REVIEW

URRENT C OPINION

Management of the adnexal mass in pregnancy

William Goh a, Justin Bohrer b, and Ivica Zalud c

Purpose of review With the increased use of ultrasonography in the first trimester, up to 1% of all pregnancies are diagnosed with an adnexal mass. Yet, the management of asymptomatic adnexal masses in pregnancy continues to be controversial as management guidelines are mainly based on casecontrol or observational studies. The purpose of this article was to review the recent literature and provide clinical guidance on patient management. Recent findings This review will highlight the increasing sensitivity of ultrasound imaging in diagnosing the rare malignant lesion, allowing for antenatal expectant management of benign asymptomatic adnexal masses until delivery or postpartum. The recent literature also highlights the well tolerated use of laparoscopy for the antenatal removal of suspicious or symptomatic masses and that expectant management of asymptomatic masses does not increase the risk of adverse pregnancy outcomes. Summary Most adnexal masses are benign and ultrasound characteristics can help guide the assessment of asymptomatic ovarian masses. When surgical management is chosen, laparoscopy can be safely performed in pregnancy. Ovarian torsion is a complication for persistent masses in pregnancy. Keywords adnexal mass, expectant management, laparoscopy, pregnancy

INTRODUCTION
The incidental finding of an adnexal mass in pregnancy has become a more common clinical scenario, and the reported incidence of ovarian masses in pregnancy has increased with the routine use of ultrasonography [1]. Although most ovarian masses are self-limiting, a minority will go on to develop complications that may have an adverse effect on maternal or fetal health. Thus, the presence of a mass is relevant to the practicing clinician. Because of the unique circumstances of pregnancy, there is controversy surrounding the diagnostic evaluation and appropriate management of these patients.

simple ovarian cysts defined as greater than or equal to 3 cm in the first trimester. Only 1.5% of patients in this cohort had persistent cysts beyond 14 weeks gestation. Goh et al. [6 ] analyzed 24 868 pregnancies and found a 4.9% incidence of adnexal masses in pregnancy. A large (defined as greater than or equal to 5 cm) persistent mass was observed in only 0.7% of individuals in this population. Bernhard et al. [4] analyzed over 18 000 obstetrical ultrasounds and found a rate of 2.3% incidence of adnexal masses in pregnancy. A total of 75% were simple cysts measuring less than 5 cm. No adverse outcomes (defined as surgical intervention, ovarian torsion or malignancy) were associated with these pregnancies. The remainder were large and complex
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INCIDENCE
The reported incidence of adnexal masses in pregnancy varies widely and is dependent on the criteria defining the mass that includes size and longevity of the lesion [2,3]. An overwhelming majority of small cysts discovered in the first trimester will be corpus luteum or other functional cysts and will regress spontaneously [4]. In a study of over 10 000 pregnancies, Glanc et al. [5] found a 5.3% incidence of
Hawaii Permanente Medical Group, Honolulu, Hawaii, bUniversity of Wisconsin School of Medicine, Madison, Wisconsin and cJohn A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA Correspondence to William Goh, MD, MSCR, Moanalua Medical Center, 3288 Moanalua Road, Honolulu, HI 96819, USA. E-mail: wgoh@ hawaii.edu Curr Opin Obstet Gynecol 2014, 26:4953 DOI:10.1097/GCO.0000000000000048
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Maternal fetal medicine

KEY POINTS
 Most adnexal masses in pregnancy are benign.  When malignant, adnexal masses in pregnancy tend to be low stage and nonepithelial.  Laparoscopy in the second trimester can be safely performed for persistent masses.  Ovarian torsion may complicate patients who are managed expectantly.

masses, and there was an over 90% spontaneous resolution rate with observation in this subgroup.

DIFFERENTIAL DIAGNOSIS
Although the majority of adnexal masses resolve without intervention, some persist and can be associated with adverse outcomes. Ultrasound characteristics of a persistent mass can aid in generating a differential diagnosis (Table 1). Most simple cysts are physiological or functional cysts, or unilocular serous or mucinous cystadenomas [7]. Complex ultrasound features can be associated with corpus luteum, teratomas, endometriomas, or theca lutein cysts. Solid masses may represent fibromas or leiomyomas. Data from several series are remarkably consistent in predicting adnexal disease [6 ,7]. The most common adnexal masses found in pregnancy are dermoids, followed by cystadenomas. The vast majority of masses in pregnancy are benign, but up to 5% do represent a malignant tumor [8]. Using a population-based review of over 3 million deliveries, Smith et al. found that ovarian cancer was the fifth most common malignancy
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diagnosed during pregnancy (0.04 cases per 1000 pregnancies) after breast, thyroid, and Hodgkins disease. Leiserowitz et al. [9] analyzed California hospital discharge records from 1991 to 1999 and found a 0.93% incidence of ovarian malignancy in pregnancy or approximately 1 cancer per 56 000 deliveries. A total of 1.25% of these masses were borderline tumors. Therefore, the cumulative incidence of clinically relevant ovarian neoplasms in pregnancy was 1 in 23 800 deliveries. The summary stages of ovarian cancer and borderline tumors were localized 65.5%/81.7%, regional 6.9%/7.8%, remote 23%/4.4%, and unknown 4.6%/6.1%, respectively. The specific maternal mortality rate in this cohort was 4.7%. When the Leiserowitz cohort was examined pathologically, 51% were epithelial (both malignant and borderline) [9]. Germ cell tumors accounted for 39% of this cohort, and were primarily dysgerminomas and malignant teratomas. The lower stage and higher proportion of germ cell tumors are in line with the generally younger age of pregnant women.

DIAGNOSTIC MODALITIES
Adnexal masses in pregnancy can be evaluated as given below:

Ultrasound
Ultrasound (both transvaginal and transabdominal) is often the best first-line imaging modality used to evaluate adnexal masses in pregnancy [10 ]. There have been numerous scoring systems proposed to diagnose ovarian malignancy, but no single system has been shown to be sufficiently accurate [11]. Sonographic features associated with an increased risk of malignancy include size greater than 7 cm, solid components or heterogeneous/complex appearance, excrescences/papillary projections, internal septations, bilaterality, irregular borders, solid components, increased vascularity, low resistance blood flow, and ascites [11]. Zanetta et al. [12] prospectively followed 82 cysts in 79 pregnant women. Expectant management was used except in symptomatic patients or suspected malignancy (which they defined as solid parts, irregular capsule or border, ascites, and irregular vascularization). This group showed that ultrasound allows for the differential diagnosis of benign complex masses and even borderline-like tumors. Similarly, other studies have shown that the more complex a mass is on ultrasound (septations and solid components), the higher the risk of malignancy [13]. Conversely, Whitecar et al. [3] showed that 89 of 91 masses diagnosed with a simple cyst on ultrasound were
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Table 1. Differential diagnosis of an adnexal mass in pregnancy

Benign Corpus luteum Simple cyst Hemorrhagic cyst Dermoid Cystadenoma Endometrioma Pedunculated fibroid Ovarian hyperstimulation Hydrosalpinx Paraovarian/tubal cyst Theca lutein cyst Malignant Germ cell tumors Epithelial tumors Low malignant potential Invasive Sex cord stromal tumors

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Management of the adnexal mass in pregnancy Goh et al.

found to be benign when examined pathologically. Doppler flow evaluations have been used to improve the sensitivity of ultrasound in diagnosing ovarian cancer in nonpregnant patients. Unfortunately, there is a significant overlap in the blood flow patterns between malignant and benign lesions in pregnancy [14].

Ovarian torsion
Torsion of the adnexa accounts for 3% of all surgical emergencies of acute gynecologic complaints [18]. The incidence of ovarian torsion in pregnancy is felt to be a rare event, with a reported incidence of 110 per 10 000 spontaneous pregnancies [19]. In a multicenter cohort, Goh et al. [6 ] found that of 12 of 118 patients admitted with an adnexal mass and pain, 10 of 118 were found to have ovarian torsion (8.5% incidence). This was similar to an earlier study by Schmeler et al. [20] that found a 6.8% incidence of ovarian torsion in masses measuring greater than 5 cm in pregnancy. Hasson et al. [19] showed that the presentation of adnexal torsion is similar in pregnant and nonpregnant women, and the majority complained of acute abdominal or pelvic pain that lasted for several hours. Patients in this casecontrol cohort described the pain as acute, sharp, and intermittent or constant. Interestingly, 43% of pregnant women with ovarian torsion did not have peritoneal irritation signs compared to 19% of nonpregnant patients. A total of 63% of pregnant women had associated nausea and vomiting. In both pregnant and nonpregnant torsions, there was high false-negative normal Doppler blood flow in patients later found to have surgically confirmed adnexal torsion. Pregnancies conceived through assisted reproductive techniques are at an increased risk of ovarian torsion, likely because of the increased risk of ovarian hyperstimulation. Smorgick et al. [21] reviewed 38 cases of surgically proven torsion in pregnancy and found that 49% were conceived either through ovulation induction or in-vitro fertilization. The size of an adnexal mass may play a role in the risk of torsion. Koo et al. [18] found that a mass size of 610 cm had a significantly higher risk of torsion than a mass less than 6 cm. As with the risk of malignancy, masses of 1015 cm were not at increased risk of torsion when compared with masses less than 6 cm. Yen et al. [22] prospectively followed 174 pregnant patients with adnexal masses and found that masses measuring between 6 and 8 cm in size had a 22% incidence of ovarian torsion. Ovarian torsion occurs most commonly in the first trimester [18,22]. Koo et al. [18] found an incidence of 68% in the first trimester, 20% in the second, and 22% in the third. Yen et al. [22] found that 60% of ovarian torsions occurred between the 10th and 17th week of gestation, and only 6% occurred after 20 weeks.
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MRI
Unlike CT, which exposes the mother and fetus to 24 rads per examination, MRI is considered to be well tolerated in pregnancy and can be useful in evaluating up to 20% of sonographically indeterminate adnexal lesions [15]. Masses of uncertain origin and solid or complex cystic lesions can be evaluated with MRI, which has been shown to be accurate for identifying the origin of a mass and characterizing its tissue content. MRI may also be useful in evaluating the extent of invasive malignant disease and in diagnosing the bowel processes such as appendicitis or inflammatory bowel disease. We must emphasize though that the use of MRI in pregnancy should be considered only when there is an inconclusive ultrasound result.

Tumor markers
The interpretation of tumor markers in pregnancy poses a unique challenge. CA-125, a commonly used epithelial ovarian cancer tumor marker, can be elevated in pregnancy during the first trimester and postpartum in normal pregnancy [16]. After the first trimester, however, a severely elevated CA-125 (1000 10 000) in the second trimester or beyond should alert the clinician to the possibility of a malignancy. Other serum markers used for aneuploidy screening may also be elevated with an ovarian malignancy in pregnancy. Alpha feto-protein elevations (greater than nine multiples of the median) can be seen with germ cell tumors [17]. Other tumor markers such as beta human chorionic gonadotropin and lactate dehydrogenase are of limited value in pregnancy because they can be altered by pregnancy alone. As a general rule, tumor markers should not be routinely drawn in the setting of pregnancy because of the limitations previously discussed. However, if tumor markers have been drawn, or an abnormality is incidentally detected using a marker for aneuploidy screening, the results should be interpreted cautiously taking into consideration the physiologic changes of pregnancy.

COMPLICATIONS OF ADNEXAL MASSES

The complications associated with persistent masses include the following:

Labor dystocia and ovarian rupture

Other adverse effects from an adnexal mass have been reported in pregnancy. Goh et al. [6 ] found
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that 25% of patients who had an adnexal mass underwent a cesarean section for labor dystocia. There are reports of hemoperitoneum resulting from ovarian rupture from enlarged adnexal masses [23].

Malignancy
The management of ovarian malignancy in pregnancy should be multidisciplinary comprising of obstetricians, neonatologists, medical and gynecologic oncologists, and psychologists [24 ]. After surgery, chemotherapy regimens are generally prescribed, but these drugs have risks of fetal toxicity that are mainly related to the gestational age. During organogenesis (between weeks 4 and 12 of gestation), there is a high susceptibility to teratogens and fetal malformation [25]. During the second and third trimester, chemotherapy can be associated with growth restriction and prematurity, though the risk of malformations is low [26].
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The incidental detection of adnexal masses at the time of a cesarean delivery is not rare with an incidence of 1 of 329 [30]. Up to 5% of the masses were bilateral and the majority were preoperatively undiagnosed mature cystic teratomas. The recommendation would be cystectomy for a simple cyst and excision when the mass is large or heterogeneous in nature for pathologic analysis [31]. Schwartz et al. also recommend removal of paraovarian or paratubal cysts so as not to confound further imaging studies.

Expectant
The benefits of expectant management include avoidance of surgery and its associated complications. The risk of expectant management is the risk of ovarian torsion that could have been avoided with a laparoscopic procedure, along with the risk of pregnancy loss with emergent surgery. Goh et al. [6 ] reviewed 126 pregnancies complicated by persistent ovarian masses greater than or equal to 5 cm. A total of 0.3% of this cohort were admitted for pain and 8.3% eventually were diagnosed with ovarian torsion. They found that the majority of patients with adnexal masses can be conservatively managed if there are no ultrasound findings suspicious for malignancy, without a significant increase in antenatal or postpartum complications. Schmeler et al. [20] reviewed 177 pregnancies with adnexal masses. One-third of this cohort had surgery for torsion and suspicions for malignancy. The remaining patients were observed and operated via cesarean section or postpartum again without significant differences on obstetrical outcomes between the patients who had antepartum surgery and those managed expectantly. There is no consensus on the management strategies of ovarian masses with reference to the size of the mass. Recently, Koo et al. [18] analyzed over 470 women with adnexal masses who underwent surgery during their pregnancies. Masses of at least 15 cm had a 12-fold higher risk of malignancy compared with the masses that measured less than 6 cm. For masses of 1015 cm, however, the risk of malignancy was not higher than those of masses less than 6 cm. Earlier reviews [32] have used cutoffs of 5 cm to triage patients after a diagnosis of adnexal masses is made. Glanc et al. recommend serial ultrasounds in asymptomatic women with a mass greater than 5 cm until 16 weeks to allow for spontaneous resolution of the mass. If the mass increased in size or complexity, then further evaluation (by imaging or surgery) was recommended.
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MANAGEMENT
The management options of adnexal masses in pregnancy are as follows:

Surgery
When there is a suspicion for malignancy or if a patient has symptoms, surgical intervention is warranted. Traditionally, if the mass was solid or had mixed solid and cystic features and ascites, a midline laparotomy was performed to remove the mass, obtain a diagnosis, examine the contralateral ovary, obtain peritoneal washings, and complete a staging procedure if malignancy was confirmed [17]. Until the 1990s, pregnancy had been considered a contraindication to use laparoscopy. The laparoscopic approach in pregnancy for maternal ovarian torsion offers several advantages over an open laparotomy, including decreased postoperative pain, lower narcotic use, and lower wound infection rates [27]. Koo et al. [28] analyzed 88 pregnancies who underwent laparoscopic surgery for adnexal masses in pregnancy (mean gestational age 11.6 weeks) and found that obstetrical complications such as low birth weight, preterm birth, tocolysis, low Apgar scores, and fetal anomalies were acceptable. Some concerns for laparoscopic surgery in pregnancy are decreased uterine blood flow, carbon dioxide absorption, fetal hypotension, and fetal hypoxia [17]. In an analysis of women undergoing both first and second trimester laparoscopic procedures, mean uterine resistance index and umbilical artery pulsatility index remained constant during the procedures, indicating that laparoscopy did not modify uteroplacental perfusion [29 ].
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CONCLUSION
The majority of adnexal masses diagnosed during pregnancy will be benign. Laparoscopy in
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Management of the adnexal mass in pregnancy Goh et al.

pregnancy is well tolerated and should be the primary option in the symptomatic patient or if cancer is suspected. For asymptomatic patients, both prophylactic removal of the mass and expectant management are the reasonable options. Expectant management may best serve patients who wish to avoid the risks associated with surgery in pregnancy. However, these patients should be counseled on the risk of torsion and the possible need for a more invasive procedure later in gestation. Additional prospective studies are needed to determine the best treatment plan for patients with an adnexal mass in pregnancy. Acknowledgements None. Conflicts of interest Declaration of interest: The authors report no conflicts of interest.

REFERENCES AND RECOMMENDED READING

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