Management of gestational trophoblastic diseases: subsequent pregnancy experience.

Patients with gestational trophoblastic disease (GTD) can usually achieve complete sustained remission while retaining their fertility even in the presence of wide-spread metastasis. Following complete and partial mole, our patients had 1,239 and 205 later pregnancies, respectively, which resulted in 68.6% and 74.1% term live births, respectively. Patients with either type of hydatidiform mole have, in general, a normal later pregnancy experience. After one molar pregnancy, the risk of a molar pregnancy in a later conception was about 1%. Our patients who received chemotherapy for persistent gestational trophoblastic tumor had 522 later pregnancies, which resulted in 358 (68.6%) term live births and only 10 (2.5%) major and minor congenital anomalies. Data from other centers involving 2,598 later pregnancies also indicate that after chemotherapy patients can generally anticipate a normal future reproductive outcome.

Natural history of partial molar pregnancy.

Between January 1979 and August 1984, 81 patients with partial molar pregnancy were observed at the New England Trophoblastic Disease Center. The preevacuation clinical diagnosis in 74 (91.3%) patients was either missed or incomplete abortion. The uterine size was either small or appropriate for gestational age in 78 (96.3%) patients. Only five (6.2%) patients presented with excessive uterine size or toxemia and were thought to have a molar pregnancy. Preevacuation human chorionic gonadotropin (hCG) levels exceeded 100,000 mIU/mL in only two (6.6%) of 30 patients. No patient had prominent theca lutein cysts. After evacuation, eight (9.9%) patients developed nonmetastatic gestational trophoblastic disease. Patients with partial moles usually do not present with the clinical features that are characteristic of complete molar pregnancy. The diagnosis of partial mole is generally only considered after histologic review of curettage specimens.

A clinicopathologic study of 153 cases of complete hydatidiform mole (1980-1990): histologic grade lacks prognostic significance.

Although the significance of histologic grading in hydatidiform mole has previously been investigated, most studies evaluated patients treated before 1975. Since 1975, many advances have been made in the understanding and treatment of hydatidiform mole, including the division of molar pregnancy into complete and partial hydatidiform mole. We retrospectively studied 153 cases of complete hydatidiform mole diagnosed and treated at the Brigham and Women's Hospital between 1980-1990 to determine the current prognostic significance of histologic grading in this disease. The histologic grade (based on the criteria of Hertig and Sheldon) was compared with the subsequent clinical course, including the rates of spontaneous remission, persistent gestational trophoblastic tumor, metastatic disease, "high-risk" metastatic disease, chemotherapy resistance, and survival. The histologic grade of the original complete hydatidiform mole did not correlate significantly with any index of clinical outcome evaluated.

Clinical experience with placental site trophoblastic tumors at the New England Trophoblastic Disease Center.

From 1982-1986, seven patients with pathologically confirmed placental site trophoblastic tumors underwent treatment at the New England Trophoblastic Disease Center. All seven patients presented with nonmetastatic disease; the presenting symptom was vaginal bleeding in six patients and amenorrhea in one patient. Mitotic counts of the tumor may vary among endometrial curettings, hysterectomy specimens, and metastatic lesions. When placental site trophoblastic tumor is diagnosed on endometrial curettage, a thorough metastatic workup should be undertaken. Because of this tumor's poor response to chemotherapy, a diagnosis of nonmetastatic placental site trophoblastic tumor should be followed by prompt hysterectomy.

Metastatic gestational trophoblastic disease: experience at the New England Trophoblastic Disease Center, 1965 to 1985.

This report reviews the results of therapy in 93 patients with metastatic gestational trophoblastic tumor treated from 1965-1985. Complete remission was achieved in all 42 patients with low-risk metastatic disease and in 34 of 51 patients (67%) with high-risk metastatic disease. Single-agent chemotherapy induced complete remission in 38 of 42 patients (91%) with low-risk metastatic disease. Survival of high-risk patients has improved markedly over the past two decades; complete remission was attained in 13 of 24 high-risk patients (54%) from 1965-1975, and in 21 of 27 (78%) from 1976-1985. Survival correlated with the number of high-risk factors, the prognostic score, and the type of treatment. From 1965-1975, 54% (13 of 24) of high-risk patients were treated with single-agent chemotherapy alone, while in the last decade only 7% (two of 27) were so treated. Twenty-one patients with traditional high-risk factors had a prognostic score of 7 or less, and all achieved remission, with 67% (14 of 21) treated with primary single-agent chemotherapy. The prognostic scoring system was more effective than traditional high-risk criteria at predicting which patients require intensive combination chemotherapy to attain remission.

Repetitive complete and partial hydatidiform mole.

Fifteen patients with repetitive hydatidiform mole were followed at the New England Trophoblastic Disease Center between 1965-1988. The medical records were examined to determine the patients' age, gravidity, parity, clinical presentation, development of post-molar tumor, and subsequent pregnancy experience. Each molar tissue was reviewed pathologically. Seven patients had repetitive complete hydatidiform mole and three developed persistent post-molar disease after their later mole. Five patients had an initial complete hydatidiform mole followed by a partial hydatidiform mole; two developed persistent post-molar disease after the partial mole. One patient had an initial partial hydatidiform mole followed by a complete hydatidiform mole and required chemotherapy after her complete mole. Two patients had repetitive partial hydatidiform mole, and neither developed post-molar disease. Four of the patients with repetitive mole later achieved a normal viable pregnancy. Molar pregnancies must be categorized as either complete or partial to provide meaningful data concerning repetitive hydatidiform mole.

Outcome of pregnancies occurring within 1 year of hydatidiform mole.

OBJECTIVE: To determine the outcome of subsequent pregnancies in patients with partial or complete molar pregnancy who conceive before completing the recommended hCG follow-up of at least 6 months. METHODS: Retrospective record review of patients with partial or complete mole who conceived before the standard gonadotropin follow-up of 6 months was completed during 1980-1998. RESULTS: Sixty-seven patients with molar pregnancy who conceived before completion of hCG follow-up were identified. Thirty-five (52.2%) patients had a prior partial mole, and 32 (47.8%) had a prior complete mole. The mean interval from first achieving undetectable hCG level to new pregnancy was 3.1 and 3.4 months in patients with partial and complete mole, respectively. Eleven patients underwent elective termination, and 12 were lost to follow-up. Of the remaining 44 patients, 33 (75.0%) had live births, 10 had spontaneous abortions, and one had an ectopic pregnancy. A viable pregnancy outcome was achieved in 20 (83.3%) of 24 patients with partial mole and 13 (65.0%) of 20 patients with complete mole. None of the patients developed any evidence of postmolar persistent gestational trophoblastic tumor. None of the live births had any detectable fetal anomalies. CONCLUSION: The risk of persistent tumor is low and reproductive outcome is favorable once undetectable hCG levels are achieved. Pregnancies occurring before the completion of recommended hCG follow-up may be allowed to continue under careful surveillance.

Methotrexate with citrovorum factor rescue for gestational trophoblastic neoplasms.

Thirty-five patients with nometastatic gestational trophoblastic neoplasms and 3 patients with metastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor rescue. The antecedent pregnancy was molar in all patients. The known histologic diagnosis in 34 patients was hydatdiform mole and choriocarcinoma in 3. Up to March 1977, the duration of remissions ranged from 1 to 21 months. Complete and sustained remission was achieved in 91% of patients with nonmetastatic disease and in 2 of the 3 patients with metastases, without evidence of marrow or hepatic and with substantially reduced epithelial toxicity. Response to treatment and the number of courses required to achieve remission were determined solely on the basis of the human chorionic gonadotropin response as measured by the beta subunit radioimmunoassay.

Natural history of recurrent molar pregnancy.

Seven patients with recurrent molar pregnancy were managed at the New England Trophoblastic Disease Center (NETDC) between July 1965 and December 1978. Recurrent molar pregnancy was associated with a worsening histology and an increased incidence of proliferative trophoblastic sequelae in the successive episodes of hydatidiform mole. While none of the initial 7 patients with molar pregnancy required any further treatment after evacuation, 5 of the 7 patients needed chemotherapy to achieve complete sustained remission of the recurrent episodes of hydatidiform mole. None of the patients with recurrent hydatidiform mole had normal viable pregnancies after 2 or more consecutive molar gestations. The literature regarding recurrent molar pregnancy is reviewed in the context of the authors' current observations.

A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy.

Hydropic placentas may be classified by histopathology into hydropic abortus, partial hydatidiform mole, and complete hydatidiform mole. We studied 142 hydropic placentas: 39% were complete hydatidiform moles, 35% partial hydatidiform moles, and 26% hydropic abortuses. Villous vesicle size was predictive of histologic diagnosis. We determined DNA ploidy in 137 cases. Seventy-three percent of hydropic abortuses were diploid and 11% were triploid. Ninety percent of partial moles were triploid or near-triploid; one partial mole was haploid and one diploid. Of the complete moles, 50% were diploid, 43% were tetraploid, 3.6% polyploid, and 1.7% triploid. Partial moles had lower pre-evacuation beta-hCG levels than complete moles. Persistent tumor followed 33% of complete moles and 12% of partial moles. Although the numbers were small, no patient with a diploid, tetraploid, aneuploid, or haploid partial mole developed persistent disease. Among complete moles, the pre-evacuation beta-hCG level was not predictive of persistence (P = .15). Subdividing complete moles by ploidy, we found that tetraploid moles were associated with higher pre-evacuation beta-hCG levels than were diploid moles. However, tetraploidy was not associated with increased persistent tumor among complete moles. Although most partial moles were triploid and most complete moles were diploid or tetraploid, there was wider DNA heterogeneity among molar gestations than previously reported. In this series, DNA ploidy was not an independent predictor of persistence in complete moles.

Flow cytometric analysis of DNA content in partial hydatidiform moles with persistent gestational trophoblastic tumor.

Hydatidiform moles may be classified as partial or complete based on genetic and pathologic criteria. Between January 1979 and January 1990, 17 (5.5%) of 310 patients followed for partial mole developed persistent gestational trophoblastic tumor. Tissues from 14 partial moles were available for flow cytometric analysis of DNA content. Eleven partial moles (85%) were triploid, two (15%) were diploid, and one DNA histogram was uninterpretable. All patients with triploid partial moles achieved complete remission with one course of single-agent chemotherapy. The two with diploid partial mole required multiple courses of chemotherapy to achieve gonadotropin remission. Although the DNA content of most partial moles with persistent gestational trophoblastic tumor was triploid, diploid partial moles with persistent tumor were less sensitive to single-agent chemotherapy.

Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus.

OBJECTIVE: To investigate the clinical features and natural history of twin conceptions consisting of complete hydatidiform mole and a coexisting fetus. METHODS: Since 1973, eight well-documented cases of twin pregnancy with complete hydatidiform mole and coexisting fetus have been treated at the New England Trophoblastic Disease Center (NETDC). The clinical features of these eight patients were compared to 71 patients with singleton complete hydatidiform mole treated at the NETDC and with the published experience of other investigators. Flow cytometric analysis of DNA content was performed in addition to histologic inspection to assist in confirming the diagnosis of twin pregnancy with complete hydatidiform mole and coexisting fetus. RESULTS: Five of the eight patients in this series developed persistent gestational trophoblastic tumor requiring chemotherapy. Three of these five patients developed metastases requiring multi-agent chemotherapy to achieve remission. The presenting symptoms of twin pregnancy with complete hydatidiform mole and coexisting fetus were similar to those in patients with a singleton complete mole. However, compared to singleton complete molar gestation, a twin pregnancy with complete mole and coexisting fetus was diagnosed at a later gestational age, had higher preevacuation beta-hCG levels, and had a greater propensity to develop persistent gestational trophoblastic tumor. CONCLUSION: Our findings indicate that patients with complete hydatidiform mole and coexisting fetus are at high risk for developing persistent gestational trophoblastic tumor.

Progressive angiomyolipoma with inferior vena cava tumor thrombus.

A 45-year-old man presented with an incidentally discovered benign renal angiomyolipoma. This lesion initially demonstrated renal vein involvement. On referral to our institution 3 years later, there was interval progression of tumor thrombus to the intrahepatic inferior vena cava. Intravascular extension of benign angiomyolipoma, though rare, has been reported. We present a new example and review the literature concerning this unusual complication of a common renal neoplasm.

Subsequent pregnancy experience in patients with gestational trophoblastic disease. New England Trophoblastic Disease Center, 1965-1992.

We reviewed the subsequent pregnancy outcome in patients with partial mole, complete mole and persistent gestational trophoblastic tumor treated at the New England Trophoblastic Disease Center from June 1, 1965, to December 31, 1992. Such patients can be assured that they can anticipate a normal future reproductive outcome. However, when a patient has had a molar pregnancy, she is at increased risk (1%) of developing molar disease in a subsequent conception.

Reproductive experience after complete and partial molar pregnancy and gestational trophoblastic tumors.

We reviewed the subsequent pregnancy experience in patients with complete and partial mole and gestational trophoblastic tumors who were managed at the New England Trophoblastic Disease Center between June 1965 and December 1989. Such patients should be reassured that they can anticipate a normal reproductive outcome in the future.

Management of low-risk metastatic gestational trophoblastic tumors.

The clinical course of 48 patients with low-risk metastatic gestational trophoblastic tumors (GTTs) treated with primary single-agent chemotherapy was reviewed. All patients achieved sustained remission, although 25 (51%) required a second single-agent regimen, and 7 (14%) needed combination chemotherapy to achieve it. An average of 3.4 courses of chemotherapy were necessary to achieve remission, and 6 patients (12%) underwent resection of resistant tumor foci. Primary single-agent chemotherapy is a reasonable treatment option in patients with low-risk metastatic GTT.

Evolving concepts of molar pregnancy.

Molar pregnancy is composed of two distinct clinical and pathologic entities, complete and partial mole. Knowledge of the cytogenetic origin, natural history and treatment of complete and partial hydatidiform mole is evolving.

Subsequent pregnancy outcome in patients with molar pregnancy and gestational trophoblastic tumors.

Subsequent pregnancy outcome was reviewed in patients with complete and partial mole and persistent gestational trophoblastic tumors who were treated at the New England Trophoblastic Disease Center between Jun 1, 1965, and Dec 31, 1986. In general, these patients can be reassured that they can anticipate a normal reproductive outcome in the future.

Management of complete molar pregnancy.

This review of the current management of complete molar pregnancy is based upon the clinical experience at the New England Trophoblastic Disease Center. Suction curettage is the preferred method of molar evacuation regardless of uterine size in patients who desire to preserve fertility. Prophylactic chemotherapy may be useful in the management of high-risk molar pregnancy, especially when hormonal follow-up is either unavailable or unreliable. All patients must be followed with serial human chorionic gonadotropin levels to ensure that remission has occurred.

Recent advances in gestational trophoblastic disease.

Recent advances have increased our understanding of gestational trophoblastic disease, and epidemiologic studies have demonstrated that there are important differences in risk factors for complete and partial mole. Complete moles are now increasingly being diagnosed in the first trimester, affecting their clinical presentation and pathologic characteristics. While important advances have been made in chemotherapy, it is now recognized that etoposide is associated with a risk of second tumors. Several studies have advanced understanding of the molecular biology of gestational trophoblastic disease, and this is important for the eventual development of new and innovative therapy.