Triplet pregnancy involving complete hydatidiform mole and two fetuses: genetic analysis by deoxyribonucleic acid fingerprint.

A case of a triplet pregnancy involving a dizygous twin pregnancy and a complete hydatidiform mole after therapy with human menopausal gonadotropin and human chorionic gonadotropin is reported. Two female fetuses, two placentas in one mass with two amnions and two chorions, and a tumor mass with a grapelike appearance were spontaneously delivered at 19 weeks of gestation. The deoxyribonucleic acid fingerprints of the two placentas and tumor tissue were compared with those of the parents. The fingerprints of the placentas showed patterns different from each other; however, all their polymorphic fragments could be traced back to either the father or mother. All polymorphic fragments of the tumor tissue were inherited only from the father (androgenesis). These results indicated that this triplet pregnancy involved a dizygous twin pregnancy and a complete hydatidiform mole.     

Complete hydatidiform mole in a triplet pregnancy coexisting two viable fetuses: case report and review of the literature

We report a rare case of a complete hydatidiform mole with two or more coexisting fetuses where both infants survived without complications. A male infant weighing 1258 g and a female infant weighing 880 g were delivered without complications and discharged 95 days after the birth. The analysis of DNA microsatellite polymorphisms indicated that the mole was of paternal origin and probably homozygous. The mother suffered from multiple pulmonary metastasis of the hydatidiform mole which was detected 3 days after the surgery and was successfully treated with methotrexate. A complete hydatidiform mole with two or more coexisting fetuses produces a dilemma between immediate termination and pregnancy continuation. Although the present case resulted in a favorable outcome, a review of the 14 reported cases suggests that the high fetal loss rate (90%) must be a consideration in the decision regarding management of such a pregnancy.     

Serum human placental lactogen (HPL) levels in patients with intact hydatidiform mole.

Serum human placental lactogen (HPL) levels in forty cases of intact hydatidiform mole were measured by radioimmunoassay. The HPL values were generally lower than normal pregnancies of the corresponding period of gestation. However, normal and occasionally higher than normal values were observed in a few cases. Serum HPL level alone is of some clinical use in the diagnosis of hydatidiform mole. When combined with human chorionic gonadotropin (HCG), a low HPL/HCG ratio for the corresponding period of amenorrhoea is a useful index in the diagnosis of hydatidiform mole.     

Comparative assay of HCG, HCT and HCS in molar pregnancy

The secretion patterns of human chorionic gonadotropin (HCG), human chorionic somatomammotropin (HCS), and human chorionic thyrotropin (HCT) were studied in 10 women with hydatidiform mole and 30 women in the early stage of normal pregnancy. Serum levels of the chorionic hormones were determined by radioimmunoassay with the double-antibody method. In the cases of hydatidiform mole, HCG and HCT levels were considerably higher than values normally obtained during pregnancy, while HCS levels were abnormally low. HCG and HCT levels did not change 6 hours after molar delivery, though HCS levels rapidly decreased and became undetectable shortly thereafter. It required 3 weeks for HCG to fall to the level of pituitary luteinizing hormone and 5 days for HCT to become undetectable. The observed differences are regarded as characteristic findings in hydatidiform mole. It was concluded that simultaneous assay of HCG, HCT, and HCS is a useful indicator of the completeness of treatment of hydatidiform mole.     

Plasma human chorionic gonadotropin disappearance in hydatidiform mole: a central registry report from the Netherlands

The disappearance time of serum human chorionic gonadotropin (hCG) after the evacuation of hydatidiform mole, partial mole, and hydropic degeneration was investigated. A statistically significant difference existed between the disappearance time of serum hCG after the evacuation of hydatidiform mole as compared with partial mole and hydropic degeneration. The average disappearance time of serum hCG after hydatidiform mole was 99.3 days, after partial mole 58.9 days, and after hydropic degeneration 50.7 days. It is not recommended to start chemotherapy for persistent trophoblastic disease before 100 days after the evacuation of hydatidiform mole, provided there is a steady downward course of the serum hCG level. It is advised to submit cases of supposed hydatidiform and partial moles to a tissue committee for a second opinion.     

Hydatidiform mole with coexistent fetus. Cytogenetic features, diagnosis, and management

Hydatidiform mole with coexistent fetus is an unusual entity caused by two distinct types of pregnancy: the first one is a partial hydatidiform mole, while the second is a twin pregnancy in which a mole coexists with a normal fetus. In these two separate genetic entities, the counseling and the mother-fetus prognosis are different. Two cases of mole with coexistent fetus are reported: a partial hydatidiform mole typically tripliod and a partial mole with unusual diploid karyotype. Prenatal diagnosis is remarkable for the evaluation of fetus development related with his karyotype. Triplody excludes all hope of a non-malformed surviving child and termination of pregnancy is desirable, while normal karyotype the possibility of a continuation of pregnancy may be considered.     

Clinical management of a quadruplet pregnancy combining a triplet pregnancy with a classical hydatidiform mole: case report and review of literature

A 28-year-old Taiwanese woman who had received ovulation induction by clomiphene citrate (CC), follicular-stimulating hormone (FSH), and human chorionic gonadotrophin (hCG) treatment was diagnosed with a quadruplet pregnancy containing a hydatidiform mole and three fetuses at nine weeks' gestation. Expectant management failed to achieve any viable neonate due to massive antepartum haemorrhage and preterm delivery at 25 weeks' gestation. Five other cases previously reported involving quadruplets or triplets with a complete hydatidiform mole and two or three fetuses are reviewed. All cases ended as premature non-viable fetuses. Analysis of the clinical features, management, and outcome both in our patient and these reports suggest that more efficacious treatment planning, such as selective feticide, should be considered in order to improve the likelihood of attaining an advanced gestational age for a single fetus.     

Partial hydatidiform mole with subsequent trophoblastic tumor; a case report.

A case of partial hydatidiform mole revealed by genetic marker analysis one maternal and two paternal chromosome complements. Levels of serum human chorionic gonadotropin were persistently elevated during follow-up. Avillous curettage specimens prior to chemotherapy were morphologically suspicious for gestational choriocarcinoma. It is still uncertain whether the risk for gestational choriocarcinoma preceded by partial mole exceeds the risk related to non-molar abortions. Careful follow-up with serial serum human chorionic gonadotropin levels is required to detect persistent disease.     

Measurement of CA-125 in trophoblastic disease

OBJECTIVES: Physicians treating hydatidiform mole are still seeking means of identifying those patients who will require chemotherapy. The standard accepted method is to follow human chorionic gonadotropin levels but CA-125 measurement has been suggested as a supplement that may be clinically useful. This study was undertaken to validate or refute the one previous study that addresses this issue. CA-125 was measured at the time of hydatidiform mole evacuation to determine (1) whether it would predict the need for chemotherapy and (2) whether it correlated with human chorionic gonadotropin and tumor load in following patients with hydatidiform mole and metastatic gestational trophoblastic disease. PATIENTS AND METHODS: CA-125 was measured in serial weekly samples selected from diagnostic groups of patients with trophoblastic disease. Sixteen patients had hydatidiform mole with spontaneous resolution, fourteen had nonmetastatic gestational trophoblastic tumor, and four had low-risk metastatic disease. Six patients had high-risk metastatic disease. Ten patients had partial hydatidiform mole and one of these required chemotherapy. One patient had primary ovarian choriocarcinoma and three had placental site tumor. RESULTS: The mean preevacuation CA-125 among the 15 patients with complete hydatidiform mole was 40.9 U/ml: 52.5 U/ml for 5 patients who required chemotherapy and 36.2 U/ml for 10 patients who did not require chemotherapy. There was no statistical difference between these values. There was no correlation of CA-125 with hCG. Frequently CA-125 became negative when hCG was still elevated. Among six patients with high-risk disease, CA-125 was elevated in four but in all six patients hCG remained elevated when CA-125 became negative. In nine patients with partial hydatidiform mole CA-125 was elevated prior to mole evacuation and then became negative. The patient with a tetraploid conceptus who required chemotherapy had negative CA-125. With placental site tumor CA-125 was negative, but it was elevated with ovarian choriocarcinoma. CONCLUSION: CA-125 levels do not provide reliable information in the management of patients with gestational trophoblastic disease.     

Characterization and comparison of two forms of human chorionic gonadotropin from hydatidiform moles with low and high immunoreactivity

Two glycoproteins (LM-hCG and HM-hCG) with gonadotropic activity were purified from the chorionic tissue of patients with hydatidiform mole with low and high urinary human chorionic gonadotropin levels and were compared to each other. The immunologic, biologic, and physicochemical properties of the two preparations were very similar. Also, the quantities of LM-hCG and HM-hCG recovered from molar tissue from the two types of patients were similar. However, the molar tissue from patients who excreted high levels of human chorionic gonadotropin immunoreactivity also contained other molecular forms with apparent human chorionic gonadotropin immunoreactivity tissues from patients who excreted low levels did not. These latter molecular forms may account for the differences in the levels of human chorionic gonadotropin immunoreactivity excreted by the two types of patients.     

双胎之一完全性葡萄胎的产前诊断及处理

目的 探讨双胎之一完全性葡萄胎(a twin pregnancy consisting of acomplete mole and coexisting fetus,CMCF)的产前诊断及处理。方法 回顾性分析2例CMCF的临床资料。结果 第1例患者在孕10周时,B超发现胎儿与葡萄胎胎盘共存,患者要求终止妊娠,刮宫物间期细胞荧光原位杂交(fluorescent in situ hybridization,FISH)和核型分析提示,胎儿与葡萄胎均为二倍体,证实为CMCF。第2例患者在孕21周时,B超发现胎儿与葡萄胎胎盘共存,B超引导下经腹壁绒毛活组织检查(活检)和羊膜腔穿刺,葡萄胎和羊水的间期细胞FISH和核型分析提示,胎儿与葡萄胎均为二倍体,证实为CMCF双胎之一完全性葡萄胎,患者继续妊娠,在孕28周时胎膜早破,因继发感染而行剖宫产终止妊娠,胎儿存活,胎盘、新生儿外周血的核型分析结果与产前诊断相符。结论 产前一旦发现胎儿与葡萄胎胎盘共存,应立即进行CMCF和部分性葡萄胎(partial hydatidiform mole,PHM)的鉴别,如果绒毛和羊水行间期细胞FISH和核型分析为二倍体,则为CMCF,是否继续妊娠,需采取个体化原则;如果为三倍体,则为部分性葡萄胎,应及时终止妊娠。     

Duration of human chorionic gonadotropin surveillance for partial hydatidiform moles

OBJECTIVE: Partial hydatidiform moles infrequently progress to gestational trophoblastic neoplasia. The purpose of this study was to determine the optimal duration of human chorionic gonadotropin surveillance. STUDY DESIGN: We retrospectively reviewed the clinical follow-up of all women who were diagnosed with partial hydatidiform mole at our institution from 1983 to 2003. RESULTS: One hundred sixty-three patients were identified with a median age of 23 years (range, 14-42 years). Seventy-four patients (45%) attained undetectable levels of human chorionic gonadotropin; none of the patients had gestational trophoblastic neoplasia. Forty patients completed the 6 months of recommended follow-up; 6 patients conceived during surveillance, and 28 patients did not return for any further office visits 1 to 5 months after achieving remission. Eighty-three patients (51%) were lost to follow-up before normalization of human chorionic gonadotropin. Six women (4%) had stage I gestational trophoblastic neoplasia during surveillance. CONCLUSION: Our results support the suggestion that a single undetectable human chorionic gonadotropin level after evacuation is sufficient follow-up to ensure remission in patients with partial hydatidiform moles.     

Role of plasma nitric oxide in complete hydatidiform mole

PURPOSE OF INVESTIGATION: This prospective study aimed to evaluate any relationship between development of complete hydatidiform mole and plasma levels of nitric oxide (a biologically active mediator derived from L-arginine), and human chorionic gonadotropin beta (beta-hCG; a metabolite involved in trophoblast production). METHODS: Levels of plasma nitric oxide and beta-hCG were measured in 38 patients with complete hydatidiform mole pregnancies, and nitric oxide levels were measured in 31 women with normal pregnancies who formed the control group. RESULTS: For patients compared with controls, mean plasma concentrations of nitric oxide were significantly higher (35.84 vs 29.54 microM; p < 0.001) and significantly associated with increased risk of hydatidiform mole (odds ratio 1.0105, 95% confidence interval 1.0034-1.0176). No significant relationship was found between plasma levels of nitric oxide and beta-hCG in the patient group. CONCLUSION: In patients with complete hydatidiform mole compared with controls, plasma nitric oxide levels were found to be significantly higher and associated with increased molar risk.     

Overdiagnosis of complete and partial hydatidiform mole in tubal ectopic pregnancies.

Partial or complete hydatidiform mole (HM) affects approximately 1 in 500 to 1,000 pregnancies. Previous small series suggest that histopathologic diagnosis of HM may be difficult in tubal ectopic pregnancies. The histopathology database of a regional Trophoblastic Disease Unit was searched to identify cases with a referral diagnosis of tubal HM, and the histopathologic findings were reviewed. During the study period (1986-2004 inclusive), there were 132 cases. After central review by specialist histopathologists, the final diagnosis was ectopic partial mole in two, ectopic complete mole in five, and ectopic hydatidiform mole (not otherwise specified) in one. The final diagnosis of definite hydatidiform mole was made in eight (6%) cases, significantly less than in referred uterine curettage specimens, in which approximately 90% have a confirmatory diagnosis of HM (Z = 12.9; p < 0.0001). No cases in this series developed persistent gestational trophoblastic disease, the human chorionic gonadotropin concentration spontaneously returning to normal. Ectopic pregnancies, where managed surgically, should be submitted for histopathologic examination; however, the pathologist should be aware that the degree of extravillus trophoblastic proliferation may appear more florid compared with evacuated uterine products of conception. Molar pregnancy should only be diagnosed when strict criteria regarding morphologic abnormalities previously described in uterine evacuation material are applied.     

Application of the radioreceptor assay for human chorionic gonadotropin in pregnancy testing and management of trophoblastic disease.

A commercially prepared radioreceptor assay (RRA) for human chorionic gonadotropin (hCG) has been evaluated as a pregnancy test and in a quantitative assay to follow patients with hydatidiform mole. The RRA demonstrated almost 100% agreement in comparison with radioimmunoassay (RIA) and urinary hCG tests. In the quantitative assay, a limiting reliable concentration of 70 mIU/ml of hCG in serum could be obtained. Extremely good correlation was achieved between the RRA and RIA test for hCG in 2 patients with hydatidiform mole over a span of 3 months of followup after evacuation of the mole. The usefulness of the RRA as a replacement of RIA tests for hCG is discussed.     

Hormonal contraception and trophoblastic sequelae after hydatidiform mole (a Gynecologic Oncology Group Study)

A prospective randomized study was undertaken to determine whether the administration of oral contraceptives after the evacuation of a hydatidiform mole affects the human chorionic gonadotropin serum level in a way that leads to an increased frequency in the diagnosis of postmolar trophoblastic disease. Between 1981 and 1988, 266 patients were randomly assigned to either oral contraceptives or barrier contraception after evacuation of a hydatidiform mole. Patients were followed up until serum levels of human chorionic gonadotropin were normal or until specific criteria for the diagnosis of postmolar trophoblastic disease were met. Twenty-three percent of patients receiving oral contraceptives had postmolar trophoblastic disease, whereas those using a barrier method had a rate of 33%. The median time to spontaneous regression in the oral contraceptives group was 9 weeks, whereas the median time to regression in the barrier group was 10 weeks. Twice as many patients in the barrier group became pregnant in the immediate follow-up period. We conclude that oral contraceptives are the preferred method of contraception after evacuation of a hydatidiform mole.     

Radioimmunoassay of free beta-subunit of human chorionic gonadotropin in diagnosis of high-risk and low-risk gestational trophoblastic disease

A radioimmunoassay was performed with monoclonal antibody 1E5, which distinguishes free beta-subunit of human chorionic gonadotropin in the presence of intact human chorionic gonadotrophin. Serum samples were obtained from 68 pregnant women, 9 with hydatidiform mole who underwent spontaneous remission, 12 with hydatidiform mole who developed gestational trophoblastic disease, 5 with metastatic gestational trophoblastic disease of high-risk category, and 1 with choriocarcinoma concomitant with pregnancy. The concentrations of free beta-subunit of human chorionic gonadotropin and total beta-subunit were determined on the sera. The assay data were expressed as a ratio of nanograms of free beta-subunit per 1000 mIU of total beta-subunit. The ratios, analyzed by the Wilcoxon two-sample test, indicated a highly significant correlation between high ratios and the eventual diagnosis of high-risk gestational trophoblastic disease (p = 0.0019). This study suggests that the excessive production of free beta-subunit of human chorionic gonadotrophin may identify patients with high-risk gestational trophoblastic disease much earlier and identify gestational trophoblastic disease in patients during pregnancy.     

Recurrent gestational trophoblastic disease after hCG normalization following hydatidiform mole in The Netherlands

OBJECTIVES: To determine the risk for recurrent trophoblastic disease after spontaneous normalization of human chorionic gonadotropin (hCG) levels in patients with hydatidiform mole and to determine the risk for tumor relapse after apparent remission following chemotherapy in patients with low- and high-risk persistent trophoblastic disease. METHODS: From 1994 until 2004, 355 patients with hydatidiform mole were registered at the Dutch Central Registry of Hydatidiform Mole and were monitored by sequential hCG assays in serum at the department of Chemical Endocrinology of the Radboud University Nijmegen Medical Centre. HCG regression curves were analyzed together with clinical information collected from the Hydatidiform Mole Database. RESULTS: Among the 355 registered hydatidiform mole patients, 265 patients attained spontaneous normalization following evacuation. Of the 265 patients, one patient (0.38%) subsequently required chemotherapeutic treatment for recurrent trophoblastic disease (95% confidence interval 0.0% to 2.1%). HCG levels did not decline to normal (<2.0 ng/ml) spontaneously in 90 patients; those patients were subsequently treated. Relapse rates were 8.1% (6/74) and 6.3% (1/16) for the low- and high-risk category respectively. CONCLUSION: Our analysis indicates that relapse risk in hydatidiform mole patients with spontaneous normalization is extremely low (one in 265 patients) after two normal hCG levels (<2.0 ng/ml) are achieved. Our results support the suggestion that two subsequent normal hCG levels may be sufficient to ensure sustained remission after hydatidiform mole evacuation. In contrary, in order to assure sustained remission, the relapse rates after chemotherapy in the current study emphasize the need for surveillance of trophoblastic tumor patients even after complete remission has apparently been achieved.     

Androgenetic complete mole coexistent with a twin live fetus.

OBJECTIVE: The aim of this study was to evaluate the clinical course and the management policy of complete mole coexistent with a twin live fetus confirmed with DNA polymorphism in a single hospital. METHODS: From 1981 to 1995, six patients with androgenetic complete hydatidiform mole coexistent with a twin live fetus were diagnosed by DNA polymorphism analysis. The clinical course of these six patients was analyzed. RESULTS: Two patients chose to terminate pregnancies and four patients desired to continue the pregnancy. However, the pregnancy had to be interrupted in two patients because of severe preeclampsia and sudden intrauterine fetal death. In two patients, fetuses were growing unremarkably and normal babies were delivered at term. The development of persistent trophoblastic tumor (PTT) in these rare pregnancies was higher (50.0%: 3/6) than that of single complete mole. In three patients, serum hCG titers during pregnancy were monitored. Although serum hCG levels progressively decreased during pregnancy in one patient without PTT, hCG levels initially decreased, but subsequently increased or showed a plateau with advancing gestational age in two patients with PTT. CONCLUSIONS: In patients with complete mole coexistent with a live fetus, the pregnancy may be allowed to continue when the fetal karyotype and development are normal and serum hCG titers are constantly falling with advancing gestational age.     

Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease

ObjectiveA twin pregnancy consisting of a complete hydatidiform mole with a coexisting normal fetus is extremely rare with an incidence of 1/22,000 to 1/100,000. The incidence of preterm delivery is high and few pregnancies reach near term with a viable fetus.Case reportA 34-year-old woman presented at 20 weeks of gestation with increased levels of serum beta human chorionic gonadotropin (beta-HCG) at 4.74 multiples of the median (310277.7 mIU/mL). Ultrasonography showed a hydatidiform mole together with a normal fetus. Fetal karyotyping revealed 46XY. The serum beta-HCG levels were followed up throughout the remainder of the pregnancy. A male infant weighting 2260 g and the molar tissue were delivered at 37 weeks of gestation. The karyotype of the molar tissue showed 46XX and the histopathological report confirmed our diagnosis. At 4 months postpartum, metastatic gestational trophoblastic disease of the lung was diagnosed in the mother by a computed tomography scan due to increased beta-HCG levels. The patient received three unsuccessful cycles of methotrexate and folinate. Another four cycles of chemotherapy consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) were initiated and the beta-HCG levels returned to normal. There was no evidence of recurrence in the subsequent 5 years of regular follow up.ConclusionA pregnancy with a complete hydatidiform mole and a living cotwin can be a serious threat to the health of both the mother and the fetus. Early diagnosis depends on a combination of detecting an unusually high level of serum beta-HCG and ultrasound examination. We suggest that continuation of the pregnancy may be an acceptable option and that the pregnancy may continue until term if a normal fetal anatomy is assured and maternal complications are under control. Patients require careful postpartum follow up and any recurrent disease should be managed aggressively.