Gestational Trophoblastic Disease in Malta

Hydatidiform Moles

Hydatidiform moles are the most common type of GTD. Hydatidiform moles are most commonly diagnosed in the first half of pregnancy [6] and in this study period all cases were diagnosed in the first trimester of pregnancy. Only 3.6% of patients were noted to have molar pregnancy on ultrasound without any other symptoms. Overall, 19.3% (16 patients) of cases had ultrasound diagnosis of GTD prior to treatment and 80.7% (67 patients) were diagnosed only from the histology result. Hydatidiform moles are divided into partial and complete moles. In both these two conditions, the placental villi become oedematous and this is caused through a defect in gametogenesis or fertilization [6, 7]. Table 4 represents the different features of partial and complete mole. Despite the differences mentioned in this table, their management is similar. In our study 27.7% had suction curettage under general anaesthesia in theatre, 14.5% had medical treatment only with vaginal misoprostol and 41% had first medical management which was followed by surgical evacuation in theatre. The RCOG Green-top guideline states that suction curettage is the method of choice for the removal of complete molar pregnancies. In complete molar pregnancies there will be no foetal parts, so suction removal is the method of choice irrespective of the uterine size [5]. Suction curettage is also the method of choice for partial moles except when the size of fetal parts deters the use of suction curettage and then medical removal is preferred [5]. In this study, high number of patients with partial moles, 39 cases out of the 66 partial moles (59.1%) where treated with vaginal misoprostol.

The medical management of complete molar pregnancy should be avoided. In a study of more than 4000 women with GTD, it was found that the risk of developing GTN and requiring chemotherapy was 16-fold higher when the medical methods of removal were used compared with the surgical removal [8]. In this study population, 4 out of the 14 cases (28.6%) of complete moles received medical management, however none of them had any complications and they did not require further treatment such as chemotherapy. The 3 cases of complete moles that required additional chemotherapy had immediate surgical treatment with suction curettage. The International Federation of Gynaecology and Obstetrics (FIGO) add that hysterectomy can be an alternative to suction curettage if child-bearing is complete. It is stated that by performing a hysterectomy one would provide permanent sterilization and also decreases the need for subsequent chemotherapy by eliminating the risk of local myometrial invasion as a cause of persistent disease [9]. Case reports on uterine artery embolization as part of the treatment for GTD have been reported Carlini L, et al. [10, 11]. This modality has been used in cases of persistent GTD and selective uterine artery embolization was carried out instead of invasive surgery and they managed to achieve both the control of the hemorrhage and also the control of the disease [10]. This modality of treatment can also be used for GTN [11]. In this study population, we had one case in October 2020 of complete molar pregnancy who had uterine artery embolization prior to ERPC. The patient is still being followed up but did not require any further treatment such as chemotherapy. In this 6-year study period, there were no cases of twin pregnancies with one viable foetus and the other molar pregnancy. In such rare cases, women should be counselled about the potential increased risk of perinatal morbidity. Sebire, et al. [12] published a study in 2002 on the outcome of 77 mothers with twin pregnancies who had complete mole and healthy co-twin. They concluded that although there is high risk of spontaneous abortion, they had 40% live births and no significant increase in persistent GTD.

The optimum follow–up care was changed in the last updated Green-top guideline. Before the latest update of September 2020, the follow-up for complete and partial moles were the same [13]. In the latest Green-top guideline, the follow–up for partial moles was changed. For complete mole, if the HCG level has reverted to normal values within 56 days of the pregnancy event, then follow-up will be for 6 months from the date of uterine removal [5]. On the other hand, if hCG level has not returned to normal values within 56 days of the pregnancy event, then follow-up will be for 6 months from the normalisation of the hCG level [5]. The new follow-up for partial moles is now shorter. The follow- up is concluded once the HCG level has returned to normal values on two samples, at least 4 weeks a part [5]. Also, it is now clearly stated that women who have not received chemotherapy for GTD no longer need to have hCG measured after any subsequent pregnancy even, as the incidence of GTD in a subsequent pregnancy event in these women is very low [14]. In this study we noted that the follow-up that the patients received was inconsistent and did not follow any regular protocols, with 19.3% of patients who came for follow-up at Mater Dei Hospital had between 7 to 15 hospital visits. These were mainly out-patients visits just for the HCG results and these were visits that were carried out in the same antenatal clinic with other pregnant mothers.

The Faculty of Sexual Health and Reproductive Health (FSRH) Guideline also recommends that after complete molar pregnancy, women are advised to avoid subsequent pregnancy for at least 6 months to allow hCG monitoring for ongoing GTD [15]. And after partial molar pregnancy, women are advised to avoid pregnancy until two consecutive monthly HCG levels are normal [15]. Women are advised that most methods of contraception can be safely used after treatment for GTD and can be started immediately after uterine evacuation, with the exception of intrauterine contraception (IUC). The IUC should not be inserted in women with persistently elevated HCG levels or malignant disease.

Gestational Trophoblastic Neoplasia

Gestational trophoblastic neoplasia (GTN) is malignant lesions that arise from placental villous and extra-villous trophoblast [16]. GTN occurs in 1 every 40,000 pregnancies and is also more common in Asia than it is in Europe or North America. It mainly consists of 4 different pathological conditions: the invasive mole that follows either after a complete mole or a partial mole, choriocarcinoma, PSTT and ETT [16]. Each of these 4 conditions can penetrate the uterine wall, metastasize and can even lead to death if left untreated. In our 6-year study period we had only 3 cases of GTN out of the 83 total cases of GTD. The process of specifying the aetiological risk factors which could cause GTN progression is not easy [17]. Pregnancy after 40 years and abnormal forms of hydatidiform moles are the main aetiological risk factors of complete mole progression [18]. The development of invasive mole happens when the molar villi exceed the uterine myocytes. Nearly about 15% of complete moles would cause local tumor invasion, and 5% of complete moles will metastases commonly into the vagina or lungs [17]. On the other hand, the progression of local tumor invasion after partial moles happens is about 0.5% of patients, while the occurrence rate of metastatic disease is much less [17].

Approximately 50% of cases of GTN arise from molar pregnancy, 25% from miscarriage or tubal pregnancy, and 25% from term or preterm pregnancy [19]. Invasive mole and choriocarcinoma, which make up the vast majority of these tumors, always produce substantial amounts of HCG and are highly responsive to chemotherapy with an overall cure rate of over 90%, making it usually possible to achieve cure while also preserving fertility [19]. In contrast, PSTT and ETT, which rarely occur, produce very little amounts of HCG and are relatively resistant to chemotherapy [19]. Because PSTTs and epithelioid tumours are not much sensitive to chemotherapy, their mortality rate is higher than that of a choriocarcinoma [17].

Women with GTN are now assessed using the FIGO 2000 scoring system before chemotherapy treatment [5]. Table 5 shows this FIGO 2000 scoring system adapted from the RCOG Green-top guideline. Women with scores of 6 or less are considered as low risk and are treated with single- agent intramuscular methotrexate, alternating daily with folinic acid for 1 week followed by 6 rest days [5]. Women with scores of 7 or greater are considered as high risk and are most commonly treated with intravenous multi-agent chemotherapy, which includes combinations of methotrexate, dactinomycin, etoposide, cyclophosphamide and vincristine. However, the best combination of chemotherapy for GTN was not established in the Cochrane database review that was published in 2016 by Izzam, et al. [5, 9, 20].