CHIEF EDITORS NOTE: This article is part of a series of continuing education activities in this Journal through which a total

of 36 AMA/PRA category 1 credits

TM
can be earned in 2006. Instructions for how CME credits can be earned appear on the
last page of the Table of Contents.
Managing Ovarian Masses
During Pregnancy
Gary S. Leiserowitz, MD
Professor, Chief, Division of Gynecologic Oncology, Division of Gynecologic Oncology, Department of
Obstetrics and Gynecology, University of California, Davis Medical Center, Sacramento, California
The management of adnexal masses during pregnancy can be challenging for the patient and
the clinician. The specter of a possible malignancy can sway the decision for intervention
versus expectant management. The etiologies of ovarian masses are reflective of the patients
age; and, therefore, benign entities such as functional ovarian cysts, benign cystic teratomas,
and serous cystadenomas predominate. In the unusual cases when cancer is present, they are
typically germ cell and borderline ovarian tumors, and are commonly low stage and low grade.
Ultrasound is the primary modality used to detect ovarian masses and to assess the risk of
malignancy. Morphologic criteria more accurately identify benign cysts compared with malig-
nant tumors. Tumor markers are used primarily to monitor disease status after treatment rather
than establish the ovarian tumor diagnosis as a result of lack of specificity, because several
markers can be elevated inherent to the pregnancy itself (eg, CA-125, -hCG). Expectant
management is recommended for most pregnant patients with asymptomatic, nonsuspicious
cystic ovarian masses. Surgical intervention during pregnancy is indicated for large and/or
symptomatic tumors and those that appear highly suspicious for malignancy on imaging tests.
The extent of surgery depends on the intraoperative diagnosis of a benign versus a malignant
tumor. Conservative surgery is appropriate for benign masses and borderline ovarian tumors.
More aggressive surgery is indicated for ovarian malignancies, including surgical staging.
Although rarely necessary, chemotherapy has been used during pregnancy with minimal fetal
toxicity in patients with advanced-stage ovarian cancer in which the risk of maternal mortality
outweighs the fetal consequences.
Target Audience: Obstetricians & Gynecologists, Family Physicians
Learning Objectives: After completion of this article, the reader should be able to recall the prevalence
of ovarian tumors during pregnancy; explain the risk of malignancy, the use of diagnostic testing, and
management options; and summarize potential maternal and fetal outcomes.
With the advent of nearly routine prenatal ultrasound
(US), the detection of ovarian masses has become com-
monplace. The presence of adnexal masses in preg-
nancy is not unusual with an estimated incidence
between 1% and 2% (13). In the era before routine
prenatal US, adnexal masses were discovered either
incidentally on physical examination or as a result of
symptoms. In either case, detection would tend to favor
masses that were problematic as a result of either size or
complications. This historic mindset tended to push for
surgical intervention to avoid the risks of rupture, tor-
sion, or obstructed labor and as well as a concern for
possible ovarian malignancy. However, a contemporary
The author has disclosed that he has no financial relationships
with or interests in any commercial companies pertaining to this
educational activity.
Lippincott Continuing Medical Education Institute, Inc. has
identified and resolved all faculty conflicts of interest regarding
this educational activity.
Reprint requests to: Gary S. Leiserowitz, MD, 4860 Y Street, Suite
2500, Sacramento, CA 95817. E-mail: gsleiserowitz@ucdavis.edu.
CME REVIEWARTICLE
Volume 61, Number 7
OBSTETRICAL AND GYNECOLOGICAL SURVEY
Copyright 2006
by Lippincott Williams & Wilkins
19
463
understanding of the benign nature and uncomplicated
course of adnexal masses diagnosed incidentally by US
has led to a more conservative approach to management
of adnexal masses in pregnancy.
The scope of this review discusses the etiology of
adnexal masses, including the risk of malignancy,
diagnostic testing, management options during preg-
nancy, maternal and fetal outcomes, and manage-
ment of ovarian cancer during pregnancy.
ETIOLOGY
Just like in the nonpregnant state, adnexal masses
have various gynecologic and nongynecologic causes.
However, most are gynecologic and are usually ovarian
or uterine in origin. Table 1 lists the most common
types of ovarian tumors encountered during pregnancy.
Functional cysts are particularly common in pregnancy,
including theca-lutein cysts, which are usually related to
presence of gestational trophoblastic disease (4). The
relative frequency of all other nonfunctional ovarian
tumors is largely a reflection of the patients age rather
than something intrinsic to the pregnancy itself.
In descending order, the most common ovarian tu-
mors found during pregnancy include: functional ovar-
ian cysts (follicular, corpus luteum, and theca-lutein),
benign cystic teratomas, serous cystadenomas, parao-
varian cysts, mucinous cystadenomas, endometriomas,
and malignant tumors (1,3,58). Surgery (excision or
biopsy) followed by a pathologic examination is re-
quired to definitively determine the etiology of the
adnexal mass. Consequently, the frequency of tumors
that either resolve spontaneously (ie, functional cysts)
or are managed nonsurgically tends to be underre-
ported. Similarly, the timing of detection of the adnexal
mass during pregnancy influences the likely etiology of
the mass. Cystic adnexal masses less than 5 cm that are
detected in the first 16 weeks are usually functional and
almost always resolve spontaneously (2). Ovarian tu-
mors that persist beyond 16 weeks are more likely to be
neoplastic; and, therefore, are more likely to result in
surgical intervention. This issue is further discussed
subsequently in the section on management of adnexal
masses.
Ovarian malignancy is estimated to occur in approx-
imately 2% to 3% of the masses identified during preg-
nancy (1,3,57,9,10), but the frequency reported in the
different case series is quite variable from study to
study. Ovarian tumors of lowmalignant potential (LMP
or borderline ovarian tumors) are usually included in
the category of ovarian malignancies, although their
biologic aggressiveness is usually bland and indolent.
The frequency of various ovarian malignancies is
highly age-dependent and reflects the younger cohort of
reproductive-age women compared with postmeno-
pausal women who are more commonly diagnosed with
epithelial ovarian cancer.
We recently investigated the frequency of ovarian
masses during pregnancy and analyzed the risk of
ovarian malignancy during pregnancy (11). We com-
bined several California databases for our analysis,
including the California Vital Statistics database, the
California Office of Statewide Health Planning and
Development (OSHPD), and the California Cancer
Registry (CCR). We identified 4,846,505 obstetric
patients from the vital statistical database in the pe-
riod of 1991 to 1999. Nine thousand three hundred
seventy-five pregnant women were identified with a
hospital discharge diagnosis that included any type of
ovarian tumor (0.19% of all obstetric deliveries).
These included 8267 ovarian cysts, 5910 benign
ovarian neoplasms, 144 ovarian LMP tumors, 174
ovarian malignancies, and 19 secondary ovarian ma-
lignancies (the total was greater than 9375, because
some patients had more than one diagnosis). His-
topathologic confirmation was obtained in only 117
LMP and 89 ovarian invasive cancers (see Table 2),
resulting in a conservatively estimated occurrence
TABLE 1
Etiology of ovarian tumors during pregnancy
Benign Tumors Malignant Tumors
Functional cysts Borderline ovarian tumors
Follicular cysts Malignant epithelial tumors
Corpus luteum cysts Malignant germ cell tumors
Theca-lutein cysts Sex cord/stromal tumors
Hemorrhagic cysts Granulosa cell tumor
Paraovarian cysts Cancer metastatic to the ovary
Benign cystic teratomas Krukenberg tumors
Serous cystadenoma Pseudomyxoma peritonei
Mucinous cystadenoma
Endometriomas
TABLE 2
Histology of ovarian malignancies occurring in California women
during pregnancy, 19911999
Histology Cancer
Low Malignant
Potential Tumor
Serous (including papillary) 14 83
Mucinous 10 34
Endometrioid 5
Clear cell 3
Other epithelial 14
Pseudomyxoma peritonei 8
Germ cell 34
Granulosa cell 1
Total 89 117
464 Obstetrical and Gynecological Survey
rate of ovarian malignancy in ovarian masses during
pregnancy of 89 of 9375 (0.93%). This is lower than
the 3% figure commonly quoted in the literature. The
California statistics suggest an occurrence of one
malignancy for every 54,644 deliveries.
Notably, the majority of the ovarian malignancies
are actually LMP tumors. Ninety-five percent of the
LMP tumors and 83.8% of the ovarian cancers are
stage I. Nearly 40% of the ovarian cancers are germ
cell tumors, which is typical for younger women who
are in their reproductive years. Interestingly, 8 were
classified as pseudomyxoma peritonei, which are
now generally believed to be metastatic mucinous
tumors of gastrointestinal (usually appendiceal) ori-
gin. Although incompletely reported in the CCR da-
tabase, low-grade (grades 1 and 2) tumors were more
common in the cohort of pregnant women than in the
more typical group of other women with ovarian
cancer.
The finding that most ovarian cancers are low stage
and low grade is consistent with previous reports
(12,13). Most germ cell tumors are dysgerminomas,
which are predominantly low stage (1,12). Conse-
quently, the overall prognosis of pregnant patients
with either an LMP tumor or an ovarian cancer is
highly favorable. These findings should strongly in-
fluence the management of adnexal masses during
pregnancy.
DIAGNOSTIC EVALUATION
The vast majority of adnexal masses during preg-
nancy will be identified by US either as an incidental
finding or to evaluate a symptomatic pelvic mass.
The safety of diagnostic US as well as its ability to
delineate anatomic relationships and characterize the
morphology of pelvic masses makes it ideal as the
primary initial evaluation tool. A variety of algo-
rithms exist to differentiate between benign and ma-
lignant ovarian tumors, or to stratify the risk of
malignancy, using elements such as tumor size, mor-
phology, and color flow Doppler. These algorithms
have a high specificity to identify benign ovarian
masses, but are less specific when used to distinguish
benign from malignant when applied to complex
ovarian masses.
Marino et al (3) used a modification of a weighted
scoring system of ovarian tumors developed by Le-
rner et al (14) to determine the risk of malignancy
(Table 3). Using Lerners scoring system against a
cohort of 302 benign masses, 31 malignant masses,
and one LMP tumor, they found a positive predictive
value of 29.4% and a negative predictive value of
99.6% (14). Thus, it is easier to make a confident
diagnosis of a benign tumor than a malignant one,
because benign and malignant neoplasms often share
similar complex morphologic features.
Some authors feel that various ovarian tumor types
are sufficiently characteristic on US that they could
accurately predict the histology. Bromley and Ben-
acerraf (15) found that they could accurately identify
95% of dermoid cysts, 80% of endometriomas, and
71% of simple cysts seen during pregnancy. Zanetta
et al (16) used US criteria to develop the following
categories: simple cyst, endometriosis or corpus
luteum-like, dermoid-like, complex benign, borderline-
like, and suspicious. They used their system to triage
pregnant patients with adnexal masses into those who
warranted surgical intervention (suspicious masses)
versus those who were candidates for expectant man-
agement (all the other categories). In the limited
number of patients who had adnexal surgery either
antepartum or postpartum, the final pathology gen-
erally matched well with their US diagnoses.
Use of color flow Doppler has been offered as
another tool to help differentiate between a benign or
malignant ovarian tumor. Unfortunately, there is suf-
ficient overlap in blood flow patterns such that the
false-positive rate is nearly 50% (17), which offers no
advantage over use of US morphology indexing alone.
Magnetic resonance imaging (MRI) can be safely
used during pregnancy to evaluate adnexal masses
(3). The primary advantages of MRI relate to its
capacity to develop 3-dimensional planar images,
delineate tissue planes, and characterize tissue com-
position. This is particularly helpful in the pelvis
where US has a limited role in assessing the bony and
muscular structures. For example, Weinreb et al
found that MRI was able to identify leiomyomata,
bowel loops, and an abdominal pregnancy; differen-
tiate between a solid mass and hemorrhagic fluid-
filled cyst; and evaluate the parametria in a patient
with cervical cancer (18). Keir et al (19) found in
TABLE 3
Risk of ovarian malignancy based on sonographic criteria
Risk of Ovarian Cancer Sonographic Criteria
Low Cystic, unilocular
Size 5 cm
Intermediate Cystic, multilocular
Complex
Thin septations
High Solid mass
Nodules
Thick septations
Size 5 cm
Managing Ovarian Masses During Pregnancy Y CME Review Article 465
their limited series of pelvic masses during preg-
nancy that MRI correctly identified the etiology in 17
of 17 (100%) pelvic masses, whereas US was accu-
rate in 12 of 17 (71%). Although MRI can provide
valuable diagnostic information beyond the ability of
US, the number of situations in which this is clini-
cally important is limited. Both modalities are very
dependent on the experience of the physician who
interprets the scan. MRI probably adds minimally to
the evaluation of most ovarian masses compared with
US but may be valuable when the US diagnosis is
uncertain and when a radiologist experienced in in-
terpreting MRI of adnexal masses and pregnancy is
available.
Serum tumor markers are primarily used for surveil-
lance of known, treated ovarian malignancies but are of
variable benefit in the initial assessment of ovarian
masses. CA-125 is elevated in 80%of epithelial ovarian
malignancies with mucinous adenocarcinomas being a
notable exception. CA-125 has limited diagnostic accu-
racy in premenopausal women, because multiple benign
gynecologic conditions are associated with elevated val-
ues such as menses, uterine fibroids, and especially
pregnancy (20). When elevated, the CA-125 can pro-
vide a baseline value before treatment of ovarian cancer
but will not help differentiate between benign and ma-
lignant masses during pregnancy. Various other tumor
markers are used to monitor germ cell tumors (AFP
endodermal sinus tumor, -hCGchoriocarcinoma,
lactic dehydrogenasedysgerminoma) (21). Although
germ cell tumors are among the most common ovarian
malignancies seen in pregnancy, both -hCG and AFP
have very limited use as tumor markers during preg-
nancy. Tumor markers should be obtained before any
surgical intervention when there is a suspicion of
ovarian malignancy to provide a baseline should a
malignancy be diagnosed. Any elevation in the
tumor markers should be considered in conjunc-
tion with the results of the imaging tests to avoid
unnecessary intervention when possible.
MANAGEMENT OPTIONS
Conservative
The main consideration in choosing intervention
versus expectant management centers on the risks to
the mother and fetus. The specter of malignancy is
quickly raised whenever an ovarian mass is detected.
However, a rational decision should be based on an
accurate assessment of the malignancy risk. As noted
previously, ovarian masses in pregnancy have a can-
cer risk that ranges between 0.9% and 3%. More
importantly, sonographic criteria can successfully
stratify the risk. For example, those few masses that
have suspicious complex features can be separated
from the majority that is usually benign. Therefore,
treatment considerations are best divided into those
masses that warrant conservative (expectant) versus
surgical management.
Most ovarian cysts discovered during pregnancy
will resolve spontaneously and/or require no inter-
vention. In their series of over 18,000 obstetric US
scans, Bernhard (2) found that 76% of 432 masses
were simple cysts less than 5 cm in diameter. They
did not intervene in this group, and there were no
complications. The remaining 24% (102) of the
masses were either complex and/or greater than 5
cm. Nearly 69% of these masses also resolved spon-
taneously. Hogston (22) and colleagues evaluated
26,110 prenatal US examinations and detected 137
asymptomatic ovarian cysts. One hundred twenty-three
patients were treated conservatively, but 3 required
subsequent intervention during pregnancy as a result of
pain. Ninety-six percent of the remaining 120 women
had repeat scans, and 89% of these had complete res-
olution, including 82% of the cysts 6 cm.
Zanetta (16) used their sonographic criteria to iden-
tify a group of women with nonsuspicious ovarian
masses who were candidates for expectant manage-
ment during pregnancy (see previously for details).
Only cysts 3 cm were included in their study. In
6636 US scans, they found 82 cysts in 79 women. No
masses suspicious for malignancy were identified.
Three cysts required surgery for torsion. The remain-
ing 79 were followed expectantly during the preg-
nancy. They noted either complete disappearance or a
reduction of 50% in 69% of the simple cysts, 77% of
the endometriosis-like cysts, 57% of the complex
benign cysts, and none of either the dermoid-like or
borderline-like cysts (54.5% total). Thirty-one masses
persisted after pregnancy and 19 patients had surgery
with a variety of histologies, including 3 borderline
tumors (all of which were identified by their US
criteria), but no ovarian cancer. There were also no
pregnancy losses. Thus, observation of the major-
ity of ovarian masses appears to be a viable man-
agement option.
Surgical
Ovarian masses that warrant intervention usually
have at least one of the following indications: 1) a
strong suspicion of malignancy and/or large size
(810 cm), 2) symptomatic complaints, or 3) an
increased risk of torsion/rupture/obstruction of labor.
466 Obstetrical and Gynecological Survey
The likelihood of malignancy with a complex ovar-
ian mass is relatively low (29.4% in Lerners study
[14]), but increases if there are other associated find-
ings such as ascites or omental thickening. Histori-
cally, many authors have emphasized the risks of
torsion, cyst rupture, and obstruction of labor, but
these usually occurred in large, symptomatic masses.
Struyk et al (8) reported their experience with ovar-
ian tumors in pregnancy and noted torsion in 12%,
rupture in 9%, and obstruction of labor in 17%. In
Whitecars series (7), 16 of 130 women underwent
urgent laparotomy for acute abdominal pain, 14 be-
fore delivery. Eleven of the 16 either had docu-
mented or presumptive torsion (11 of 130 [8.5%]).
Bromley and Benacerraf in their series of 131 ovar-
ian masses in 125 pregnant women reported a far
lower rate of antepartum problems (15). Only one
patient had an ovarian torsion and one patient was
explored for an ovarian cyst that was not found at
laparotomy. Bernhard reported a 1% risk of torsion
in their series of 102 ovarian masses (2) and that
one occurred in a patient with a palpable mass.
Overall, it appears that later studies report lower
risks of torsion and rupture than earlier studies.
This probably reflects a higher proportion of
asymptomatic, US-detected ovarian masses that
are less prone to complicate the pregnancy.
The choice of laparotomy versus laparoscopy is
dependent on the risks of malignancy, the urgency
of the procedure, and the skills of the surgeon. As
surgeons gain training and experience, there has
been acceleration in the frequency of laparoscopic
operations during pregnancy. Laparoscopic sur-
gery has been commonly reported for treatment of
appendicitis and cholecystitis during pregnancy
with generally excellent results and minimal risk
of fetal loss and preterm delivery (23,24). Lapa-
roscopy for adnexal masses has become increas-
ingly standard management for benign ovarian
masses in nonpregnant women (25), and it has
been used in selected cases of ovarian cancer (26).
Consequently, it has also been adopted in manage-
ment of some pregnant patients with adnexal tu-
mors (24,2731). The presumptive benefits of
laparoscopy in pregnancy include a minimally in-
vasive approach with decreased recuperative time
and risk of fetal loss/preterm delivery compared
with laparotomy (23). The most recent case series
demonstrate that experienced laparoscopic sur-
geons are able to manage a spectrum of adnexal
pathologies, including ovarian cysts, adnexal tor-
sion, heterotopic pregnancy, and bleeding ovarian
cysts (2931).
Patients who potentially benefit the most by laparo-
scopic surgery of the adnexal mass should fit the fol-
lowing criteria: first or second trimester of pregnancy
and an ovarian mass that is not suspicious for malig-
nancy. Sound clinical judgment is critical for patient
selection and is clearly tempered by the surgeons skill
and experience. Caution is strongly advised when con-
sidering laparoscopic management of possible ovarian
cancer. Port site recurrences are noted in 2.3% of pa-
tients treated laparoscopically for their malignancy in a
recent review (32), although these were most common
in patients with primary peritoneal cancer and recurrent
cancer. Ovarian masses, especially suspicious ones,
must be removed intact when possible. Although it
remains controversial (25), spillage or rupture of a
malignant ovarian cyst was associated with decreased
survival in a recent study (33). The risk of adverse fetal
outcomes is not eliminated with a minimally invasive
approach. Soriano reported that the rates of spontaneous
abortion were 12.8% (5 of 39) in the first trimester and
8% (2 of 25) in the second trimester, although all
these miscarriages occurred in women with ovar-
ian torsion (30).
Patients with very large ovarian masses fall into 2
groups: those with large but simple unilocular cysts
and those with complex cysts. In both groups, con-
sideration can be given to expectant management
with surgical intervention reserved for symptoms re-
sulting from possible torsion or rupture or if the mass
risks obstructing vaginal delivery. Alternatively,
multiple case series report that aspiration of simple
unilocular cysts can avoid the need for major surgery
and provide symptomatic relief (16,34,35). However,
aspiration of a complex ovarian cyst runs the poten-
tial risk of malignant fluid spillage. Surgical inter-
vention for large complex ovarian masses should be
by laparotomy because these masses will not fit into
endoscopic bags.
Whether by laparoscopy or laparotomy, consider-
ation can be given to ovarian cystectomy if the US
criteria for a benign mass are met. Otherwise, oopho-
rectomy is appropriate. If there is a risk of disrupting
a corpus luteum cyst up to 12 weeks gestation, then
progesterone support is indicated.
Surgical management of ovarian cancer is dis-
cussed separately subsequently.
MATERNAL AND FETAL OUTCOMES
The adverse consequences to mother and fetus are
primarily a result of complications from the ovarian
mass and/or the interventions for the mass. If an
ovarian malignancy is present, then there are also
Managing Ovarian Masses During Pregnancy Y CME Review Article 467
risks of the cancer and the consequences of its treat-
ment as well. In reviewing the literature, it is often
difficult to determine if the adverse effects were the
result of the adnexal mass, the treatment of the mass,
or unrelated (eg, spontaneous abortion of fetus with
multiple anomalies in a patient with an ovarian
mass). Nevertheless, surgical intervention for benign
adnexal masses in pregnancy is associated with a
higher risk of preterm deliveries and low neonatal
birth weights compared with those patients who did
not have surgery (11).
Pain is the most common symptom in pregnant
patients with adnexal masses (26% in the Struyk
study [8]). This ranges from mild (which can be
managed expectantly) to severe (requiring emergent
laparotomy). The etiology of the pain is usually tor-
sion, although ovarian rupture also occurs. Whitecar
reported in his series that nearly half of the patients
with acute abdominal pain required emergency lap-
arotomy for ovarian masses and uterine leiomyomas
(7). The rate of torsion is quite variable in many
series, from 1% to 22% (5,15). Rupture appears to
be less common, ranging from 0% to 9% (7,8,15).
Obstruction of labor is also reported to occur in 2%
to 17% of patients (8,10). Other less frequent prob-
lems include bleeding and infection. Struyk noted the
relationship between tumor size and the risk of com-
plications as 35% for tumors between 5 and 6 cm in
diameter and up to 85% for larger tumors (8). How-
ever, no other authors reported such a high maternal
complication rate. Observational US studies by Bern-
hard and Zanetta report far lower complication rates
resulting from problems of torsion and obstruction of
labor (2,16).
Adverse fetal outcomes are most commonly the
result of an abdominal catastrophe from ovarian tor-
sion or rupture associated with abdominal surgery. In
many cases, the relationship of poor fetal outcomes
to the adnexal mass is not apparent. Elective surgical
intervention is preferably timed for the second tri-
mester in which the risk of subsequent fetal loss is
minimized (3). Whitecar found that adverse preg-
nancy outcomes, including preterm deliveries and
fetal loss, were significantly less frequent if laparot-
omy occurred before 23 weeks gestational age (odds
ratio 0.15, P .005) (7). The effectiveness of
tocolytics for suppression of preterm delivery is un-
clear. In Whitecars series, tocolytics were adminis-
tered in 13 patients who had surgeries in the second
and third trimesters. Six of 13 had preterm de-
liveries, although only 2 occurred within 2 weeks
of laparotomy.
MANAGEMENT OF OVARIAN CANCER
DURING PREGNANCY
Both ovarian malignancies and LMP ovarian tu-
mors should be surgically managed as in the non-
pregnant patient. If there is a preoperative suspicion
of malignancy, then a surgeon who is both knowl-
edgeable and capable should be available to complete
the standard surgical staging that includes peritoneal
washings, peritoneal biopsies, omentectomy, plus
pelvic and paraaortic lymphadenectomy (1). There
are situations in which complete surgical staging is
not feasible (eg, large gravid uterus that obscures the
surgical field, no qualified surgeon available), and
then the subsequent treatment must be based on
incomplete information. Fortunately, the majority of
both ovarian malignancies and borderline tumors are
low grade and low stage, which may allow for de-
finitive surgical staging to be completed either at the
time of cesarean section or postpartum.
Conservative, fertility-sparing surgery is appropriate
when the malignancy is apparently unilateral. Survival
does not appear to be compromised by sparing the
normal contralateral ovary (36,37). Borderline ovarian
tumors are candidates for either unilateral salpin-
gooophorectomy or even ovarian cystectomy. The re-
currence rates for borderline tumors are higher with
ovarian cystectomy, but almost all recurrences are sal-
vageable with further surgery (38,39). In the unusual
case in which gross metastatic disease is present, then
aggressive surgical debulking of the extraovarian dis-
ease is indicated. A decision regarding sparing of the
intrauterine pregnancy is based on gestational age. In
the first trimester, sacrifice of the pregnancy may be the
best choice, because exposure to subsequent chemo-
therapy may be teratogenic. In the second and third
trimesters, preservation of the pregnancy is gener-
ally recommended because limited clinical experi-
ence has failed to demonstrate an adverse fetal
effect with chemotherapy given during the preg-
nancy (see subsequently).
In all cases, use of expert frozen section pathology
is required for critical decision-making. If there is
any doubt regarding the frozen section pathologic
diagnosis, then it is best to defer definitive surgical
treatment until the final pathological report, espe-
cially if the tumor appears limited to a single ovary.
Fortunately, the accuracy of frozen section diagnosis
of ovarian tumors is over 90%, with one study re-
porting an overdiagnosis (false-positive) rate of 2.2%
and an underdiagnosis (false-negative) rate of 5.4%
(40). The frozen section accuracy rates are best for
468 Obstetrical and Gynecological Survey
benign tumors followed by malignant and then bor-
derline tumors.
The maternal and fetal outcomes associated with
ovarian cancer are a special situation. The adverse con-
sequences of the symptomatic malignant ovarian neo-
plasm and surgical intervention are applicable to the
previous discussion. There are also the unique risks of
the malignancy and its treatment to the mother and
fetus. In our own series derived from the CCR (11), the
following maternal outcomes were statistically more
frequent in patients with ovarian cancer and LMP tu-
mors compared with noncancer cases: cesarean section,
blood transfusions, hysterectomy, postpartum stay 5
days, and total hospital charges $10,000. Interest-
ingly, neonatal outcomes were not adversely affected
by the presence of the ovarian neoplasm, including low
birth weight, prematurity, neonatal death, readmission
to the hospital, prolonged hospital stay, and excessive
hospital charges. The risk of maternal death was
strongly associated with the timing of diagnosis. The
mortality rate of ovarian cancer was zero if the diagno-
sis was made 9 to 12 months before delivery, 5.6% if
made zero to 9 months before delivery, 6.3% if made at
delivery, and 18.5% if made zero to 12 months after
delivery.
The need for adjuvant chemotherapy after a diag-
nosis of ovarian cancer is based on the tumor stage,
histologic type, and grade. The potential benefits of
cancer control versus the risks to the mother and
fetus must be carefully balanced. In general, chemo-
therapy should not be delayed to allow for delivery
when the risk of cancer progression threatens mater-
nal survival. The findings of extraovarian metastases
and/or highly aggressive germ cell tumors usually
require urgent administration of chemotherapy.
However, patients with low-staged malignancies
with intermediate risk factors for recurrence (such as
adverse histology or high-grade tumors) might be
managed conservatively and then given chemother-
apy after delivery.
The risks of chemotherapy during pregnancy are
well described (41,42). Although almost all chemo-
therapeutic agents are toxic to animals, the risks to
the developing fetus appear to be less ominous ex-
cept for certain classes such as the antimetabolites
(42). The U.S. Food and Drug Administration assigns
risk categories to drug use during pregnancy, and most
chemotherapeutic agents are placed in the C, D, or X
categories (12). Chemotherapy should be avoided dur-
ing the first trimester, because the teratogenic risks of
fetal malformation are the greatest (43). In the
second and third trimesters, impairment of fetal
growth and functional development are a greater
concern than malformation. There does not appear
to be a greater risk of adverse fetal effects from
multiagent versus single agent chemotherapy (43).
Use of chemotherapy to treat ovarian cancer during
pregnancy has limited experience. Ebert noted only 11
cases reported from 1983 to 1995 of chemotherapy
given to patients with ovarian cancer (42). Chemother-
apy use has been reported in the treatment of both germ
cell and epithelial ovarian malignancies. Cytotoxic
agents reportedly used for ovarian cancer during preg-
nancy include cyclophosphamide, doxorubicin, vincris-
tine, bleomycin, etoposide, cisplatin, carboplatin, and
paclitaxel (41,44,45). In epithelial ovarian cancer, there
has been more experience with cisplatin than carbopla-
tin and only 2 case reports of paclitaxel use. Perinatal
complications included preterm delivery, gesta-
tional diabetes, and neonatal hyaline membrane
disease/respiratory distress syndrome. Long-term
infant outcomes (such as neurologic and physical
development) appear to be good for those fetuses
exposed to chemotherapy in utero (41). Therefore,
when there are strong indications for chemother-
apy use during pregnancy (in the second and third
trimesters), it should not be withheld as a result of
concerns of fetal effects.
Overall, the management of pregnant patients with
a malignant ovarian neoplasm is similar to what is
recommended in the nonpregnant state. The primary
difference lies in considering adjustments in the sur-
gical and/or chemotherapy treatment to allow for
fetal viability if the patient desires this. A limited
delay in the timing of definitive surgical resection or
chemotherapy until after delivery is unlikely to result
in a worse prognosis unless the patient has obvious
metastatic disease. In the setting of aggressive can-
cer, however, consideration can be given to preterm
delivery and/or use of chemotherapy during preg-
nancy if the maternal life is threatened.
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