Benign neoplasms are common and include leiomyomas, ovarian neoplasms, and endocervical polyps. Cancer in these organs may also complicate pregnancy, and of these, cervical neoplasia makes up the majority (Fig. 63-2).
These are overgrowths of endocervical stroma covered by epithelium. They typically appear as single, red, elongated fleshy masses of variable size that extend outward from the endocervical canal. Usually benign, they can bleed and can be a source of Pap test results describing atypical glandular cells of undetermined significance—AGUS. With removal and histological evaluation of these polyps, dysplasia is diagnosed in up to 0.5 percent, and there is malignant transformation in up to 0.1 percent (Esim Buyukbayrak, 2011; Long, 2013).
Few formal data guide management in pregnancy. Small asymptomatic lesions may be left alone to slough during delivery or puerperal remodeling. Removal and histological evaluation is reasonable if malignancy is suspected or if bleeding is troublesome. For those with a slender stalk, the polyp is grasped with ring forceps and twisted repeatedly about its base to strangulate feeding vessels. With repeated twisting, the base narrows and avulses. Monsel paste, which is ferric subsulfate, can be applied with pressure to the stalk stub for hemostasis. A thick-pedicle polyp may sometimes warrant surgical ligation and excision.
Pregnancy provides an opportune time to screen for cervical intraepithelial neoplasia (CIN), especially in women without regular access to health care. With Pap test screening, pregnancy status is noted on the requisition form because interpretation may be hindered by pregnancy-associated physiological changes. Some of these changes include presence of decidual cells and less often, Arias-Stella reaction. The latter gives an appearance of endocervical gland hyperplasia, which can make differentiating this from truly atypical glandular cells difficult.
Screening guidelines also applicable in pregnant women were updated in 2012 by the American Society for Colposcopy and Cervical Pathology (ASCCP). These include: (1) no screening until age 21, (2) cytology alone every 3 years in those aged 21 to 29 years, and (3) in those older than 30, human papillomavirus (HPV) and cytology co-testing every 5 years, or cytology alone every 3 years (Massad, 2013). High-risk conditions for cervical neoplasia include human immunodeficiency virus (HIV) infection, other immunocompromised states, and in utero diethylstilbestrol (DES) exposure. For women with HIV infection, initiation of cervical cancer screening with cytology alone begins within the first year after HIV diagnosis (American College of Obstetricians and Gynecologists, 2016b).
This virus infects cervical epithelia. In most instances, the infection clears, but in a smaller number, the virus may promote benign, premalignant, or cancerous neoplastic growth. The prevalence of HPV infection in pregnant women approximates 15 percent (Hong, 2013; Liu, 2014). There are more than 100 serotypes, and several are associated with high-grade intraepithelial lesions and invasive cancer. The most prominent of these are serotypes 16 and 18. Cervical cancer screening that combines both cytology and testing for high-risk HPV serotypes is termed co-testing and is suitable for women 30 years and older. Notably, as a new paradigm for screening, primary HPV testing alone can be considered an appropriate sole method for women older than 25 years (Huh, 2015). With this, identification of serotypes 16 or 18 prompts colposcopic evaluation.
Serotypes HPV 6 and 11 are linked with benign maternal genital warts. Congenital HPV infection from vertical transmission—mother to fetus or newborn—beyond transient skin colonization is rare. Still, conjunctival, laryngeal, vulvar, or perianal warts present at birth in the neonate or that develop within 1 to 3 years of birth are most likely due to perinatal exposure to these maternal HPV serotypes. This is described further in Chapter 65 (Vaginitis). Importantly, cesarean delivery does not lower the risk of neonatal laryngeal papillomatosis.
The clear link between HPV infection and cervical neoplasia has prompted development of three approved vaccines. These are not administered during pregnancy, are compatible with breastfeeding, and are discussed in Chapter 65 (Vaginitis).
Abnormal Cytology and Histology
The incidence of abnormal cervical cytology during pregnancy is at least as high as that reported for nonpregnant women. Abnormal cytological findings and their suggested management according to consensus guidelines are summarized in Table 63-1. Many of these cytological abnormalities should prompt colposcopy, and the main goal during pregnancy is exclusion of invasive cancer. Accordingly, lesions suspicious for high-grade disease or cancer should undergo biopsy. Unsatisfactory colposcopic evaluation is less common during pregnancy because the transformation zone is better exposed due to cervical eversion. With insufficient visualization of the zone, colposcopy is repeated in 6 to 8 weeks. During this time, the squamocolumnar junction usually will further evert to permit satisfactory examination.
TABLE 63-1Management of Pap Test Abnormalities in Pregnancy ||Download (.pdf) TABLE 63-1 Management of Pap Test Abnormalities in Pregnancy
|Abnormality ||Women Aged 25+ Years ||Women Aged 21 to 34 Years |
|NILM/HPV positivea ||Repeat Pap in 1 year; colposcopy if current |
Pap is 2nd NILM/HPV positive
|Not applicable |
|ASC-US || || |
| HPV positive ||Colposcopy preferred; deferral of colposcopy until 6 weeks postpartum acceptable ||Repeat Pap in 1 year |
| HPV negative ||Routine screening ||Routine screening |
| HPV unknown ||Repeat cytology 1 year; colposcopy if current Pap is 2nd ASC-US || |
|LSIL ||Colposcopy preferred; deferral of colposcopy until 6 weeks postpartum acceptable ||Repeat Pap in 1 year |
|Colposcopy during pregnancyb |
Women with histologically confirmed CIN during pregnancy may be allowed to deliver vaginally, with further evaluation planned after delivery. For those with CIN 1, the recommended management is reevaluation postpartum. For those with CIN 2 or 3 in which invasive disease has been excluded, deferring reevaluation until at least 6 weeks postpartum is acceptable. Alternatively, repeat colposcopic and cytological evaluations are performed at intervals no more frequent than 12 weeks. Repeat biopsy is recommended only if appearance of the lesion worsens or if cytology suggests invasive cancer (Massad, 2013).
Regression of a CIN lesion is common during pregnancy or postpartum. In a study of 1079 pregnant women with cervical dysplasia in which biopsy correlated with colposcopic findings, 61 percent of lesions reverted to normal postpartum (Fader, 2010). In another study, Yost and colleagues (1999) reported postpartum lesion regression in 70 percent of women with CIN 2 or 3. And, although 7 percent of women had CIN 2 lesions that progressed to CIN 3, no lesion progressed to invasive carcinoma. In another study of 77 women with carcinoma in situ (CIS) diagnosed during pregnancy, a third had postpartum regression of their lesion, two thirds had persistent CIS, and only two women had microinvasive cancer on cone biopsy after delivery (Ackermann, 2006).
Adenocarcinoma in situ (AIS) is managed similarly to CIN 3 (Dunton, 2008). Thus, unless invasive cancer is identified, treatment of AIS is not recommended until 6 weeks postpartum.
If invasive epithelial lesions are suspected, conization is indicated and may be done with loop electrosurgical excisional procedure (LEEP) or by cold-knife conization. However, the epithelium and underlying stroma within the endocervical canal cannot be extensively excised without the risk of membrane rupture. Logically, residual disease is common. Of 376 cone biopsies during pregnancy, Hacker and associates (1982) found residual neoplasia in 43 percent of subsequent specimens. In addition, nearly 10 percent of 180 pregnant women required transfusion after conization (Averette, 1970). Thus, if possible, conization is avoided in pregnancy because of its higher risks for abortion, membrane rupture, hemorrhage, and preterm delivery.
Women with CIN treated before pregnancy may also encounter pregnancy complications. First, cicatricial cervical stenosis is uncommon but may follow conization, LEEP, or laser surgery. Cervical stenosis almost always yields during labor. A so-called conglutinated cervix may undergo almost complete intrapartum effacement without dilation, and the presenting part is separated from the vagina by only a thin layer of cervical tissue. Spontaneous dilation usually promptly follows firm pressure with a fingertip, although instrumented dilation or cruciate incisions may be required.
Second, preconceptional cold-knife conization is associated with cervical insufficiency and preterm birth. That said, the relationship between preterm birth and LEEP continues to be debated (Castanon, 2012; Conner, 2014; Stout, 2015; Werner, 2010). The size of tissue excised seems to be directly related to adverse outcomes (Weinmann, 2017).
The incidence of invasive cervical carcinoma has dramatically declined in the United States as a result of PAP testing (American College of Obstetricians and Gynecologists, 2016b). This cancer is found in approximately 1 in 8500 pregnancies (Bigelow, 2017; Pettersson, 2010). The diagnosis is confirmed with biopsies taken during colposcopy, with conization, or from a grossly abnormal lesion. Of the histological types, squamous cell carcinomas account for 75 percent of all cervical cancers, whereas adenocarcinomas compose the remainder. Cancers may appear as exophytic or endophytic growth; as a polypoid mass, papillary tissue, or barrel-shaped cervix; or as focal ulceration or necrosis. A watery, purulent, foul, or bloody discharge may also be present. Biopsy with Tischler forceps is warranted for suspicious lesions. Abnormal tumor vessels may cause heavier than expected biopsy-site bleeding, which is usually controlled by Monsel paste and pressure.
Cervical cancer is staged clinically, and 70 to 75 percent of cases that are diagnosed in pregnancy are stage I (Bigelow, 2017; Morice, 2012). Physiological pregnancy changes may impede accurate staging, and the extent of cancer is more likely to be underestimated in pregnant women. Specifically, induration of the broad ligament base, which characterizes tumor spread beyond the cervix, may be less prominent due to cervical, paracervical, and parametrial pregnancy-induced softening. Staging in pregnancy typically incorporates findings from pelvic examination and from renal sonography, chest radiography, cystoscopy, proctoscopy, and perhaps cone biopsy. Although MR imaging is not formally considered for clinical staging, it can be used without gadolinium contrast to ascertain involvement of the urinary tract and lymph nodes (Fig. 63-3).
Sagittal T2-weighted magnetic resonance image of a gravid uterus at 32 weeks’ gestation with a large cervical carcinoma (arrows).
Cervical cancer treatment in pregnant women is individualized, and factors include the clinical stage, fetal age, and individual desire to continue pregnancy. Stage IA1 is termed microinvasive disease and describes lesions with deepest invasion ≤3 mm and widest lateral extension ≤7 mm (FIGO Committee on Gynecologic Oncology, 2009). If diagnosed by cone biopsy, then treatment follows guidelines similar to those for intraepithelial disease. In general, continuation of pregnancy and vaginal delivery are considered safe, and definitive therapy is reserved until 6 weeks postpartum.
In contrast, invasive cancer demands relatively prompt therapy. During the first half of pregnancy, immediate treatment is advised by most, but this depends on the decision whether to continue pregnancy. During the latter half of pregnancy, most agree that pregnancy can safely be continued until fetal lung maturity is attained (Greer, 1989). In two studies with a total of 40 women past 20 weeks’ gestation with either stage I or stage IIA carcinoma, delayed treatment was considered reasonable in women without bulky lesions (Takushi, 2002; van Vliet, 1998). Another option is to complete staging using laparoscopic lymphadenectomy and to delay treatment if metastases are excluded (Alouini, 2008; Favero, 2010). In a metaanalysis, neoadjuvant chemotherapy, that is, prior to surgery, with platinum derivatives was found to be promising for treatment in pregnancy (Zagouri, 2013a).
Although surgical therapy and radiation are equally effective, radical hysterectomy plus pelvic lymphadenectomy is the preferred treatment for invasive cervical cancer in most young women with stage I and early stage IIA lesions. Disadvantageously, radiotherapy for cervical cancer destroys ovarian and possibly sexual function, and frequently causes intestinal and urinary tract injury. In 49 women with pregnancy-associated stage IB cancer, a 30-percent severe complication rate accompanied radiotherapy compared with that of only 7 percent with radical surgery (Nisker, 1983). With surgery before 20 weeks’ gestation, radical hysterectomy is usually performed with the fetus in situ. In later pregnancy, however, hysterotomy is often performed first.
Although less commonly selected during pregnancy, other procedures have been investigated for early-stage cervical cancers. Ungár and colleagues (2006) performed abdominal radical trachelectomy before 20 weeks’ gestation for stage IB1 cancer in five pregnant women. Yahata and associates (2008) treated four women at 16 to 23 weeks for stage IA1 adenocarcinoma with laser conization, and all delivered at term. Van Calsteren and coworkers (2008) reported similar success.
For more advanced-stage cancer, radiotherapy is given. External beam radiation in early in pregnancy typically leads to spontaneous abortion. If miscarriage does not ensue, curettage is performed. During the second trimester, spontaneous abortion may not promptly occur and may necessitate hysterotomy in up to a fourth of cases. This is selected because labor induction or dilation and evacuation may pose serious hemorrhage risks.
Pregnancy does not have a negative effect on the prognosis of cervical cancer, and survival outcomes are similar for pregnant and nonpregnant women (Amant, 2014; Mogos, 2013). In a case-control study of 44 women with pregnancy-associated cervical cancer, the overall 5-year survival rate approximated 80 percent in both pregnant women and nonpregnant controls (van der Vange, 1995).
Any adverse prognostic effects that vaginal delivery through a cancerous cervix might have are unknown. For this reason, the mode of delivery is controversial, especially for small, early-stage lesions. In some cases of bulky or friable tumors, significant hemorrhage from the cancer may complicate vaginal delivery. Also, recurrences have been reported in the episiotomy scar, which result from tumor cells apparently “seeding” the episiotomy (Goldman, 2003). Thus, most favor cesarean delivery.
Pregnancy after Radical Trachelectomy
There is growing experience with pregnancy in women who have undergone fertility-sparing radical trachelectomy for stage IB1 and IB2 cervical cancer before conception. During the typically vaginal procedure, the cervix is amputated at the level of the internal os, and a permanent-suture cerclage is placed around the isthmus for support in future pregnancies. The uterine isthmus is then reconstructed to the vagina. Because of the permanent cerclage, a classical cesarean incision is required for delivery.
Shepherd and colleagues (2006) presented outcomes for 123 such women cared for at their institution. Of 63 women who attempted pregnancy, 19 had 28 live births. All underwent classical cesarean delivery, and one fourth delivered before 32 weeks. Similar findings were reported by Kim (2012) and Park (2014) and their coworkers.
Also known as myomas and somewhat erroneously called fibroids, uterine leiomyomas are common benign smooth-muscle tumors. Their incidence during pregnancy approximates 2 percent, and the cited range depends on the frequency of routine sonography and population characteristics (Qidwai, 2006; Stout, 2010). In one study of 4271 women, the first-trimester leiomyoma prevalence was highest in black women—18 percent—and lowest in whites—8 percent (Laughlin, 2009).
Leiomyomas vary in location and may develop as submucous, subserosal, or intramural growths. Less often, these develop in the cervix or broad ligament. Some become parasitic and their blood supply is derived from adjacent structures such as the highly vascularized omentum. In one rare manifestation–leiomyomatosis peritonealis disseminata–numerous, small, benign subperitoneal smooth-muscle tumors appear similar to carcinomatosis. The tumors are likely caused by estrogen stimulation of multicentric subcoelomic mesenchymal cells to become smooth-muscle cells (Bulun, 2015). These growths often regress after pregnancy.
The stimulatory effects of pregnancy progesterone on myoma growth are unpredictable and can be impressive. These tumors respond differently in individual women and may grow, regress, or remain unchanged in size during pregnancy (Laughlin, 2009; Neiger, 2006).
Especially during pregnancy, myomas can be confused with other adnexal masses, and sonographic imaging is indispensable (Fig. 63-4). In women in whom sonographic findings are unclear, MR imaging performed after the first trimester may be necessary. Once diagnosed, leiomyomas do not require surveillance with serial sonography unless associated complications are anticipated.
Sonogram of a pregnant uterus with a large uterine leiomyoma. The heterogeneous mass (arrows) lies beside the fetus (seen in cross section) and has the classic appearance of a leiomyoma in pregnancy. The placenta is located anteriorly, and the mass originates from the posterior lower uterine segment and occupies more than half of the total uterine volume.
Most leiomyomas are asymptomatic, but acute or chronic pain or pressure may develop. Large myomas more often require admission for pain (Doğan, 2016). For chronic pain secondary to large tumor size, nonnarcotic analgesic drugs usually suffice. More acutely, some myomas can outgrow their blood supply and hemorrhagic infarction follows, which is termed red or carneous degeneration. Clinically, there is acute focal abdominal pain and tenderness, and sometimes a low-grade fever and leukocytosis. As such, tumor degeneration may be difficult to differentiate from appendicitis, placental abruption, ureteral stone, or pyelonephritis. Sonographic imaging can be helpful, but close observation is requisite because an infarcted myoma is essentially a diagnosis of exclusion. In some women, preterm labor is stimulated by associated inflammation.
Treatment of a degenerated myoma is analgesic medications, and symptoms usually abate within a few days. In severe cases, close observation may be needed to exclude a septic cause. Although surgery is rarely necessary during pregnancy, myomectomy in highly selected cases has resulted in good outcomes. Of 23 reported cases, women were 14 to 20 weeks’ gestation, and in almost half, surgery was performed because of pain (Celik, 2002; De Carolis, 2001). In some, an intramural leiomyoma was in contact with the implantation site. Except for one loss immediately following surgery at 19 weeks, most underwent cesarean delivery later, at term.
Occasionally, a pedunculated subserosal myoma will undergo torsion with subsequent painful necrosis. Laparoscopy or laparotomy can be used to ligate the stalk and resect the necrotic tumor. That said, we believe that surgery should be limited to tumors with a discrete pedicle that can be easily clamped and ligated.
Myomas are associated with several complications that include preterm labor, placental abruption, fetal malpresentation, obstructed labor, cesarean delivery, and postpartum hemorrhage. In a review of pregnancy outcomes in 2065 women with leiomyomas, Coronado and colleagues (2000) reported that placental abruption and breech presentation were each increased fourfold; first-trimester bleeding and dysfunctional labor, twofold; and cesarean delivery, sixfold. Salvador and associates (2002) reported an eightfold higher second-trimester abortion risk in these women.
Factors most important in determining morbidity in pregnancy are leiomyoma number, size, and location (Ciavattini, 2015; Jenabi, 2018; Lam, 2014). If the placenta is adjacent to or implanted over a leiomyoma, rates of abortion, preterm labor, placental abruption, and postpartum hemorrhage are all increased. Retroplacental myomas are also associated with fetal-growth restriction (Knight, 2016). Tumors in the cervix or lower uterine segment may obstruct labor, as did the one shown in Figure 63-5. Despite these complications, Qidwai and associates (2006) reported a 70-percent vaginal delivery rate in women in whom myomas measured ≥10 cm. These data argue against empirical cesarean delivery for leiomyomas, and we allow a trial of labor unless myomas clearly obstruct the birth canal. If cesarean delivery is indicated, uterine malrotation should be excluded prior to hysterotomy. Myomas are generally left alone unless they cause recalcitrant bleeding. An important caveat is that cesarean hysterectomy may be technically difficult because of lateral ureteral displacement by the masses.
Cesarean delivery performed because of a large leiomyoma in the lower uterine segment. A classical vertical uterine incision, seen to the left of the myoma, was required for delivery of the fetus.
Bleeding due to myomas may develop during pregnancy from any of several factors. Especially common is bleeding with miscarriage, preterm labor, placenta previa, and placental abruption. Much less often, bleeding may result from a submucous myoma that has prolapsed from the uterus and into the cervix or vagina. In this unusual circumstance, although heavy or persistent bleeding may require earlier intervention, the stalk, if accessible, can be ligated vaginally near term to avoid tumor avulsion during delivery.
Fortunately, myomas rarely become infected (Genta, 2001). When infection develops, it usually is postpartum, especially if the tumor is located immediately adjacent to the implantation site (Lin, 2002). They also may become infected with an associated septic abortion and myoma perforation by a sound, dilator, or curette.
Despite the relatively high prevalence of myomas in young women, it is not clear whether they diminish fertility, other than by possibly causing miscarriage. In a review of 11 studies, Pritts (2001) concluded that submucous myomas did significantly affect fertility. He also found that hysteroscopic myomectomy improved infertility and early miscarriage rates in these women. If truly implicated in infertility, myomas in other locations may require laparoscopy or laparotomy for excision.
Some of these methods of treatment for infertility may affect subsequent pregnancies. For example, after myomectomy, the gravid uterus can rupture either before or during labor (American College of Obstetricians and Gynecologists, 2016a). Management is individualized, and review of the prior operative report is prudent. If resection resulted in a defect into or immediately adjacent to the endometrial cavity, then cesarean delivery is usually done before labor begins.
Although less effective than surgery, uterine artery embolization of myomas has also been used to treat infertility or symptoms (Mara, 2008). Women so treated have higher rates of miscarriage, cesarean delivery, and postpartum hemorrhage (Homer, 2010). The Society of Interventional Radiology considers myoma embolization relatively contraindicated in women who plan future pregnancies (Stokes, 2010).
Finally, outside the United States, ulipristal—a selective progesterone-receptor modulator—can be used for myoma regression. Successful subsequent pregnancies without tumor regrowth have been reported (Luyckx, 2014).
Occasionally, endometriosis can develop after delivery from endometrial tissue implanted within cesarean delivery or episiotomy scars (Bumpers, 2002). Here, they form a palpable mass and can cause cyclic localized pain. Endometriomas within an ovary are discussed in the next section.
Adenomyosis is traditionally found in late reproductive life and beyond. Its acquisition may be at least partially related to disruption of the endometrial-myometrial border during sharp curettage for abortion (Curtis, 2002). In a case-control study, Hashimoto and colleagues (2017) reported significantly higher associated rates of second-trimester abortion, preeclampsia, fetal malposition, and preterm delivery.
Endometrial carcinoma is an estrogen-dependent neoplasia also usually found in women older than 40 years. Thus, it is seen only rarely with pregnancy. Of 27 cases that were identified during pregnancy or within the first 4 months postpartum, most were found in first-trimester curettage specimens (Hannuna, 2009). These are usually early-stage, well-differentiated adenocarcinomas for which treatment consists primarily of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Much less commonly, to preserve future fertility, curettage with or without postprocedural progestational therapy has been used for the rare patient with cancer identified in a miscarriage curettage specimen (Schammel, 1998).
Many more studies describe a conservative approach for well-selected nonpregnant women diagnosed with endometrial cancer who wish to preserve fertility. One study followed 13 women treated with progestins for early-stage, well-differentiated adenocarcinoma who then later conceived after apparent remission (Gotlieb, 2003). Nine had liveborn neonates, and four of six women with a recurrence responded to another course of therapy. Similar outcomes were described in 12 women by Niwa (2005) and in 21 women by Signorelli (2009), each with their coworkers. Despite these acceptable pregnancy rates, recurrences and death have been reported, and conservative management is not considered standard (Erkanli, 2010).
Ovarian masses found during pregnancy are relatively common. Among studies, incidences vary depending on the frequency of prenatal sonography, the ovarian size threshold used to define a clinically significant “mass,” and whether the study site is tertiary or primary care. Thus, the incidence of ovarian masses not surprisingly ranges from 1 in 100 to 2000 pregnancies (Whitecar, 1999; Zanetta, 2003). Of ovarian malignancies, the absolute incidence in the California Cancer Registry was 1 in 19,000 pregnancies (Smith, 2003).
The most frequent types of ovarian masses are corpus luteum cysts, endometriomas, benign cystadenomas, and mature cystic teratomas. Because pregnant women are usually young, malignant tumors and those of low malignant potential are proportionately uncommon. Our experiences from Parkland Hospital are similar to those of Leiserowitz and associates (2006), who found that 1 percent of 9375 ovarian masses were frankly malignant and that another 1 percent were of low malignant potential. In surgically excised masses, rates of malignancy are higher, vary from 4 to 13 percent, and probably reflect a greater preoperative concern for cancer (Hoffman, 2007; Sherard, 2003).
Most ovarian masses are asymptomatic in pregnant women. Some cause pressure or chronic pain, and acute abdominal pain may be due to torsion, rupture, or hemorrhage. Seldom is blood loss significant enough to cause hypovolemia.
Many ovarian masses are detected during routine prenatal sonography or during imaging done for other indications, including evaluation of symptoms. The typical sonographic appearance of these masses is shown in Figure 63-6. In some instances, MR imaging can be used to evaluate complicated anatomy.
Sonographic characteristics of common adnexal masses in pregnancy. A. A simple anechoic cyst with smooth walls is characteristic of a physiological corpus luteum cyst or benign cystadenoma. B. Cystic structure with diffuse internal low-level echoes suggestive of an endometrioma or hemorrhagic corpus luteum. C. Mature cystic teratoma appears as an adnexal cyst (marked by calipers) with accentuated lines and dots that represent hair in both longitudinal and transverse planes. At the central inferior aspect of this cyst, a mural nodule—Rokitansky protuberance—is seen. These typically rounded protuberances range in size from 1 to 4 cm, they are predominantly hyperechoic, and they create an acute angle with the cyst wall. Although not seen here, fat-fluid levels are often identified with cystic teratomas. (Used with permission from Dr. Elysia Moschos.)
Cancer antigen 125 (CA125) serves as a tumor marker, and levels are frequently elevated with ovarian malignancy. Importantly, concentrations of CA125 in early pregnancy and early puerperium are normally elevated, possibly from the decidua (Aslam, 2000; Spitzer, 1998). As shown in the Appendix (Serum and Blood Constituents), from the second trimester until term, levels are not normally higher than those in the nonpregnant woman (Szecsi, 2014). With severe preeclampsia, however, levels are abnormally elevated (Karaman, 2014). Other tumor markers that are not useful for diagnosis or posttreatment surveillance in pregnancy include human chorionic gonadotropin (hCG), alpha-fetoprotein, inhibins A and B, and the multimarker OVA1 test (Liu, 2011).
The two most common are torsion and hemorrhage. Torsion usually causes acute constant or episodic lower abdominal pain that frequently is accompanied by nausea and vomiting. Sonography often aids the diagnosis. With color Doppler, presence of an ovarian mass with absent flow strongly correlates with torsion. However, minimal or early twisting may compromise only venous flow, thus leaving the arterial supply intact. If torsion is suspected, laparoscopy or laparotomy is warranted. Contrary to prior teaching, adnexectomy is generally unnecessary to avoid clot release, thus, most recommend attempts at untwisting (McGovern, 1999; Zweizig, 1993). With a salvageable ovary, within minutes, congestion is relieved, and ovarian volume and cyanosis diminish. If cyanosis persists, however, then removal of the infarcted adnexum is typically indicated.
If the adnexum is healthy, there are options. First, neoplasms are resected. However, ovarian cystectomy in an ischemic, edematous ovary may be technically difficult, and adnexectomy may be necessary. Second, unilateral or bilateral oophoropexy has been described to minimize the risk of repeated torsion (Djavadian, 2004; Germain, 1996). Techniques described include shortening of the uteroovarian ligament or fixing the uteroovarian ligament to the posterior uterus, the lateral pelvic wall, or the round ligament (Fuchs, 2010; Weitzman, 2008).
The most common cause of ovarian hemorrhage follows rupture of a corpus luteum cyst. If the diagnosis is certain and symptoms abate, then observation and surveillance is usually sufficient. Concern for ongoing bleeding will typically prompt surgical evaluation. If the corpus luteum is removed before 10 weeks’ gestation, progestational support is recommended to maintain the pregnancy. Suitable regimens include: (1) micronized progesterone (Prometrium) 200 or 300 mg orally once daily; (2) 8-percent progesterone vaginal gel (Crinone), one premeasured applicator vaginally daily plus micronized progesterone 100 or 200 mg orally once daily; or (3) intramuscular 17-hydroxyprogesterone caproate, 150 mg. The first two regimens are given until 10 completed weeks. For the last, if given between 8 and 10 weeks’ gestation, only one injection is required immediately after surgery. If the corpus luteum is excised between 6 and 8 weeks’ gestation, then two additional doses should be given 1 and 2 weeks after the first.
Asymptomatic Adnexal Mass During Pregnancy
Because most of these are incidental findings, management considerations include whether resection is necessary and its timing. A cystic benign-appearing mass that is <5 cm often requires no additional antepartum surveillance. Early in pregnancy, this is likely a corpus luteum cyst, which typically resolves by the early second trimester. For cysts ≥10 cm, because of the substantial risk of malignancy, torsion, or labor obstruction, surgical removal is reasonable. Tumors between 5 and 10 cm should be carefully evaluated by sonography along with color Doppler and possibly MR imaging. If they have a simple cystic appearance, these cysts can be managed expectantly with sonographic surveillance (Schmeler, 2005; Zanetta, 2003). Resection is done if cysts grow, begin to display malignant qualities, or become symptomatic. Those with classic findings of endometrioma or mature cystic teratoma may be resected postpartum or during cesarean for obstetrical indications.
On the other hand, if sonographic characteristics suggest cancer—thick septa, nodules, papillary excrescences, or solid components—immediate resection is indicated (Caspi, 2000). In one review of 563 masses, approximately half were simple, and the other half complex (Webb, 2015). Among simple masses, 1 percent were malignant, and of complex masses, 9 percent were cancerous.
Approximately 1 in 1000 pregnant women undergoes surgical exploration for an adnexal mass (Boulay, 1998). In general, we plan resection at 14 to 20 weeks’ gestation because most masses that will regress will have done so by this time. As outlined in Chapter 46 (Medications and Surgeries), laparoscopic removal is ideal (Naqvi, 2015; Sisodia, 2015). Importantly, in any instance in which cancer is strongly suspected, the American College of Obstetricians and Gynecologists (2017b) recommends consultation with a gynecologic oncologist.
Pregnancy-Related Ovarian Tumors
One group of ovarian masses results directly from the stimulating effects of various pregnancy hormones on ovarian stroma. These include pregnancy luteoma, hyperreactio luteinalis, and ovarian hyperstimulation syndrome.
Of these, pregnancy luteoma is a rare, benign ovarian neoplasm that arises from luteinized stromal cells and classically causes elevated testosterone levels (Hakim, 2016; Irving, 2011). Up to 25 percent of affected women will be virilized, and of these affected women, nearly half of their female fetuses will have some degree of virilization. However, most mothers and their fetuses are unaffected because the placenta rapidly converts testosterone to estrogen (Kaňová, 2011).
In typical cases, an adnexal mass along with maternal virilization will prompt sonography and measurement of testosterone and CA125 levels. Luteomas range in size from microscopic to >20 cm. They appear as solid tumors, may be multiple or bilateral, and may be complex because of internal hemorrhage (Choi, 2000). Concerns for malignancy may be further investigated with MR imaging (Kao, 2005; Tannus, 2009).
Total testosterone levels are increased, but notably, levels in normal pregnancy can be substantially elevated (Appendix, Serum and Blood Constituents). Differential diagnoses include granulosa cell tumors, thecomas, Sertoli-Leydig cell tumors, Leydig cell tumors, stromal hyperthecosis, and hyperreactio luteinalis.
Generally, luteomas do not require surgical intervention unless there is torsion, rupture, or hemorrhage (Masarie, 2010). These tumors spontaneously regress during the first few months postpartum, and androgen levels drop precipitously during the first 2 weeks following delivery (Wang, 2005). Lactation may be delayed a week or so by hyperandrogenemia (Dahl, 2008). Recurrence in subsequent pregnancies is rare.
In this condition, one or both ovaries develop multiple, large theca-lutein cysts, typically after the first trimester. Cysts are caused by luteinization of the follicular theca interna layer, and most are in response to stimulation by exceptionally high hCG levels (Russell, 2009). For this reason, they are more common with gestational trophoblastic disease, twins, fetal hydrops, and other conditions with increased placental mass. Maternal virilization may develop, but fetal virilization has not been reported (Kaňová, 2011; Malinowski, 2015).
As reported by Baxi and coworkers (2014), these ovarian tumors appear sonographically to have a “spoke wheel” pattern (Fig. 20-3). If the diagnosis is confident, and unless complicated by torsion or hemorrhage, surgical intervention is not required. These masses resolve after delivery. Few data allow prediction of risk in a subsequent pregnancy, but in one case report, a woman had hyperreactio with three pregnancies (Bishop, 2016).
Ovarian Hyperstimulation Syndrome
This is typified by multiple ovarian follicular cysts accompanied by increased capillary permeability. It most often is a complication of ovulation-induction therapy for infertility, although it rarely may develop in an otherwise normal pregnancy. It has also been reported with a partial molar pregnancy (Suzuki, 2014). Its etiopathogenesis is thought to involve hCG stimulation of vascular endothelial growth factor (VEGF) expression in granulosa-lutein cells (Soares, 2008). This causes greater vascular permeability that can lead to ascites, pleural or pericardial effusion, hypovolemia with acute kidney injury, and hypercoagulability. Serious complications are renal dysfunction, adult respiratory distress syndrome, ovarian rupture with hemorrhage, and VTE. Unlike hyperreactio lutealis, virilization is absent (Suzuki, 2004).
Detailed guidelines for management are outlined by the American Society for Reproductive Medicine (2016). Treatment is primarily supportive with attention to maintaining vascular volume and thromboprophylaxis. In severe cases, paracentesis can be helpful.
Malignancies of the ovary are the leading cause of death from genital-tract cancers in all women (American Cancer Society, 2017). Still, it is uncommon in young women, and the incidence of ovarian malignancy ranges from 1 in 20,000 to 1 in 50,000 births (Eibye, 2013; Palmer, 2009). Fortunately, 75 percent of these found in pregnancy are early-stage cancers that carry a 5-year survival rate between 70 and 90 percent (Brewer, 2011). The types of malignancy are also markedly different in pregnant women compared with those in older women. In gravidas, these are, in decreasing order of frequency, germ cell and sex cord-stromal tumors, low-malignant-potential tumors, and epithelial tumors (Morice, 2012).
Pregnancy apparently does not alter the prognosis of most ovarian malignancies. Management is similar to that for nonpregnant women, with the usual proviso that it may be modified depending on gestational age. Thus, if frozen section histopathological analysis verifies malignancy, surgical staging is done with careful inspection of all accessible peritoneal and visceral surfaces (Giuntoli, 2006). Peritoneal washings are taken for cytology, biopsies are obtained from the diaphragmatic surface and peritoneum, omentectomy is completed, and pelvic and infrarenal paraaortic lymph nodes are sampled, if accessible.
If there is advanced disease, bilateral adnexectomy and omentectomy will decrease most tumor burden. In early pregnancy, hysterectomy and aggressive surgical debulking procedures may be elected. In other cases, minimal debulking as described in the previous paragraph is done and the operation terminated. In some cases of aggressive or large-volume disease, chemotherapy can be given during pregnancy while awaiting pulmonary maturation. Monitoring maternal CA125 serum levels during chemotherapy is not accurate in pregnancy (Aslam, 2000; Morice, 2012).
Paratubal and paroovarian cysts are either distended remnants of the paramesonephric ducts or are mesothelial inclusion cysts. Although most measure ≤3 cm, they occasionally attain worrisome dimensions. Their reported incidence is influenced by size, but one autopsy series in nonpregnant women cited this to be 5 percent (Dorum, 2005). The most common paramesonephric cyst is the hydatid of Morgagni, which is pedunculated and typically dangles from one of the fimbria. These cysts infrequently cause complications and are most often identified at the time of cesarean delivery or puerperal sterilization. In these instances, they can simply be excised or drained by creating a large window in the cyst wall. Neoplastic paraovarian cysts are rare, sonographically and histologically resemble tumors of ovarian origin, and rarely are of borderline potential or frankly malignant (Korbin, 1998).
Preinvasive disease in young women—vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VAIN)— are seen more often than invasive disease and are commonly associated with HPV infection. As with cervical neoplasia, these premalignant conditions are treated after delivery.
Cancer of the vulva or vagina is generally a malignancy of older women, and thus, these are rarely associated with pregnancy. Even so, any suspicious lesions should be biopsied. Treatment is individualized according to the clinical stage and depth of invasion. In a review of 23 cases, investigators concluded that radical surgery for stage I disease was feasible during pregnancy—including in the last trimester (Heller, 2000).
We and others question the necessity of resection in late pregnancy because definitive therapy can often be delayed due to these cancers’ typically slow progression (Anderson, 2001). It appears that vaginal delivery is not contraindicated if vulvar and inguinal incisions are well healed. Vulvar sarcoma, vulvar melanoma, and vaginal malignancies are rare in pregnancy and are the subjects of case reports (Alexander, 2004; Kuller, 1990; Matsuo, 2009).