Guideline sources The following summarized guidelines for the evaluation and management of gestational trophoblastic disease (GTD) are prepared by our editorial team based on guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG 2021), the Society of Obstetricians and Gynaecologists of Canada (SOGC 2021), the American College of Radiology (ACR 2019), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG 2017), and the European Society of Medical Oncology (ESMO 2013). 1 2 3 4 5 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s https://web.pathway.md/diseases/recvnulMd4asYAt0n 1/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway Guidelines 1. Screening and diagnosis Clinical presentation: Recognize the clinical presentation of molar pregnancy: Situation Guidance Irregular vaginal bleeding Most commonly Positive pregnancy test Supporting ultrasound evidence B Hyperemesis Less common Excessive uterine enlargement Hyperthyroidism Early-onset preeclampsia Abdominal distension due to theca lutein cysts E Dyspnea and hemoptysis due to pulmonary metastasis Very rare New-onset seizures or paralysis due to brain metastasis. B Recognize that any patient developing persistent vaginal bleeding after a pregnancy is at risk of having GTD. B 2. Classification and risk stratification Prognosis: As per SOGC 2021 guidelines: Recognize that: the outlook for patients treated for gestational trophoblastic neoplasia is generally excellent with an overall cure rate close to 100% further pregnancies are achieved in approximately 80% of patients following treatment for gestational trophoblastic neoplasia with either methotrexate alone or multi-agent chemotherapy there is an increased risk of premature menopause in patients treated with combination agent chemotherapy. B https://web.pathway.md/diseases/recvnulMd4asYAt0n 2/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway Warn patients, especially if approaching the age of 40 years, of the potential negative impact of combination agent chemotherapy on fertility, particularly with high-dose chemotherapy. B As per ESMO 2013 guidelines: Use the FIGO scoring system to determine the risk of gestational trophoblastic neoplasia becoming resistant to single-agent chemotherapy, recognizing that it is of no value in placental site trophoblastic tumor/epithelioid trophoblastic tumor. B Recognize that residual lung or uterine masses following chemotherapy for low- or high-risk diseases are not predictive of recurrence. B 3. Diagnostic investigations Pregnancy testing: As per RCOG 2021 guidelines: Advise patients to do a urinary pregnancy test 3 weeks after a miscarriage or medical abortion. E Obtain urine hCG in all patients with persistent or irregular vaginal bleeding lasting > 8 weeks after pregnancy. E As per RANZCOG 2017 guidelines, obtain pregnancy testing in all cases of persistent or irregular vaginal bleeding after a pregnancy event. E Serum hCG levels: obtain serum hCG levels in female patients of reproductive age presenting with abnormal uterine bleeding, bleeding > 6 weeks following pregnancy, or evidence of metastatic disease to promptly diagnose and manage GTD. B Show 3 more Diagnostic imaging: As per SOGC 2021 guidelines: Obtain CXR during initial workup for post-molar gestational trophoblastic neoplasia to look for lung metastases, and pelvic ultrasound to assess extent of disease in the pelvis. B Obtain the following during initial workup for suspected choriocarcinoma, gestational trophoblastic neoplasia after a non-molar pregnancy, and/or post-molar gestational trophoblastic neoplasia with lung metastases on CXR: pelvic ultrasound chest and abdomen CT (with arterial phase through the liver) brain MRI. B As per ACR 2019 guidelines, obtain transabdominal and/or transvaginal ultrasound and Doppler ultrasound for suspected or initial diagnosis of GTD as well as for local staging and risk assessment of suspected or established gestational trophoblastic neoplasia. B Show 4 more 4. Diagnostic procedures https://web.pathway.md/diseases/recvnulMd4asYAt0n 3/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway Histopathology: As per RCOG 2021 guidelines, perform histological examination for definitive diagnosis of molar pregnancy. B Show 5 more As per SOGC 2021 guidelines: Perform histological examination of any products of conception appearing abnormal at the time of dilatation and curettage to rule out GTD. B Differentiate complete hydatidiform mole, partial hydatidiform mole, and malignant trophoblastic disease by a gynecologic pathologist for tailored follow-up and management of gestational trophoblastic neoplasia. B As per RANZCOG 2017 guidelines, avoid performing a biopsy in patients with vaginal gestational trophoblastic neoplasia located in the fornices or suburethrally because of their highly vascular nature. D Show 2 more Prenatal karyotyping: consider performing prenatal invasive fetal karyotyping if it is unclear if the pregnancy is a complete mole with a coexisting normal twin or a possible singleton partial molar pregnancy, or in patients with an abnormal placenta, such as suspected mesenchymal hyperplasia of the placenta. C 5. Medical management Setting of care: As per RCOG 2021 guidelines, consider referring all patients with persistently elevated human chorionic gonadotrophin either after an ectopic pregnancy has been excluded, or after two consecutive treatments with methotrexate for a pregnancy of unknown location to a GTD center. E Show 5 more As per SOGC 2021 guidelines: Manage patients with GTD in specialized centers and record their data in centralized (regional and/or national) registries, if possible. A Refer patients with gestational trophoblastic neoplasia to a specialist in gynecologic oncology for staging, risk scoring, and treatment. A Chemotherapy: As per RCOG 2021 guidelines: Consider offering single-agent or multi-agent chemotherapy in patients with gestational trophoblastic neoplasia. C Offer treatment based on the International Federation of Gynecology and Obstetrics 2000 scoring system for gestational trophoblastic neoplasia following assessment at the treatment center. B https://web.pathway.md/diseases/recvnulMd4asYAt0n 4/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway As per SOGC 2021 guidelines, consider offering prophylactic chemotherapy only in high-risk patients unlikely to return for regular follow-up. C Show 3 more As per ESMO 2013 guidelines, consider offering either single-agent methotrexate (with or without folinic acid) or actinomycin D in patients with a FIGO score of 0-6. B Show 6 more Anti-D immunoglobulin: As per RCOG 2021 guidelines, administer anti-D prophylaxis following removal of a molar pregnancy. E As per SOGC 2021 guidelines, administer anti-D immune globulin after uterine evacuation to prevent alloimmunization in all Rh-negative patients. A As per ESMO 2013 guidelines, administer anti-D prophylaxis following suction dilation and curettage of partial hydatidiform mole. B 6. Surgical interventions Uterine curettage and hysterectomy, indications: As per RCOG 2021 guidelines, consider performing suction curettage as the method of choice for removal of complete molar pregnancies. E Show 2 more As per SOGC 2021 guidelines: Perform surgical evacuation by suction dilatation and curettage or hysterectomy followed by hCG surveillance for the treatment of patients with hydatidiform mole. B Offer performing either suction evacuation of the uterus or hysterectomy as the initial management of patients with suspected hydatidiform mole. B Consider performing hysterectomy in selected patients with low-risk gestational trophoblastic neoplasia. B As per ESMO 2013 guidelines, perform suction dilation and curettage in patients with singleton molar pregnancies. B Show 3 more Uterine curettage and hysterectomy, technical considerations: As per RCOG 2021 guidelines, consider using ultrasound guidance during removal and curettage to minimize the chance of perforation and to ensure that as much tissue as possible is removed. E Show 4 more As per RANZCOG 2017 guidelines, perform suction evacuation as the preferred initial management regardless of uterine size. E Repeated surgery: As per RCOG 2021 guidelines: https://web.pathway.md/diseases/recvnulMd4asYAt0n 5/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway Perform urgent surgery in patients experiencing heavy or persistent vaginal bleeding causing acute hemodynamic compromise, particularly in the presence of retained pregnancy tissue on ultrasound. E Counsel with the relevant GTD referral center before performing surgery for the second time in the same pregnancy, outside the context of acute compromise. B As per RANZCOG 2017 guidelines: Consider performing a second evacuation in selected cases because of problematic bleeding. Consider performing hysteroscopy in order to locate persistent focus during the second evacuation. E Do not perform repeat evacuation if -hCG > 5,000 or in the presence of metastases. D As per ESMO 2013 guidelines, perform second dilation and curettage for recurrence in patients with singleton molar pregnancy only after discussion with a GTD reference center, as it usually does not prevent the subsequent need for chemotherapy. B 7. Specific circumstances Patients with ectopic pregnancy: Manage patients with ectopic pregnancy suspected to be molar in nature as any other case of ectopic pregnancy. E Send a tissue specimen to a center with appropriate expertise for pathological review, if there is a local tissue diagnosis of ectopic molar pregnancy. E 8. Patient education General counseling: As per RCOG 2021 guidelines: Counsel patients with a twin pregnancy where there is one viable fetus and the other pregnancy is molar about the potential increased risk of perinatal morbidity and the outcome for gestational trophoblastic neoplasia. B Warn patients, especially if approaching the age of 40 years, of the potential negative impact of combination agent chemotherapy on fertility, particularly with high-dose chemotherapy. B As per SOGC 2021 guidelines: Refer patients with recurrent GTD for genetic counseling and testing, as this is a rare scenario that may be associated with a familial gene mutation. B Refer patients with recurrent GTD for genetic counseling and testing as this is a rare scenario that may be associated with a familial gene mutation. B 9. Follow-up and surveillance Serial hCG monitoring: https://web.pathway.md/diseases/recvnulMd4asYAt0n 6/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway As per RCOG 2021 guidelines, follow-up patients with complete molar pregnancy for 6 months from the date of uterine removal, if hCG has reverted to normal within 56 days of the pregnancy. B Show 3 more As per SOGC 2021 guidelines, obtain serial hCG monitoring during post-molar follow-up. A Show 3 more Serial hCG monitoring (RAZNCOG): Obtain weekly quantitative -hCG levels monitoring post-evacuation until three consecutive normal levels are seen. Do not obtain further testing for partial moles. Continue monthly monitoring until cleared for complete moles. E Diagnose persistent GTD in case of a rise of > 10% over 2 weeks (3 weekly -hCG levels) or a fall of < 10% over 3 weeks (4 weekly -hCG levels). Obtain a metastatic screening and assess the WHO risk score in such cases. E Contraception: As per RCOG 2021 guidelines, advise patients not to conceive until their follow-up is complete. B Show 2 more As per SOGC 2021 guidelines: Recognize that hormonal contraception can be safely prescribed and intrauterine contraceptive devices can be inserted after normalization of hCG levels. B Administer reliable contraception throughout the entire duration of follow-up in patients undergoing follow-up after molar pregnancy. B As per RANZCOG 2017 guidelines, delay the insertion of an intrauterine device for at least 6 weeks after the evacuation of the uterus and hCG normalization to minimize the risk of perforation of the uterus. E Post-treatment hormone therapy: consider using exogenous estrogens, other fertility drugs and HRT once hCG levels have returned to normal. E Subsequent pregnancy: As per RCOG 2021 guidelines: Do not obtain post-pregnancy hCG in pregnant patients following a previous molar pregnancy not required treatment for gestational trophoblastic neoplasia. D Do not perform histological examination of the placental tissue from any normal pregnancy, after a molar pregnancy. D As per SOGC 2021 guidelines: Obtain early ultrasound, close examination of the placenta and histologic examination of any nonviable pregnancy during follow-up of subsequent pregnancy in patients with previous gestational trophoblastic neoplasia or recurrent molar pregnancy. A Refer patients becoming pregnant during follow-up for GTD or gestational trophoblastic neoplasia to gynecologic oncology and maternal-fetal medicine for assessment and https://web.pathway.md/diseases/recvnulMd4asYAt0n 7/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway management. B Subsequent pregnancy (RAZNCOG): advise avoiding pregnancy during follow-up. Consider prescribing oral contraceptives. E Clinical findings Symptoms Past medical history Abdominal pain Nephrotic syndrome Amenorrhea Abdominal exam Back pain Bloating Bilateral ovarian enlargement Chest pain Integument exam Cough Dizziness Jaundice Galactorrhea Virilization Headache Hemoptysis Hematological findings Hyperemesis Polycythemia Loss of appetite Seizure Shortness of breath Vaginal bleeding Vaginal discharge Vomiting Weight loss Neurological exam ICP Gynecologic exam Uterine enlargement Lab findings hCG serum free T3 serum free T4 serum TSH Imaging findings Molar pregnancy https://web.pathway.md/diseases/recvnulMd4asYAt0n 8/9 7/1/23, 12:02 AM Gestational trophoblastic disease Pathway Likelihood Ratios Pertinent positives The following findings increase the probability of gestational trophoblastic disease in adults. 5 Finding LR+ Value Presence of molar pregnancy 1.7 Pertinent negatives The following findings decrease the probability of gestational trophoblastic disease in adults. 5 Finding LR- Value Absence of molar pregnancy 0.8 References 1. No authors listed. Management of Gestational Trophoblastic Disease: Green-top Guideline No. 38 June 2020. BJOG. 2021 Feb;128 3):e1-e27. Open 2. M J Seckl, N J Sebire, R A Fisher et al. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi39 50. Open 3. Lua Eiriksson, Erin Dean, Alexandra Sebastianelli et al. Guideline No. 408 Management of Gestational Trophoblastic Diseases. J Obstet Gynaecol Can. 2021 Jan;43 1 91 105.e1. Open 4. Paul Duggan, Yee Leung, Deborah Neesham et al. Management of gestational trophoblastic disease. RANZCOG. 2017 Mar. Open 5. Expert Panel on Women s Imaging Panel, Kika M Dudiak, Katherine E Maturen et al. ACR Appropriateness Criteria Gestational Trophoblastic Disease. J Am Coll Radiol. 2019 Nov;16 11S S348 S363. Open 6. Fowler DJ, Lindsay I, Seckl MJ et al. Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center. Ultrasound Obstet Gynecol. 2006 Jan;27 1 56 60. Open https://web.pathway.md/diseases/recvnulMd4asYAt0n 9/9