The finding of an incidental adnexal mass in pregnancy has become more common with the routine use of ultrasonography in prenatal care. Approximately 1–4% of pregnant women are diagnosed with an adnexal mass.1,2 The majority of these masses are corpus luteum or other functional cysts that usually resolve by 16 weeks of gestation. Some adnexal masses persist, and 1–8% of these masses represent malignant tumors.3–7
The management of asymptomatic adnexal masses that persist during pregnancy remains controversial. Traditionally, these patients are treated by exploratory laparotomy and tumor resection at 16–20 weeks of gestation.8 Surgery is performed to rule out malignancy and prevent complications such as torsion, cyst rupture, and obstruction of labor. Abdominal surgery during pregnancy is associated with its own complications, including spontaneous miscarriage, rupture of membranes, preterm labor, and preterm birth.9 Advances in ultrasonography have caused practitioners to question whether surgical intervention is warranted in all pregnant patients with adnexal masses. High-resolution imaging provides increased sensitivity to distinguish benign from malignant disease.1,7 Observation has therefore been proposed for select patients with an adnexal mass during pregnancy.5,10
Although several institutions have published reviews of small numbers of cases of adnexal masses in pregnancy, no specific protocols exist for the appropriate management of these patients.1,4–6,10–12 In addition, no prospective studies randomizing between observation and surgery have been performed. This study reviews the pathologic and obstetric outcomes of patients diagnosed with an adnexal mass (≥ 5 cm) during pregnancy at a large tertiary care hospital. Our specific aim was to address the risk of antepartum surgery as opposed to delaying surgery until the postpartum period in this cohort of patients.
SUBJECTS AND METHODS
This study was an institutional review board–approved review of records from a single hospital between the years 1990 and 2003. The hospital information system was queried for patients with an adnexal mass or ovarian neoplasm during pregnancy by using International Classification of Diseases, Ninth Revision, codes. Patients were included in this study if the mass was 5 cm or greater in size.
The medical records were reviewed for patient age, gravity/parity, gestational age at diagnosis, presenting symptoms, and physical examination findings. Information was also collected regarding history of ovulation induction agent use and treatment type. For patients undergoing surgery, the type of surgery, type of anesthesia, tocolytic use, gestational age, and duration of surgery were recorded. Pregnancy outcome, complications, and surgical pathology were reviewed. Ultrasound examinations were evaluated for mass size, presence/absence of septae, echogenicity, wall thickness, papillary projections, border characteristics, and vascularity. Any mass with septations, solid components, or papillary projections was considered complex.
Data were analyzed using Fisher exact test and Kruskal-Wallis rank sum test. A value of P < .05 was considered statistically significant. All analyses were performed using STATA 8.0 (College Station, TX). Our sample is a convenience sample of patients seen at our institution over the past 14 years. No a priori sample size calculation was performed because our study is descriptive rather than analytic.
Between 1990 and 2003, 127,177 deliveries were performed at our institution. Sixty-three of these patients (0.050%) were found to have an adnexal mass 5 cm or greater in diameter. Final pathologic diagnosis was available for 59 patients. The remaining 4 patients were lost to follow-up and excluded from the analysis. Median maternal age at diagnosis was 30 years, with a range of 15–41 years. The median gestational age at diagnosis was 12 weeks (range 4–41 weeks). Thirty women (51%) were nulliparous. A history of ovulation induction agent use was reported by 5 patients. Fifty-four patients (92%) were asymptomatic, and the remaining 5 women (8%) presented with pain. The mass was diagnosed on routine prenatal ultrasound examination in 47 women (80%) and at the time of cesarean delivery in 12 patients (20%).
Ultrasound examinations were available for 31 patients and were reviewed by 2 board-certified radiologists with expertise in gynecologic imaging. For the remaining 28 patients, the ultrasound reports were reviewed rather than the images, which had been destroyed because they were more than 5 years old. The median mass size was 7.4 cm in largest diameter (range 5.0–19.0 cm). Seventy-two percent of masses were complex, and 28% were simple cysts. Septations were noted in 17% of cases. There were no patients with bilateral masses.
Seventeen patients (29%) underwent surgery during pregnancy at the discretion of their physicians (Table 1). Laparotomy was performed in 15 cases and laparoscopy in 2 cases. The median gestational age at time of surgery was 17 weeks(range 9–36). Four patients underwent emergent surgery secondary to ovarian torsion at 9, 13, 25, and 34 weeks of gestation. In the first 2 patients, the mass had been previously identified and was being followed. Both patients underwent cystectomy for torsion and subsequently had uncomplicated spontaneous vaginal deliveries at term. The third patient had preterm premature rupture of membranes at 23 weeks of gestation. She developed abdominal pain at 25 weeks of gestation and was diagnosed with a torsed adnexal mass requiring exploratory laparotomy with oophorectomy. She later developed chorioamnionitis at 28 weeks of gestation, resulting in delivery. The fourth patient was being followed for her adnexal mass when she presented with torsion at 34 weeks of gestation. She underwent a repeat cesarean delivery and unilateral oophorectomy. There were no adverse fetal outcomes.
The remaining 13 patients had surgery because of ultrasound findings that were concerning for malignancy. These findings included mixed cystic and solid components, septations, papillary projections, wall nodularity, and poorly defined borders. Postoperatively, one patient experienced vaginal bleeding, and one had preterm contractions. Both of these women delivered at term without complications. None of the patients experienced rupture of membranes or pregnancy loss as a result of antepartum surgery. The remaining patients were observed, with surgery performed in the postpartum period or at time of cesarean delivery. Six of the 17 patients had surgery in the first half of this 13-year study, and 11 patients underwent surgery in the second half.
The pathologic diagnoses are shown in Table 2. The most common diagnosis was dermoid cyst. Four patients (6.8% of masses, 0.0032% of deliveries) were diagnosed with a malignancy (Table 3). In addition, one patient had a tumor of low malignant potential. Four of the 5 women were nulliparous, compared with 24 (44%) of the women with benign masses. The malignant masses all had complex features on ultrasonography, compared with 16 (30%) of benign masses (P < .01). All 5 patients were found to have stage I disease at the time of antepartum surgery. There were no statistically significant differences in mass size, gestational age at delivery, mode of delivery, infant weight, or Apgar scores between the patients with malignant and those with benign masses (Table 4). All 5 patients with a malignancy are currently without evidence of disease, and 2 of the patients had subsequent pregnancies that were uncomplicated.
The median gestational age at delivery for all patients was 39.3 weeks (range 27.9–42.6 weeks). Thirty-eight patients (70%) had cesarean deliveries. Thirteen were scheduled repeat cesareans. Twenty-four were performed for obstetrical reasons, including breech presentation (n = 7), arrest of dilatation (n = 5), arrest of descent (n = 4), fetal distress (n = 4), macrosomia (n = 2), and twin gestation (n = 2). Cystectomy or oophorectomy for the adnexal mass was performed at the time of cesarean delivery in all cases. In addition, one patient had a planned primary cesarean delivery with ovarian cystectomy specifically because of the adnexal mass. Median Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. The median infant weight was 3,305 g, with a range of 1,070–4,515 g. There were no statistically significant differences in obstetrical outcomes between the patients who had antepartum surgery and those managed with observation.
The finding of an adnexal mass during pregnancy has been reported to range from 1 in 25 to 1 in 8,000 pregnancies.2–4,6–8,13 This large variation is due in part to differences in the definition of clinically significant masses. In our study, we chose to review only cases where the mass was 5 cm or greater in size. Although it is possible to have small malignant masses, previous studies have reported no malignancies during pregnancy in lesions less than 5 cm in largest diameter.1,10,12,14 In addition, the majority of smaller masses have been shown to resolve spontaneously.1,10,14 Table 5 compares our findings with previous studies using similar parameters.
In our cohort, 4 patients (6.8%) were diagnosed with a malignancy. This is a slightly higher rate than that in previous reports4–7,11,12 and is presumably due to our strict inclusion criteria of masses greater than 5 cm. One patient in our study was diagnosed with a mixed dysgerminoma/endodermal sinus tumor. Although malignant germ-cell tumors account for fewer than 5% of ovarian cancers, they occur in young women and are occasionally diagnosed in pregnancy.15,16 Studies similar to ours have found that germ-cell and sex cord–stromal tumors represent a high proportion of the malignancies diagnosed in pregnancy.4–6 Tumors of low malignant potential are also more common in reproductive-age women.17 Our findings are consistent with previous reports showing that tumors of low malignant potential represent 0–8.9% of adnexal masses diagnosed during pregnancy.4–7,11,12
There have been significant recent improvements in ultrasound technology, resulting in the ability to better characterize adnexal masses.18,19 These include the development of transvaginal transducers, as well as improved image resolution technology. In addition, the use of color doppler imaging has been shown to significantly improve the ability to distinguish benign from malignant masses. 20–22 Bromley and Benaceraff evaluated the ultrasound characteristics of 131 lesions in 125 patients. Eleven percent of masses had findings suggestive of malignancy, with one of these patients having ovarian carcinoma. The authors were able to recognize the malignancy, as well as correctly identify 95% of dermoids, 80% of endometriomas, and 71% of simple cysts. They concluded that ultrasonography can be used to correctly determine the cause of most adnexal masses in pregnancy and that antepartum surgery can be avoided in most cases.7 Our findings concur with these conclusions, with all cancer cases in our study correctly identified as having ultrasound findings suggestive of malignancy. Of note, there was no statistically significant difference in size between the malignant and benign masses. However, our sample size and power to address this question was limited, raising the possibility of a type II error.
Seventeen women (29%) in our cohort underwent antepartum surgery. Previous reports have shown increased rates of miscarriage, premature rupture of membranes, and preterm delivery associated with abdominal surgery during pregnancy.4,5,9 Usui et al5 reported on 68 patients who underwent antepartum surgery for adnexal masses. Three percent of the women had spontaneous abortions, 12% delivered before 37 weeks of gestation, and there were 3 (5%) perinatal deaths. No studies to date have examined the psychological effects on women undergoing surgery during pregnancy. By postponing surgery until the postpartum period, one can avoid the possible adverse effects of surgery and anesthesia on the fetus and mother. In addition, if a cesarean delivery is performed for obstetrical reasons, ovarian cystectomy can be done at that time, avoiding the need for additional surgical intervention.
Ovarian torsion is a potential complication of observing large adnexal masses during pregnancy. Four patients (6.8%) in our cohort required emergent surgery due to torsion. This is slightly higher than reported in similar studies (0–5.4%, Table 5).4–6,11,12 Hess et al23 reported a higher rate of adverse pregnancy outcome associated with emergent surgery (6/15, 40%), compared with elective removal of the adnexal mass in the second trimester (1/39, 2%). More recent studies have shown significantly lower complication rates associated with emergent surgery.6,7 Whitecar et al4 reported no adverse pregnancy outcomes in 7 patients (5.4%) who underwent emergent surgery for torsion. In our study, one patient developed chorioamnionitis 3 weeks after surgery, requiring delivery at 28 weeks of gestation. This was presumed to be related to the preterm premature rupture of membranes that occurred at 23 weeks of gestation and not caused by the antepartum surgery for torsion. There were no adverse maternal or fetal outcomes in any of the other women who underwent antepartum surgery.
Only 3 patients in our study had tumor markers measured as part of their evaluation. They all had normal CA 125 levels and were subsequently diagnosed with benign disease. In the patients diagnosed with a malignancy, tumor markers were used postoperatively to monitor treatment with chemotherapy. For several reasons, we do not recommend the use of tumor markers as part of the evaluation of adnexal masses in pregnancy. Serum CA 125 levels have been shown to be elevated and to fluctuate widely in normal pregnancy, particularly in the first trimester and immediately following delivery.24,25 They can also be elevated in many of the benign conditions that affect this population, particularly endometriomas.26 In addition, CA 125 levels are elevated in only 50% of patients with early stage ovarian cancer.27,28 Normal or abnormal serum CA 125 levels should not change the approach to the patient with an adnexal mass during pregnancy, and ultrasound characteristics are of principle importance in the evaluation and management of these women.
Our study has several limitations. The data were collected in a retrospective manner. Additionally, the choice of operative intervention versus observation during pregnancy was made at the discretion of the referring physician and was therefore not uniform. The study included patients treated over a 13-year time period. There have been significant improvements in ultrasound technology during this time, which may have influenced the management of these patients. In addition, only 15% of cases were prospectively presented to our multidisciplinary tumor board, which includes gynecologic oncologists and radiologists with expertise in ovarian pathology. Color doppler imaging was not used consistently among the patients, so we are unable to comment on its contribution to distinguishing malignant from benign masses in this population. The small sample size of our study is also a limitation. Four of 59 cases (6.8%) resulted in torsion (95% confidence limits 1.9%, 16.5%). The relatively imprecise confidence limits are due to our small sample size and large margin of error. A sample size of 300 masses in pregnancy would be required for 95% confidence limits of ±4% (3%, 11%).
The strengths of our study include the fact that it is a large series of women with clinically significant adnexal masses observed during pregnancy. Recent studies are important because ultrasound technology has changed rapidly, and we are now better able to characterize masses based on imaging. We conclude that the sonographic characterization of masses can assist in determining which patients are at risk for malignancy and require antepartum surgery, as opposed to those patients with benign disease who can be followed. Our data support observation with postpartum surgery for select patients with large, persistent adnexal masses in pregnancy, provided the ultrasonographic findings are not highly suspicious for malignancy. Further studies are needed to better define the imaging and patient characteristics that distinguish between benign and malignant masses in this population.
1. Hill LM, Connors-Beatty DJ, Nowak A, Tush B. The role of ultrasonography in the detection and management of adnexal masses during the second and third trimesters of pregnancy. Am J Obstet Gynecol 1998;179:703–7.
2. Nelson MJ, Cavalieri R, Graham D, Sanders RC. Cysts in pregnancy discovered by sonography. J Clin Ultrasound 1986;14:509–12.
3. Creasman WT, Rutledge F, Smith JP. Carcinoma of the ovary associated with pregnancy. Obstet Gynecol 1971;38:111–6.
4. Whitecar MP, Turner S, Higby MK. Adnexal masses in pregnancy: a review of 130 cases undergoing surgical management. Am J Obstet Gynecol 1999;181:19–24.
5. Usui R, Minakami H, Kosuge S, Iwasaki R, Ohwada M, Sato I. A retrospective survey of clinical, pathologic, and prognostic features of adnexal masses operated on during pregnancy. J Obstet Gynaecol Res 2000;26:89–93.
6. Sherard GB 3rd, Hodson CA, Williams HJ, Semer DA, Hadi HA, Tait DL. Adnexal masses and pregnancy: a 12-year experience. Am J Obstet Gynecol 2003;189:358–63.
7. Bromley B, Benacerraf B. Adnexal masses during pregnancy: accuracy of sonographic diagnosis and outcome. J Ultrasound Med 1997;16:447–54.
8. Novak ER, Lambrou CD, Woodruff JD. Ovarian tumors in pregnancy: an ovarian tumor registry review. Obstet Gynecol 1975;46:401–6.
9. Mazze RI, Kallen B. Reproductive outcome after anesthesia and operation during pregnancy: a registry study of 5,405 cases. Am J Obstet Gynecol 1989;161:1178–85.
10. Thornton JG, Wells M. Ovarian cysts in pregnancy: does ultrasound make traditional management inappropriate? Obstet Gynecol 1987;69:717–21.
11. Platek DN, Henderson CE, Goldberg GL. The management of a persistent adnexal mass in pregnancy. Am J Obstet Gynecol 1995;173:1236–40.
12. Bernhard LM, Klebba PK, Gray DL, Mutch DG. Predictors of persistence of adnexal masses in pregnancy. Obstet Gynecol 1999;93:585–9.
13. Agarwal N, Parul Kriplani A, Bhatla N, Gupta A. Management and outcome of pregnancies complicated with adnexal masses. Arch Gynecol Obstet 2003;267:148–52.
14. Osmers R. Sonographic evaluation of ovarian masses and its therapeutical implications. Ultrasound Obstet Gynecol 1996;8:217–22.
15. Zanagnolo V, Sartori E, Galleri G, Pasinetti B, Bianchi U. Clinical review of 55 cases of malignant ovarian germ cell tumors. Eur J Gynaecol Oncol 2004;25:315–20.
16. Gershenson DM. Update on malignant ovarian germ cell tumors. Cancer 1993;71:1581–90.
17. Barnhill DR, Kurman RJ, Brady MF, Omura GA, Yordan E, Given FT, et al. Preliminary analysis of the behavior of stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study. J Clin Oncol 1995;13:2752–6.
18. Mais V, Guerriero S, Ajossa S, Angiolucci M, Paoletti AM, Melis GB. The efficiency of transvaginal ultrasonography in the diagnosis of endometrioma. Fertil Steril 1993;60:776–80.
19. Mais V, Guerriero S, Ajossa S, Angiolucci M, Paoletti AM, Melis GB. Transvaginal ultrasonography in the diagnosis of cystic teratoma. Obstet Gynecol 1995;85:48–52.
20. Wheeler TC, Fleischer AC. Complex adnexal mass in pregnancy: predictive value of color Doppler sonography. J Ultrasound Med 1997;16:425–8.
21. Guerriero S, Ajossa S, Lai MP, Risalvato A, Paoletti AM, Melis GB. Clinical applications of colour Doppler energy imaging in the female reproductive tract and pregnancy. Hum Reprod Update 1999;5:515–29.
22. Cohen L, Fishman DA. Ultrasound and ovarian cancer. Cancer Treat Res 2002;107:119–32.
23. Hess LW, Peaceman A, O’Brien WF, Winkel CA, Cruikshank DP, Morrison JC. Adnexal mass occurring with intrauterine pregnancy: report of fifty-four patients requiring laparotomy for definitive management. Am J Obstet Gynecol 1988;158:1029–34.
24. Aslam N, Ong C, Woelfer B, Nicolaides K, Jurkovic D. Serum CA125 at 11–14 weeks of gestation in women with morphologically normal ovaries. BJOG 2000;107:689–90.
25. Spitzer M, Kaushal N, Benjamin F. Maternal CA-125 levels in pregnancy and the puerperium. J Reprod Med 1998;43:387–92.
26. Koninckx PR, Riittinen L, Seppala M, Cornillie FJ. CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis. Fertil Steril 1992;57:523–30.
27. Einhorn N, Sjovall K, Knapp RC, Hall P, Scully RE, Bast RC Jr, et al. Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol 1992;80:14–8.
28. Einhorn N, Bast RC Jr, Knapp RC, Tjernberg B, Zurawski VR Jr. Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer. Obstet Gynecol 1986;67:414–6.