Fidelma B. Rigby and Angela M. Tran
History of present illness
A 40-year-old gravida 2, para 0 woman at 14 weeks’gestation by last menstrual period presents to the emergency department with painless vaginal bleeding. The bleeding began this morning. She is changing a pad every two hours. She has had persistent nausea and vomiting for the past two days.
She has not previously sought prenatal care. The pregnancy was unplanned.
Her one prior pregnancy was a hydatidiform mole treated by dilation and curettage (D&C). She has had no other surger- ies. She has no medical problems. She takes no medications.
She does not desire future pregnancy.
Physical examination
General appearance:Ill-appearing woman in moderate discomfort
Vital signs:
Temperature: 37.1°C Pulse: 110 beats/min
Blood pressure: 160/110 mmHg Respiratory rate: 14 breaths/min Oxygen saturation: 99% on room air
HEENT:Dry mucous membranes, no exophthalmos, no thyromegaly
Cardiovascular:Tachycardic, regular rhythm, no murmurs, rubs, or gallops
Lungs:Clear to auscultation bilaterally
Abdomen:Bowel sounds normoactive; soft, nondistended, and nontender to palpation; fundus palpable 2 cm under the umbilicus; no fetal heart tones audible with Doppler Pelvic:External genitalia unremarkable; moderate amount of blood from closed cervical os; no cervical motion or adnexal tenderness; no masses; uterus consistent with 18 weeks’size; ovaries not palpable
Extremities:No edema Neurologic:No focal deficits Laboratory studies:
Serum beta-hCG: 500 000 mIU/mL Hb: 11 g/dL
Clean catch urinalysis: 3+ protein, no blood, ketones, nitrites, or leukocyte esterase
Imaging:Ultrasound was obtained of the uterus (Fig. 52.1).
Bilateral ovarian cysts were also present, each measuring 6 cm in diameter
How would you manage this patient?
This patient has a complete molar pregnancy, also known as a hydatidiform mole. Her combination of hypertension and
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
Fig. 52.1 Sagittal ultrasound image of the uterus.
Note the vesicular pattern, characteristic of hydatidiform mole. (Image provided by Steven Cohen, MD.)
proteinuria was indicative of preeclampsia. Platelets, creatin- ine, and liver function tests were normal. She was admitted to the hospital and her elevated blood pressure was controlled with hydralazine. Her nausea and vomiting were treated with ondansetron. She was typed and cross-matched for two units of packed red blood cells. Chest x-ray was unremarkable.
Given her preeclampsia, recurrent mole, and adamant desire not to get pregnant again, she was treated by total abdominal hysterectomy (Fig. 52.2). Her blood pressure had normalized by postoperative day 1. She had an unremarkable postopera- tive course. The tissue was sent to pathology, and confirmed the diagnosis of complete mole. Her theca lutein cysts resolved after 12 weeks. She was followed with serial serum quantitative beta-human chorionic gonadotropin (beta-hCG) testing, which confirmed resolution of the mole.
Molar pregnancy
Hypertension is common in the emergency care setting, and can be transient and related to patient fear and nervousness and underlying hypertensive disorders. In the setting of early pregnancy bleeding, these two causes likely explain nearly all hypertension present at the time of initial evaluation. It can also be a rare presentation of preeclampsia, which can occur prior to 20 weeks in the setting of molar pregnancy.
Preeclampsia is typically defined as systolic pressure greater than or equal to 40 mmHg or diastolic pressure greater than or equal to 90 mmHg on two measurements 6 hours apart, or elevated proteinuria on urine dip or 24-hour collection. It nearly always occurs in the third trimester.
Complete moles are part of a larger spectrum of diseases of the placenta called gestational trophoblastic disease (GTD),
which consists of partial and complete hydatidiform mole and gestational trophoblastic neoplasia (GTN). GTN includes placental site trophoblastic tumor, invasive mole, and chorio- carcinoma. A hydatidiform mole is an abnormal pregnancy that results from proliferation of cytotrophoblasts and syncy- tiotrophoblasts of the placenta. It is characterized by swelling of chorionic villi [1]. Differences between complete and partial moles are summarized inTable 52.1[1,2,3]. Complete moles are most commonly 46,XX and result from fertilization of an empty ovum by a sperm that duplicates. Most partial moles result from fertilization of a normal ovum by two sperm or fertilization of a normal ovum by one sperm that duplicates.
This usually results in a karyotype of 69,XXY [2,4,5]. Partial moles have some component of fetal tissue, varying from nucleated red blood cells to a full fetus. The karyotype of this fetus is usually 69,XXY and early second-trimester fetal growth restriction is typically present. Elevated levels of vascular endo- thelial growth factor (VEGF) have been implicated in pree- clampsia, and increased placental expression of VEGF has been noted in pregnancies with hydatidiform mole [6]
This patient has the two most common risk factors for the development of a complete mole: extremes of maternal age and prior molar pregnancy. Women older than 40 years have a 7.5 times increased risk compared to women aged 21–35, and 1 in 3 pregnancies in women older than 50 years result in a molar pregnancy [4,5]. Partial molar pregnancies do not seem to be associated with increased maternal age [4].
There is a 1% risk for a subsequent molar pregnancy in patients who have had a previous one [1]. Other less well- defined risk factors include oral contraceptive pill use, tobacco use, and vitamin deficiencies.
The most frequent presenting symptoms for hydatidiform moles are painless vaginal bleeding and hyperemesis, which are found in 87% and 8% of cases respectively [5]. The patient in this case has both of these classic findings. Painless vaginal
Fig. 52.2Uterus at time of hysterectomy. The uterus is enlarged greater than expected by dates. The specimen has been opened. Hydropic villi are visible.
(Image provided by Steven Cohen, MD.) Table 52.1 Comparison of partial and complete moles*
Feature Complete mole Partial mole
Karyotype 46,XX (90% of
cases) or 46,XY 69,XXX or 69, XXY
Fetal tissue Absent Present
Chorionic villi Diffusely hydropic Focal with variable edema Trophoblastic
hyperplasia Diffuse, severe Focal, minimal Uterine size 28–50% of cases
are larger for gestational age
Small for gestational age
Medical complications (hyperemesis, hyperthyroidism, and preeclampsia)
Rare but may
occur Much less
common than in complete moles Risk for gestational
trophoblastic neoplasia (GTN)
20% <5%
* Dighe et al. [1], Berkowitz and Goldstein [4], Zhao et al. [6].
bleeding is a common symptom, and mole is a rare cause of the bleeding. Threatened and spontaneous abortion or ectopic pregnancy are far more common causes of first-trimester bleeding, and are generally the focus offirst-trimester bleeding evaluations. Hydatidiform mole should also be included in the differential, although much less frequent than the other causes.
In this instance, where preeclampsia was diagnosed so early in pregnancy, molar pregnancy should be specifically investi- gated. Vaginal bleeding is also common in partial moles, but they may also present as an incomplete or missed abortion where the diagnosis is not made until the specimen undergoes pathologic analysis [5].
This patient has several common physicalfindings includ- ing uterine size greater than expected for gestational age, which is found in 28% of patients. She also had significant hyperten- sion, which should prompt evaluation for preeclampsia as this currently occurs in approximately 1% of patients with moles.
This low incidence reflects the current ability to diagnose molar pregnancy early through ultrasound. Older studies from when molar pregnancy was frequently not diagnosed until the second trimester had incidences of preeclampsia as high as 27%. The patient in this case has been diagnosed at 14 weeks, and has a significantly elevated risk. All patients with pree- clampsia presenting prior to 20 weeks’ gestation should be assessed for molar pregnancy. Rarely, respiratory failure may occur. Unilateral or bilateral theca lutein ovarian cysts occur in about 50% of patients and are caused by hyperstimulation by high levels of hCG [6]. They may be palpable on physical exam.
This patient had moderate-sized theca lutein cysts, which were not palpable, likely because the enlarged uterus had caused the ovaries to be located above the level of the pelvis.
Patients with undiagnosed vaginal bleeding should have ultrasonography. Ultrasonography is the diagnostic imaging of choice for hydatidiform moles, and is effective in ruling out the more common causes of first-trimester bleeding. Earlier diagnosis in the first trimester, instead of second or third trimester, coupled with improved ultrasound resolution has led to a notable change in the ultrasound findings of a com- plete hydatidiform mole. The textbook“snowstorm”descrip- tion has been replaced by a vesicular pattern, as seen in this patient (Fig. 52.1) [1]. While definitive diagnosis typically requires a pathologic specimen, presence of these ultrasound findings are adequate to guide management. Partial moles may also show similar cystic spaces within the placenta, though the appearance will be more focal in distribution and the trans- verse diameter of the gestational sac may be increased [4].
Ultrasound may also visualize theca lutein cysts.
Patients with hydatidiform mole can have other medical problems, particularly hyperthyroidism and preeclampsia.
Advances in ultrasound resolution and the availability of beta-hCG testing have allowed earlier diagnosis, making pre- eclampsia and hypertension much less frequent than in the past. Patients with hypertension should be assessed for pre- eclampsia and patients with hyperthyroid symptoms should have thyroid studies ordered. Anemia is present in 5% of
patients. The hyperemesis and preeclampsia found in complete molar pregnancies are very rare in partial moles [5]. All resolve rapidly after evacuation of the mole.
Typical laboratory findings include a markedly elevated serum hCG level. Complete molar pregnancies may present with normal levels of serum hCG, but about half of patients with complete moles have hCG levels greater than 100 000 mIU/mL. Less than 10% of patients with partial moles have an hCG this high [1]. Because hCG levels peak in the latefirst trimester, a time when a molar pregnancy is often being considered, a single hCG value is not as useful and a complete mole must be differentiated from a normal intrauterine preg- nancy, multiple gestation, and pregnancies characterized by large placentas such as ones with intrauterine infections [5].
Hydatidiform mole is primarily managed by surgical evacuation by suction D&C. Patients being taken to the oper- ating room should have a complete blood count with platelets, clotting functions, metabolic panel, and blood type and screen.
For those who do not desire fertility, hysterectomy is an option.
Patients are still at risk for metastatic GTN after hysterectomy [4,5]. This patient, who was 40 years old, no longer desired fertility, was having her second molar pregnancy, and had developed preeclampsia, chose to have a hysterectomy as it decreased her risk of a future mole and metastatic GTN with this mole, and might allow her preeclampsia to resolve more quickly. Prior to surgery, chest x-ray is typically done to rule out pulmonary edema or metastases [2]. Any associated com- plications, such as preeclampsia or hyperthyroidism, should be addressed [4,5]. Special considerations include patients with respiratory compromise by physical examination, or when concern is raised by abnormal chest x-rayfindings. Respiratory distress syndrome can occur due to high output congestive heart failure, anemia, hyperthyroidism, or preeclampsia.
Central venous catheter monitoring and prolonged intubation can be considered in these patients. The patient must also be monitored intraoperatively for respiratory distress, which can occur from trophoblastic embolization, high-output congest- ive heart failure, and iatrogenicfluid overload [5]. This patient had her blood pressure controlled. In late pregnancy, magne- sium is typically administered to patients with preeclampsia to prophylax against seizures. No recommendations exist for seizure prophylaxis in thefirst half of pregnancy. As this patient was having her procedure under general and was having a procedure that should resolve her preeclampsia quickly, magnesium was not administered.
Patients with theca lutein cysts are at risk for ovarian torsion because of their ovarian enlargement and should be counseled regarding symptoms [1]. This risk should be low after hysterec- tomy. These cysts should be managed expectantly as they usu- ally resolve within 8–12 weeks after the molar pregnancy is evacuated. They should not be removed at time of hysterectomy [3]. An ultrasound can be done to document resolution.
While risk of persistent GTN is low after hysterectomy, the patient’s hCG levels should still be monitored on a weekly basis until they normalize for three weeks, followed by Case 52: A 40-year-old woman with hypertension andfirst-trimester bleeding
monthly monitoring for six months, as they would be if she had the usual evacuation by D&C. After evacuation, effective contraception is extremely important to ensure a new preg- nancy does not start until it is certain that there is no persistent GTN. This is not an issue after hysterectomy.
With early diagnosis and appropriate treatment, prognosis is generally excellent. Availability of hCG assays and ready access to ultrasound has generally allowed earlier diagnosis, and outcomes are better than in the past. With current chemo- therapy regimens, most women with GTN are cured, and even those with widespread metastatic disease have greater than 90% cure rates [2,5].
Key teaching points
Patients with preeclampsia prior to 20 weeks’gestation need evaluation for a hydatidiform mole.
Most hydatidiform moles are diagnosed early, where medical complications such as hyperthyroidism and preeclampsia are rare. In moles that are diagnosed later, medical complications are more frequent.
Vaginal bleeding is the most common presentation. Most patients with bleeding have other more common diagnoses which must be ruled out.
An extremely elevated human chorionic gonadotropin (hCG) level (>100 000 mIU/mL) should raise suspicion for a complete hydatidiform mole.
Ultrasonography is the diagnostic imaging procedure of choice. With earlier diagnosis, classicfindings such as uterine size greater than expected for gestational age and the“snowstorm”appearance of the mole on
ultrasonography are much less common.
Suction dilation and curettage is the treatment of choice for molar pregnancies. In unusual circumstances in women no longer desiring fertility, hysterectomy may be
appropriate.
Human chorionic gonadotropin levels should be followed after treatment of a molar pregnancy. Levels of hCG that plateau or are persistently elevated should prompt an immediate evaluation for gestational trophoblastic neoplasia.
References
1. Dighe M, Cuevas C, Moshiri M, Dubinsky T, Dogra VS. Sonography in first trimester bleeding.J Clin
Ultrasound2008;36(6):352–66.
2. Soper JT, Mutch DG, Schink JC.
Diagnosis and treatment of gestational trophoblastic disease. Practice Bulletin No. 53.Gynecol Oncol2004;93:575–85.
3. Berkowitz RS, Goldstein DP. Molar pregnancy.N Engl J Med2009;360:
1639–45.
4. Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases.Gynecol Oncol2009;105:3–4.
5. Lurain JR. Gestational trophoblastic disease I: Epidemiology, pathology, clinical presentation and diagnosis of
gestational trophoblastic disease, and management of hydatidiform mole.
Amer J Obstet Gynecol2010;6:531–9.
6. Zhao M, Yin Y, Guo F, et al. Placental expression of VEGF is increased in pregnancies with hydatidiform mole:
Possible association with developing very early onset preeclampsia.Early Hum Dev2013;89:583–8.