Marilyn R. Bernstein

The changing clinical presentation of complete molar pregnancy

Objective To determine if the clinical presentation of complete hydatidiform mole has changed in recent years compared with historic controls (1965–1975). Methods Chart review of all 74 patients referred to the New England Trophoblastic Disease Center for the primary management of complete hydatidiform mole during 1988–1993 was performed and comparison made to historic controls (1965–1975). Results Vaginal bleeding remained the most common presenting symptom, occurring in 62 of 74 (84%) current patients, compared with 297 of 306 (97%) controls (P = .001). However, anemia was present in only four of 74 (5%) current patients, compared with 165 of 306 (54%) controls (P = .001). Excessive uterine size, preeclampsia, and hyperemesis occurred in only 21 of 74 (28%), one of 74 (1.3%), and six of 74 (8%) current patients, respectively, compared with 156 of 306 (51%), 83 of 306 (27%), and 80 of 306 (26%), respectively, of historic controls (P = .001). No cases of clinical hyperthyroidism or respiratory distress were found in recent years. Ultrasound diagnosed complete hydatidiform mole before the onset of clinical symptoms in seven of 69 (10%) current patients. Among patients not receiving chemoprophylaxis, persistent gestational trophoblastic tumor developed in 23% of current patients and 18.6% of historic controls. Conclusion Fewer current patients with complete hydatidiform mole present with the traditional symptoms of complete hydatidiform mole (excessive uterine size, anemia, preeclampsia, hyperthyroidism, or hyperemesis) when compared with historic controls. However, there has been no statistically significant change in the development of persistent gestational trophoblastic tumor in current patients compared with historic controls.

Ten years' experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease

Methotrexate and folinic acid was administered as primary therapy in 185 patients with gestational trophoblastic disease between 1974 and 1984. Methotrexate and folinic acid induced complete remission in 147 (90.2%) of 163 patients with nonmetastatic disease and in 15 (68.2%) of 22 patients with low-risk metastatic disease. Sustained remission was achieved in 132 (81.5%) patients following only one course of chemotherapy. All patients with methotrexate resistance subsequently achieved remission with Actinomycin D or combination chemotherapy. Methotrexate when administered with folinic acid was associated with granulocytopenia, thrombocytopenia, and hepatotoxicity in 11 (5.9%), 3 (1.6%), and 26 (14.1%) patients, respectively. The human chorionic gonadotropin (hCG) regression curve served as a reliable guide for the administration of chemotherapy and enabled the attainment of a high remission rate while limiting chemotherapy exposure. Methotrexate and folinic acid achieves an excellent therapeutic outcome with limited chemotherapy exposure and effectively limits systemic toxicity.

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.

Risk factors for complete molar pregnancy from a case-control study.

Demographic, reproductive, and dietary histories for 90 white women with complete molar pregnancy were compared in a multivariate analysis with those of 90 parous controls matched to cases by residence, birth year, and race. Women with molar pregnancy were more likely to have been born outside North America (relative risk = 1.9, p = 0.05), were more likely to have been past age 30 at time of their molar pregnancy (relative risk = 1.6, p = 0.05), and were more likely to have diets deficient in the vitamin A precursor carotene. Women with dietary scores for carotene above the control median had a relative risk for molar pregnancy of 0.6 (p = 0.02). In addition, there was a significant trend for decreasing risk for molar pregnancy with increasing consumption of carotene. Although other nutritional deficiencies in patients with complete molar pregnancy may exist, carotene is a biologically plausible candidate for a nutritional risk factor that could explain the geographic distribution of molar pregnancy.

Persistent gestational trophoblastic tumor after partial hydatidiform mole

The current study investigates the clinical characteristics of patients with partial molar pregnancy who developed persistent gestational trophoblastic tumor (GTT). Between January 1979 and January 1989, 16 of 240 (6.6%) patients, who were followed for partial mole, developed persistent GTT. Fifteen (94%) patients were diagnosed as having a missed abortion before evacuation and only 1 patient presented with excessive uterine size and theca lutein ovarian cysts and was felt to have molar disease. No patient presented with toxemia, hyperemesis, or hyperthyroidism. All 16 patients developed nonmetastatic GTT. Fifteen patients achieved complete remission with methotrexate-citrovorum factor and only 1 patient required combination chemotherapy to attain remission. None of the patients had histologic evidence of choriocarcinoma. Patients with partial mole who developed persistent GTT did not have clinical or pathological characteristics that distinguished them from other patients with partial mole. All patients with partial mole should be followed with measurement of hCG levels to assure gonadotropin remission.

Methotrexate with citrovorum factor rescue as primary therapy for gestational trophoblastic disease

Methotrexate with citrovorum rescue (MTX‐CF) was administered as primary treatment in 106 patients with gestational trophoblastic disease (GTD). Ninety‐six patients (90.6%) achieved complete remission with MTX‐CF and 77 of these patients (80.2%) required only one course of MTX‐CF to attain remission. MTX‐CF induced sustained remission in 89 (94.7%) of 94 patients with nonmetastatic GTD and in seven (59.3%) of 12 patients with low‐risk metastatic GTD. Resistance to MTX‐CF was more common in patients with disseminated disease and with pretreatment hCG titers ≥50,000 milliIU/ml. Following MTX‐CF, granulocytopenia, thrombocytopenia and hepatotoxicity was observed in only seven (6.6%), three (2.8%), and ten (9.4%) patients, respectively. MTX‐CF should be the preferred primary treatment in nonmetastatic and low‐risk metastatic GTD.

Modified triple chemotherapy in the management of high-risk metastatic gestational trophoblastic tumors

Modified triple chemotherapy (MAC III: methotrexate with citrovorum factor, actinomycin D, and cyclophosphamide) was administered as primary treatment to 14 patients with high-risk metastatic gestational trophoblastic tumors (GTT). Ten (71.4%) patients attained complete remission with 1 to 4 courses of MAC III (mean = 2.7 courses). Three of the remaining patients subsequently achieved remission with the modified Bagshawe regimen or vinblastine, bleomycin, and cis-platinum. Following 38 courses of MAC III, moderate hepatotoxicity (SGOT greater than or equal to 150 U) developed after 1 (2.6%) course. Marked thrombocytopenia (platelets less than 50,000/mm3) and marked granulocytopenia (granulocytes less than 500/mm3) developed after 7 (18.4%) and 19 (50%) of the courses, respectively. Platelet transfusions were administered after 4 (10.5%) courses of MAC III and no patient required granulocyte transfusions. MAC III is an effective alternative treatment for patients with high-risk metastatic GTT.

Methotrexate infusion and folinic acid in the primary therapy of nonmetastatic gestational trophoblastic tumors

Thirty-two patients with nonmetastatic gestational trophoblastic tumors were treated with methotrexate infusion and folinic acid and the results of this therapy were compared to our prior experience with the 8-day methotrexate-folinic acid regimen. Complete remission was achieved in 22 of 32 (68.7%) patients treated with methotrexate infusion and 147 of 163 (90.2%) patients treated with the 8-day regimen (P less than 0.01). One course of chemotherapy induced complete remission in 19 (86.3%) patients treated with methotrexate infusion and 121 (82.2%) patients treated with the 8-day regimen. All 10 patients resistant to methotrexate infusion later achieved remission with other chemotherapy. Following methotrexate infusion, no patient developed myelosuppression, hepatotoxicity, or alopecia. Efforts should continue to identify new chemotherapeutic protocols that maximize remission rates and minimize toxicity and hospitalization.

Methotrexate with citrovorum factor rescue reduced chemotherapy toxicity in the management of gestational trophoblastic neoplasms

The comparative systemic toxicity of methotrexate (MTX) with citrovorum factor rescue (CF), MTX alone and actinomycin‐D (Act‐D) in the treatment of gestational trophoblastic neoplasms (GTN) was evaluated in the present study. Treatment with MTX‐CF was associated with only a 4% incidence (1 of 25 patients) of hepatic and/or hematologic toxicity and total absence of either a generalized rash or marked alopecia. In contrast, both MTX alone and Act‐D were associated with a 48% incidence (12 of 25 patients) of hepatic and/or hematologic toxicity. Actinomycin‐D also induced a generalized rash and marked alopecia in 24% (6 of 25 patients) and 52% (13 of 25 patients) of the patients respectively. We found that MTX‐CF is the least toxic single agent chemotherapeutic regimen in the management of GTN.

Case-control study of risk factors for partial molar pregnancy.

OBJECTIVE The purpose of our study was to identify risk factors for partial molar pregnancy from a womans general, reproductive, and dietary history. STUDY DESIGN Sixty-five women with pathologically confirmed partial molar pregnancy were interviewed, and their experiences were compared with those of 130 age-matched control women who had successfully completed a pregnancy with delivery of a live infant at the same hospital during the same calendar period. RESULTS Multivariate analysis revealed that exposures which independently and significantly predicted increased risk for partial molar pregnancy included irregular cycles, pregnancy histories including only male infants among prior live births, and oral contraceptive use for > 4 years. Dietary factors previously postulated for complete molar pregnancy including protein, fat, vitamin A, or carotene were found not to be related to risk for partial molar pregnancy. CONCLUSION Epidemiologic patterns for complete and partial molar pregnancies appear to differ somewhat; risk for partial mole is associated with reproductive history but not dietary factors.