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Etiologies of ovarian masses reflect the patient's age; benign entities predominate. Expectant management is recommended for most pregnant patients. Surgery is indicated for large and / or symptomatic tumors. Chemotherapy has been used during pregnancy with minimal fetal harm.
Etiologies of ovarian masses reflect the patient's age; benign entities predominate. Expectant management is recommended for most pregnant patients. Surgery is indicated for large and / or symptomatic tumors. Chemotherapy has been used during pregnancy with minimal fetal harm.
Etiologies of ovarian masses reflect the patient's age; benign entities predominate. Expectant management is recommended for most pregnant patients. Surgery is indicated for large and / or symptomatic tumors. Chemotherapy has been used during pregnancy with minimal fetal harm.
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. 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