Gestational trophoblastic disease (GTD) is a spectrum of tumours tumour. The last three are termed gestational trophoblastic .. ACOG Technical Bulletin Gestational trophoblastic disease (GTD) forms a group of disorders spanning the conditions of complete and partial molar pregnancies through to the malignant. Gestational Hypertension and Preeclampsia ACOG Practice Bulletin # Diagnosis and Treatment of Gestational Trophoblastic Disease If you are an ACOG Fellow and have not logged in or registered to Obstetrics & Gynecology, please follow these Thyroid Disease in Pregnancy · Practice Bulletin No.

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Skip to main content. Log In Sign Up. Diagnosis and treatment of gestational trophoblastic disease: The information phoblastic tumor. Histologically distinct disease entities encompassed by this is designed to aid practitioners general terminology include complete and partial hydatidiform moles, invasive in making decisions about moles, gestational choriocarcinomas, and placental site trophoblastic tumors.

These guidelines and efficacious chemotherapy, the morbidity and mortality from gestational tro- should not be construed as phoblastic disease were substantial. The purpose of this document is to address current be warranted based on the evidence regarding the diagnosis, staging, and management of gestational tro- needs of the individual patient, phoblastic disease. Background Estimates for the incidence of various forms of gestational trophoblastic disease vary.

Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53.

In the United States, hydatidiform moles are observed trophkblastic approximately 1 in therapeutic abortions and 1 in 1, pregnancies 1. Most patients with postmolar gestational trophoblastic disease will have nonmetastatic molar pro- liferation or invasive moles, but gestational choriocarcinomas and metastatic disease can develop in this setting.

Gestational choriocarcinoma occurs in approximately 1 in 20,—40, pregnancies: Although presentations see Table 1.

The average initial serum much rarer than hydatidiform moles or gestational chori- hCG levels usually are higher in patients with complete ocarcinomas, placental site trophoblastic tumors can moles than in patients with partial moles 7. Although an develop after any type of pregnancy 5, 6. To allow opti- increasing proportion of moles are diagnosed as missed mal management, practicing trophlblastic abortions on the basis of an early ultrasound examination should be able to diagnose and manage primary aocg in the absence of symptoms 8most patients with com- pregnancies, diagnose and stage malignant gestational plete moles have a clinical or ultrasonographic diagnosis trophoblastic disease, and assess risk in women with of hydatidiform mole.

Experience, patients with complete moles 1. These patients may such as that found at regional gestational trophoblastic present with vaginal bleeding or expulsion of molar vesi- disease treatment centers, improves outcomes in the cles. Medical complications of molar pregnancy, includ- management of malignant gestational trophoblastic dis- ing pregnancy-induced hypertension, hyperthyroidism, ease.

Any woman for whom initial therapy for invasive anemia, and hyperemesis gravidarum, are more frequent- mole has failed or who has a choriocarcinoma diagnosis ly seen among patients with complete moles 9.

Classification Partial and complete hydatidiform moles are distinct dis- Diagnosis ease processes with characteristic cytogenetic, histologic, Hydatidiform moles usually are diagnosed during the and clinical features 4.

The distinct pathologic features first trimester of pregnancy 8, The most common and clinical presentation of these 2 entities are outlined in symptom is abnormal bleeding. Other signs and symp- Table 1.

Despite the cytogenetic, pathologic, and clinical toms include uterine enlargement greater than expected differences between the 2 diagnoses, the management of for gestational age, absent fetal heart tones, cystic patients with complete and partial moles is similar. Principals and practice of gynecologic oncology, 2nd ed. A new intrauterine pregnancy should be ruled out on the Pregnancy-induced hypertension in the first half of basis of hCG levels and ultrasonography, especially pregnancy, although uncommon, is suggestive of hyda- when there has been a long delay in follow-up of gestationxl tidiform mole.

Ultrasonography has replaced disezse other hCG levels and noncompliance with contraception. Molar tissue typically is identified as a diffuse mixed Malignant Gestational echogenic pattern replacing the placenta, produced by Trophoblastic Disease villi and intrauterine blood clots, but these findings may be subtle or lacking in adog of early complete or partial Histologic Considerations moles 8, The clinical presentation of malignant gestational tro- phoblastic disease is more important in determining Management After Evacuation of treatment and outcome than the precise histologic diag- Hydatidiform Mole nosis 4.

Postmolar gestational trophoblastic disease is As long as hCG values are decreasing after molar evac- only one of many forms of malignant gestational tropho- uation, there is no role for chemotherapy. However, if blastic disease; it comprises noninvasive trophoblastic hCG levels increase or plateau over several weeks, proliferation, invasive moles, and gestational choriocar- immediate evaluation and treatment for malignant post- cinoma.


Gestational choriocarcinomas are derived from molar gestational trophoblastic disease are indicated. The rarest form of caused by heterophilic antibodies cross-reacting with the malignant gestational trophoblastic disease, placental hCG test. Such false-positive test results, also known as site trophoblastic tumor, can follow any pregnancy. The term invasive mole is used to describe disease The diagnosis of malignant sequelae as indicated by confined to the uterus and is characterized by the pres- the need for chemotherapy include the plateau or ence of edematous chorionic villi with trophoblastic increase of hCG levels after evacuation of hydatidiform proliferation that invade directly into the myometrium.

Repeat caused by uterine perforation.

Gestational choriocarci- curettage is not recommended because it does not often noma is a malignancy, comprising both trolhoblastic syn- induce remission or influence treatment and may result cytiotrophoblast and cytotrophoblast elements without in uterine perforation and hemorrhage Gestational choriocarcinomas tend A variety of hCG criteria have been used to diag- to develop early systemic metastasis the vagina, lung, nose postmolar gestational trophoblastic disease 1—3, liver, and brain are the most common sitesand 13, Recently, the International Federation of chemotherapy is indicated when it is diagnosed histo- Gynecologists and Obstetricians FIGO standardized logically.

When indicated, chemotherapy should be hCG criteria for the diagnosis of postmolar gestational initiated in a timely manner to avoid bleeding complica- trophoblastic disease Based on consensus commit- tions at metastatic sites.

They are characterized by absence of villi Trophoblastic Disease, and the International Gyne- with proliferation of intermediate trophoblast cells. The cologic Cancer Society, the following criteria were pro- number of syncytiotrophoblast cells observed is posed by FIGO Persistence of detectable hCG for more than most patients have disease confined to the uterus and are 6 months after molar evacuation cured by hysterectomy. Common medical complications include anemia, infection, hyperthyroid- Postmolar gestational trophoblastic disease is most fre- ism, pregnancy-induced hypertension, and coagulopathy.

Women with malignant gestational will need more intensive evaluation ie, thyroid-stimulat- trophoblastic disease following nonmolar pregnancies ing hormones ttophoblastic coagulopathy studies.

Moles should may have subtle signs and symptoms of disease, which be evacuated as soon as possible after stabilization of any make the diagnosis difficult Abnormal bleeding for medical caog. Metastases of gesta- be given to performing the evacuation in disesse facility with an tional choriocarcinoma have been reported in virtually intensive care unit, a blood bank, and anesthesia servic- every body site, most commonly the vagina, liver, lung, es.

Medical induction of labor with sary and may cause excessive bleeding. Central nervous oxytocin or prostaglandin and hysterotomy are not rec- system metastases may produce neurologic symptoms, ommended for evacuation because they increase blood intracranial hemorrhage, or mass lesions.

A serum hCG determination plete the evacuation of moles after medical induction of and exclusion of pregnancy are all that are required to labor 9. Evacuation usually is performed with the diagnose metastatic gestational trophoblastic disease in patient under general anesthesia, but local or regional these circumstances.

After serial dilation of the cervix, uterine evacuation is accomplished with the largest cannula that Clinical Considerations and can be introduced through the cervix. In some cases, Recommendations ultrasound guidance may facilitate complete evacuation of the uterus. In Pulmonary complications are frequently observed these cases, patients should be monitored with serial around the time of molar visease among patients with determinations of quantitative hCG values. A baseline marked uterine enlargement 9, 17, Although the postevacuation chest X-ray should be considered.

Patients with prior partial or rarely need to be removed. Two randomized studies have evaluated trophoblatsic chemotherapy after molar evacuation.

Patients who received lae promptly. Ideally, serum hCG levels should be In the second study, a single course of prophylactic obtained within 48 hours of evacuation, every 1—2 weeks dactinomycin was given to patients after evacuation of while elevated, and then at monthly intervals for an addi- high-risk moles Postmolar trophoblastic disease tional 6 months 4.

In both studies, there were monitored. Frequent pelvic examinations are performed no deaths in the treatment or control groups caused by ges- while hCG values are elevated to monitor the involution tational trophoblastic disease or treatment toxicity 21, of pelvic structures and to aid in the early identification However, there are anecdotal cases of fatalities caused of vaginal metastases.

In compliant patients, the low morbidity develop malignant postmolar gestational trophoblastic and mortality achieved by monitoring patients with serial disease. Although rare instances of long latent periods hCG determinations and instituting chemotherapy only in have been reported, most episodes of malignant sequelae patients with postmolar gestational trophoblastic disease after hydatidiform moles occur within approximately outweighs the potential risk and small benefit of routine 6 months of evacuation 2, 3.

Although pregnancies after prophylactic chemotherapy. Oral contraceptives do not increase the incidence of postmolar gestational trophoblastic disease or alter the Co-existence of a fetus with molar changes of the pla- pattern of regression of hCG values 13, In a ran- centa is relatively rare, occurring in 1 in 22,—, domized study, patients treated with oral contraceptives pregnancies Most of the literature covering this had one half as many intercurrent pregnancies as those entity consists of case reports, small case series, and using barrier methods, and the incidence of postmolar reviews of cases reported in the literature.


Both complete trophoblastic disease was lower in patients using oral and partial moles with co-existent fetuses have been contraceptives After completion of documented reported A variety of criteria have been used to remission for 6—12 months, women who desire preg- evaluate these pregnancies. Many of the reports that ante- nancy may discontinue contraception, and hCG monitor- dated the histologic and cytogenetic distinction between VOL.

They should be counseled about these risks and gestations. There may be an increased incidence of co- the increased risk of postmolar trophoblastic disease after existing mole and fetus related to an increase in multife- evacuation or delivery.

Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No.

If the fetal karyotype is normal, tal pregnancies associated with ovulation induction, but major fetal malformations are excluded by ultrasound this may reflect reporting bias Medical complications gesttational hydatidiform mole ton hydatidiform mole. Compared with singleton hydatidiform moles, twin pregnancies with a fetus and a mole carry an increased Rarely, women have persistently elevated hCG levels but risk for postmolar gestational trophoblastic disease, with are subsequently found to have a false-positive hCG a higher proportion of patients having metastatic disease assay result, sometimes after receiving chemotherapy or and requiring multiagent chemotherapy 23— Among surgery for presumed malignant gestational trophoblastic patients with co-existent moles and fetuses who continue disease.

Many of these patients have an unde- physicians in Japan in24 underwent first-trimester dksease previous pregnancy event and do not have radi- evacuation, with In compar- False-positive hCG values also may appear after ison, False-positive test results patients with proved complete hydatidiform moles in should be suspected if hCG values plateau at relatively association with a fetus subsequently were treated for low levels and do not respond to therapeutic maneuvers, postmolar acg trophoblastic disease 26but it is such as methotrexate given for a presumed persistent not certain whether this trophoblastiv risk resulted from mole or ectopic pregnancy.

Evaluation should include selection bias. Major congenital abnormalities have not evaluation of serum hCG levels using a variety of assay been reported in surviving infants. False-positive hCG assays sound examination should be repeated to exclude retro- usually will not be affected by serial dilution of patient placental hematoma, other placental abnormalities, or sera and will have marked variability using different degenerating myoma and to fully evaluate the fetopla- assay techniques, with most assays reflecting unde- cental unit for evidence of a partial mole or gross fetal tectable hCG levels 27, Heterophilic antibodies are malformations.

If the diagnosis is still suspected and con- not excreted in the urine; therefore, urinary hCG values tinuation of the pregnancy is desired, fetal karyotype will not be detectable if they are the cause of serum hCG should be obtained, a chest X-ray performed to screen for level elevation Other techniques also are available metastases, and serial serum hCG values monitored. It is important to exclude the possibility of plications of pregnancy requiring evacuation, including false-positive hCG values before subjecting these ACOG Practice Bulletin No.

The original analyses of patients treated for metasta- Three systems have been used to categorize patients with tic gestational trophoblastic disease at the NIH led to the malignant gestational trophoblastic disease: This system seg- 2 the Clinical Classification system developed from early regates patients with nonmetastatic disease from those experience with chemotherapy for patients treated at the with metastatic disease because virtually all patients National Institutes of Health NIHand 3 the FIGO stag- with nonmetastatic disease can be cured using initial sin- ing system, which was revised in The original gle-agent chemotherapy, regardless of other risk factors anatomic FIGO staging system did not take into account 33, Patients with metastatic disease are further sub- other factors that might reflect disease outcome, such as divided depending on the presence or absence of factors hCG level, duration of disease, or type of antecedent that correlate with response to initial single-agent pregnancy The revised FIGO staging system chemotherapy 34, Those who lack any of the includes a modification of the WHO prognostic index high-risk clinical factors are likely to respond to initial score for risk assessment Table 2.