurosurgical complications during pregnancy (1113). In addition, women with large pituitary
gland tumors may have undiagnosed adrenal insufficiency, a condition that poses significant health risks. For
women with microadenomas (tumor diameter <10 mm)
that secrete prolactin, the risk of pituitary insufficiency
and neurosurgical complications during pregnancy is
very low (<1%) (1113). Observational studies indicate
that during 4 6 years of observation, 95% of microadenomas do not increase in size (14, 15).
Age-Related Ovulation Dysfunction and

Premature Ovarian Failure
As the ovarian follicular pool depletes with age, the
remaining follicles appear to be less capable of fertilization and establishing a successful pregnancy. Inhibin B
production by the small follicles decreases with age, the
inhibin suppression of FSH secretion decreases, and
pituitary gland secretion of FSH increases. An elevated

random FSH level in amenorrheic or severely oligomenorrheic women or an elevated day-3 FSH level in women
with menses is highly sensitive and specific for identifying women with a depleted ovarian follicular pool (16).
If initial attempts at ovulation induction do not result in
a pregnancy in women older than 37 years, consultation
with an infertility specialist may be advisable to develop
a plan for when assisted reproductive procedures, such
as IVF-ET or oocyte donation should be pursued.
Treatments proposed to induce ovulation in women
with premature ovarian failure include 1) oral contraceptive suppression of gonadotropins followed by discontinuation of the oral contraceptive to allow a rebound in
gonadotropin secretion and ovarian function, 2) GnRHagonist suppression of gonadotropin secretion followed
by high-dose gonadotropin injections, and 3) glucocorticoid suppression of the immune system. None of these
treatments has demonstrated efficacy in randomized
clinical trials for inducing ovulation in women with premature ovarian failure (17). Women with infertility, ovulatory dysfunction, and an elevated FSH level should be
referred to a physician with specialized expertise in
treating infertility.
Luteal Phase Deficiency

Luteal phase deficiency is a theoretical disorder in which
ovulation occurs, but there is insufficient progesterone
production by the corpus luteum to allow for successful
implantation. Luteal phase deficiency is thought to cause
recurrent pregnancy loss, especially in the first trimester,
and is believed to be responsible for a subset of cases of
infertility. Studies that have attempted to establish luteal
phase deficiency as a cause of infertility have not included control groups of fertile women. However, women
who have regular menstrual cycles may have luteal phase
abnormalities in as many as 31% of their cycles (18).
Methods to diagnose and treat luteal phase deficiencies,
therefore, are largely speculative. Because current infertility treatment often includes empiric treatment for
unexplained infertility, most women who have luteal
phase deficiencies and are infertile will receive treatment
that includes controlled ovarian hyperstimulation.
Therefore, a therapy specific to luteal phase deficiency is
not being aggressively pursued.
Treatment Options
Clomiphene Citrate
The precise mechanism of action of clomiphene citrate is
not completely understood. The administration of
clomiphene to anovulatory women with endogenous

349
estrogen secretion often is followed by an increase in

both hypothalamic GnRH secretion and pituitary LH and
FSH secretion, which causes follicle growth, triggering
the LH surge and ovulation.
Clomiphene treatment is most effective in women
with normal FSH levels and adequate endogenous production of estrogen and is least effective in women with
hypothalamic amenorrhea or in women with an elevated
basal FSH concentration (19). In women with PCOS, the
presence of obesity, elevated testosterone concentration,
and severe insulin resistance decreases the efficacy of
clomiphene citrate (20). Most women with hypogonadotropic hypogonadism do not ovulate in response to
treatment with clomiphene.
Most clomiphene-induced pregnancies occur within
the first three menstrual cycles, and the vast majority occur
within 6 months. There is no benefit to increasing the
dosage once ovulation has occurred or to continuing
beyond 6 months of treatment (21). Clomiphene administration in anovulatory women differs from superovulation, or controlled ovarian hyperstimulation, which is
frequently attempted in couples with unexplained infertility. With clomiphene, monofolliculogenesis is the goal,
and adjunctive treatments, such as intensive follicle monitoring and intrauterine insemination, do not have a
defined role. With superovulation, women are already
ovulatory; clomiphene, if administered, is typically given
with human chorionic gonadotropin (hCG) to ensure ovulation, and intrauterine insemination also is appropriate.
Gonadotropin Injection
Gonadotropins can be administered using human urinary
menopausal gonadotropins, which contain both LH and
FSH, or by using recombinant FSH. Both types of
gonadotropins are effective in treating anovulation in
women with PCOS. The use of gonadotropin injections
to induce ovulation in women with PCOS is resource
intensive and is associated with a high risk of adverse
outcomes, such as ovarian hyperstimulation and highorder multiple pregnancy.
Gonadotropin injections are effective in the treatment of hypothalamic anovulation. Women with hypothalamic anovulation who have a baseline serum LH
level lower than 0.5 IU/L should be treated with both
FSH and LH because they have a deficiency in both
gonadotropins. Women with hypothalamic amenorrhea
and a baseline LH level higher than 0.5 IU/L can be successfully treated with FSH alone (22). In most circumstances, the use of FSH injections to induce ovulation
should be performed by physicians with advanced training in treating infertility.
350

Metformin
Metformin is an oral biguanide antihyperglycemic agent
approved for the treatment of adult-onset diabetes mellitus. It is a category-B drug used by some clinicians to
treat diabetes mellitus in pregnant women. Metformin
decreases blood glucose levels by inhibiting hepatic glucose production and by enhancing peripheral glucose
uptake. Metformin increases insulin sensitivity at the
postreceptor level and stimulates insulin-mediated glucose disposal. Unlike sulfonylureas, metformin does not
cause hypoglycemia because it does not increase insulin
secretion. Unlike phenformin, metformin does not block
mitochondrial metabolism of lactate unless the patient
has renal failure (renal failure will cause lactate to accumulate to very high concentrations) or severe hypoxia
(mitochondrial dysfunction). Metformin is not approved
by the U.S. Food and Drug Administration (FDA) for
ovulation induction.
Dopamine Agonists
Dopamine-agonist drugs (bromocriptine, pergolide,
cabergoline) are the treatment of choice for ovulation
induction in women with hyperprolactinemia (23).
Dopamine-agonist drugs directly suppress prolactin production by the tumor and cause an increase in endogenous GnRH secretion, which stimulates pituitary gland
secretion of LH and FSH and consequently induces follicle development and ovulation. In addition, dopamine
agonists decrease the size of prolactin-secreting pituitary
gland tumors.
With dopamine-agonist therapy, a near-maximal
decrease in serum prolactin levels should be achieved
after 4 weeks of treatment. Serum prolactin levels should
be measured approximately 1 month after initiating therapy and about 1 month after a change in the dosage or
drug. Normalization of prolactin levels is the therapeutic
goal, as well as assuring that the tumor is responding to
the dopamine agonists. If the serum prolactin concentration is normal and no side effects have occurred, the initial dosage should be continued. If the serum prolactin
level has not decreased to normal and no side effects are
present, the dosage should be gradually increased. The
maximal dosage of bromocriptine is 5 mg twice daily;
pergolide, 0.25 mg once daily. Cabergoline is the newest
of these agents; it can be administered less frequently and
may induce nausea less often. However, as a result of
FDA approval, its use in pregnancy is extremely limited.
Women who do not tolerate the side effects of bromocriptine may need to be referred to a practitioner with additional expertise in the field to discuss in detail the risks
and benefits of newer therapies that have not been tested
as thoroughly.
Clinical Considerations and

Recommendations
Before using ovulation-inducing medications, it is

useful to consider evaluating the couple for male factor
infertility by performing a semen analysis. Routinely performing hysterosalpingography is unnecessary. However,
if the woman has a history of sexually transmitted diseases, pelvic inflammatory disease, appendicitis with
rupture, in utero exposure to diethylstilbestrol, or previous pelvic surgery, hysterosalpingography should be considered to establish tubal patency. Laparoscopy is not
routinely necessary before ovulation induction. The age
of the woman strongly influences the pregnancy rate with
ovulation induction (see Fig. 1). In older women, this
may lead to a greater sense of urgency and a rapid progression to more intensive treatments, with their greater
associated risks (26, 27).
If the serum prolactin level does not decrease to normal, switching to a different dopamine agonist may be
effective. If the patient cannot tolerate the dopamine agonist initially prescribed, a different dopamine agonist
may be associated with fewer side effects. If the patient
experiences side effects with all dopamine agonists, vaginal administration can be tried. If the patient cannot
tolerate any of the dopamine agonists, transsphenoidal
surgery may be effective in removing the tumor, returning prolactin secretion to normal, and causing the
resumption of ovulatory menses.
Following correction of hyperprolactinemia, about
80% of women will ovulate, and cumulative pregnancy
rates of 80% are commonly observed (24). Treatment
usually is discontinued once pregnancy is diagnosed.
However, in women with a macroprolactinoma, therapy
should be continued throughout pregnancy to decrease
the risk of tumor growth and neurosurgical complications, such as compression of the optic nerve.
In the small percentage of women with hyperprolactinemia who do not respond to dopamine-agonist
therapy, standard ovulation induction therapy with clomiphene citrate may be considered. In rare cases, gonadotropin therapy may be considered.
Does weight loss improve fertility in obese

women?
In women with a high BMI, abnormal hypothalamic

GnRH secretion, pituitary gland LH and FSH secretion,
insulin resistance, and anovulation are common (28).
Women with a BMI greater than 30 and oligo-ovulation
often have PCOS.
Epidemiologic studies have demonstrated that a
BMI greater than 27 is associated with an increased risk
of ovulatory infertility. For example, in one study of 597
cumulative pregnancy rate in women younger than 35 years

cumulative pregnancy rate in women older than 35 years
How is the diagnosis of ovulatory dysfunction

established?
If the patient is amenorrheic, the minimal laboratory

evaluation should include measurement of serum levels
of FSH, thyroid-stimulating hormone, and prolactin. If
the patient has evidence of hyperandrogenism (eg, hirsutism, acne, signs of virilization), measurement of
testosterone and DHEAS may have clinical value if ovulation induction is planned. Clinical evaluation may be
used to determine if testing for Cushings syndrome or
Addisons disease should be performed. If the patient has
a BMI higher than 30, testing for diabetes mellitus may
be indicated before inducing ovulation (25). To decrease
the risk of congenital malformations, diabetes mellitus
should be treated before inducing pregnancy. In women
with irregular menses, attempting to obtain a luteal-phase
progesterone measurement may be cumbersome and
unnecessary if menses are relatively infrequent.
Documenting ovulation by basal body temperature evaluation or LH surge testing may be helpful. Women with
regular menses can be assessed for ovulatory status by
any of the techniques described previously.
Figure 1. Cumulative pregnancy rates for hypogonadotropic

anovulatory women treated with gonadotropins. (From
Lunenfeld B, Insler V. Human gonadotropins. In: Wallach EE,
Zacur HA, eds. Reproductive medicine and surgery. St. Louis:
Mosby-Year Book, 1995:617)

351
women with ovulatory infertility and 1,695 controls, the

women with a BMI higher than 27 had a relative risk of
ovulatory infertility of 3.1 (95% confidence interval,
2.2 4.4) when compared with the control group with a
BMI of 2024.9 (29).
Many studies (most without a control group) have
demonstrated that in women who have PCOS and are
obese, weight loss often is associated with a decrease in
serum testosterone concentration, resumption of ovulation,
and, for infertile women, pregnancy. For example, in one
study, 18 obese women with PCOS were treated with a
hypocaloric diet (30). Before the diet, the mean weight of
the women was 77 kg; after the diet, it was 57 kg. The plasma testosterone concentration was 0.75 ng/mL before the
diet and 0.39 ng/mL after (P <0.001). Many of the women
resumed ovulation after weight loss. Another study evaluated the effects of weight loss on 20 obese women with
PCOS (31). Before the diet, the women had a mean BMI
of 32, amenorrhea for more than 3 months, and increased
plasma concentrations of androstenedione, testosterone, or
DHEAS. Following a hypocaloric diet of 1,0001,500
kcal per day, weight loss ranged from 4.8 kg to 15.2 kg.
After weight loss, significant reductions in the concentration of LH (45% decrease), fasting insulin (40% decrease),
and testosterone (35% decrease) were observed. After
weight loss, most of the women ovulated, and many of the
infertile women became pregnant.
In a small trial that examined the effect of weight
loss on reproductive function in 12 obese women with
PCOS, the women were randomized to either a weight
reduction program or a waiting list observation control
group (32). The six women randomized to the weight
reduction program had a mean weight decrease of 16 kg,
a significant decrease in circulating testosterone concentration, and a decrease in fasting insulin; four of the six
women resumed ovulating. The women randomized to
the observational control group had no weight change
during the study. All of the women in the control group
who were anovulatory before the study (five) remained
anovulatory during the study.
Weight reduction is best achieved by a combination
of diet and exercise. However, exercise at levels greater
than 60 minutes per day has been associated with an
increase in ovulatory infertility (33).
How is clomiphene citrate administered?
The FDA has approved clomiphene dosages of 50 mg or

100 mg daily for a maximum of 5 days per cycle. After
spontaneous menses or the induction of menses with a
progestin withdrawal, clomiphene is started on cycle day
3, 4, or 5 at 50 mg daily for 5 days. Starting clomiphene
on cycle day 3 or 5 does not appear to influence the preg-
352

nancy rate (34). It is important to give clomiphene only

after menstrual bleeding to help ensure that the patient is
not pregnant. In properly selected women, approximately 50% will ovulate using the 50-mg daily dosage, and
another 25% will ovulate if the dosage is increased to
100 mg daily (35). If lower dosages are not successful in
inducing ovulation, many clinicians will prescribe
150 mg daily for 5 days; a few have used dosages as high
as 250 mg daily for 5 days. However, the pregnancy rates
associated with the use of clomiphene at dosages higher
than 150 mg daily for 5 days are very low (21). In general, if the 150-mg dosage is not successful, alternative
approaches to ovulation induction should be considered.
Of those women who ovulate while taking clomiphene,
between 40% and 80% will become pregnant. In one
study of 3,022 women taking clomiphene, the pregnancy
rate per ovulatory cycle was 20% (36). The pregnancy
rate decreases substantially after six cycles of clomiphene therapy (37).
Patients taking clomiphene should be monitored for
ovulation, pregnancy, and ovarian enlargement, as clinically indicated. Ovulation can be determined by measuring serum progesterone levels (about 14 days after the
last dose of clomiphene), basal body temperature charting, or properly timed endometrial biopsy. Detection of
an LH surge in the urine suggests a preovulatory follicle
has triggered the surge. Intense cycle monitoring with
frequent measurement of serum estradiol levels and pelvic ultrasonography is generally not necessary with the
use of clomiphene but is required for gonadotropin therapy. Clomiphene treatment can be associated with luteal
phase defects and the suboptimal production of cervical
mucus. Some clinicians recommend an endometrial biopsy in a test cycle of clomiphene treatment to assess
whether clomiphene-induced ovulation is associated with
luteal phase defect (38). A few authorities recommend a
postcoital test be performed during the first clomiphene
cycle to assess cervical mucus quality and quantity.
However, little evidence exists to support either practice.
Of clomiphene-induced pregnancies, 7% are twin
gestations and 0.3% are triplet gestations (39). The rate
of spontaneous abortion after clomiphene-induced pregnancy is approximately 15%. The incidence of birth
defects is similar to that seen in spontaneous pregnancy
(40). The most common symptoms experienced by
women taking clomiphene include vasomotor symptoms
(20%), adnexal tenderness (5%), nausea (3%), headache
(1%), and, rarely, blurring of vision or scotomata (21,
41). Many clinicians permanently discontinue clomiphene treatment in women with clomiphene-induced
visual changes. The main contraindications to the use of
clomiphene are pregnancy, hypersensitivity to the medication, and ovarian cysts.
In women who do not ovulate using clomiphene alone, can the chances of ovulation be
improved by adding glucocorticoids?
In women who do not ovulate using clomiphene alone, can the chances of ovulation be
improved by adding an hCG injection?
In women who do not respond to clomiphene, does ovarian diathermy increase the
chances of ovulation more than FSH?
A number of surgical techniques have been described

that may increase the rate of ovulation in women with
PCOS. To date, no randomized, controlled clinical trial
has demonstrated the efficacy of surgery in this setting,
but case series totaling more than 1,000 subjects have
been published. Although ovarian wedge resection was
the initial surgical procedure reported to increase ovulation in women with PCOS, this procedure has been
replaced by laparoscopic techniques that use electrosurgical or laser energy. Overall, the case series report ovulation rates of 80% and pregnancy rates of 50% (45). For
women with PCOS, ovulation induction with FSH also is
associated with pregnancy rates of 50% (46). Injections
with FSH for ovulation induction are associated with a
high rate of multiple gestations (approximately 20%),
and it is not known if ovarian diathermy affects ovarian
reserve. Thus, treatment should be individualized.
The combination of clomiphene plus a single dose of

hCG may increase the efficacy of clomiphene induction
of ovulation when women fail to ovulate with standard
dosages of clomiphene (43). After the last dose of
clomiphene, pelvic ultrasonography can be used to monitor follicle size. When the mean diameter of the lead
follicle reaches 18 mm, a single dose of hCG can be
administered. Ovulation occurs approximately 3644
hours after the injection. There are no randomized controlled clinical trials that document the efficacy of this
approach.
It has been proposed that a regimen of 2 months of
oral contraceptives before ovulation induction with
clomiphene followed by an hCG injection when follicle
ripening has occurred may improve the rate of ovulation
and pregnancy. No randomized clinical trial supports this
approach. However, a clinical trial without controls
reported oral contraceptive treatment followed by
clomiphene therapy (100 mg daily for 5 days) plus an
Women with PCOS and a serum DHEAS concentration

higher than the middle of the normal range (>2 g/mL)
appear to have decreased ovulation and pregnancy rates
when they are treated with clomiphene. Some studies
suggest treatment with clomiphene plus a glucocorticoid
improves pregnancy rates in these women. One study
randomized 64 anovulatory infertile women to receive
either clomiphene, 50 mg daily on cycle days 59, or
clomiphene plus 0.5 mg dexamethasone daily (42). If
ovulation did not occur, the dosage of clomiphene was
increased by 50-mg increments up to 150 mg daily for
5 days each cycle. The investigators observed significantly higher rates of ovulation and conception in
women treated with clomiphene plus dexamethasone
than with clomiphene alone. The impact of combined
therapy was especially marked in the women with a
DHEAS concentration higher than 2 g/mL. Of the
women with a DHEAS concentration higher than
2 g/mL, 12 were randomized to receive clomiphene
alone, and 13 were randomized to receive clomiphene
plus dexamethasone. Among the 12 women receiving
clomiphene alone, six (50%) ovulated and four (33%)
became pregnant. Among the 13 women who received
clomiphene plus dexamethasone, 13 (100%) ovulated
and 11 (85%) became pregnant.
hCG injection was an inexpensive and potentially effective approach to treating women with PCOS who had
failed to ovulate and become pregnant with standard
clomiphene therapy (44). In that study, 38 infertile
women with PCOS who had failed to ovulate when treated with clomiphene (150 mg daily for 5 days) and who
had a DHEAS concentration lower than 2 g/mL took
oral contraceptives (ethinyl estradiol 0.03 mg, and desogestrel 0.15 mg daily) for 2 months followed by
clomiphene. Instead of the usual 7-day pill-free interval
between cycles, the investigators prescribed a regimen
with a 3-day pill-free interval. On cycle days 59 after
completion of the second month of oral contraceptives,
clomiphene (100 mg daily for 5 days) was prescribed.
Transvaginal ultrasonography was initiated on cycle day
12 and repeated every 12 days until hCG was administered. When the mean diameter of the lead follicle
reached 20 mm, hCG (10,000 units) was administered.
The 38 women completed 95 treatment cycles. Sixtynine of the 95 cycles were ovulatory (73%), and 29 of
the 38 women (76%) ovulated. Twenty-two pregnancies
occurred. Most of the pregnancies (82%) occurred in one
of the first three treatment cycles.
In women with hyperprolactinemia, which

medical treatments stimulate the resumption
of ovulation?
Bromocriptine has been used for more than 25 years to

induce ovulation in women with hyperprolactinemia. In
one study of 280 women with hyperprolactinemia,

353
bromocriptine normalized the circulating prolactin level

in 82% of the women (47). The main side effects associated with bromocriptine are nausea, vomiting, and orthostatic hypotension. To minimize these potential side
effects, it is recommended that bromocriptine be initiated at a dosage of 1.25 mg at bedtime. After 1 week, the
dosage can be increased to 1.25 mg twice daily. The
dosage can then be increased to 2.5 mg twice daily, a
standard dosage that successfully decreases serum
prolactin levels in most women with hyperprolactinemia (47).
Pergolide, an ergot dopamine agonist, is approved
by the FDA for the treatment of Parkinsons disease but
is not approved for the treatment of hyperprolactinemia.
Unlike bromocriptine, pergolide can be given once per
day. Pergolide is the least expensive of the dopamine
agonists.
In women with PCOS, what is the role of

gonadotropins in inducing ovulation?
In one randomized clinical trial, low-dose FSH treatment

appeared to improve outcomes and decrease adverse
events when compared with standard-dose FSH treatment in women with PCOS (48). In this study, 50 infertile women with PCOS who had failed to conceive with
clomiphene therapy were randomized to receive either
conventional FSH treatment (75 IU daily, increasing by
75 IU every 56 days until follicular ripening occurred)
or low-dose FSH treatment (75 IU daily for 14 days of
treatment, increasing by 37.5 IU every 7 days thereafter
until follicular ripening was complete). Compared with
standard FSH treatment, women who received longterm, low-dose FSH treatment had more cycles with the
development of a single dominant follicle (74% versus
27%), fewer high-order multiple gestations, and a higher pregnancy rate (40% versus 24%).
When should metformin be added for the

treatment of ovulatory infertility?
Insulin sensitizers can be used alone or in combination

with clomiphene to induce ovulation in infertile women
with oligo-ovulation, hyperandrogenism, and insulin
resistance (49). To date, no large-scale clinical trials have
been published that demonstrate the impact of metformin on live birth rates in women with PCOS and
insulin resistance. A few small clinical trials have been
published demonstrating that in women with PCOS the
combination of clomiphene plus metformin is associated
with higher rates of ovulation and pregnancy than
clomiphene plus a placebo (50, 51). In one study, women
with PCOS who did not ovulate when treated with
clomiphene (150 mg daily for 5 days) were randomized
354

to receive either metformin (1,500 mg daily) or placebo

for 7 weeks (51). During the initial 7-week treatment
period, one of the 12 women in the metformin group
ovulated, and none of the 15 women in the placebo
group ovulated. After this initial treatment period, all of
the women received clomiphene citrate, beginning at a
dosage of 50 mg daily for 5 days, with dosage escalation
if ovulation did not occur. Nine of the 12 women in the
metformin-plus-clomiphene group ovulated, compared
with four of the 15 women in the placebo-plusclomiphene group (P < 0 .02). Of the women who
completed the clinical trial, six (of 11) in the metforminplus-clomiphene group became pregnant, and one (of
14) in the placebo-plus-clomiphene group became pregnant (P <0.02). Of the six pregnancies in the metforminplus-clomiphene group, two resulted in spontaneous
abortion and four resulted in live singleton births. The
one pregnancy in the placebo-plus-clomiphene group
resulted in a live singleton birth.
A commonly used dosage of metformin is 500 mg
three times daily. The most common side effects of
metformin are gastrointestinal disturbances, including
diarrhea, nausea, vomiting, and abdominal bloating. To
minimize gastrointestinal side effects, many clinicians
recommend starting metformin at 500 mg daily for 1
week, increasing to 500 mg twice daily for 1 week, and
then increasing to 500 mg three times daily. Once the full
dosage is achieved, some clinicians switch to a dosing
regimen of 850 mg twice daily to improve patient compliance. Progesterone measurements can be periodically
obtained to determine whether ovulation has occurred, or
the patient can keep a basal body temperature chart. If
ovulation has not occurred after 48 weeks of metformin therapy, clomiphene (50 mg daily for 5 days) can
be administered after progestin-induced menstrual withdrawal bleeding. If the patient becomes pregnant, the
metformin therapy can be discontinued. Ovulation, if it
is going to occur, can be expected to occur within 68
weeks.
In rare cases, metformin therapy has caused fatal
lactic acidosis. In most of these cases, renal insufficiency or severe hypoxia (congestive heart failure, septic
shock) was present. Before treatment with metformin is
initiated, it is recommended that serum creatinine levels
be demonstrated to be lower than 1.4 mg/dL. Women
with liver dysfunction should not take metformin. Also,
metformin should be discontinued 48 hours beforeand
not restarted for 72 hours afterany radiologic test
involving intravenous contrast or before surgery.
Metformin appears to improve the ovulatory
response in women with PCOS treated with FSH injections. A trial randomized 20 infertile women with PCOS
and insulin resistance who had failed to ovulate when
Is a postcoital test useful in a patient taking

clomiphene citrate?
The postcoital test has low reproducibility and low interobserver reliability and has not been proved to help
guide treatment recommendations (5355). In addition,
there is little consensus on what constitutes an abnormal
postcoital test result. Given these limitations, there is little scientific rationale for performing a postcoital test.
However, clinical experience suggests that clomiphene,
acting as an antiestrogen in the cervix, can cause cervical mucus production that is abnormal in quantity and
quality. Therefore, some clinicians recommend performing a postcoital test to assess the impact of clomiphene
on cervical mucus production.
Can the risk of multiple gestation be minimized?
The risk of ovarian cancer is increased in women who are

nulligravid (voluntarily and involuntarily) and women
with a strong family history of ovarian cancer. The risk of
ovarian cancer is decreased by pregnancy, use of oral contraceptives for more than 6 months, surgical tubal ligation,
and hysterectomy. Preliminary studies reported ovulationinducing medications may be associated with a small
increase in the risk of ovarian tumors (borderline tumors
and cancer) and that the risk may increase with the extended use of ovulation-inducing agents for many months (57,
58). In one of these studies, the strongest risk occurred
among 13 nulligravid women who had used infertility
drugs and had never become pregnant. In this subset, the
association was statistically significant, but the confidence
interval was wide, suggesting a great deal of variation, and
the sample size was small (n=13). Some practitioners
believe infertility (involuntary childlessness) is a more
powerful risk factor for ovarian tumors than treatment
with an ovulation-inducing medication. However, given
the low pregnancy rates observed after six cycles of ovulation induction with an induction agent (such as
clomiphene) and the potential (although low) risk that 12
or more cycles of clomiphene may be associated with an
increased risk of ovarian tumors, it is reasonable to limit
clomiphene treatment to fewer than 12 cycles. There are
no evidence-based guidelines about the appropriate duration of gonadotropin administration; however, given the
possibility that such agents can cause harm, it seems
appropriate to use them sparingly and only with clear-cut
indications.
Summary of
Recommendations
The following recommendations are based on limited or inconsistent scientific evidence (Level B):
In obese women with PCOS, weight loss should be
considered because it is associated with a decrease
in circulating testosterone concentration, an
increase in the frequency of ovulation, and in some
women, pregnancy.
Is the risk of ovarian cancer increased with

the use of induction agents, such as
clomiphene or gonadotropin injections?
Multiple gestation is a growing problem. Public awareness is increasing about the hazards associated with
multiple births, as well as the long-term costs and consequences (56). Monofolliculogenesis is the goal of therapy in infertile patients.
To decrease the risk of multiple gestation, treatments associated with low rates of multiple gestation
should be used. For example, in women with PCOS,
ovulation induction with weight loss, clomiphene,
clomiphene plus metformin, clomiphene plus glucocorticoid, and ovarian surgery are associated with low rates
of triplet pregnancy. Gonadotropin injections and in vitro
fertilization are associated with higher rates of multiple
gestation (48). When using gonadotropin injections, the
use of low-dose regimens appears to be associated with
lower rates of multiple gestation than the use of standard
dose regimens. In addition, the risk of multiple gestation
with FSH injections can probably be decreased by withholding hCG and prescribing a barrier contraceptive
whenever more than three follicles greater than 15 mm in
diameter are detected with pelvic ultrasonography.
treated with clomiphene (150 mg daily for 5 days) to

receive either FSH injections alone or FSH injections plus
metformin (500 mg three times daily) (52). The mean
BMI of the subjects was approximately 27. Compared
with the women who received FSH alone, the women
who received both FSH and metformin had fewer dominant follicles (2.4 versus 4.5, P <0.01), a lower peak estradiol concentration (450 pg/mL versus 720 pg/mL,
P <0.001), and a lower cycle cancellation rate (0% versus
32%, P < 0.03). The investigators concluded a combination of FSH plus metformin is associated with an orderly
follicular response that probably decreases the risk for
ovarian hyperstimulation and multiple pregnancy.
In obese women with PCOS who did not ovulate

when treated with clomiphene, the combination of
clomiphene plus metformin may be considered
because the rate of ovulation is greater than it is with
clomiphene alone.

355
In women with PCOS and a serum DHEAS level

higher than 2 g/mL, the combination of clomiphene plus glucocorticoid may be considered
because the rate of ovulation is greater than it is with
clomiphene alone.
In women with hypothalamic amenorrhea and a

BMI lower than 20, weight gain should be considered because it may be associated with the resumption of ovulation and pregnancy.
In women with PCOS receiving gonadotropin injections for ovulation induction, low-dose FSH may be
considered because it is associated with a higher
rate of cycles with the development of a single dominant follicle and fewer high-order multiple gestations.
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The MEDLINE database, the Cochrane Library, and

ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles published between January 1985 and June 2001. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of
Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I
Evidence obtained from at least one properly designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consistent scientific evidence.
Level BRecommendations are based on limited or inconsistent scientific evidence.
Level CRecommendations are based primarily on consensus and expert opinion.
Copyright February 2002 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system, or
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920
Washington, DC 20090-6920
12345/65432
Management of infertility caused by ovulatory dysfunction. ACOG
Practice Bulletin No. 34. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2002;99:347358
358

ACOG
EDUCATIONAL and
PRACTICE BULLETINS
LIST
OF
TITLES FEBRUARY 2002
Educational and Practice Bulletins provide obstetricians and gynecologists with

current information on established techniques and clinical management guidelines. ACOG continuously surveys the field for advances to be incorporated in
these series and monitors existing bulletins to ensure they are current. Individual
bulletins are withdrawn from and added to these series on a continuing basis.
Also listed are current Practice Patterns, which provide evidence-based guidelines.
A list of withdrawn and replaced titles appears at the end.
General
Current Bulletins
8
15
22
29
210
246
260
Psychosocial Risk Factors: Perinatal Screening and Intervention

(November 1999, Obstet Gynecol Vol. 94, No. 5)
258
Breastfeeding: Maternal and Infant Aspects (July 2000, Obstet Gynecol

Vol. 96, No. 1)
Obstetrics

7
14
21
28
207
244
258
6
13
20
27
34
236
255
5
12
19
26
33
230
253
4
11
18
25
32
227
251
1
3
9 10
16 17
23 24
30 31
218 222
247 248
255
VOL. 99, NO. 2, FEBRUARY 2002
1 Premature Rupture of Membranes (June 1998, Obstet Gynecol Vol. 91, No. 6)
4 Prevention of Rh D Alloimmunization (May 1999, Obstet Gynecol Vol. 93, No. 5)
5 Vaginal Birth After Previous Cesarean Delivery (July 1999, Obstet Gynecol
Vol. 94, No. 1)
6 Thrombocytopenia in Pregnancy (September 1999, Obstet Gynecol Vol. 94, No. 3)
8 Management of Herpes in Pregnancy (October 1999, Obstet Gynecol Vol. 94, No. 4)
9
10
12
13
Antepartum Fetal Surveillance (October 1999, Obstet Gynecol Vol. 94, No. 4)
Induction of Labor (November 1999, Obstet Gynecol Vol. 94, No. 5)
Intrauterine Growth Restriction (January 2000, Obstet Gynecol Vol. 95, No. 1)
External Cephalic Version (February 2000, Obstet Gynecol Vol. 95, No. 2)
17 Operative Vaginal Delivery (June 2000, Obstet Gynecol Vol. 95, No. 6)
19 Thromboembolism in Pregnancy (August 2000, Obstet Gynecol Vol. 96, No. 2)
20 Perinatal Viral and Parasitic Infections (September 2000, Obstet Gynecol Vol.
96, No. 3)
22 Fetal Macrosomia (November 2000, Obstet Gynecol Vol. 96, No. 5)
24 Management of Recurrent Early Pregnancy Loss (February 2001, Obstet Gynecol
Vol. 97, No. 2)
27 Prenatal Diagnosis of Fetal Chromosomal Abnormalities (May 2001, Obstet
Gynecol Vol. 97, No. 5)
29 Chronic Hypertension in Pregnancy (Obstet Gynecol 2001;98:177185)
*30 Gestational Diabetes (Obstet Gynecol 2001;98:525538)
*31 Assessment of Risk Factors for Preterm Birth (Obstet Gynecol 2001;98:709716)
ACOG Educational and Practice Bulletins List of Titles
359
21 Prevention of Deep Vein Thrombosis and Pulmonary

Embolism (October 2000, Obstet Gynecol Vol. 96, No. 4)
23 Antibiotic Prophylaxis for Gynecologic Procedures

(January 2001, Obstet Gynecol Vol. 97, No. 1)
18 The Use of Hormonal Contraception in Women with

Coexisting Medical Conditions (July 2000, Obstet
*32 Thyroid Disease in Pregnancy (Obstet Gynecol

2001;98:879888)
*33 Diagnosis and Management of Preeclampsia and
Eclampsia (Obstet Gynecol 2002;99:159167)
207 Fetal Heart Rate Patterns: Monitoring, Interpretation and
Management (July 1995)
218 Dystocia and the Augmentation of Labor (December 1995)
227 Management of Isoimmunization in Pregnancy (August
1996)
230 Assessment of Fetal Lung Maturity (November 1996)
244 Antiphospholipid Syndrome (February 1998)
236 Teratology (April 1997)
248 Viral Hepatitis in Pregnancy (July 1998, Obstet Gynecol
Vol. 92, No. 1)
251 Obstetric Aspects of Trauma Management (September
1998, Obstet Gynecol Vol. 92, No. 3)
253 Special Problems of Multiple Gestation (November
260 Smoking Cessation During Pregnancy (September
16 Surgical Alternatives to Hysterectomy in the

Management of Leiomyomas (May 2000, Obstet
25 Emergency Oral Contraception (March 2001, Obstet

26 Medical Management of Abortion (April 2001, Obstet
28 Use of Botanicals for Management of Menopausal
Symptoms (June 2001, Obstet Gynecol Vol. 97, No. 6)
*34 Management of Infertility Caused by Ovulatory
Dysfunction (Obstet Gynecol 2002;99:347358)
210 Health Maintenance for Perimenopausal Women (August
1995)
222 Sterilization (April 1996)
(continued)
Obstetrics
Reproductive Endocrinology and Fertility
11 Medical Management of Endometriosis (December

3 Medical Management of Tubal Pregnancy (December

7 Prophylactic Oophorectomy (September 1999, Obstet
14 Management of Anovulatory Bleeding (March 2000,

Obstet Gynecol Vol. 95, No. 3)
Gynecology
15 Premenstrual Syndrome (April 2000, Obstet Gynecol

Vol. 95, No. 4)
246 Osteoporosis (April 1998, Obstet Gynecol

Vol. 91, No. 4)
247 Hormone Replacement Therapy (May 1998, Obstet
Practice Patterns
5 Routine Ultrasound in Low-Risk Pregnancy
(August 1997)
6 Management of Postterm Pregnancy (October 1997)
7 Shoulder Dystocia (October 1997)
For ordering information, contact the ACOG Distribution Center at 800-762-2264, or order online at sales.acog.com.
*Title issued since publication of last listing

Practice Bulletin
360
AT005
The following Educational and Technical Bulletins will be replaced by Ethics in Obstetrics and Gynecology:
136 Ethical Decision-Making in Obstetrics and Gynecology
The following Educational and Technical Bulletins will be replaced by Adolescent Health:
249 Confidentiality in Adolescent Health Care
254 Primary and Preventive Health Care for Female Adolescents
256 Oral Contraceptives for Adolescents: Benefits and Safety
The following Educational and Technical Bulletins will be replaced by Special Issues in Womens Health:
194 Substance Abuse
201 Pediatric Gynecologic Disorders
240 Smoking and Womens Health
242 Sexual Assault
252 Adolescent Victims of Sexual Assault
257 Domestic Violence
259 Adult Manifestations of Childhood Sexual Abuse
The following Educational and Technical Bulletins have been withdrawn from circulation:
109 Methods of Midtrimester Abortion
125 Infertility
128 Amenorrhea
156 Nonmalignant Conditions of the Breast
160 Immunization During Pregnancy
162 Carcinoma of the Endometrium
163 Fetal and Neonatal Neurologic Injury
164 The Intrauterine Device
171 Rubella and Pregnancy
173 Women and Exercise
175 Invasive Hemodynamic Monitoring in Obstetrics and Gynecology
176 Diagnosis and Management of Fetal Death
178 Management of Gestational Trophoblastic Disease
181 Thyroid Disease in Pregnancy (replaced by Practice Bulletin No. 32)
182 Depression in Women
183 Cervical Cytology: Evaluation and Management of Abnormalities
186 Vulvar Cancer
187 Ultrasonography in Pregnancy
189 Exercise During Pregnancy and the Postpartum Period
191 Hysteroscopy
193 Genital Human Papillomavirus Infections
195 Substance Abuse in Pregnancy
197 Managing the Anovulatory State: Medical Induction of Ovulation
198 Hormonal Contraception
199 Blood Component Therapy
200 Diabetes and Pregnancy (replaced by Practice Bulletin No. 30)
202 Hyperandrogenic Chronic Anovulation
203 Evaluation and Treatment of Hirsute Women
204 Septic Shock
205 Preconceptional Care
206 Preterm Labor (replaced by Practice Bulletin No. 31)
208 Genetic Technologies
211 Sexual Dysfunction
213 Urinary Incontinence
214 Pelvic Organ Prolapse
215 Gynecologic Ultrasonography
216 Umbilical Artery Blood AcidBase Analysis
223 Chronic Pelvic Pain
224 Pulmonary Disease in Pregnancy
225 Obstetric Analgesia and Anesthesia
226 Vaginitis
229 Nutrition and Women
231 Seizure Disorders in Pregnancy
235 Hemorrhagic Shock
238 Lower Urinary Tract Operative Injuries
239 Operative Laparoscopy
241 Vulvar Nonneoplastic Epithelial Disorders
243 Postpartum Hemorrhage
245 Antimicrobial Therapy for Obstetric Patients
250 Ovarian Cancer
VOL. 99, NO. 2, FEBRUARY 2002
361
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The fourth edition retains much of the original,
classic text, including explanations of forceps devices
and techniques. It also provides the latest related ACOG
guidelines, a chapter on vaccum assisted deliveries, and
information on the current and changing status of forceps deliveries.
Forceps and vacuum deliveries continue to play a
role in modern obstetric practice as we strive to seek
alternatives to cesarean delivery. Dennens Forceps
Deliveries, the time-honored definitive treatise on the
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with an obstetric practice in any way, you will find this
book vital and relevant.
2001, 154 pages

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The American College of

Obstetricians and Gynecologists
Womens Health Care Physicians
Order today! Call 800-762-2264, ext 333 or order online at sales.acog.com
ACOG Committee Opinions

List of Titles
February 2002
Committee Opinions are intended to provide timely information on controversial issues, ethical concerns, and emerging approaches to clinical management. They represent the considered views of the sponsoring committee based on
interpretation of published data in peer-reviewed journals. Committee Opinions are reviewed periodically for continued relevance or needed update. Note: Because individual Committee Opinions are withdrawn from and added to the
series on a continuing basis, the titles listed in this index may not be identical to those contained in complete sets.
A list of withdrawn and replaced titles appears at the end.
Number
Title
Committee on Coding and Nomenclature

205 Tubal Ligation with Cesarean Delivery (Obstet Gynecol Vol. 92, No. 2)
249 Coding Responsibility (Obstet Gynecol Vol. 97, No. 1)
250 Inappropriate Reimbursement Practices by Third-Party Payers
(Obstet Gynecol Vol. 97, No. 1)
Committee on Genetics (to be published as a separate volume)
161 Fragile X Syndrome
162 Screening for TaySachs Disease
183 Routine Storage of Umbilical Cord Blood for Potential Future
Transplantation (Joint with Committee on Obstetric Practice)
189 Advanced Paternal Age: Risks to the Fetus
192 Genetic Screening of Gamete Donors
212 Screening for Canavan Disease (Obstet Gynecol Vol. 92, No. 5)
223 First-Trimester Screening for Fetal Anomalies with Nuchal Translucency
230 Maternal Phenylketonuria (Obstet Gynecol Vol. 95, No. 1)
238 Genetic Screening for Hemoglobinopathies (Obstet Gynecol Vol. 96, No. 1)
239 BreastOvarian Cancer Screening (Obstet Gynecol Vol. 96, No. 2)
257 Genetic Evaluation of Stillbirths and Neonatal Deaths
Committee on Gynecologic Practice
152 Recommendations on Frequency of Pap Test Screening
164 Incidental Appendectomy
186 Role of the ObstetricianGynecologist in the Diagnosis
and Treatment of Breast Disease
191 Length of Hospital Stay for Gynecologic Procedures
195 Role of Loop Electrosurgical Excision Procedure in the Evaluation
of Abnormal Pap Test Results
203 Hepatitis Virus Infections in ObstetricianGynecologists
224 Tamoxifen and the Prevention of Breast Cancer in High-Risk Women
226 Hormone Replacement Therapy in Women with Previously Treated
Breast Cancer (Obstet Gynecol Vol. 94, No. 5)
232 Tamoxifen and Endometrial Cancer (Obstet Gynecol Vol. 95, No. 4)
235 Hormone Replacement Therapy in Women Treated
for Endometrial Cancer (Obstet Gynecol Vol. 95, No. 5)
240 Statement on Surgical Assistants (Obstet Gynecol Vol. 96, No. 2)
(Joint with Committee on Obstetric Practice)
242 Concurrent Chemoradiation in the Treatment of Cervical Cancer
243 Performance and Interpretation of Imaging Studies
by ObstetricianGynecologists (Obstet Gynecol Vol. 96, No. 5)
Publication
Date
Reaffirmed
Date
August 1998
January 2001
January 2001
October 1995
November 1995
2000
2000
April 1997
October 1997
October 1997
November 1998
2000
2000
2001
2000
October 1999
January 2000
July 2000
August 2000
2001
May 2001
March 1995
December 1995
1998
2000
September 1997
October 1997
2000
2000
November 1997
2000
July 1998
2001
October 1999
2001
November 1999
April 2000
2001
2001
May 2000
2001
August 2000
October 2000
November 2000
ACOG Committee Opinions List of Titles
363
Number
Title
Committee on Gynecologic Practice (continued)

244 Androgen Treatment of Decreased Libido
245 Mifepristone for Medical Pregnancy Termination
246 Primary and Preventive Care: Periodic Assessments
247 Routine Cancer Screening (Obstet Gynecol Vol. 96, No. 6)
253 Nongynecologic Procedures (Obstet Gynecol Vol. 97, No. 3)
*262 Risk of Breast Cancer with EstrogenProgestin Replacement Therapy
(Obstet Gynecol 2001;98:11811183)
*263 Von Willebrands Disease in Gynecologic Practice
(Obstet Gynecol 2001;98:11851186)
Committee on Obstetric Practice
125 Placental Pathology
138 Utility of Umbilical Cord Blood AcidBase Assessment
158 Guidelines for Diagnostic Imaging During Pregnancy
163 Perinatal Care at the Threshold of Viability
(Joint with AAP Committee on Fetus and Newborn)
173 Prevention of Early-Onset Group B Streptococcal Disease in Newborns
174 Use and Abuse of the Apgar Score (Joint with AAP Committee
on Fetus and Newborn)
180 New Ultrasound Output Display Standard
183 Routine Storage of Umbilical Cord Blood for Potential
Future Transplantation (Joint with Committee on Genetics)
197 Inappropriate Use of the Terms Fetal Distress and Birth Asphyxia
210 Antenatal Corticosteroid Therapy for Fetal Maturation
228 Induction of Labor with Misoprostol (Obstet Gynecol Vol. 94, No. 5)
231 Pain Relief During Labor (Joint with American Society
of Anesthesiologists) (Obstet Gynecol Vol. 95, No. 2)
234 Scheduled Cesarean Delivery and the Prevention of Vertical Transmission
of HIV Infection (Obstet Gynecol Vol. 95, No. 5)
240 Statement on Surgical Assistants (Joint with Committee
on Gynecologic Practice) (Obstet Gynecol Vol. 96, No. 2)
248 Response to Searles Drug Warning on Misoprostol
252 Fetal Surgery for Open Neural Tube Defects
256 Optimal Goals for Anesthesia Care in Obstetrics (Joint with American Society
of Anesthesiologists) (Obstet Gynecol Vol. 97, No. 5)
*258 Fetal Pulse Oximetry (Obstet Gynecol 2001;98:523524)
*260 Circumcision (Obstet Gynecol 2001;98:707708)
*264 Air Travel During Pregnancy (Obstet Gynecol 2001;98:11871188)
*265 Mode of Term Singleton Breech Delivery
(Obstet Gynecol 2001;98:11891190)
*266 Placenta Accreta (Obstet Gynecol 2002;99:169170)
*267 Exercise During Pregnancy and the Postpartum Period
(Obstet Gynecol 2002;99:171173)
*268 Management of Asymptomatic Pregnant or Lactating Women
Exposed to Anthrax (Obstet Gynecol 2002;99:366368)
*269 Analgesia and Cesarean Delivery Rates (Obstet Gynecol 2002;99:369370)
Committee on Primary Care
227 Complementary and Alternative Medicine
Committee on Professional Liability
236 Coping with the Stress of Malpractice Litigation
237 Informed Refusal (Obstet Gynecol Vol. 95, No. 6)
Publication
Date
Reaffirmed
Date
November 2000
December 2000
December 2000
December 2000
March 2001
December 2001
December 2001
July 1993
April 1994
September 1995
2000
2000
2000
November 1995
June 1996
1997
1999
July 1996
November 1996
1999
2000
April 1997
February 1998
2000
2001
October 1998
November 1999
2001
February 2000
2001
May 2000
2001
August 2000
December 2000
March 2001
May 2001
September 2001
October 2001
December 2001
December 2001
January 2002
January 2002
February 2002
February 2002
November 1999
2001
June 2000
June 2000
For ordering information, contact the ACOG Distribution Center at 800-762-2264, or order online at sales.acog.com.
*Title issued since publication of last index.
364
The following Committee Opinions will be replaced by Ethics in Obstetrics and Gynecology:
46 Endorsement of Institutional Ethics Committees
108 Ethical Dimensions of Informed Consent
136 Preembryo Research: History, Scientific Background, and Ethical Considerations
144 Sexual Misconduct in the Practice of Obstetrics and Gynecology: Ethical Considerations
156 End-of-Life Decision Making: Understanding the Goals of Care
159 Ethical Guidance for Patient Testing
170 Physician Responsibility Under Managed Care: Patient Advocacy in a Changing Health Care Environment
177 Sex Selection
181 Ethical Issues in ObstetricGynecologic Education
194 ObstetricianGynecologists Ethical Responsibilities, Concerns, and Risks Pertaining to Adoption
204 Institutional Responsibility to Provide Legal Representation
214 Patient Choice and the MaternalFetal Relationship
215 Nonselective Embryo Reduction: Ethical Guidance for the ObstetricianGynecologist
216 Sterilization of Women, Including Those with Mental Disabilities
217 Ethical Issues Related to Expert Testimony by Obstetricians and Gynecologists
225 Responsibilities of Physicians Regarding Surrogate Motherhood
233 Ethical Dimensions of Seeking and Giving Consultation
254 Commercial Enterprises in Medical Practice: Selling and Promoting Products
255 Human Immunodeficiency Virus: Ethical Guidelines for Obstetricians and Gynecologists
259 Guidelines for Relationships with Industry
261 Medical Futility
The following Committee Opinions will be replaced by Adolescent Health:
139 Adolescents Right to Refuse Long-Term Contraceptives
154 Condom Availability for Adolescents
190 Prevention of Adolescent Suicide
The following Committee Opinions will be replaced by Special Issues in Womens Health:
200 Mandatory Reporting of Domestic Violence
201 Cultural Competency in Health Care
202 Access to Health Care for Women with Physical Disabilities
The following Committee Opinions have been withdrawn from circulation:
87 Deception
101 Current Status of Cystic Fibrosis Carrier Screening
104 Anesthesia for Emergency Deliveries
105 Postpartum Tubal Sterilization
121 Obstetric Management of Patients with Spinal Cord Injury
129 Commercial Ventures in Medicine: Concerns About the Patenting of Procedures
133 Colposcopy Training and Practice
149 Financial Influences on Mode of Delivery
151 Female Genital Mutilation
153 Absence of Endocervical Cells on a Pap Test
167 Perinatal and Infant Mortality Statistics
171 Cost Containment in Medical Care
172 Home Uterine Activity Monitoring (replaced by Practice Bulletin No. 31)
175 Scope of Services for Uncomplicated Obstetric Care
179 Rate of Vaginal Births After Cesarean Delivery
184 Hepatitis B Immunization for Adolescents
187 Fetal Fibronectin Preterm Labor Risk Test (replaced by Practice Bulletin No. 31)
196 Vitamin A Supplementation During Pregnancy
207 Liability Implications of Recording Procedures or Treatments
213 Ethical Considerations in Research Involving Pregnant Women
221 Telecommunication in Medicine
222 Quality of Laboratory and Imaging Services: Physician Responsibility in the Age of Managed Care
241 Screening for Hypothyroidism (replaced by Practice Bulletin No. 32)
251 SalEst as a Predictor of Risk for Preterm Labor (replaced by Practice Bulletin No. 31)
Current Committee Opinions
125
189
228
244
262
138
191
230
245
263
152
192
231
246
264
158
195
232
247
265
161
197
234
248
266
162
203
235
249
267
163
205
236
250
268
164
210
237
252
269
173
212
238
253
174
223
239
256
180
224
240
257
183
226
242
258
186
227
243
260
365

No. 34. Management of Infertility Caused by Ovulatory Dysfunction

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ACOG

This Practice Bulletin was

VOL. 99, NO.2, FEBRUARY 2002

ACOG Practice Bulletin No. 34 Management of Infertility

Polycystic Ovary Syndrome

ACOG Practice Bulletin No. 34 Management of Infertility

In women with PCOS, many therapies are available

A Step-by-Step Approach to Ovulation Induction

OBSTETRICS & GYNECOLOGY

exercise and stress also may help improve the rate of

Age-Related Ovulation Dysfunction and

VOL. 99, NO.2, FEBRUARY 2002

pituitary gland secretion of FSH increases. An elevated

Luteal Phase Deficiency

ACOG Practice Bulletin No. 34 Management of Infertility

estrogen secretion often is followed by an increase in

ACOG Practice Bulletin No. 34 Management of Infertility

OBSTETRICS & GYNECOLOGY

Clinical Considerations and

Before using ovulation-inducing medications, it is

Does weight loss improve fertility in obese

In women with a high BMI, abnormal hypothalamic

cumulative pregnancy rate in women younger than 35 years

How is the diagnosis of ovulatory dysfunction

If the patient is amenorrheic, the minimal laboratory

VOL. 99, NO.2, FEBRUARY 2002

Figure 1. Cumulative pregnancy rates for hypogonadotropic

ACOG Practice Bulletin No. 34 Management of Infertility

women with ovulatory infertility and 1,695 controls, the

How is clomiphene citrate administered?

The FDA has approved clomiphene dosages of 50 mg or

ACOG Practice Bulletin No. 34 Management of Infertility

nancy rate (34). It is important to give clomiphene only

OBSTETRICS & GYNECOLOGY

VOL. 99, NO.2, FEBRUARY 2002

A number of surgical techniques have been described

The combination of clomiphene plus a single dose of

Women with PCOS and a serum DHEAS concentration

In women with hyperprolactinemia, which

Bromocriptine has been used for more than 25 years to

ACOG Practice Bulletin No. 34 Management of Infertility

bromocriptine normalized the circulating prolactin level

In women with PCOS, what is the role of

In one randomized clinical trial, low-dose FSH treatment

When should metformin be added for the

Insulin sensitizers can be used alone or in combination

ACOG Practice Bulletin No. 34 Management of Infertility

to receive either metformin (1,500 mg daily) or placebo

OBSTETRICS & GYNECOLOGY

Is a postcoital test useful in a patient taking

Can the risk of multiple gestation be minimized?

The risk of ovarian cancer is increased in women who are

VOL. 99, NO.2, FEBRUARY 2002

Is the risk of ovarian cancer increased with

treated with clomiphene (150 mg daily for 5 days) to

In obese women with PCOS who did not ovulate

ACOG Practice Bulletin No. 34 Management of Infertility

In women with PCOS and a serum DHEAS level

In women with hypothalamic amenorrhea and a

ACOG Practice Bulletin No. 34 Management of Infertility

of pituitary tumors and other abnormal intrasellar masses.

OBSTETRICS & GYNECOLOGY

25. Legro RS, Kunselman AR, Dodson WC, Dunaif A.

VOL. 99, NO.2, FEBRUARY 2002