Gestational trophoblastic disease (GTD) is the name for a group of rare complications related to pregnancy, they are all conditions caused by the abnormal growth of cells from placental tissue.
You may be more familiar with terms such as; molar pregnancy also known as hydatidiform mole, choriocarcinoma (molar pregnancy that became cancerous) or even trophoblastic tumour. This article will aim to try and explain what you might need to know about GTD including causes, signs and symptoms, and treatment.
GTD can be described as the abnormal growth of cells that would normally develop into the placenta. GTD is rare, occurring in 1 in every 714 live births in the UK.1 There are various types of GTD, but with the right specialist medical care, they are treatable with good outcomes for most individuals.
Types of gestational trophoblastic disease
The different types of GTD can be divided into pre-cancerous types or cancerous types.
Pre cancerous types
Hydatidiform moles are tumours that form from metastasized placental tissue as a result of incorrect fertilisation of the egg by the sperm; they’re also known as molar pregnancies. They can be categorised in two ways:
- Complete hydatidiform mole: The most common type where no parts of the foetus are formed
- Partial hydatidiform mole: Though some parts of the foetus may be formed, it is important to understand that the complete foetal development will not be possible
- Invasive mole / persistent trophoblastic disease: Though uncommon, it can sometimes occur after the initial removal of a hydatidiform mole sub-type where the molar cells will continue to grow and become cancerous
- Choriocarcinoma: The chorio (the outer covering of the foetus) cells from molar pregnancies, normal pregnancies, ectopic pregnancies or miscarriages become cancerous and can also spread to other parts of the body2
- Placental site trophoblastic tumour and Epithelioid trophoblastic tumour: These are tumours that grow from the womb tissue formed during pregnancy. They can happen following any type of pregnancy and at any time point after the pregnancy. Both these subtypes are rare, making up less than 2% of the GTD cases2
Causes of gestational trophoblastic disease
GTD may occur due to genetic abnormalities rather than any specific action by an individual.
Though the exact cause of all GTD is not known, we know most about the causes of hydatidiform mole pregnancies.
In a complete hydatidiform mole pregnancy the egg from the mother contains no genetic tissue and so the single sperm cell that has fertilised the “empty” egg duplicates its genetic tissue to form a complete hydatidiform mole. Less commonly, two different sperm cells can fertilise the same “empty” egg and this will also form a complete hydatidiform mole.
In a partial hydatidiform mole pregnancy, the egg from the mother does have genetic tissue in it but gets fertilised at the same time by two different sperm leading to an extra set of chromosomes.
Signs and symptoms of gestational trophoblastic disease
As the cells in GTD are pregnancy-related cells, many of the signs and symptoms are therefore related to having too many of these additional cells or due to the increased amount of the pregnancy hormone (hCG) that they create.
Most common presentations:
- Abnormal vaginal bleeding
- Positive pregnancy test
- Ultrasound evidence
Less common presentations:
- Severe nausea and vomiting
- Abrnormanl enlargement of the uterus
- Pelvic pain or discomfort
- Persistent abnormal vaginal bleeding after any pregnancy
- Signs and symptoms of an overactive thyroid: the excess hCG hormone can cause an increase in the release of thyroid hormone
- Coughing up blood or seizures due to spread of disease to the lungs or brain
The medical professional reviews the patient’s medical history and also performs physical exams if necessary. The common diagnostic methods are:
- Internal pelvic exam: This is done to feel for any lumps or changes in the shape of the uterus
- Pap smear test: The cells collected from the cervix are examined under the microscope to detect changes that may be cancer or may lead to cancer and to check for noncancerous conditions, such as infection or inflammation
- Transvaginal ultrasound (ultrasonography): This ultrasound test uses a small instrument (transducer) that is placed in the vagina to look at the uterus and nearby tissue
- Blood tests: Done to check the levels of certain hormones and other substances that may be impacted by the presence of GTD
- Urinalysis: GTD may alter the amount of sugar, protein, bacteria and certain hormones in urine
Management and treatment for gestational trophoblastic disease
The type and stage of GTD will determine the management or treatment required. Routinely this involves the removal of the abnormal tissue. In case of cancer, chemotherapy and regular follow-up with a specialist unit will be required.
For hydatidiform moles, removal of the abnormal tissue through surgery is recommended, where the neck of the womb is dilated and the tissue is removed using a suction curette.3 This is performed under general anaesthesia.
Removal of the womb (hysterectomy) is a possible alternative if the patient does not wish for any further pregnancies, but this is a more significant operation that would need to be considered carefully for each individual case.
Invasive moles and choriocarcinoma are usually treated with chemotherapy. Patients will be individually assessed and treated with either single or multi-agent chemotherapy. Methotrexate and dactinomycin (actinomycin D) are commonly used chemotherapy agents for GTD, however, dactinomycin has been shown to be effective for the treatment of low-risk gestational trophoblastic neoplasia.4
Radiotherapy is a possible treatment option in cases where abnormal tissue has spread to other organs such as the brain.
Placental site trophoblastic tumour and epithelioid trophoblastic tumour are less sensitive to chemotherapy and so may be treated with surgery.3
Routine follow-ups are extremely important for all those who have been diagnosed with GTD until the level of the pregnancy hormone hCG is back to normal and remains the same for a certain number of weeks.
Patients will have urine tests, blood tests or both performed every two weeks at a specialist hospital. Blood tests can be done at your local hospital or GP.
It is important for a patient not to get pregnant again until they have completed their follow-up and been told it is okay to do so. It is okay to use most contraceptives after GTD, however, intra-uterine contraceptive devices need to be avoided until the specialized medical practitioner gives their approval.
At the end of any future pregnancies, regardless of their outcome, those who have previously had GTD will be asked to contact their specialist hospital and will have follow-up until their pregnancy hormone levels return to normal.
The future use of hormone replacement therapy or fertility drugs for those undergoing assisted reproductive treatment after GTD is acceptable as long as the patient’s pregnancy hormone level is back to normal and they have completed their follow-up.3
The following have all been known to affect the risk of GTD:
- Age: There is a higher chance of getting GTD in those becoming pregnant before 20 or after 35 years of age 1
- Ethnicity: Molar pregnancy is twice as common in those of Asian ethnicity2
- History of previous molar pregnancy: A history of previous molar pregnancy increases your risk of developing a molar pregnancy in the future by 10 to 20 times2
- History of previous spontaneous miscarriage: A history of previous spontaneous miscarriage increases your risk molar pregnancy by 2 to 3 times2
How can I prevent gestational trophoblastic disease?
There are no specific ways to prevent GTD. If you suspect your symptoms to be GTD, please consult your GP for a proper diagnosis and treatment plan. It is also important to follow the advice of your specialist if diagnosed with GTD and to go for regular follow-ups.
How common is gestational trophoblastic disease?
Gestational trophoblastic disease is rare, it is seen occurring in 1 in every 714 live births in the UK.
Can gestational trophoblastic disease come back?
The recurrence of GTD varies from type to type.
- The risk of recurrence for a hydatidiform mole is low, ranging from 1% to 3%
- The risk of recurrence for an invasive mole is 2% to 20%
- The risk of recurrence for choriocarcinoma is 10% to 20%
Completing follow-ups and following the advice of your specialist hospital after a diagnosis of GTD is important.
When should I see a doctor?
If you have any abnormal vaginal bleeding and a positive pregnancy test you should seek medical advice. All those with a history of GTD should contact their specialist hospital after any pregnancy, no matter what the outcome of that pregnancy.
It is important to remember that gestational trophoblastic disease is a rare condition, and though it requires specialised medical care, the prognosis for the majority of patients is excellent. The overall recurrence rate of GTD is low and varies from type to type. Patients with a previous history of GTD are advised to contact their specialist hospital after any pregnancy and do regular follow-ups until the pregnancy hormone levels become normal and remain the same for a period of time.
- Ngan HYS, Seckl MJ, Berkowitz RS, Xiang Y, Golfier F, Sekharan PK, et al. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet. 2018 Oct;143 Suppl 2:79–85. https://obgyn-onlinelibrary-wiley-com.nottingham.idm.oclc.org/doi/10.1002/ijgo.12615
- Ning F, Hou H, Morse AN, Lash GE. Understanding and management of gestational trophoblastic disease. F1000Res. 2019;8:F1000 Faculty Rev-428. https://www-ncbi-nlm-nih-gov.nottingham.idm.oclc.org/pmc/articles/PMC6464061/
- Management of gestational trophoblastic disease: green‐top guideline no. 38 – june 2020. BJOG: Int J Obstet Gy [Internet]. 2021 Feb [cited 2023 Jun 15];128(3). Available from: https://onlinelibrary.wiley.com/doi/10.1111/1471-0528.16266
- Lawrie TA, Alazzam M, Tidy J, Hancock BW, Osborne R. First‐line chemotherapy in low‐risk gestational trophoblastic neoplasia. Cochrane Database of Systematic Reviews [Internet]. 2016 [cited 2023 Jun 16];(6). Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007102.pub4/full