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Hydatidiform Mole
Article Last Updated: Dec 4, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 12  
Author: Lisa E Moore, MD, FACOG, Assistant Professor, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of New Mexico Health Sciences Center
Lisa E Moore is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, and Society for Maternal-Fetal Medicine
Editors: Jordan G Pritzker, MD, MBA, FACOG, Assistant Professor of Obstetrics, Gynecology, and Women's Health, Women's Comprehensive Health Center, Albert Einstein College of Medicine; Physician-In-Charge, Dept of Obstetrics and Gynecology, Long Island Jewish Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; A David Barnes, MD, PhD, MPH, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital, Mammoth Lakes, California, Pioneer Valley Hospital, Salt Lake City, Utah, Warren General Hospital, Warren, Pennsylvania and Mountain West Hospital, Tooele, Utah; Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Assumption Community Hospital; David Chelmow, MD, Professor of Obstetrics and Gynecology, Tufts University School of Medicine; Program Director, Tufts University Affiliated Hospitals OB/GYN Residency Program; Chair, Tufts University Health Sciences Campus Institutional Review Board
Author and Editor Disclosure
Synonyms and related keywords:
gestational trophoblastic disease, placental site trophoblastic tumors, molar pregnancy, complete mole, partial mole, cystic mole, hydatidiform mole, choriocarcinomas, invasion moles, trophoblastic hyperplasia, nonmetastatic trophoblastic disease, theca lutein cysts, diet deficient in animal fat, diet deficient in carotene, hyperemesis, trophoblastic malignancy, vaginal bleeding, hyperthyroidism, absence of fetal heart tones, preeclampsia, toxemia, proteinuria, edema with hyperreflexia
Background
Gestational trophoblastic disease encompasses several disease processes that originate in the placenta. These include complete and partial moles, placental site trophoblastic tumors, choriocarcinomas, and invasive moles.
Almost all women with malignant gestational trophoblastic disease can be cured with preservation of reproductive function. The following discussion is limited to hydatidiform moles (complete and partial).
Pathophysiology
A complete mole contains no fetal tissue. Ninety percent are 46,XX, and 10% are 46,XY. Complete moles can be divided into 2 types:
- Androgenetic complete mole
- Homozygous
- These account for 80% of complete moles.
- Two identical paternal chromosome complements, derived from duplication of the paternal haploid chromosomes.
- Always female; 46,YY has never been observed.
- Heterozygous
- These account for 20% of complete moles.
- May be male or female.
- All chromosomes are of parental origin, most likely due to dispermy.
- Biparental complete mole: Maternal and paternal genes are present but failure of maternal imprinting causes only the paternal genome to be expressed.
- The biparental complete mole is rare.
- A recurrent form of biparental mole, which is familial and appears to be inherited as an autosomal recessive trait, has been described. Al-Hussaini describes a series of 5 women with as many as 9 consecutive molar pregnancies.1
- A candidate region of chromosome arm 19q13.4 has been identified.2, 3
With a partial mole, fetal tissue is often present. Fetal erythrocytes and vessels in the villi are a common finding. The chromosomal complement is 69,XXX or 69,XXY. This results from fertilization of a haploid ovum and duplication of the paternal haploid chromosomes or from dispermy. Tetraploidy may also be encountered. As in a complete mole, hyperplastic trophoblastic tissue and swelling of the chorionic villi occur.
Frequency
United States
In Western countries, 1 of every 1000-1500 pregnancies is affected. Hydatiform mole is an incidental finding in approximately 1 of every 600 therapeutic abortions.4, 5, 6
International
In Asian countries, the rate of molar pregnancies is as much as 15 times higher than in the United States. Japan has a reported rate of 2 cases per 1000 pregnancies. In the Far East, some sources estimate the rate as high as 1 case per 120 pregnancies. The highest frequencies of molar gestations are seen in Mexico, Iran, and Indonesia.7
Mortality/Morbidity
Of patients with hydatidiform mole, 20% develop a trophoblastic malignancy. After a complete mole develops, uterine invasion occurs in 15% of patients, and metastasis occurs in 4%. No cases of choriocarcinoma have been reported after a partial mole, although 4% of patients with partial moles develop persistent nonmetastatic trophoblastic disease requiring chemotherapy.
Race
The incidence of molar pregnancies varies among ethnic groups and is highest in some countries in Latin America and the Middle and Far East.7
Sex
Hydatidiform mole is a disease of pregnancy and therefore a disease of women.
Age
Hydatidiform mole is more common at the extremes of reproductive age. Women in their early teenage or perimenopausal years are most at risk. Women older than 35 years have a 2-fold increase in risk. Women older than 40 years experience a 7-fold increase in risk compared to younger women. Parity does not affect the risk.
History
- Complete mole: The typical clinical presentation of complete molar pregnancies has changed with the advent of high-resolution ultrasonography. Most moles are now diagnosed in the first trimester before the onset of the classic signs and symptoms.
- Vaginal bleeding: The most common classic symptom of a complete mole is vaginal bleeding. Molar tissue separates from the decidua, causing bleeding. The uterus may become distended by large amounts of blood, and dark fluid may leak into the vagina. This symptom occurs in 97% of cases.
- Hyperemesis: Patients may also report severe nausea and vomiting. This is due to extremely elevated human chorionic gonadotropin (HCG) levels.
- Hyperthyroidism: Approximately 7% of patients may present with tachycardia, tremor, and warm skin.
- Partial mole: Patients with partial mole do not have the same clinical features as those with complete mole. These patients usually present with signs and symptoms consistent with an incomplete or missed abortion.
- Vaginal bleeding
- Absence of fetal heart tones
Physical
- Complete mole
- Size inconsistent with gestational age: A uterine enlargement greater than expected for gestational age is a classic sign of a complete mole. Unexpected enlargement is caused by excessive trophoblastic growth and retained blood. However, patients present with size-appropriate enlargement or smaller-than-expected enlargement at a similar frequency.
- Preeclampsia: Approximately 27% of patients with complete mole develop toxemia characterized by hypertension (blood pressure [BP] >140/90 mm Hg), proteinuria (>300 mg/d), and edema with hyperreflexia. Convulsions rarely occur.
- Theca lutein cysts: These are ovarian cysts greater than 6 cm in diameter and accompanying ovarian enlargement. These cysts are not usually palpated on bimanual examination but are identified by ultrasonography. Patients may report pressure or pelvic pain. Because of the increased ovarian size, torsion is a risk. These cysts develop in response to high levels of beta-HCG and spontaneously regress after the mole is evacuated.
- Partial mole
- Uterine enlargement and preeclampsia is reported in only 3% of patients.
- Theca lutein cysts, hyperemesis, and hyperthyroidism are rare.
- Twinning
- Twinning with a complete mole and a fetus with a normal placenta has been reported. Cases of healthy infants in these circumstances have been reported.
- Women with coexistent molar and normal gestations are at higher risk for developing persistent disease and metastasis5. Termination of pregnancy is a recommended option.
- The pregnancy may be continued as long as the maternal status is stable, without hemorrhage, thyrotoxicosis, or severe hypertension. The patient should be informed of the risk of severe maternal morbidity from these complications.
- Prenatal genetic diagnosis by chorionic villus sampling or amniocentesis is recommended to evaluate the karyotype of the fetus.
Causes
A diet deficient in animal fat and carotene may be a risk factor.
Hyperemesis Gravidarum
Hypertension
Hypertension, Malignant
Hyperthyroidism
Lab Studies
- Quantitative beta-HCG: HCG levels greater than 100,000 mIU/mL indicate exuberant trophoblastic growth and raise suspicion that a molar pregnancy should be excluded. A molar pregnancy may have a normal HCG level.
- Complete blood cell count with platelets: Anemia is a common medical complication, as is the development of a coagulopathy.
- Clotting function: Test clotting function to exclude the development of a coagulopathy or to treat one if discovered.
- Liver function tests
- Blood urea nitrogen (BUN) and creatinine studies
- Thyroxin: Although women with molar pregnancies are usually clinically euthyroid, plasma thyroxin is usually elevated above the reference range for pregnancy. Hyperthyroidism may be the presenting symptom.
- Serum inhibin A and activin A: Serum inhibin A and activin A have been shown to be 7- to 10-fold higher in molar pregnancies than normal pregnancies at the same gestational age. The fall in inhibin A and activin A after evacuation may be helpful in following the course of remission.8
Imaging Studies
- Ultrasonography is the criterion standard for identifying both complete and partial molar pregnancies. The classic image, using older ultrasonographic technology, is of a snowstorm pattern indicating hydropic chorionic villi. High-resolution ultrasonography shows a complex intrauterine mass containing many small cysts.
- Once a molar pregnancy is diagnosed, a baseline chest radiograph should be taken. The lungs are a primary site of metastasis for malignant trophoblastic tumors.
Histologic Findings
- Complete mole: Fetal tissue is absent, and severe trophoblastic proliferation, hydropic villi, and chromosomes 46,XX or 46,XY are present. Additionally, complete moles show overexpression of several growth factors, including c-myc, epidermal growth factor, and c-erb B-2, compared to normal placenta.
- Partial mole: Fetal tissue is often present as well as amnion and fetal red blood cells. Hydropic villi and trophoblastic proliferation are also observed.
Medical Care
- Stabilize the patient.
- Transfuse for anemia.
- Correct any coagulopathy.
- Treat hypertension.
Surgical Care
- Evacuation of the uterus by dilation and curettage is always necessary.
- Prostaglandin or oxytocin induction is not recommended because of the increased risk of bleeding and malignant sequelae.
- Intravenous oxytocin should be started with the dilation of the cervix and continued postoperatively to reduce the likelihood of hemorrhage. Consideration of using other uterotonic formulations (eg, Methergine, Hemabate) is also warranted.
- Respiratory distress is often observed at the time of surgery. This may be due to trophoblastic embolization, high-output congestive heart failure caused by anemia, or iatrogenic fluid overload. Distress should be aggressively treated with assisted ventilation and monitoring, as required.
Consultations
A gynecologic oncologist should be consulted if the patient is believed to be at risk for or has developed malignant disease.
Diet
No special diet is required.
Activity
- Patients may resume activity as tolerated.
- Pelvic rest is recommended for 4-6 weeks after evacuation of the uterus, and the patient is instructed not to become pregnant for 12 months. Adequate contraception is recommended during this period.
- Monitor serial beta-HCG values to identify the rare patient who develops malignant disease. If a pregnancy does occur, the elevation in beta-HCG would be confused with development of malignant disease.
Prophylactic chemotherapy for hydatidiform mole is controversial. Most women are cured by evacuation of the mole.
Further Outpatient Care
The duration of follow up after a molar pregnancy is a current topic of investigation. ACOG recommends the following:9
- Serial quantitative beta-HCG levels should be determined.
- Draw the first level 48 hours after evacuation and then every 2 weeks until the levels are within reference ranges.
- Levels should consistently drop and should never increase.
- Once levels have reached reference ranges, check them each month for a year.
- Any rise in levels should prompt a chest radiograph and pelvic examination to facilitate early detection of metastases.
- Contraception is recommended for 6 months to a year after evacuation.
- Patients with a prior complete or partial molar pregnancy have a 10-fold risk of a second mole in a future pregnancy. Evaluate all future pregnancies early with ultrasonography.
In a retrospective review of 126 patients (72 complete moles and 54 partial moles), 72 patients completed the recommended follow up, and 54 did not complete the standard protocol. No patients who achieved undetectable hCG titers relapsed.4 A separate study of 320 patients also found that the disease did not recur in patients who achieved at least 1 undetectable hCG level.10 The authors suggest that a revision of the duration of follow up should be considered.
Complications
- Perforation of the uterus during suction curettage sometimes occurs because the uterus is large and boggy. If perforation is noted, the procedure should be completed under laparoscopic guidance.
- Hemorrhage is a frequent complication during the evacuation of a molar pregnancy. For this reason, intravenous oxytocin should be started prior to beginning the procedure. Methergine and/or Hemabate should also be available. The patient should be typed and crossed and have blood readily available.
- Malignant trophoblastic disease develops in 20% of molar pregnancies. For this reason, quantitative HCG should be serially monitored for 1 year postevacuation until results are negative.
- Factors released by the molar tissue have fibrinolytic activity. All patients should be screened for disseminated intravascular coagulopathy (DIC).
- Trophoblastic embolism is believed to cause acute respiratory insufficiency. The greatest risk factor is a uterus larger than that expected for a gestational age of 16 weeks. The condition may be fatal.
Prognosis
- Because of early diagnosis and appropriate treatment, the current mortality rate from hydatidiform mole is essentially zero. Approximately 20% of women with a complete mole develop a trophoblastic malignancy. Gestational trophoblastic malignancies are 100% curable.
- Clinical factors that have been associated with risk of malignant disease are advanced maternal age, high levels of HCG (>100,000 mIU/mL), eclampsia, hyperthyroidism, and bilateral theca lutein cysts.5 Most of these factors appear to reflect the amount of trophoblastic proliferation. Predicting who will develop gestational trophoblastic disease remains difficult, and treatment decisions should not be based on the presence of any or all of these risk factors.
Patient Education
- Because of the small but real potential for development of malignant disease and because these malignancies are absolutely curable, the importance of consistent follow-up care must be emphasized.
- The patient must avoid pregnancy for 1 year to avoid any confusion about the development of malignant disease. Effective contraception should be used. If a pregnancy occurs, the elevation in beta-HCG levels cannot be differentiated from the disease process.
- Future pregnancies should undergo early sonographic evaluation because of the increased risk of recurrence of a molar gestation.
- The risk of recurrence is 1-2%. After 2 or more molar pregnancies, the risk of recurrence has been reported as 1 in 6.5 to 1 in 17.5.6
- For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Birth Control Overview and Birth Control FAQs.
Medical/Legal Pitfalls
- Failure to consider the diagnosis in a patient who presents with hyperemesis: Many patients with molar gestations develop intractable nausea and vomiting because of the high levels of circulating HCG.
- Failure to explain the importance of close follow-up care after evacuation of the mole: Approximately 20% of patients with molar gestations develop trophoblastic malignancy.
- Failure to recognize the significance of plateauing beta-HCG levels: If beta-HCG levels plateau, serious consideration must be given to the possibility of persistent or malignant disease. A chest radiograph should be performed for metastasis. If metastatic disease is found, staging by CT scanning of the abdomen, pelvis, and brain should be performed, and the patient should be treated based on those findings.
- Failure to consider the diagnosis in a patient who presents with preeclampsia before 24 weeks' gestation: Twenty-seven percent of patients with a complete mole develop preeclampsia.
- Failure to recognize a molar gestation with a coexistent normal fetus: Twinning and higher order multiples with molar gestations have been described. The risk for malignant disease with metastasis is high, as is the risk of maternal morbidity from bleeding, eclampsia, or other complications of the molar gestation.
The period of follow-up after a molar gestation is under scrutiny. Certainly the prolonged follow-up currently in use may not be cost effective and may produce an additional burden for the woman and her family both in the need for repeat visits and in delayed childbearing.
The following article describes a protocol used in the United Kingdom with follow-up for 6 months after a negative hCG titer.
Sebire NJ, Foskett M, Short D, Savage P, et al. Shortened duration of human chorionic gonadotropin surveillance following complete or partial hydatidiform mole: evidence for revised protocol of a UK regional trophoblastic disease unit. BJOG Jun 2007;114(6):760-2. [Medline]
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Complete mole with an area of clot near cervix consistent with bleeding. |
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- Al-Hussaini TK, Abd el-Aal DM, Van den Veyver IB. Recurrent pregnancy loss due to familial and non-familial habitual molar pregnancy. Int J Gynaecol Obstet. Nov 2003;83(2):179-86. [Medline].
- Hodges MD, Rees HC, Seckl MJ, et al. Genetic refinement and physical mapping of a biparental complete hydatidiform mole locus on chromosome 19q13.4. J Med Genet. Aug 2003;40(8):e95. [Medline].
- Lawler SD, Fisher RA, Dent J. A prospective genetic study of complete and partial hydatidiform moles. Am J Obstet Gynecol. May 1991;164(5 Pt 1):1270-7. [Medline].
- Batorfi J, Vegh G, Szepesi J, et al. How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data. Eur J Obstet Gynecol Reprod Biol. Jan 15 2004;112(1):95-7. [Medline].
- Hurteau JA. Gestational trophoblastic disease: management of hydatidiform mole. Clin Obstet Gynecol. Sep 2003;46(3):557-69. [Medline].
- Sebire NJ, Fisher RA, Foskett M, et al. Risk of recurrent hydatidiform mole and subsequent pregnancy outcome following complete or partial hydatidiform molar pregnancy. BJOG. Jan 2003;110(1):22-6. [Medline].
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- ACOG. Management of gestational trophoblastic disease. ACOG Technical Bulletin Number 178-March 1993. Int J Gynaecol Obstet. Sep 1993;42(3):308-15. [Medline].
- Feltmate CM, Batorfi J, Fulop V, et al. Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time for reevaluation. Obstet Gynecol. Apr 2003;101(4):732-6. [Medline].
- Bentley RC. Pathology of gestational trophoblastic disease. Clin Obstet Gynecol. Sep 2003;46(3):513-22. [Medline].
- Fallahian M. Familial gestational trophoblastic disease. Placenta. Aug 2003;24(7):797-9. [Medline].
- Fisher RA, Hodges MD. Genomic imprinting in gestational trophoblastic disease--a review. Placenta. Apr 2003;24 Suppl A:S111-8. [Medline].
- Lurain JR, Brewer JI, Torok EE, Halpern B. Natural history of hydatidiform mole after primary evacuation. Am J Obstet Gynecol. Mar 1 1983;145(5):591-5. [Medline].
- Schlaerth JB, Morrow CP, Montz FJ, d''Ablaing G. Initial management of hydatidiform mole. Am J Obstet Gynecol. Jun 1988;158(6 Pt 1):1299-306. [Medline].
- Schlaerth JB, Morrow CP, Rodriguez M. Diagnostic and therapeutic curettage in gestational trophoblastic disease. Am J Obstet Gynecol. Jun 1990;162(6):1465-70; discussion 1470-1. [Medline].
- Wolf NG, Lage JM. Genetic analysis of gestational trophoblastic disease: a review. Semin Oncol. Apr 1995;22(2):113-20. [Medline].
Hydatidiform Mole excerpt Article Last Updated: Dec 4, 2007
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