1-877-327-4636 Alcohol and Substance
1-800-436-8477 Morning Sickness
1-888-246-5840 HIV and HIV Treatment
1-877-439-2744 Motherisk Helpline
416-813-6780 Motherisk Helpline
Pregnancy & Breastfeeding Resources
Motherisk Update 2014
Fetal Alcohol Canadian Expertise (FACE) Satellite Meeting,
Details to be announced
- Read more in our News Archive
Current Studies at Motherisk
Diclegis Surveillance Program Study
Diclectin Surveillance Program Study
Study seeks women between 4 and 12 weeks in their pregnancy with morning sickness (NVP)
Pregnancy in Women with Multiple Sclerosis
Environmental Exposures and Children's Health
Alcohol Use during Pregnancy
Control of Hypertension in Pregnancy Study
Folic Acid Before and During Pregnancy
Lamisil in Pregnancy
Meridia in Pregnancy
Autoimmune Diseases in Pregnancy Project
Cancer in Pregnancy: Ovarian Tumors and Pregnancy
Ovarian cancer is the second most frequent gynecologic cancer complicating pregnancy1. Although the overall incidence of ovarian cancer in pregnancy is low, the increased use of ultrasound in early fetal evaluation has led to more frequent findings of adnexal mass in pregnancy. The average estimated incidence of ovarian tumors in pregnancy is approximately 1 in 1000 deliveries.2,3 The vast majority of tumors detected during pregnancy are benign. Approximately 2 to 5 percent of adnexal masses are true malignant neoplasms.2,4-6
A significant number of patients are asymptomatic and are found to have an adnexal mass on physical examination, during routine ultrasound, or at the time of cesarean delivery 7. However, other presentations include abdominal pain, increasing abdominal girth, obstructed labour and emergency laparatomy due to torsion or rupture of the mass.7-9
Adnexal masses during pregnancy are managed according to characteristics of the mass and sonographic appearance, gestational age and patient symptomatology. High resolution transabdominal ultrasound is the initial imaging tool and essential diagnostic method10. It is best used in combination with high-frequencytransvaginal transducer applied transabdominally11. Observation and repeat ultrasound at 14 to 16 weeks gestational age to document resolution is appropriate for those masses < 6 cm that are unilateral, unilocular, mobile and asymptomatic. In contrast, laparotomy has been traditionally recommended if the mass is > 6 cm, solid or of complex appearance, bilateral or persists into the second trimester. Elective surgery for removal of these masses is preferable since urgent procedures for adnexal torsion or rupture have been associated with higher rates of spontaneous abortion and premature delivery 12.
Elective surgery should be delayed until the second trimester to decrease the chance of fetal complications. Intervention may be delayed until after delivery when an asymptomatic mass is detected in the third trimester13. Careful examination of the adnexal mass and intraoperative confirmation of pathology is mandatory. If benign pathology is confirmed, a simple cystectomy is usually sufficient 14. Management of malignant pathology depends on the tumor type, gestational age and patient wishes. Although serum tumor markers remain important in the preoperative assessment of all women with adnexal mass, their interpretation in pregnancy is not always reliable since they are often elevated and fluctuate with gestational age13.
Stages referred to in this article are similar to those defined by the International Federation of Gynaecology and Obstetrics (FIGO) 1999 for ovarian epithelial carcinoma.
Most of the patients with ovarian cancer diagnosed during pregnancy have disease confined to the pelvis or abdomen. Staging is primarily surgical. Laparoscopy may be a reasonable initial approach to explore adnexal masses in patients who do not show evidence of extra-ovarian pathology. Despite concerns regarding fetal risk, uterine injury and restricted operative field, the safety of this technique is growing15,16.As mentioned previously, ultrasound is an effective tool to evaluate adnexal masses and can be done serially with little risk to the fetus or mother. Magnetic Resonance Imaging (MRI) (with its multiplanar capability and improved tissue characterization), is a valuable adjunct. Also, MRI is not associated with ionizing radiation exposure 17,18. In general, decisions regarding the use of radiological investigations must take into account the age of the fetus and the estimated dose of radiation delivered with the respective imaging study.
Pathology and biology
The vast majority of adnexal masses are benign and are diagnosed at an early stage when the disease is still confined to the ovary. Of those that are malignant, the following tumor types have been described: epithelial, germ cell, sex-cord stromal and much less commonly, metastatic involvement of the ovary from another primary site (Krukenberg tumor). The relative frequency of tumor types reflects the young age of presentation. Depending on the series, germ cell tumors are either the most common or second only to epithelial tumors 2,19,20.
The epithelial tumors tend to be early stage and low grade although advanced stage tumors have been reported 4,8,21.
In the germ cell category, dysgerminomas are the most frequently encountered in pregnancy. Endodermal sinus tumors have also been reported 2. Both tumor types tend to be confined to the ovary (approximately 80 percent) at the time of diagnosis in pregnancy. Ten retrospective cases of serous neoplasms of low malignant potential resected during pregnancy, were reported with clinical and microscopic features suggesting aggressive behavior. However, these features subsided significantly after delivery and years after, all patients are still alive with no evidence of disease22.
Sex cord-stromal tumor types that have been described include granulosa, Sertoli-Leydig and 'unclassified'5. The differential diagnosis of sex cord stromal tissues includes other benign conditions which can mimic malignancy. These include luteoma of pregnancy, luteinized follicular cyst, granulosa cell proliferations, hilus cell hyperplasia and ectopic decidua 6,19. These conditions are characterized by regression after pregnancy.
There is no evidence that pregnancy alters the course or affects the prognosis of pure dysgerminoma23,24. However, the prognosis of non-dysgerminomatous germ cell tumors associated with pregnancy may be uncertain, since two fatal cases of rapidly progressive disease during the second trimester were described in the literature24.
Surgical exploration using a midline incision at 16 -18 weeks gestation is recommended. For benign pathology, cystectomy is warranted. A frozen section diagnosis must be made to guide further decisions. Careful examination of both ovaries is essential as well as standard surgical exploration and staging for more advanced cancers.
This may include omental biopsy/sampling, peritoneal biopsies and pelvic washings for cytology. In cases of ovarian dysgerminoma, pelvic/paraaortic lymph node biopsy is mandatory, since the tumor spreads predominantly through the lymphatics. Under-staging is common if lymphadenectomy is omitted13. Contralateral ovarian biopsy is warranted only if the ovary appears to be involved with the tumor. Routine biopsy or wedge resection of a normal-appearing contralateral ovary is no longer recommended25.
Germ cell tumors confined to the ovary may be managed with conservative surgery, ie. oophorectomy/salpingo - oophorectomy. This allows for preservation of the uterus and contralateral ovary. It is often possible to continue the pregnancy after surgical staging and tumor debulking. One case report described successful outcomes of a 9-week pregnancy managed by bilateral salpingo-oophorectomy for ovarian cancer26.
Similarly, low malignant potential and sex cord-stromal tumors with early stage disease can be managed with adnexectomy or oophorectomy.
Epithelial ovarian cancers are staged in a similar manner to the non-pregnant population. If fertility preservation is an issue, unilateral salpingo oophorectomy may be used to treat patients with stage IA, low grade tumors. The literature describes successful pregnancy and preservation of normal ovarian function, in cases of advanced-stage metastatic, low malignant potential tumors treated by successful tumor debulking27,28. All higher stage tumorsshould undergo standard surgery with debulking, i.e. total abdominal hysterectomy, salpingo oophorectomy, omentectomy, lymph node sampling, perioneal cytology and careful inspection of the liver and diaphragm. For those patients with advanced disease, decisions regarding debulking procedures should take into account fetal viability, patient health and patient desires at the time of surgery. Hysterectomy during pregnancy is rarely indicated unless it contributes significantly to tumor debulking. A recently published retrospective study of 174 patients undergoing adnexal surgery during pregnancy showed no evidence of increasing risk of fetal loss when surgery was performed after the seventh week of gestation29.
Cancer chemotherapeutic drugs are very potent teratogens. Currently, there is very little information on the effect of cancer chemotherapy on the fetus 30. The risk of malformations when chemotherapy is administered in the first trimester has been estimated to be around 10% for single agent chemotherapy31 and 25% for combination chemotherapy32. It is generally suggested that chemotherapy be avoided during the first trimester, when cells are actively dividing. Use of these agents in the second and third trimesters has been associated with an increased risk of stillbirth, intrauterine growth retardation and low birth weight30,33,34. When chemotherapy is administered during pregnancy, timing of delivery of the infant should take into account the expected bone marrow depression and potential problems such as bleeding or infections. Self limiting fetal haematopoetic depression has been described and the neonate should be monitored for complications of this 35. Long term neurodevelopmental complications of in utero chemotherapy exposure have not been extensively studied. Limited data exist to suggest that this may be normal in the offspring of patients with haematologic malignancies treated during various stages of the pregnancy 36.
Post operative observation with chemotherapy reserved for relapse is a reasonable option for patients with stage IA pure dysgerminoma. With the exception of Stage IA grade I immature teratoma, and low malignant potential epithelial cancer, both ovarian germ cell and epithelial invasive tumors are usually considered for adjuvant chemotherapy. Cure rates for ovarian germ cell tumors are high - on average, 95% for stage I and 75% for the advanced disease37. Recent evidence suggests that survival may not be compromised if stage I tumors are managed by surveillance, reserving chemotherapy for relapse38. It is unclear whether maternal outcome would be compromised by a delay in adjuvant therapy until after delivery. Although limited, there are case reports of cytotoxic treatment for germ cell tumors in the second and third trimesters using agents such as vincristine, vinblastine, actinomycin-D, cyclophosphamide, bleomycin, cisplatinum and etoposide. Fetal outcome was good 39-45. Long term toxicity information is generally lacking.
Epithelial tumors of low malignant potential are known for their indolent disease course and good prognosis. Even in late-stage disease, chemotherapy is apparently not needed.
Patients with poor prognosis stage I (high grade tumors or stage IC) or more advanced invasive epithelial ovarian cancers are considered candidates for post operative therapy - usually cisplatin-based chemotherapy plus paclitaxel. There are isolated reports of favorable fetal outcome after treatment with cisplatin based therapy for advanced epithelial cancers 46-49. Cases of adjuvant cisplatin and cyclophosphamide therapy initiated in the second trimester of pregnancy are described in the literature, with good response to therapy and subsequent delivery of a healthy baby50.
There is no published data regarding the use of Taxol during human pregnancy.
There is no evidence that pregnancy alters the prognosis of ovarian tumors compared to the non-pregnant population when patients are matched for tumor histology and stage. In general, pregnant patients with ovarian cancer have a better prognosis overall due to the age related tumor distribution and early stage of diagnosis in a significant number of patients. Lactation
Cytotoxic agents administered systemically may reach significant levels in breast milk and thus breastfeeding while on chemotherapy is contraindicated. A similar situation exists for the use of radioiodine. See also Breastfeeding and anti-cancer chemotherapy.
- Boulay R, Podczaski E. Ovarian cancer complicating pregnancy. Obstetric and Gynecology Clinics of North America. 25(2):385-99, 1998.
- Beischer NA, Buttery BW, Fortune DW, et al. Growth and malignancy of ovarian tumors in pregnancy. Aust N Z Obstet Gynaecol 1971;11:208.
- White KC. Ovarian tumors in pregnancy: a private hospital ten year survey. Am J Obstet Gynecol 1973;116:544.
- Munnell EW. Primary ovarian cancer associated with pregnancy. Clin Obstet Gynecol 1963;6:983.
- Ashkenazy M, Kessler I, Czernobilsky B, et al. Ovarian tumors in pregnancy. Int J Obstet Gynecol 1988;27:79.
- El Yahia AR, Rahman J, Rahman MS, et al. Ovarian tumors in pregnancy. Aust NZ J Obstet Gynecol 1991;31:327.
- Norton JA, Levin B, Jensen RT. Cancer of the endocrine system. In: DeVita VT, Hellman S, Rosenberg SA, ed. Cancer: principles and practice of oncology. 4 ed. Philadelphia: JB Lippincott, 1993:1333.
- Rosvoll R, Winship T. Thyroid carcinoma and pregnancy. Surg Gynecol Obstet 1965;121:1038.
- Schneider V. Arias-Stella reaction of the endocervix: Frequency and location. Acta Cytol 1981;25:224.
- Bromley B, Benacerraf B. Adnexal masses during pregnancy: Accuracy of sonographic diagnosis and outcome. Journal of Ultrasound in Medicine.16(7):447-52; quiz 453-4, 1997.
- Sherer DM, Eisenberg C, Abulafia O. Transabdominal application of transvaginal transducer enhancing depiction of mature cystic teratoma at 34 weeks' gestation. American Journal of Perinatology.16(7):361-3, 1999.
- Asteris CT, DeGroot L. Thyroid cancer: relationship to radiation exposure and to pregnancy. J Reprod Med 1976;17:209.
- Zanotti K, Belinson J, Kennedy A. Treatment of gynecological cancers in pregnancy. Seminars in Oncology,Vol.27,No6, 2000.
- Hod M, Sharonay R, Friedman S, et al. Pregnancy in thyroid carcinoma: a review of incidence, course, and prognosis. Obstet Gynecol Surv 1989;44:774.
- Soriano D, Yefet Y, Seidman DS, et al. Laparoscopy versus laparotomy in the management of adnexal masses during pregnancy. Fertil Steril 71:955-960,1999.
- Yuen PM, Chang AM. Laparoscopic management of adnexal mass during pregnancy. Acta obstetricia et gynecologica Scandinavica. 76(2):173-6,1997.
- Kobayashi K, Tanaka Y, Ishiguro S, et al. Rapidly growing thyroid carcinoma during pregnancy. J Surg Oncol 1994;55:61.
- Shivvers SA, Miller DS. Preinvasive and invasive breast and cervical cancer prior to or during pregnancy. Clin Perinatol 1997;24:369-389.
- Dgani R, Shoham Z, Atar E, et al. Ovarian carcinoma during pregnancy: a study of 23 cases in Israel between the years 1960 and 1984. Gynae Oncol 1989;33:326.
- Creasman WT, Rutledge F, Smith JP. Carcinoma of the ovary associated with pregnancy. Obstet Gynecol 1971;38:111.
- Gustafsson DC, Kottmeier HL. Carcinoma of the cervix associated with pregnancy. Acta Obstet Gynecol Scand 1962;41:1.
- Mooney J, Silva E, Tornos C, Gershenson D. Unusual features of serous neoplasms of low malignant potential during pregnancy. Gynecologic Oncology. 65(1):30-5,1997.
- Antonelli NM, Dotters DJ, Katz VL, et al. Cancer in pregnancy: a review of the literature. Obstet and Gynecol Survey 1996;51:125-142.
- Bakri YN, Ezzat A, Akhtar, Dohami, Zahrani. Malignant germ cell tumors of the ovary. Pregnancy considerations. Eur. Journal of Obstetrics, Gynecology & Repr. Biology.90(1):87-91, 2000.
- American College of Obstetrician and Gynecologists: Ovarian Cancer. Educational Bulletin 250,Washington, DC. 1998.
- Colavita M, Garzetti G, Baiocchi G, Grosso G, Di Re E. Successful outcome of a 9-week pregnancy managed by bilateral salpingo-oophorectomy for ovarian cancer: Case report. European Journal of Gynecological Oncology.17(6):522-3, 1996.
- Miller DM, Ehlen TG, Saleh EA. Successful term pregnancy following conservative debulking surgery for a stage IIIA serous low-malignant potential tumor of the ovary: a case report. Gynecologic Oncology.66(3):535-8, 1997.
- Shibahara H, Wacimoto E, Mitsuo M, et al. A case of a patient diagnosed with malignant mixed Mullerian tumor of the ovary who conceived after conservative surgery and adjuvant chemotherapy. Gynecologic Oncology.65(2):363-365, 1997.
- Wang PH, Chao HT, et al. Ovarian tumors complicating pregnancy. Emergency and elective surgery. Journal of Reproductive Medicine. 44(3):279-87, 1999.
- Zemlickis D, Lishner M, Koren G. Review of fetal effects of cancer chemotherapeutic agents. In: Koren G, Lishner M, Farine D, ed. Cancer in pregnancy. 1 ed. Cambridge: Press Syndicate of the University of Cambridge, 1996:168.
- Nicholson H. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynecol Br Commonwealth 1968;75:307.
- Doll DC, Ringenberg S, Yarbro DW. Management of cancer during pregnancy. Arch Intern Med 1988;148:2058.
- Zemlickis D, Lishner M, Degendorfer P, et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 1992;166:781-787.
- Zemlickis D, Lishner M, Degendrofer P, et al. Fetal outcome following in utero exposure to cancer chemotherapy: the Toronto study. Arch Inter Med 1992;15:573.
- Blatt J, Milvihill JJ, Ziegler JL, et al. Pregnancy outcome following cancer chemotherapy. Am J Med 1980;39:828.
- Aviles A, Diaz-Maqueo JC, Talavera A, et al. Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol 1991;36:243.
- Williams SD: Chemotherapy of ovarian germ cell tumors. Hematol. Oncol Clin North Am 5:1261-1269, 1991.
- Dark GG, BOwer M, Newlands ES et al. Surveillance policy for Stage I ovarian germ cell tumors. J Clin Oncol 1997;15:620.
- Horbelt D, Delmore J, Meisels R, et al. Mixed germ cell malignancy of the ovary concurrent with pregnancy. Obstet Gynecol 1984;84:662.
- Malone JM, Gershenson DM, Creasy RK, et al. Endodermal sinus tumor of the ovary associated with pregnancy. Obstet Gynecol 1986;68:86S.
- Montz FJ, Horenstein J, Platt LD, et al. The diagnosis of immature teratoma by maternal serum alpha-fetoprotein screening. Obstet Gynecol 1989;73:522.
- Kim DS, Park MI. Maternal and fetal survival following surgery and chemotherapy of endodermal sinus tumor of the ovary during pregnancy: a case report. Obstet Gynecol 1989;73:503.
- Metz SA, Day TG, Pursell SH. Adjuvant chemotherapy in a pregnant patient with endodermal sinus tumor of the ovary. Gynecol Oncol 1989;32:371.
- Christman JE, Teng NNH, Lebovic GS, et al. Delivery of a normal infant following cisplatin, vinblastine, and bleomycin (PVB) chemotherapy for malignant teratoma of the ovary during pregnancy. Gynecol Oncol 1990;37:292.
- Buller RE, Darrow V, Manetta A, et al. Conservative surgical management of dysgerminoma concomitant with pregnancy. Obstet Gynecol 1992;79:887.
- Malfetano JH, Goldkrand JW. Cis-platinum combination chemotherapy during pregnancy for advanced epithelial ovarian carcinoma. Obstet Gynecol 1990;75:545.
- King LA, Nevin PC, Williams PP, et al. Treatment of advanced epithelial ovarian carcinoma in pregnancy with cisplatin-based chemotherapy. Gynecol Oncol 1991;41:78.
- Henderson CE, Elia G, Garfinkel D, et al. Platinum chemotherapy during pregnancy for serous cystadenocarcinoma of the ovary. 49 1993:92.
- Koc ON, McFee M, Gerson SL. Detection of platinum-DNA adducts in cord blood lymphocytes following in utero platinum exposure. Eur J Cancer 1994;30A:718.
- Bayhan G, Aban M, et al : Cis-platinum combination chemotherapy during pregnancy for mucinous cystadenocarcinoma of the ovary. Case report. Eur J Gyn Oncol 20:231-232,1999.