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The management of ovarian pathology in pregnancy
Best Practice & Research Clinical Obstetrics and Gynaecology 23 (2009) 539–548
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The management of ovarian pathology in pregnancy Tommaso Bignardi, MD, Associate Lecturer *, George Condous, MRCOG, FRANZCOG, Associate Professor Acute Gynaecology, Early Pregnancy, and Advanced Endosurgery Unit, Nepean Centre for Perinatal Care, Nepean Clinical School, University of Sydney, Nepean Hospital Penrith, Sydney, Australia
Keywords: ovarian cysts adnexal masses ovarian cancer pregnancy expectant management
The extensive use of ultrasound in early pregnancy populations has led to more ovarian lesions being diagnosed incidentally in asymptomatic gravid women. The majority of these lesions are physiological in nature and tend to resolve spontaneously as the pregnancy progresses. Expectant management or a ‘‘watch and wait’’ approach is the benchmark standard of care for a woman with an ovarian mass diagnosed during pregnancy. This approach assumes the woman is relatively asymptomatic, and the likelihood of malignancy is negligible. The prevalence of malignancy in pregnancy is rare indeed, i.e. 1 in 15,000–32,000. It is the discriminatory ability of ultrasound, in experienced hands, to distinguish between benign and malignant ovarian lesions that allow appropriate triaging during pregnancy. Discriminating benign from malignant masses is crucial not only to optimize the management of malignancies, but also to avoid unnecessary intervention that may adversely affect maternal or foetal outcomes. This review will focus on the management of ovarian masses in pregnancy. Ó 2009 Elsevier Ltd. All rights reserved.
For the purposes of this review, we define an ovarian/adnexal mass as an enlarged structure in the region of the pelvic adnexae that can either be palpated on examination or visualised using imaging techniques. Several conditions can be associated with an adnexal mass - these include malignancies arising from the ovary or the fallopian tube, metastatic disease from a different site (i.e. breast, gastrointestinal tract), as well as many benign pathologies.
* Corresponding author. E-mail address: [email protected] (T. Bignardi). 1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2009.01.009
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Prevalence, etiology and natural history We performed an electronic search in the database MEDLINE and a manual search of reference lists of review articles and original articles, using the keywords: ‘‘ovarian cysts’’, ‘‘adnexal masses’’ and ’’pregnancy’’. A summary of the relevant studies from this search is reported in Table 1.1–20 Data about the prevalence of ovarian masses in pregnancy and the risk of malignancy are limited to retrospective cohort or population-based studies. Few studies are prospective longitudinal follow-up studies.3–6,8 According to these studies, the prevalence of an ovarian mass in pregnancy varies between 0.19 and 8.8%. The prevalence of malignancy among ovarian masses diagnosed in pregnancy varies from 0 to 6.8%. Ovarian tumours of low malignant potential (LMP or borderline ovarian tumours) are usually considered as ovarian malignancy in these studies. As the frequency of ovarian cancer depends on age, the relatively low prevalence of cancer found in ovarian masses diagnosed in pregnancy reflects the younger age of the women studied compared with women around the time of the menopause and beyond, who are more commonly diagnosed with ovarian cancer. The reported prevalence ranges quite widely between studies. This may reflect differences in referral patterns and the nature of the
Table 1 Prevalence of ovarian masses and ovarian malignancies in pregnancy. Author
Study type
Number of Prevalence of Deliveries inclusion masses ovarian masses criteria
Bernhard LM et al.6
Prospective study; ultrasound follow-up
422
2.3%
18,391
Schmeler KM et al.13 Bromley B et al.3
63 125
0.05% N/A
127,177 N/A
Duic´ Z et al.14
Retrospective analysis Prospective study; ultrasound follow-up Case series
8
0.05%
16472
Whitecar MP et al.2 Kumari I et al.15 Hess LW et al.1 Purnichescu V et al.17
Retrospective analysis Retrospective analysis Case series Case series
130 20 54 21
0.08% 0.12% 0.08% N/A
1312 16,260 1300 N/A
Platek DN et al.18
Retrospective analysis
–
0.07%
43,372
Zanetta G et al.4
79
1.2%
161
Mathevet et al.12
Prospective study; ultrasound follow-up Prospective study; ultrasound follow-up Retrospective analysis Retrospective analysis Retrospective population-based study Prospective study; ultrasound follow-up Retrospective analysis Prospective study; ultrasound follow-up Case series
Moore et al.16
Case series
8
Condous et al.
Glanc P et al.19 Yen et al.20 Leiserowitz GS et al.9 Lavery et al.5 Ballard et al.11 Czekierdowski et al.10
Prevalence of ovarian malignancies
unilocular <5 cm; N/A unilocular >5 cm or complex cysts Any cyst >5 cm 6.8% Any cyst >4 cm 0.8%
6636
Persistent simple or complex cysts 6 cm; any mass with complication N/A N/A N/A Symptomatic or abnormal on scan Persistent simple or complex cysts 6 cm and Any cyst >3 cm
3.6%
5.4%
N/A
Any cyst >2.5 cm
0.03%*
– 213 –
4.8% N/A 0.19%
10830 Simple cysts 3 cm N/A Any cyst 4 cm 4,846,505 N/A
N/A 2.3% 0.93%
–
2.4%
3,918
N/A
N/A
93 66
0.17% 2.94%
55,271 N/A
N/A Any cyst
2.2% 0%
47
N/A
N/A
4.3%*
14
N/A
N/A
Symptomatic or abnormal on scan; persistent masses N/A
0
6.1% 0.1% 5.9% 0.05%
0
0%
In the series marked with an asterisk, all ovarian tumours detected were of low malignant potential (LMP or borderline ovarian tumours).
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populations studied. In fact studies reported in the literature are not homogeneous with respect to the gestational age at diagnosis, for example some include ovarian masses diagnosed only at the time of delivery. It should be noted that, as pregnancy advances to term, the prevalence of ovarian cysts falls.21 This declining prevalence may be explained by two reasons. First, the majority of ovarian lesions tend to resolve spontaneously during pregnancy, due to their functional etiology. Secondly, ovarian masses may be detected more easily in early pregnancy. According to the few prospective longitudinal studies available, ovarian masses detected in pregnancy have a high rate of spontaneous resolution.3–6,8 This is a reflection of the functional nature of the vast majority of the ovarian masses seen in this setting. Functional ovarian cysts include follicular, corpus luteum, and theca-lutein cysts. Among functional cysts the most common are pregnancyrelated corpus luteal cysts, which tend to resolve by 16 weeks of gestation. After functional cysts, the most common ovarian tumours diagnosed in pregnancy include, in descending order: benign cystic teratomas, serous cystadenomas, paraovarian cysts, mucinous cystadenomas, endometriomas, and malignant tumours.2,7,22–25 Theca-lutein cysts are usually associated with high serum levels of serum hCG, as seen in the presence of gestational trophoblastic disease (GTD).26 LMP tumours or borderline ovarian tumours are the most frequent types of ovarian malignancy encountered in pregnancy (Fig. 1). In a recent large population-based investigation of ovarian masses found in pregnant women in California9, approximately 56% (114/202) of the malignant lesions were epithelial LMP tumours. Excluding these borderline lesions, 51% (44/87) of cancers were epithelial; an additional 9% (8/87) were described as pseudomyxoma peritonei. Germ cell tumours accounted for 39% (34/87) of the invasive cancers, which is typical for younger women in the reproductive age. Only one granulosa cell tumour was identified. The observation that the majority of malignancies diagnosed during pregnancy are LMP tumours or germ cell tumours is confirmed by other studies.27,28 During pregnancy, the vast majority of the LMP tumours and invasive ovarian cancers are found at stage I.9,27,28 Consequently, the prognosis of women with either an LMP tumour or an ovarian cancer discovered in pregnancy is usually highly favourable. This fact should strongly influence how we should manage ovarian/adnexal masses in pregnant women. We believe that in the absence of a high level of ultrasound suspicion of an LMP or even malignancy, surgical intervention should be postponed until after the pregnancy is concluded. Diagnostic evaluation There are two routes by which an adnexal mass may be detected in pregnant, as well as in nonpregnant women: pregnant women with symptoms may have an adnexal mass diagnosed during a clinical evaluation for those symptoms, either by pelvic examination or imaging techniques; the mass may be diagnosed coincidentally by pelvic examination or imaging techniques during a routine early pregnancy or antenatal visit. From a recent meta-analysis, the pooled sensitivity of bimanual pelvic examination for the detection of adnexal masses in pre and post-menopausal women is only 45% with a pooled specificity of 90%.29 Although the data are lacking for the specific subgroup of pregnant women, we believe that the poor performance of pelvic examination means that the management of such women must involve ultrasonographic confirmation and evaluation. Ultrasound should be the first imaging modality for the investigation of an adnexal mass in pregnant as well as non-pregnant women.30,31 The ultrasound techniques for the characterization of ovarian masses (transvaginal ultrasound, transabdominal ultrasound, color Doppler, two-dimensional (2D) and three-dimensional (3D) ultrasound) are well documented.32 Ovarian masses can be accurately classified according to the ultrasound appearance and therefore appropriate management can be made on the basis on this. Conventional grey scale ultrasound is the most common initial modality used to differentiate benign from malignant masses. Especially with the advent of high-frequency transvaginal probes, the quality of the images allows description of the gross anatomic features of the lesion (i.e.
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Fig. 1. a-b. Left sided ovarian cyst diagnosed in a 22-year-old woman coincidentally at time of a first trimester miscarriage. The sonographic pattern is unilocular with one papillation. At the ultrasound follow-up 6 weeks later another papillation appeared. (b). Laparoscopic left oophorectomy was performed and histopathology revealed a borderline serous cystadenoma of the ovary.
‘‘pattern recognition’’). However, the ultrasound characteristics of benign and malignant masses may overlap. Furthermore, diagnostic accuracy is highly affected by the experience of the operator. To overcome these limitations, several scoring systems based on grey-scale morphology have been developed.33–39 Scoring systems are based on several ultrasound parameters each
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with specific numeric scores and a cut-off value to classify masses as benign or malignant. The pooled sensitivities of these different scoring systems range from 82 to 91%, and specificities from 68 to 81%.29 Features commonly associated with malignancy are: the presence of a solid component within the cyst, papillary projections >6 mm, a high colour score, and blood flow detected within solid papillary projections. A systematic description of the use of ultrasound morphology for the discrimination of ovarian masses is beyond the purpose of this paper, and it is extensively covered in reference 32. Color Doppler ultrasound allows the assessment of tumour vascularity and may help in the discrimination between malignant and benign neoplasms. Malignant tumours are known to have more angiogenesis compared with benign neoplasms. At Doppler analysis, ovarian malignancies have showed an overall increased vascularity, with a decreased peripheral blood flow resistance and increased blood flow velocity compared with benign tumours. Doppler ultrasound can discriminate between high- and low-resistance flows, and has therefore been studied as a separate test, as well as in combination with morphological grey-scale evaluation. The presence of vascularity within the mass40–44, the count of vessels45, the presence of ‘‘color lakes’’ (abnormal dilatation of vessels)46 and a low RI47–49 have all been correlated with a higher risk of malignancy. When morphology and Doppler evaluation are combined for discriminating between benign and malignant lesions, a pooled sensitivity of 86% and a pooled specificity of 91% are reached.29 When the role of Doppler is considered, the subjective evaluation of the amount of flow in a lesion is probably the most effective way of evaluating the vascularity of a tumour – this can be expressed as the colour score. The used of impedance and velcocity indices as isolated indicators of malignancy has been largely dismissed. In particular care must be taken in premenopausal women as physiological activity in the ovary is also associated with angiogenesis and the role of colour Doppler for the evaluation of ovarian pathology in pregnancy is not known. In this particular group of women it is probably better to rely on morphological indicators of the benign or malignant nature of any mass. Although ultrasound continues to be the most common imaging modality in the evaluation and diagnosis of ovarian masses, newer technologies such as magnetic resonance imaging (MRI), CT and positron emission tomography (PET) have been studied. MRI can be safely used during pregnancy to evaluate adnexal masses.50 The primary advantage of MRI is its capacity to characterise tissue composition (i.e. the blood in endometriomas and haemorrhagic cysts, or the fat tissue within dermoid cysts). However, MRI modalities may not be as easily available as ultrasound in the clinical practice. High-resolution ultrasound remains the method of choice for the management of ovarian masses in most cases. It is simpler and cheaper than CT or MRI, and safe in pregnancy as well. Notwithstanding this, it is true that not all the adnexal masses are easily classified as benign or malignant using ultrasound. LMP tumours, papillary cystadeno(fibro)mas and struma ovarii are particularly difficult to classify.51 These represent 10% of all ovarian masses.31 In the case of a ‘‘difficult mass’’ one must balance the risks to the pregnancy from intervention versus the risk of malignancy based on ultrasound. Currently a diagnostic method for distinguishing benign from malignant ‘‘difficult masses’’ is not available; in these cases the decision to perform surgery should be based on a high index of clinical suspicion. Tumour markers in pregnancy Pregnancy may alter some maternal serum tumour markers levels, making the interpretation of the results more difficult during pregnancy. The most studied ovarian cancer associated antigen is CA-125. Elevated levels are detected in approximately 80% of ovarian carcinomas at the time of diagnosis, with the exception of mucinous adenocarcinomas.52–54 However, elevated serum levels have also been reported in a variety of benign conditions, including pregnancy. During pregnancy, the clinical significance of an abnormally high CA-125 is reduced because this marker is elevated, especially in the first trimester, and declines with advancing gestational age.54 Furthermore, CA-125 is not as commonly elevated in non-epithelial ovarian cancers. Consequently, because germ cell tumours are proportionately more
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common in pregnant women, the sensitivity of CA-125 may not be as sensitive during pregnancy. Several tumour markers are available to aid the diagnosis and follow-up of germ cell tumours (human chorionic gonadotrophin (hCG), alfa-fetoprotein (AFP), lactate dehydrogenase (LDH)). Substantially elevated levels of AFP are associated with endodermal sinus tumours. Elevated LDH levels may occur with dysgerminomas, and pregnancy does not seem to alter the serum level of LDH. To summarize, as in the non-pregnant state, maternal serum tumour markers have limited value in the diagnosis of ovarian malignancy. An ovarian malignancy may be present despite the lack of a rise of serum tumour markers. The decision to pursue surgical intervention should be on the basis of the symptoms, physical examination, and most importantly the ultrasound findings in the context of an experienced sonologist. Expectant management As previously discussed, the majority of ovarian masses in pregnancy tend to resolve spontaneously without any intervention. Ultrasound is a reliable tool for the stratification of women according to the risk of malignancy. For those having a low risk of malignancy at ultrasound examination, close observation represents a reasonable option in modern management. In a follow-up of 422 adnexal masses in pregnancy by Bernhard et al.6, the majority of patients (320; 76%) had simple cysts, which measured less than 5 cm. The remaining women (102; 24%) had complex masses or simple cysts greater than 5 cm in size. Resolution was noted in 69% (70/102) of women with large simple cysts or complex masses. In a prospective ultrasound-based longitudinal study Zanetta et al. spontaneous resolution was noted in (42/68) 62% of asymptomatic women with a cyst greater than 3 cm. One-half of the cysts were simple and anechoic at ultrasound. Fifty-seven had a diameter not exceeding 5 cm. Three cysts required surgery within a few days of diagnosis for torsion. One woman required a laparotomy at the 37th week of gestation again due to torsion. Three stage Ia borderline tumours were found, accounting for 3/82 cysts (3.6%) and 3/30 persisting masses (10%). In another large longitudinal study, Condous et al.8 evaluated 3000 consecutive gravid women by ultrasound for the presence of adnexal masses before 14 weeks. Ovarian cysts were noted in 182 of the 3000 patients (6.2%). Resolution was noted in 119 of the 182 women (71%). This study differed from the other studies in that the prevalence of ovarian pathology was assessed prospectively on the basis of screening in the first trimester. These findings are probably more representative of the mix of likely pathology found in an early pregnancy service. Expectant management of women with ovarian cysts diagnosed in the first trimester should be encouraged. Delaying surgery into the second trimester allows for a substantial reduction in the incidence of functional cysts, whilst minimizing the risk of foetal loss.7 Surgical management: indications and timing Surgical management of ovarian masses in pregnancy may be indicated in the presence of a strong suspicion of malignancy, large cysts (>8 cm), in the presence of an acute abdomen, or if a risk of obstructed labour is a consideration. As with the non-gravid state, large ovarian cysts in pregnancy have an increased potential for malignancy (8.77 vs. 0.85%, in a study by Yen et al. for cysts >10 cm20). Large ovarian cysts in pregnancy are also at risk of torsion, haemorrhage, or rupture. All these complications have been observed more frequently in large symptomatic masses.25 The published rates of torsion vary between 1 and 22%.3,23 In a study by Yen et al., adnexal masses with sizes between 6 and 8 cm had a significantly higher risk of torsion compared with other sizes (22.41 vs. 9.48%).20 Sixty percent of the torsions occurred between the 10th and 17th weeks of gestation, and only 5.9% occurred after 20 weeks. A high index of clinical suspicion is the key to diagnosing torsion in pregnancy, and as well as in the non–pregnant status is concerned other causes of acute abdomen must be excluded.
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Rupture of the cyst seems to be less frequent than torsion, ranging from 0 to 9%.2,3,25 The occurrence of an obstructed labour has been reported in 2 to 17% of women.25,55 Complication rates seem to vary between studies, with more recent studies reporting much lower rates of complications than earlier studies. This may be due to an increasing number of asymptomatic masses diagnosed at routine ultrasound, that less frequently are associated with complications. The surgical treatment options of an ovarian mass consist of enucleation of the ovarian cyst, or oophorectomy or salpingo-oophorectomy. Surgery can be performed either by laparotomy or laparoscopy. In pregnancy the decision to perform surgery must take into account some important considerations. The risk of miscarriage in relation to abdominal surgery in pregnancy is increased in the first trimester in general, with some studies reporting a miscarriage rate as high as 100% before 7 weeks of gestation.56,57 The risk of adverse outcomes (i.e. miscarriage, preterm labour, and intrauterine foetal death) is also increased if surgery is performed after 23 weeks of gestation.2 Lastly, if the surgery is performed in an emergency situation - i.e. for an acute abdomen due to a torsion or rupture - the risk of miscarriage or premature delivery is significantly higher.1,56,57 In short, planned elective laparoscopic intervention seems to be associated with the best pregnancy outcomes. Laparoscopic surgery has been performed successfully in pregnancy for many conditions, for example cholecystectomy58,59, appendicectomy60, and ovarian torsion.61,62 The benefits of laparoscopic surgery are well documented, and include shorter hospital stay, earlier return to normal activity, and reduced postoperative pain. Several studies have concluded that laparoscopic ovarian cyst excision at 9–17 weeks of gestation appears to be feasible and carries a very low morbidity.16,63 However, these conclusions should be interpreted with caution, as to date they are based only on case series. Concerns have been raised about the possibility that the CO2-pneumoperitoneum at laparoscopy may reduce the uterine blood flow, causing foetal hypoxia and acidaemia. Thus, the use of the gas-less technique in pregnancy has been suggested64, but it is still under investigation. An alternative to surgical intervention for symptomatic unilocular cysts diagnosed during pregnancy is transabdominal ultrasound-guided aspiration. This technique is described to be almost without complications, potentially avoiding the need for major surgery, whilst still providing symptomatic relief. However the frequency of recurrence is 30–50%65–67, and the ultrasound-guided aspiration should be considered an option only for selected cysts with a benign morphology at ultrasonography, as aspirating an potentially malignant ovarian cyst carries the risk of spillage of the cyst contents leading to dissemination of malignant cells and compromising the outcome for the patient. It must be remembered that the prevalence of ovarian malignancy in pregnancy is extremely low indeed (1 in 15,000–32,000 pregnancies). In the situation where there is a high index of suspicion for malignancy in an ovarian cyst diagnosed during pregnancy, the management needs to be individualized. This will depend upon the certainty of the diagnosis on ultrasound, the presence of any other ultrasound features (ascites or omental cake), the age of the woman, the gestational age, and the wishes of the woman. The gynaecological oncology team would manage such a woman the same as that in the non-pregnant state. Further surgical treatment depends on the stage, type, and presence of the metastatic pathway.67 There is limited evidence that women with LMP tumours can be managed expectantly as this does not compromise disease staging when surgery is performed after the pregnancy has completed.4 Summary Expectant management for women with an ovarian cyst in pregnancy should be the benchmark standard of care. In the absence of significant symptoms, i.e. ovarian torsion, or a high ultrasonographic index of suspicion for malignancy, we believe that all ovarian cysts in pregnancy should be left well alone. If surgery is to be contemplated, delaying this into the second trimester allows for the pregnancy to declare its viability, whilst minimizing the risk of adverse pregnancy outcome. Transvaginal ultrasound is the primary imaging technique tool of choice for the evaluation and follow-up of ovarian masses in pregnancy - as in the non-pregnant state. The experience of the sonologist is paramount when classifying ovarian pathology as benign or malignant. Maternal serum tumour markers have limited value in the diagnosis of ovarian malignancy.
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Practice points The prevalence of adnexal masses in pregnancy is 0.19–8.8%. The vast majority are functional or physiological ovarian cysts (corpus luteum cysts) and resolve spontaneously by the second trimester. Ultrasound is the primary modality used to detect ovarian masses and to assess the risk of malignancy. Tumour markers should be interpreted with caution, because several markers can be elevated as a result of the pregnancy itself (e.g., CA-125, hCG). Expectant management should be the standard of care for asymptomatic non-suspicious adnexal masses diagnosed in pregnancy. When symptomatic, simple cysts can be safely and successfully treated by transabdominal ultrasound guided aspiration. Larger adnexal masses in pregnancy are at risk of torsion (1–22%), rupture (0–9%) or obstructed labour (2–17%). If surgery is to be performed, laparoscopy at 9–17 weeks of gestation appears to be safe and effective. Persistent ovarian masses in pregnancy carry a relatively low risk of malignancy (0–6.8%). More than a half of malignancies diagnosed during pregnancy are epithelial lesions of low malignant potential (LMP). Germ cell tumours account for the majority of the invasive cancers. The large majority of ovarian malignancies in pregnancy are diagnosed at stage I.
Research agenda Improving the characterization of ‘‘difficult to classify’’ ovarian tumours and in particular the assessment of borderline or LMP tumours. Investigating the effects of CO2 laparoscopic surgery on maternal and fetal acid-base physiology compared to laparotomy.
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Timmerman D, Bourne TH, Tailor A et al. A comparison of methods for preoperative discrimination between malignant and benign adnexal masses: the development of a new logistic regression model. Am J Obstet Gynecol 1999 Jul; 181(1): 57–65. 37. Sassone AM, Timor-Tritsch IE, Artner A et al. Transvaginal sonographic characterization of ovarian disease: evaluation of a new scoring system to predict ovarian malignancy. Obstet Gynecol 1991; 78(1): 70–76. *38. Ferrazzi E, Zanetta G, Dordoni D et al. Transvaginal ultrasonographic characterization of ovarian masses: comparison of five scoring systems in a multicenter study. Ultrasound Obstet Gynecol 1997; 10(3): 192–197. 39. DePriest PD, Varner E & Powell J. The efficacy of a sonographic morphology index in identifying ovarian cancer: a multiinstitutional investigation. Gynecol Oncol 1994; 55: 174–178. 40. Guerriero S, Alcazar JL, Coccia ME et al. 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AJR Am J Roentgenol 1995; 164(2): 381–386. 45. Prompeler HJ, Madjar H & Sauerbrei W. Classification of adnexal tumors by transvaginal color Doppler. Gynecol Oncol 1996; 61(3): 354–363. 46. Valentin L. Gray scale sonography, subjective evaluation of the color Doppler image and measurement of blood flow velocity for distinguishing benign and malignant tumors of suspected adnexal origin. Eur J Obstet Gynecol Reprod Biol 1997; 72(1): 63–72. 47. Bromley B, Goodman H & Benacerraf BR. Comparison between sonographic morphology and Doppler waveform for the diagnosis of ovarian malignancy. Obstet Gynecol 1994; 83(3): 434–437. 48. Franchi M, Beretta P, Ghezzi F et al. Diagnosis of pelvic masses with transabdominal color Doppler, CA 125 and ultrasonography. Acta Obstet Gynecol Scand 1995; 74(9): 734–739. 49. Kurjak A, Schulman H, Sosic A et al. Transvaginal ultrasound, color flow, and Doppler waveform of the postmenopausal adnexal mass. Obstet Gynecol 1992; 80(6): 917–921.
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50. Hricak H, Chen M, Coakley FV et al. Complex adnexal masses: detection and characterization with MR imagingdmultivariate analysis. Radiology 2000 Jan; 214(1): 39–46. *51. Valentin L, Ameye L, Jurkovic D et al. Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings, and is there a way of making a correct diagnosis? Ultrasound Obstet Gynecol 2006. 52. Malkasian Jr. GD, Knapp RC, Lavin PT et al. Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease. Am J Obstet Gynecol 1988; 159(2): 341–346. 53. Soper JT, Hunter VJ, Daly L et al. Preoperative serum tumor-associated antigen levels in women with pelvic masses. Obstet Gynecol 1990; 75(2): 249–254. 54. Condous G, Kirk E, Syed A et al. Do levels of serum cancer antigen 125 and creatine kinase predict the outcome in pregnancies of unknown location? Hum Reprod 2005 Dec; 20(12): 3348–3354 [Epub 2005 Jul 29]. 55. Ueda M & Ueki M. Ovarian tumors associated with pregnancy. Int J Gynaecol Obstet 1996; 55: 59–65. 56. Soriano D, Yefet Y, Seidman DS et al. Laparoscopy versus laparotomy in the management of adnexal masses during pregnancy. Fertil Steril 1999; 71: 955–960. 57. Wang PH, Chao HT, Yuan CC et al. Ovarian tumors complicating pregnancy. Emergency and elective surgery. J Reprod Med 1999; 44: 279–287. 58. Pucci RO & Seed RW. Case report of laparoscopic cholecystectomy in the third trimester of pregnancy. Am J Obstet Gynecol 1991; 78: 401–402. 59. Soper NJ, Hunter JG & Petrie RH. Laparoscopic cholecystectomy during pregnancy. Surg Endosc 1992; 6: 115–117. 60. Schreiber JH. Laparoscopic appendectomy in pregnancy. Surg Endosc 1990; 4: 100–102. 61. Lang PF, Tamussino K & Winter R. Laparoscopic management of adnexal torsion during the second trimester. Int J Gynaecol Obstet 1992; 37(1): 51. 62. Shalev E, Rahav D & Romano S. Laparoscopic relief of adnexal torsion in early pregnancy: case reports. Br J Obstet Gynaecol 1990; 97: 853–854. 63. Yuen PM & Chang AM. Laparoscopic management of adnexal mass during pregnancy. Acta Obstet Gynecol Scand 1997; 76: 173–176. 64. Akira S, Yamanaka A, Ishihara T et al. Gasless laparoscopic ovarian cystectomy during pregnancy: comparison with laparotomy. Am J Obstet Gynecol 1999; 180: 554–557. 65. Caspi B, Ben-Arie A, Appelman Z et al. Aspiration of simple pelvic cysts during pregnancy. Gynecol Obstet Invest 2000; 49: 102–105. 66. Guariglia L, Conte M, Are P et al. Ultrasound-guided fine needle aspiration of ovarian cysts during pregnancy. Eur J Obstet Gynecol Reprod Biol 1998; 82: 5–9. 67. Behtash N, Karimi Zarchi M, Modares Gilani M et al. Ovarian carcinoma associated with pregnancy: a clinicopathologic analysis of 23 cases and review of the literature. BMC Pregnancy Childbirth 2008 Jan 20; 8: 3.
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11
The management of ovarian pathology in pregnancy Tommaso Bignardi, MD, Associate Lecturer *, George Condous, MRCOG, FRANZCOG, Associate Professor Acute Gynaecology, Early Pregnancy, and Advanced Endosurgery Unit, Nepean Centre for Perinatal Care, Nepean Clinical School, University of Sydney, Nepean Hospital Penrith, Sydney, Australia
Keywords: ovarian cysts adnexal masses ovarian cancer pregnancy expectant management
The extensive use of ultrasound in early pregnancy populations has led to more ovarian lesions being diagnosed incidentally in asymptomatic gravid women. The majority of these lesions are physiological in nature and tend to resolve spontaneously as the pregnancy progresses. Expectant management or a ‘‘watch and wait’’ approach is the benchmark standard of care for a woman with an ovarian mass diagnosed during pregnancy. This approach assumes the woman is relatively asymptomatic, and the likelihood of malignancy is negligible. The prevalence of malignancy in pregnancy is rare indeed, i.e. 1 in 15,000–32,000. It is the discriminatory ability of ultrasound, in experienced hands, to distinguish between benign and malignant ovarian lesions that allow appropriate triaging during pregnancy. Discriminating benign from malignant masses is crucial not only to optimize the management of malignancies, but also to avoid unnecessary intervention that may adversely affect maternal or foetal outcomes. This review will focus on the management of ovarian masses in pregnancy. Ó 2009 Elsevier Ltd. All rights reserved.
For the purposes of this review, we define an ovarian/adnexal mass as an enlarged structure in the region of the pelvic adnexae that can either be palpated on examination or visualised using imaging techniques. Several conditions can be associated with an adnexal mass - these include malignancies arising from the ovary or the fallopian tube, metastatic disease from a different site (i.e. breast, gastrointestinal tract), as well as many benign pathologies.
* Corresponding author. E-mail address: [email protected] (T. Bignardi). 1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2009.01.009
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Prevalence, etiology and natural history We performed an electronic search in the database MEDLINE and a manual search of reference lists of review articles and original articles, using the keywords: ‘‘ovarian cysts’’, ‘‘adnexal masses’’ and ’’pregnancy’’. A summary of the relevant studies from this search is reported in Table 1.1–20 Data about the prevalence of ovarian masses in pregnancy and the risk of malignancy are limited to retrospective cohort or population-based studies. Few studies are prospective longitudinal follow-up studies.3–6,8 According to these studies, the prevalence of an ovarian mass in pregnancy varies between 0.19 and 8.8%. The prevalence of malignancy among ovarian masses diagnosed in pregnancy varies from 0 to 6.8%. Ovarian tumours of low malignant potential (LMP or borderline ovarian tumours) are usually considered as ovarian malignancy in these studies. As the frequency of ovarian cancer depends on age, the relatively low prevalence of cancer found in ovarian masses diagnosed in pregnancy reflects the younger age of the women studied compared with women around the time of the menopause and beyond, who are more commonly diagnosed with ovarian cancer. The reported prevalence ranges quite widely between studies. This may reflect differences in referral patterns and the nature of the
Table 1 Prevalence of ovarian masses and ovarian malignancies in pregnancy. Author
Study type
Number of Prevalence of Deliveries inclusion masses ovarian masses criteria
Bernhard LM et al.6
Prospective study; ultrasound follow-up
422
2.3%
18,391
Schmeler KM et al.13 Bromley B et al.3
63 125
0.05% N/A
127,177 N/A
Duic´ Z et al.14
Retrospective analysis Prospective study; ultrasound follow-up Case series
8
0.05%
16472
Whitecar MP et al.2 Kumari I et al.15 Hess LW et al.1 Purnichescu V et al.17
Retrospective analysis Retrospective analysis Case series Case series
130 20 54 21
0.08% 0.12% 0.08% N/A
1312 16,260 1300 N/A
Platek DN et al.18
Retrospective analysis
–
0.07%
43,372
Zanetta G et al.4
79
1.2%
161
Mathevet et al.12
Prospective study; ultrasound follow-up Prospective study; ultrasound follow-up Retrospective analysis Retrospective analysis Retrospective population-based study Prospective study; ultrasound follow-up Retrospective analysis Prospective study; ultrasound follow-up Case series
Moore et al.16
Case series
8
Condous et al.
Glanc P et al.19 Yen et al.20 Leiserowitz GS et al.9 Lavery et al.5 Ballard et al.11 Czekierdowski et al.10
Prevalence of ovarian malignancies
unilocular <5 cm; N/A unilocular >5 cm or complex cysts Any cyst >5 cm 6.8% Any cyst >4 cm 0.8%
6636
Persistent simple or complex cysts 6 cm; any mass with complication N/A N/A N/A Symptomatic or abnormal on scan Persistent simple or complex cysts 6 cm and Any cyst >3 cm
3.6%
5.4%
N/A
Any cyst >2.5 cm
0.03%*
– 213 –
4.8% N/A 0.19%
10830 Simple cysts 3 cm N/A Any cyst 4 cm 4,846,505 N/A
N/A 2.3% 0.93%
–
2.4%
3,918
N/A
N/A
93 66
0.17% 2.94%
55,271 N/A
N/A Any cyst
2.2% 0%
47
N/A
N/A
4.3%*
14
N/A
N/A
Symptomatic or abnormal on scan; persistent masses N/A
0
6.1% 0.1% 5.9% 0.05%
0
0%
In the series marked with an asterisk, all ovarian tumours detected were of low malignant potential (LMP or borderline ovarian tumours).
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populations studied. In fact studies reported in the literature are not homogeneous with respect to the gestational age at diagnosis, for example some include ovarian masses diagnosed only at the time of delivery. It should be noted that, as pregnancy advances to term, the prevalence of ovarian cysts falls.21 This declining prevalence may be explained by two reasons. First, the majority of ovarian lesions tend to resolve spontaneously during pregnancy, due to their functional etiology. Secondly, ovarian masses may be detected more easily in early pregnancy. According to the few prospective longitudinal studies available, ovarian masses detected in pregnancy have a high rate of spontaneous resolution.3–6,8 This is a reflection of the functional nature of the vast majority of the ovarian masses seen in this setting. Functional ovarian cysts include follicular, corpus luteum, and theca-lutein cysts. Among functional cysts the most common are pregnancyrelated corpus luteal cysts, which tend to resolve by 16 weeks of gestation. After functional cysts, the most common ovarian tumours diagnosed in pregnancy include, in descending order: benign cystic teratomas, serous cystadenomas, paraovarian cysts, mucinous cystadenomas, endometriomas, and malignant tumours.2,7,22–25 Theca-lutein cysts are usually associated with high serum levels of serum hCG, as seen in the presence of gestational trophoblastic disease (GTD).26 LMP tumours or borderline ovarian tumours are the most frequent types of ovarian malignancy encountered in pregnancy (Fig. 1). In a recent large population-based investigation of ovarian masses found in pregnant women in California9, approximately 56% (114/202) of the malignant lesions were epithelial LMP tumours. Excluding these borderline lesions, 51% (44/87) of cancers were epithelial; an additional 9% (8/87) were described as pseudomyxoma peritonei. Germ cell tumours accounted for 39% (34/87) of the invasive cancers, which is typical for younger women in the reproductive age. Only one granulosa cell tumour was identified. The observation that the majority of malignancies diagnosed during pregnancy are LMP tumours or germ cell tumours is confirmed by other studies.27,28 During pregnancy, the vast majority of the LMP tumours and invasive ovarian cancers are found at stage I.9,27,28 Consequently, the prognosis of women with either an LMP tumour or an ovarian cancer discovered in pregnancy is usually highly favourable. This fact should strongly influence how we should manage ovarian/adnexal masses in pregnant women. We believe that in the absence of a high level of ultrasound suspicion of an LMP or even malignancy, surgical intervention should be postponed until after the pregnancy is concluded. Diagnostic evaluation There are two routes by which an adnexal mass may be detected in pregnant, as well as in nonpregnant women: pregnant women with symptoms may have an adnexal mass diagnosed during a clinical evaluation for those symptoms, either by pelvic examination or imaging techniques; the mass may be diagnosed coincidentally by pelvic examination or imaging techniques during a routine early pregnancy or antenatal visit. From a recent meta-analysis, the pooled sensitivity of bimanual pelvic examination for the detection of adnexal masses in pre and post-menopausal women is only 45% with a pooled specificity of 90%.29 Although the data are lacking for the specific subgroup of pregnant women, we believe that the poor performance of pelvic examination means that the management of such women must involve ultrasonographic confirmation and evaluation. Ultrasound should be the first imaging modality for the investigation of an adnexal mass in pregnant as well as non-pregnant women.30,31 The ultrasound techniques for the characterization of ovarian masses (transvaginal ultrasound, transabdominal ultrasound, color Doppler, two-dimensional (2D) and three-dimensional (3D) ultrasound) are well documented.32 Ovarian masses can be accurately classified according to the ultrasound appearance and therefore appropriate management can be made on the basis on this. Conventional grey scale ultrasound is the most common initial modality used to differentiate benign from malignant masses. Especially with the advent of high-frequency transvaginal probes, the quality of the images allows description of the gross anatomic features of the lesion (i.e.
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Fig. 1. a-b. Left sided ovarian cyst diagnosed in a 22-year-old woman coincidentally at time of a first trimester miscarriage. The sonographic pattern is unilocular with one papillation. At the ultrasound follow-up 6 weeks later another papillation appeared. (b). Laparoscopic left oophorectomy was performed and histopathology revealed a borderline serous cystadenoma of the ovary.
‘‘pattern recognition’’). However, the ultrasound characteristics of benign and malignant masses may overlap. Furthermore, diagnostic accuracy is highly affected by the experience of the operator. To overcome these limitations, several scoring systems based on grey-scale morphology have been developed.33–39 Scoring systems are based on several ultrasound parameters each
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with specific numeric scores and a cut-off value to classify masses as benign or malignant. The pooled sensitivities of these different scoring systems range from 82 to 91%, and specificities from 68 to 81%.29 Features commonly associated with malignancy are: the presence of a solid component within the cyst, papillary projections >6 mm, a high colour score, and blood flow detected within solid papillary projections. A systematic description of the use of ultrasound morphology for the discrimination of ovarian masses is beyond the purpose of this paper, and it is extensively covered in reference 32. Color Doppler ultrasound allows the assessment of tumour vascularity and may help in the discrimination between malignant and benign neoplasms. Malignant tumours are known to have more angiogenesis compared with benign neoplasms. At Doppler analysis, ovarian malignancies have showed an overall increased vascularity, with a decreased peripheral blood flow resistance and increased blood flow velocity compared with benign tumours. Doppler ultrasound can discriminate between high- and low-resistance flows, and has therefore been studied as a separate test, as well as in combination with morphological grey-scale evaluation. The presence of vascularity within the mass40–44, the count of vessels45, the presence of ‘‘color lakes’’ (abnormal dilatation of vessels)46 and a low RI47–49 have all been correlated with a higher risk of malignancy. When morphology and Doppler evaluation are combined for discriminating between benign and malignant lesions, a pooled sensitivity of 86% and a pooled specificity of 91% are reached.29 When the role of Doppler is considered, the subjective evaluation of the amount of flow in a lesion is probably the most effective way of evaluating the vascularity of a tumour – this can be expressed as the colour score. The used of impedance and velcocity indices as isolated indicators of malignancy has been largely dismissed. In particular care must be taken in premenopausal women as physiological activity in the ovary is also associated with angiogenesis and the role of colour Doppler for the evaluation of ovarian pathology in pregnancy is not known. In this particular group of women it is probably better to rely on morphological indicators of the benign or malignant nature of any mass. Although ultrasound continues to be the most common imaging modality in the evaluation and diagnosis of ovarian masses, newer technologies such as magnetic resonance imaging (MRI), CT and positron emission tomography (PET) have been studied. MRI can be safely used during pregnancy to evaluate adnexal masses.50 The primary advantage of MRI is its capacity to characterise tissue composition (i.e. the blood in endometriomas and haemorrhagic cysts, or the fat tissue within dermoid cysts). However, MRI modalities may not be as easily available as ultrasound in the clinical practice. High-resolution ultrasound remains the method of choice for the management of ovarian masses in most cases. It is simpler and cheaper than CT or MRI, and safe in pregnancy as well. Notwithstanding this, it is true that not all the adnexal masses are easily classified as benign or malignant using ultrasound. LMP tumours, papillary cystadeno(fibro)mas and struma ovarii are particularly difficult to classify.51 These represent 10% of all ovarian masses.31 In the case of a ‘‘difficult mass’’ one must balance the risks to the pregnancy from intervention versus the risk of malignancy based on ultrasound. Currently a diagnostic method for distinguishing benign from malignant ‘‘difficult masses’’ is not available; in these cases the decision to perform surgery should be based on a high index of clinical suspicion. Tumour markers in pregnancy Pregnancy may alter some maternal serum tumour markers levels, making the interpretation of the results more difficult during pregnancy. The most studied ovarian cancer associated antigen is CA-125. Elevated levels are detected in approximately 80% of ovarian carcinomas at the time of diagnosis, with the exception of mucinous adenocarcinomas.52–54 However, elevated serum levels have also been reported in a variety of benign conditions, including pregnancy. During pregnancy, the clinical significance of an abnormally high CA-125 is reduced because this marker is elevated, especially in the first trimester, and declines with advancing gestational age.54 Furthermore, CA-125 is not as commonly elevated in non-epithelial ovarian cancers. Consequently, because germ cell tumours are proportionately more
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common in pregnant women, the sensitivity of CA-125 may not be as sensitive during pregnancy. Several tumour markers are available to aid the diagnosis and follow-up of germ cell tumours (human chorionic gonadotrophin (hCG), alfa-fetoprotein (AFP), lactate dehydrogenase (LDH)). Substantially elevated levels of AFP are associated with endodermal sinus tumours. Elevated LDH levels may occur with dysgerminomas, and pregnancy does not seem to alter the serum level of LDH. To summarize, as in the non-pregnant state, maternal serum tumour markers have limited value in the diagnosis of ovarian malignancy. An ovarian malignancy may be present despite the lack of a rise of serum tumour markers. The decision to pursue surgical intervention should be on the basis of the symptoms, physical examination, and most importantly the ultrasound findings in the context of an experienced sonologist. Expectant management As previously discussed, the majority of ovarian masses in pregnancy tend to resolve spontaneously without any intervention. Ultrasound is a reliable tool for the stratification of women according to the risk of malignancy. For those having a low risk of malignancy at ultrasound examination, close observation represents a reasonable option in modern management. In a follow-up of 422 adnexal masses in pregnancy by Bernhard et al.6, the majority of patients (320; 76%) had simple cysts, which measured less than 5 cm. The remaining women (102; 24%) had complex masses or simple cysts greater than 5 cm in size. Resolution was noted in 69% (70/102) of women with large simple cysts or complex masses. In a prospective ultrasound-based longitudinal study Zanetta et al. spontaneous resolution was noted in (42/68) 62% of asymptomatic women with a cyst greater than 3 cm. One-half of the cysts were simple and anechoic at ultrasound. Fifty-seven had a diameter not exceeding 5 cm. Three cysts required surgery within a few days of diagnosis for torsion. One woman required a laparotomy at the 37th week of gestation again due to torsion. Three stage Ia borderline tumours were found, accounting for 3/82 cysts (3.6%) and 3/30 persisting masses (10%). In another large longitudinal study, Condous et al.8 evaluated 3000 consecutive gravid women by ultrasound for the presence of adnexal masses before 14 weeks. Ovarian cysts were noted in 182 of the 3000 patients (6.2%). Resolution was noted in 119 of the 182 women (71%). This study differed from the other studies in that the prevalence of ovarian pathology was assessed prospectively on the basis of screening in the first trimester. These findings are probably more representative of the mix of likely pathology found in an early pregnancy service. Expectant management of women with ovarian cysts diagnosed in the first trimester should be encouraged. Delaying surgery into the second trimester allows for a substantial reduction in the incidence of functional cysts, whilst minimizing the risk of foetal loss.7 Surgical management: indications and timing Surgical management of ovarian masses in pregnancy may be indicated in the presence of a strong suspicion of malignancy, large cysts (>8 cm), in the presence of an acute abdomen, or if a risk of obstructed labour is a consideration. As with the non-gravid state, large ovarian cysts in pregnancy have an increased potential for malignancy (8.77 vs. 0.85%, in a study by Yen et al. for cysts >10 cm20). Large ovarian cysts in pregnancy are also at risk of torsion, haemorrhage, or rupture. All these complications have been observed more frequently in large symptomatic masses.25 The published rates of torsion vary between 1 and 22%.3,23 In a study by Yen et al., adnexal masses with sizes between 6 and 8 cm had a significantly higher risk of torsion compared with other sizes (22.41 vs. 9.48%).20 Sixty percent of the torsions occurred between the 10th and 17th weeks of gestation, and only 5.9% occurred after 20 weeks. A high index of clinical suspicion is the key to diagnosing torsion in pregnancy, and as well as in the non–pregnant status is concerned other causes of acute abdomen must be excluded.
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Rupture of the cyst seems to be less frequent than torsion, ranging from 0 to 9%.2,3,25 The occurrence of an obstructed labour has been reported in 2 to 17% of women.25,55 Complication rates seem to vary between studies, with more recent studies reporting much lower rates of complications than earlier studies. This may be due to an increasing number of asymptomatic masses diagnosed at routine ultrasound, that less frequently are associated with complications. The surgical treatment options of an ovarian mass consist of enucleation of the ovarian cyst, or oophorectomy or salpingo-oophorectomy. Surgery can be performed either by laparotomy or laparoscopy. In pregnancy the decision to perform surgery must take into account some important considerations. The risk of miscarriage in relation to abdominal surgery in pregnancy is increased in the first trimester in general, with some studies reporting a miscarriage rate as high as 100% before 7 weeks of gestation.56,57 The risk of adverse outcomes (i.e. miscarriage, preterm labour, and intrauterine foetal death) is also increased if surgery is performed after 23 weeks of gestation.2 Lastly, if the surgery is performed in an emergency situation - i.e. for an acute abdomen due to a torsion or rupture - the risk of miscarriage or premature delivery is significantly higher.1,56,57 In short, planned elective laparoscopic intervention seems to be associated with the best pregnancy outcomes. Laparoscopic surgery has been performed successfully in pregnancy for many conditions, for example cholecystectomy58,59, appendicectomy60, and ovarian torsion.61,62 The benefits of laparoscopic surgery are well documented, and include shorter hospital stay, earlier return to normal activity, and reduced postoperative pain. Several studies have concluded that laparoscopic ovarian cyst excision at 9–17 weeks of gestation appears to be feasible and carries a very low morbidity.16,63 However, these conclusions should be interpreted with caution, as to date they are based only on case series. Concerns have been raised about the possibility that the CO2-pneumoperitoneum at laparoscopy may reduce the uterine blood flow, causing foetal hypoxia and acidaemia. Thus, the use of the gas-less technique in pregnancy has been suggested64, but it is still under investigation. An alternative to surgical intervention for symptomatic unilocular cysts diagnosed during pregnancy is transabdominal ultrasound-guided aspiration. This technique is described to be almost without complications, potentially avoiding the need for major surgery, whilst still providing symptomatic relief. However the frequency of recurrence is 30–50%65–67, and the ultrasound-guided aspiration should be considered an option only for selected cysts with a benign morphology at ultrasonography, as aspirating an potentially malignant ovarian cyst carries the risk of spillage of the cyst contents leading to dissemination of malignant cells and compromising the outcome for the patient. It must be remembered that the prevalence of ovarian malignancy in pregnancy is extremely low indeed (1 in 15,000–32,000 pregnancies). In the situation where there is a high index of suspicion for malignancy in an ovarian cyst diagnosed during pregnancy, the management needs to be individualized. This will depend upon the certainty of the diagnosis on ultrasound, the presence of any other ultrasound features (ascites or omental cake), the age of the woman, the gestational age, and the wishes of the woman. The gynaecological oncology team would manage such a woman the same as that in the non-pregnant state. Further surgical treatment depends on the stage, type, and presence of the metastatic pathway.67 There is limited evidence that women with LMP tumours can be managed expectantly as this does not compromise disease staging when surgery is performed after the pregnancy has completed.4 Summary Expectant management for women with an ovarian cyst in pregnancy should be the benchmark standard of care. In the absence of significant symptoms, i.e. ovarian torsion, or a high ultrasonographic index of suspicion for malignancy, we believe that all ovarian cysts in pregnancy should be left well alone. If surgery is to be contemplated, delaying this into the second trimester allows for the pregnancy to declare its viability, whilst minimizing the risk of adverse pregnancy outcome. Transvaginal ultrasound is the primary imaging technique tool of choice for the evaluation and follow-up of ovarian masses in pregnancy - as in the non-pregnant state. The experience of the sonologist is paramount when classifying ovarian pathology as benign or malignant. Maternal serum tumour markers have limited value in the diagnosis of ovarian malignancy.
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Practice points The prevalence of adnexal masses in pregnancy is 0.19–8.8%. The vast majority are functional or physiological ovarian cysts (corpus luteum cysts) and resolve spontaneously by the second trimester. Ultrasound is the primary modality used to detect ovarian masses and to assess the risk of malignancy. Tumour markers should be interpreted with caution, because several markers can be elevated as a result of the pregnancy itself (e.g., CA-125, hCG). Expectant management should be the standard of care for asymptomatic non-suspicious adnexal masses diagnosed in pregnancy. When symptomatic, simple cysts can be safely and successfully treated by transabdominal ultrasound guided aspiration. Larger adnexal masses in pregnancy are at risk of torsion (1–22%), rupture (0–9%) or obstructed labour (2–17%). If surgery is to be performed, laparoscopy at 9–17 weeks of gestation appears to be safe and effective. Persistent ovarian masses in pregnancy carry a relatively low risk of malignancy (0–6.8%). More than a half of malignancies diagnosed during pregnancy are epithelial lesions of low malignant potential (LMP). Germ cell tumours account for the majority of the invasive cancers. The large majority of ovarian malignancies in pregnancy are diagnosed at stage I.
Research agenda Improving the characterization of ‘‘difficult to classify’’ ovarian tumours and in particular the assessment of borderline or LMP tumours. Investigating the effects of CO2 laparoscopic surgery on maternal and fetal acid-base physiology compared to laparotomy.
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