Clinicopathologic characteristics and subsequent pregnancy outcome in 139 complete hydatidiform moles

OBJECTIVE: The most common form of gestational trophoblastic disease is the complete hydatidiform mole (CHM). The study reports our experience of clinicopathologic characteristics and subsequent pregnancy outcome of patients with CHM. STUDY DESIGN: One hundred fifty-one subsequent cases with initial diagnosis of CHM were re-evaluated histopathologically. Clinical characteristics, the need for chemotherapy and subsequent pregnancy outcome were evaluated. RESULTS: Twelve out of 151 cases were re-evaluated as hydropic abortion, as partial hydatidiform moles or were insufficient for morphologic examination and therefore excluded from further analysis. The leading clinical symptoms of the remaining 139 cases were irregular vaginal bleeding (67%) and uterine enlargement (41%). Twenty-six patients (19%) required chemotherapy because of gestational trophoblastic neoplasia (GTN; low-risk: 23 out of 26). All patients were cured successfully. The subsequent pregnancy rate was 15% (21/139). Five patients suffered from abortions, 12 women delivered a healthy offspring. Four women presented with recurrent CHM with a spontaneous normalization of HCG levels after D&C. CONCLUSIONS: The clinical and morphologic diagnosis of CHM is a challenge, and diagnosis as well as treatment should be multidisciplinary and centralised. One fifth of CHM are at risk of a GTN, but the cure rate is 100% with adequate management. Pregnancy outcome following CHM is complicated by an increased risk of abortion.     

Persistent trophoblast disease following partial molar pregnancy

OBJECTIVE: Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow-up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM). METHODS: Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow-up. FINDINGS: Six of the 344 patients diagnosed with PHM required treatment with single-agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow-up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour. RECOMMENDATIONS: This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow-up can be safely discontinued.     

What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients

Objective

To quantify the risk of developing post-molar gestational trophoblastic neoplasia (pGTN) beyond the first normal human chorionic gonadotrophin (hCG) in women who have had a complete (CHM) or partial molar pregnancy (PHM) and to re-evaluate the current UK Hydatidiform mole hCG surveillance guidelines.

Epidemiologic and clinicopathologic studies of partial hydatidiform mole

To determine the epidemiological and clinicopathological characteristics of partial hydatidiform mole (PHM), a comparative study of PHM and complete hydatidiform mole (CHM) was performed in molar patients who were entered in the regional registry of Niigata Prefecture and/or who were admitted for treatment at Niigata University Hospital. The results obtained are as follows. 1. From 1971 to 1988, 2,290 hydatidiform moles (HMs) were documented in the registry. The incidence of HM was annually decreasing with an almost constant ratio to the total number of pregnancies. Since 1986, the number of PHM was rising with an inverse decrease in CHM. One hundred fifty one of 1,923 CHM (7.9%) had persistent trophoblastic disease (PTD), but on the other hand only 6 of 367 cases PHM (1.6%) had. 2. In 275 patients treated in our hospital from 1971 to 1990, 134 of 240 with CHM (55.8%) and 6 of 35 with PHM (17.1%) experienced PTD. Of 6 PTD patients following PHM, 3 had invasive mole, 1 metastatic mole and 2 post molar persistent hCG, but no choriocarcinoma. 3. The recent study of DNA analysis in molar tissue revealed that one case, which had been diagnosed as PHM, coexisted with CHM and non-molar pregnancy.     

Genetic studies in hydatidiform mole with clinical correlations

In an elective study of 163 hydatidiform moles 38 were classified as partial mole (PHM) and 125 as complete mole (CHM) on the basis of pathology. Genetic studies showed the PHM to be triploid with one maternal and two paternal chromosome sets. In all cases of PHM the molar pregnancy resolved spontaneously after evacuation. On the basis of genetic studies CHM which were diploid could be subdivided into two entities: homozygous androgenetic CHMs that were 46,XX, and heterozygous CHMs which were androgenetic and usually 46,XY. In informative cases in this series the frequency of heterozygous CHM was 10 per cent. Twenty-two (17.6 per cent) of all the patients with CHM required subsequent chemotherapy for post-mole trophoblastic tumour. Where patients with CHM could be classified as having homozygous or heterozygous CHM the requirement for treatment (17.8 per cent and 25 per cent, respectively) was not found to be significantly different in the two groups.     

Gestational trophoblastic disease

Gestational trophoblastic disease is a disease of the proliferative trophoblastic allograft and includes partial mole (PM), complete hydatidiform mole (CM), invasive and metastatic mole, choriocarcinoma and placental-site trophoblastic tumour (PSTT). Suction evacuation is recommended to terminate CM or PM. PM or CM should be monitored with serum human chorionic gonadotrophin, and effective contraception should be advised for at least 6 months.About 10–20% of patients with molar pregnancy may progress to gestational trophoblastic neoplasia (GTN) which requires chemotherapy.At the 2000 FIGO Meeting, recommendations were made on the criteria for diagnosing GTN and on methods of investigation. Staging was revised to include a modified World Health Organization risk score. The first-line chemotherapy for low-risk GTN is methotrexate and, for high-risk GTN, EMA-CO is recommended. In PSTT, surgery plays a more important role than chemotherapy. Referral of patients to a centre with experience in treating GTN is important to ensure a good outcome.     

Trophoblastic debris extruded from hydatidiform molar placentae activates endothelial cells: Possible relevance to the pathogenesis of preeclampsia

IntroductionPreeclampsia is currently thought to be induced by a placental factor that triggers maternal endothelial activation. It is now well known that trophoblastic debris shed from the placenta into the maternal blood is associated with this disease. Hydatidiform mole is a pathological pregnancy characterised by hyperplastic trophoblast with little or no fetal development. Women with molar pregnancies may exhibit symptoms resembling preeclampsia. Deportation of trophoblastic debris occurs in molar pregnancies but, whether trophoblastic debris from molar pregnancies expresses pathogenic signals or activates endothelial cells is unknown.MethodsTrophoblastic debris were collected from either hydatidiform molar or normal first trimester placental explants and then exposed to monolayers of endothelial cell for 24 h. Endothelial cell activation was measured by quantifying cell-surface ICAM-1using ELISA. In addition, the expressions of High mobility group box 1(HMGB1) and heat shock protein 70 (HSP70) on molar placenta were examined by immunohistochemistry and western blotting. Circulating levels of sEndoglin in molar pregnancy was also measured.ResultsExposing trophoblastic debris from molar placentae increased endothelial cell surface ICAM-1 expression compared to endothelial cells exposed to trophoblastic debris from controls. Expression of HSP70 but not HMGB1 was significantly increased in hydatidiform molar placentae. The circulating levels of sEndoglin in hydatidiform molar pregnancy were not increased compared to controls.DiscussionOur results suggest that trophoblastic debris from molar pregnancies induces endothelial cell activation. HSP70 but not HMGB1 expressed on hydatidiform molar placenta may be a pathogenic signal to endothelial cells.     

妊娠滋养细胞肿瘤生育力保护研究现状

妊娠滋养细胞肿瘤（gestational trophoblastic neoplasms，GTN）包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤。GTN多发生于育龄妇女，因此，治疗的同时保留患者的生育力尤为重要。文章阐述了保留生育力治疗GTN的方法，如全身静脉化疗或动脉插管化疗、动脉栓塞治疗、保守性手术、免疫治疗等，并总结保留生育力治疗后的妊娠结局等相关问题。     

Clinical characteristics of persistent gestational trophoblastic neoplasia after partial hydatidiform molar pregnancy

OBJECTIVE: To identify clinical characteristics associated with developing persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform molar pregnancy (PHM). STUDY DESIGN: Utilizing the Donald P. Goldstein in patients who developed persistence between 1973 and 1989. CONCLUSION: Older age at diagnosis and history of prior mole were significantly more common in women who developed persistence after partial molar pregnancy in referral of patients the earlier cohort but not in idefined clinical the recent cohort. In recent years no clinical factor was at increase their risk significantly associated with rsistence. database at the New England Trophoblastic Disease Center, 284 women with partial molar pregnancy diagnosed between 1973 and 2003 were characteristics identified. Clinical charac- for pe teristics, such as gravidity, parity, age, uterine size, gestational age at diagnosis, human chorionic gonadotropin levels at presentation and time to development of persistence (GTN) were analyzed. Data were also divided into 2 cohorts, an earlier one (1973-1989) and a later one (1990-2003), in order to look at potential changes over time. RESULTS: GTN developed in 5.6% of partial molar pregnancies. Older maternal age was significantly associated with development of persistent GTN in the earlier cohort but not in the recent cohort. Previous molar pregnancy was also statistically significantly more common the development of +/-after PHM.     

First-trimester molecular diagnosis of complete hydatidiform mole associated with dizygotic twin pregnancy conceived by intrauterine insemination

ObjectiveTo present first-trimester molecular diagnosis of complete hydatidiform mole (CHM) associated with dizygotic twin pregnancy conceived by intrauterine insemination.Materials and methodsA 32-year-old woman presented to the hospital with a huge complex cystic mass measuring about 8.5 cm × 4.1 cm in the uterine cavity and a living co-existing fetus with fetal biometry equivalent to 9 weeks. She underwent chorionic villus sampling at 13 weeks of gestation, and microsatellite genotyping for molar pregnancy test was applied. A molar pregnancy test was performed by a short tandem repeat (STR) identifier polymerase chain reaction (PCR) polymorphic marker analysis. The pregnancy was terminated at 14 weeks of gestation. Postnatal polymorphic DNA marker analysis of the placenta by quantitative fluorescent PCR (QF-PCR) was performed. Analysis of maternal blood total β-human chorionic gonadotropin revealed a high level of 551,600 mIU/mL at 10 weeks of gestation and a level of 1.0 mIU/mL at 15 weeks postpartum. The woman was doing well at 4 months after delivery.ResultsThe results of STR identifier PCR polymorphic marker analysis showed androgenic conception in the complex cystic mass and biparental conception in the living fetus. Pathological analysis of the cystic mass confirmed the diagnosis of CHM. The results of QF-PCR showed biparental inheritance in the normal fetus and complete paternal homozygosity in the CHM of the abnormal fetus in all STRs, indicating dizygotic twinning and CHM of monospermy.ConclusionPrenatal sonographic diagnosis of placentomegaly with many grape-like vesicles should include a differential diagnosis of CHM, partial hydatidiform mole (PHM), placental mesenchymal dysplasia (PMD), and recurrent hydatidiform mole. Microsatellite genotyping for molar pregnancy testing and zygosity testing is useful in cases of prenatal diagnosis of placentomegaly associated with many grape-like vesicles and a twin pregnancy with a living fetus in the first trimester.     

Guidelines following hydatidiform mole: a reappraisal

OBJECTIVE: The aim of this study was to determine how often patients with complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic gonadotrophin (hCG) levels subsequently develop persistent or recurrent gestational trophoblast disease. METHODS: Four hundred and fourteen cases of CHM registered at the Hydatidiform Mole Registry of Victoria were reviewed retrospectively after molar evacuation. Maternal age, gestational age, gravidity and parity were determined for each patient, as well as the need for chemotherapy. RESULTS: Among the 414 patients, 55 (13.3%) required chemotherapy for persistent trophoblastic disease. None of the patients whose hCG levels spontaneously fell to normal subsequently developed persistent molar disease. CONCLUSION: Weekly hCG measurements are recommended for all patients until normal levels are achieved. For patients who attain normal hCG levels within 2 months after evacuation, it seems safe to discontinue monitoring once normal levels are achieved. Patients who fail to achieve normal hCG levels by 2 months after evacuation should be monitored with monthly hCG measurements for 1 year after normalisation to assure sustained remission.     

Twin pregnancy with complete hydatidiform mole and coexistent fetus: Obstetrical and oncological outcomes in a series of 14 cases

Objective

Twin pregnancy with complete hydatidiform mole and coexistent fetus (CHM&CF) is a rare situation and a challenge for diagnosis. Results related to fetal outcome and maternal risk of subsequent gestational trophoblastic neoplasia (GTN) are controversial. We here display a series from the French Trophoblastic Disease Reference Center, which is to date the third in number of cases registered by the same center.

Study design

By retrospective method based on patients from the French Trophoblastic Disease Reference Center data base between November 1999 and December 2006, 17 assumed cases were reviewed. In 14 cases the diagnosis of CHM&CF was ascertained. All files were reviewed to confirm diagnosis. Methods of initial diagnosis, outcome of pregnancy and evolution to GTN were studied.

Results

In 10 cases (71%) diagnosis was made by ultrasonography. Differential diagnoses were partial hydatidiform mole and mesenchymal dysplasia. Three patients in 14 (21%) delivered a healthy child. In only one case, delivery occurred after 37 weeks of gestation. Seven patients (50%) had a diagnosis of GTN. No patient had fatal evolution. Clinical events, such as vaginal bleeding, pre-eclampsia or hyperthyroidism, had no effect on the evolution to GTN. Continuation of the pregnancy did not increase the risk of GTN.

Conclusion

In case of prenatal diagnosis of CHM&CF, and even if delivery of a healthy child is possible, patients should be aware of a possibly higher risk of GTN than in CHM.     

Obstetrical and oncological outcomes of twin pregnancies with hydatidiform mole and coexisting fetus

ObjectiveTo evaluate the obstetrical and oncological progression of twin pregnancies with hydatidiform mole coexisting fetus (HMCF).Materials and methodsUsing a retrospective method based on patients from the Women's Hospital, Zhejiang University School of Medicine database between January 1990 and October 2020, 17 patients were histologically confirmed as having HMCF, and the patients' prenatal diagnosis, outcomes and development of gestational trophoblastic neoplasia (GTN) were reviewed.ResultsAmong these 17 cases, 11 (64.71%) cases were complete hydatidiform mole coexisting fetus (CHMCF), and 6 (35.29%) cases were partial hydatidiform mole coexisting fetus (PHMCF). The gestational age at diagnosis of CHMCF was significantly earlier than that of PHMCF [9 (8–24) vs. 18 (11–32) weeks, respectively, P < 0.05]. The live birth rate of PHMCF was slightly higher than that of CHMCF (33.33%; 18.18%), but this difference was not statistically significant. The overall rate of GTN incidence of HMCF was 47.06% (8/17), and the GTN rates of PHMCF and CHMCF were 33.33% (2/6) and 54.55% (6/11), respectively. There was no significant difference in the GTN rate between patients who chose to continue pregnancy and those who terminated pregnancy before 24 weeks of gestation. The GTN rate of patients with term delivery was not significantly higher than that of preterm delivery.ConclusionIn HMCF cases, the incidence rate of CHMCF was higher than that of PHMCF, and PHMCF is more difficult to diagnose in the early stage. Continuing pregnancy does not increase the risk of GTN compared to terminating pregnancy. In cases of HMCF, when the fetal karyotype is normal and maternal complications are controlled, it is safe to continue the pregnancy and extend it to term.     

Management of gestational trophoblastic disease in developing countries

In Malaysia, the incidence of molar pregnancy and gestational trophoblastic neoplasia is 2.8 and 1.59 per 1000 deliveries, respectively; the disease is more common among the Chinese compared to the Malays and Indians. While uterine suction is the preferred method of uterine evacuation of hydatidiform mole, complete evacuation was not achieved at the first attempt in 25% of cases. Partial moles comprise 30% of all moles; these need follow up similar to that for complete moles as they are potentially malignant. In the management of invasive moles, chemotherapy should not be withheld in the presence of metastases or failure of regression of hCG. Placental site tumours are rare. Prophylactic hysterectomy and prophylactic chemotherapy are not recommended. However, in those patients with unsatisfactory hCG regression curves indicating 'at risk' in developing gestational trophoblastic neoplasia (GTN), 'selective preventive chemotherapy' appears appropriate. Chemotherapy remains the main modality of treatment for GTN. As tumour bulk and location of disease are important determinants in outcome, we categorized our patients into low, medium- and high-risk groups with survivals of 100, 98 and 61.7% respectively. Surgery and radiotherapy have a limited role.     

Video Hysteroscopy in the Diagnosis of Molar Pregnancy in two Challenging Situations: Complete Mole with Normal hCG and Partial Mole with Early Gestational Age

Study ObjectiveTo present the first hysteroscopic findings of 2 cases of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) within the context of the patients’ clinical histories.DesignPresentation of 2 hysteroscopic videos with narration of the intrauterine findings of molar pregnancy (MP) from Rio de Janeiro Gestational Trophoblastic Disease Reference Center.SettingMP is characterized by abnormal fertilization that generates 2 clinical syndromes: CHM and PHM [1].InterventionsIn the first case, the patient was aged 50 years, and hysteroscopy was indicated to assess abnormal uterine bleeding in the presence of normal serum human chorionic gonadotropin (hCG) and transvaginal ultrassonography showing an endometrial cavity with heterogeneous content. Hysteroscopy found translucent hydropic structures diagnosed as CHM. The negative hCG value was due to the hook effect (hCG after dilution: 2 240 000 IU/L). In the second case, an 18-year-old patient underwent hysteroscopy to assess the endometrial cavity with retained abortion at 7 weeks in which, during conservative management, the hCG level increased over 4 weeks from 25 000 IU/L to 58 000 IU/L. Hysteroscopy visualized the embryo with its umbilical cord and hydatidiform vesicles diagnosed as PHM.ConclusionMP can be an incidental finding during hysteroscopy for abnormal uterine bleeding or retained abortion 2, 3, 4. Knowing its morphology during hysteroscopy is helpful for the correct management of this uncommon clinical situation. Hysteroscopy as an adjunct diagnostic tool (not as first-line treatment for MP) can be of significant benefit in challenging clinical scenarios. Further studies should assess the possible risk of spreading molar cells into the peritoneal cavity owing to hysteroscopic fluid.     

Medical induction prior to surgical evacuation of hydatidiform mole: is there a greater risk of persistent trophoblastic disease?

A retrospective study was undertaken to assess whether stimulation of uterine contractility prior to surgical evacuation of a molar pregnancy will lead to an increased frequency of persistent trophoblastic disease. Forty-seven patients treated with chemotherapy for persistent trophoblastic disease after a hydatidiform mole between 1971 and 1988 were evaluated. The use of medical methods in this study group was compared to a control group of 219 patients with hydatidiform mole not requiring further treatment. A medical method, mainly treatment with prostaglandins, was used in 61.7% in the study group compared to 35.2% in the control group. This difference was, however, due to different stage distribution in the groups. Persistent disease was significantly correlated to uterine size and medical methods were mainly used in patients where uterine size corresponded to 15 weeks gestation or more. In this subset of patients, a medical method was used in the same frequency in both groups. Thus, large uterine size seems to be an independent risk factor. We conclude that stimulation of uterine contractility, which in Sweden is frequently used before surgical evacuation of the uterus in patients with hydatidiform mole and large uteri, carries no additional risk.     

A case report of a patient with 12 consecutive complete molar pregnancies

Recurence is a rare complication of hydatidiform mole, although it is serious because the chances of a subsequent term pregnancy decrease, the incidence of a further episode increases, and the risk of malignancy is higher. We report a 38-year-old woman presenting at 10 weeks gestation with a history of 11 previous consecutive molar pregnancies. Ultra-sound scan revealed a molar pregnancy treated by suction evacuation of the uterus. Histology showed a complete mole with a karyotype of 46 XX. The patient refused sterilization as she wished to continue to attempt to have a child and remains well at follow-up with no evidence of persistent trophoblastic disease. Patients with a complete hyaditidiform mole should be informed about the possibility of recurrence including its adverse effect on future obstetric outcome and greater malignant potential.     

葡萄胎的分子遗传学分类与大体病理类型的关系

目的探讨葡萄胎的遗传学类型与病理形态学的关系。方法采用ＤＮＡ限制性片段长度多态性分析的方法研究３２例葡萄胎标本。结果ＤＮＡ完全来自父源性的葡萄胎有２１例,其中大体病理形态呈完全性葡萄胎者１６例,占７６％（１６／２１）,部分性葡萄胎者５例,占２４％（５／２１）;ＤＮＡ来自双亲的葡萄胎１１例,其中大体病理形态呈完全性葡萄胎者５例,占４５％（５／１１）,部分性葡萄胎者６例,占５５％（６／１１）;χ２检验结果表明葡萄胎的病理学类型与遗传学类型无明显的平行关系（Ｐ＞０．１０）。结论本研究结果不支持葡萄胎的遗传学类型与大体病理类型间有平行关系的论点     

Comparison between vacuum aspiration and forceps plus blunt curettage for the evacuation of complete hydatidiform moles

ObjectiveSuction curettage is recommended for molar evacuation rather than sharp curettage because of its safety. However, the superiority of suction curettage with respect to the incidence of gestational trophoblastic neoplasia (GTN) has not been reported. This study aimed to compare the efficacy and safety of two evacuation procedures, vacuum aspiration and forceps/blunt curettage, for complete hydatidiform moles (CHMs) to determine the differences between them.Materials and methodsPatients with androgenetic CHM determined by multiplex short tandem repeat polymorphism analysis were included in this observational cohort study. Patients underwent evacuation with forceps and blunt curettage (forceps group) before March 2013 and with vacuum aspiration (vacuum group) thereafter. GTN was diagnosed based on the International Federation of Gynecology and Obstetrics 2000 criteria. The incidence of GTN and other clinical parameters were compared.ResultsNinety-two patients were diagnosed with androgenetic CHM. The number of patients in the forceps and vacuum groups was 41 and 51, respectively. The incidence of GTN was 12.2% (5/41) and 13.7% (7/51) in the forceps and vacuum groups, respectively, which was not significantly different (P = 1, Fisher's exact test). No major adverse events, such as uterine perforation and blood transfusion, were noted in either group. The median surgery time was shorter in the vacuum group (16 min) than in the forceps group (25 min) (P = 0.05, Mann–Whitney U test).ConclusionThere were no differences in the incidence of GTN between the forceps and vacuum groups for androgenetic CHM. However, vacuum aspiration could have the advantage of a shorter surgery period. The use of vacuum aspiration for molar pregnancy seems to be safer. Therefore, we recommend suction curettage for the first evacuation of hydatidiform moles.     

Epidemiologic features of hydatidiform mole in the Netherlands

The presented study is a report of epidemiologic data collected between 1978 and 1980 from patients with gestational trophoblastic disease in the Netherlands. Review of curettings from 344 patients with hydatidiform mole and 33 patients with partial mole resulted in review diagnoses of hydatidiform mole in 283 women, of partial mole in 25 women, and of mere hydropic degeneration in 69 women. Upon review of the initial diagnosis of complete and partial hydatidiform mole, 18% of the cases were considered false-positive. After the evacuation of a molar pregnancy, 10% of the patients needed chemotherapy because of the diagnosis of persistent trophoblastic disease. In patients with a review diagnosis of hydropic degeneration, this was never necessary.