Gestational Trophoblastic Disease Definition
Gestational Trophoblastic Disease (GTD), or Gestational Trophoblastic Tumor, is the name given for a group of diseases characterized by the growth of a tumor within the womb or uterus of women [1].
Persistent GTD, marked by persistent increase in beta hCG [3], may be called Gestational Trophoblastic Neoplasia (GTN).
Gestational Trophoblastic Disease Classification
GTD can be classified into the following four types [2]:
- Hydatidiform moles (molar pregnancy)
- Invasive mole
- Choriocarcinoma (a form of malignancy)
- Placental site trophoblastic tumor (rarest form of GTD)
Gestational Trophoblastic Disease FIGO Staging
As per the International Federation of Gynecology and Obstetrics (FIGO), GTD is staged into:
- Stage I: GTD is restricted to the uterus.
- Stage II: GTD spreads beyond the uterus but restricted to the genital structures (vagina, adnexa, broad ligament).
- Stage III: GTD spreads to the lungs with or without involvement of genital tract.
- Stage IV: GTD spreads to all other metastatic areas.
Gestational Trophoblastic Disease Epidemiology
This is a rare disorder, and has a varying global incidence. Cases of hydatidiform moles have a reported incidence ranging from 23-1299 cases in every 100,000 pregnancies. The malignant forms have a much lower incidence, around 2-129 cases for the same number of pregnancies.
Gestational Trophoblastic Disease Symptoms
The signs and symptoms of GTD typically involve:
- Anemia, which can cause fatigue, respiratory shortness and chest pain
- Abnormally enlarged uterus [4]
- Abnormal abdominal swelling
- Vaginal bleeding, during the first trimester of pregnancy
- Excessive vomiting
- Preeclampsia
- Hypertension (High blood pressure), due to impaired blood flow
- Improper fetal movement
Gestational Trophoblastic Disease Etiology
The causes of GTD depend on the type of the disease that one suffers from.
- Molar pregnancies (Hydatidiform mole GTD) arise when one or more sperm cells fertilize an egg without any nucleus or DNA. Fetal tissue may not be produced during two-sperm fertilization. Single-sperm fertilization may produce fetal tissue, but without a viable fetus.
- Invasive moles occur when hydatidiform moles penetrate the muscle layer of uterus.
- Chriocarcinoma (Malignant GTD) has a fast dispersion and often spreads outside the uterus. It can occur from a hydatidiform mole after a pregnancy (full-term or one that has been prematurely terminated).
- Placental site trophoblastic tumor generally occurs after pregnancy, after the placenta gets attached to the uterus.
Gestational Trophoblastic Disease and Genetics
Genetics, or family history, does not appear to play a major role in causing GTD [6]. However, many women in the same family have been found to suffer from the disease.
Gestational Trophoblastic Disease Risk Factors
The risk factors include:
- Being female
- Being <16 years or >35 years of age
- Having a past history of GTD
- Being of Asian origin
- Having parents with ABO blood groups
- Having multiple pregnancy and previous molar pregnancy
Gestational Trophoblastic Disease Diagnosis
Most cases are diagnosed during an elevation or plateau of the serum hCG levels after hydatidiform moles are detected. In case of metastases, symptoms of metastatic disorders may be present. These include:
- Hemoptysis
- Abdominal pain
- Hematuria
- Neurologic symptoms
GTD is usually spotted in routine ultrasound findings during pregnancy. High levels of hCG (human chorionic gonadotropin) in blood during testing can also indicate its presence. A biopsy usually helps confirm the diagnosis.
Gestational Trophoblastic Disease Differential Diagnosis
Doctors should isolate the signs of GTD from those of:
- Brain tumors
- Bladder Cancer
- Biliary Obstruction
- Ovarian choriocarcinoma
- Cerebrovascular accidents
- hCG-secreting germ cell tumors
- Nephrolithiasis
- Noninfectious Hemorrhagic Cystitis
- Quiescent GTN
- Urothelial Tumors of the Renal Pelvis and Ureters
Gestational Trophoblastic Disease WHO Scoring System
As per the WHO scoring system, sufferers of high-risk metastatic GTN are classified into 2 groups:
- With WHO scores less than 7
- With WHO scores > or = 7
Gestational Trophoblastic Disease Treatment
GTD is typically cured by radiation, chemotherapy and surgery. In suspected cases of hydatidiform moles, management can be done by extraction of tumors from the uterus through suction. Most women affected once by GTD are able to have successful pregnancies in the subsequent stages.
In low-risk GTD patients, chemotherapy is initiated. The regimen includes regular administration of Methotrexate and Calcium folinate. In high-risk sufferers, two regimens should be alternated every week. Regimen 1 involves dactinomycin, etoposide, methotrexate and folinic acid while Regimen 2 includes vincristine and cyclophosphamide.
Gestational Trophoblastic Disease Complications
20% sufferers with hydatidiform moles develop malignant conditions, like persistent hydatidiform mole (with or without metastasis). Developmental problems may result from abnormal fetal movement.
The risk of recurrence is around 1 in 100 pregnancies [5]. Women with very high hCG levels are at greater risk of having recurrent GTD.
Gestational Trophoblastic Disease Prognosis
Metastatic Gestational Trophoblastic Tumor (GTT) has a positive outcome in case of no previous chemotherapy or no brain or liver metstases. Outcome is poor for Metastatic GTT in the event of brain or liver metastases and previous use of chemotherapy. Women with high-risk GTN, and requiring multi-agent chemotherapy, may be extremely susceptible to secondary cancers.
Gestational Trophoblastic Disease Pictures
The images show the physical condition of GTD sufferers.
Picture 1 – Gestational Trophoblastic Disease
Picture 2 – Gestational Trophoblastic Disease Image