Complications
Usually asymptomatic. However, exacerbated symptoms of pre-eclampsia (as a result of abnormally high serum human chorionic gonadotrophin [hCG] levels) may be present. Headache, visual disturbances, epigastric pain, breathlessness, seizures, and oliguria are uncommon and suggest severe pre-eclampsia.
A diagnosis is made if there is new-onset, persistent hypertension defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, usually after 20 weeks’ gestation, with new-onset proteinuria (protein:creatinine ratio of ≥30 mg/mmol and albumin:creatinine ratio of ≥8 mg/mmol) or evidence of systemic involvement.[69] The significant elevation of hCG associated with complete hydatidiform moles can result in earlier onset of pre-eclampsia (before 20 weeks’ gestation).
Antihypertensive therapy should be started if systolic BP is persistently between 140 and 159 mmHg and/or diastolic BP is persistently between 90 and 109 mmHg, or if there is severe hypertension (systolic BP ≥160 mmHg and/or diastolic BP ≥110 mmHg).[59][60]
In the US, magnesium sulfate is recommended for all women with severe pre-eclampsia.[59] In other countries, including the UK, a more targeted approach is recommended, allowing the physician to exercise individual judgment based on the woman's specific risk factors (e.g., presence of uncontrolled hypertension or deteriorating maternal condition).[60] Seizures reflect progression to eclampsia, and are both treated and prevented with magnesium sulfate infusions. The US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency recommend that maternal administration of magnesium sulfate should not last longer than 5-7 days during pregnancy due to the risk of skeletal adverse effects, hypercalcaemia, and hypermagnesemia in the neonate.[61][62] Despite the recommendation, magnesium sulfate is usually only used for 24-48 hours in clinical practice.
Management of molar pregnancy with a viable twin generally entails close observation for pre-eclampsia as the pregnancy is carried to either voluntary termination, forced delivery, or term. Definitive treatment of pre-eclampsia consists of delivery. The decision about when and how to deliver should only be made after a thorough assessment of the risk and benefits to the mother and co-existing twin.
There is molecular homology between subunits of thyroid-stimulating hormone and hCG. As a result, serum hCG may stimulate the production of thyroid hormone with the clinical symptoms and signs of thyrotoxicosis.[26][38][39] The higher elevations in serum hCG levels seen in complete molar pregnancies are associated with a greater incidence of severe medical sequelae, including hyperthyroidism. The absence of ophthalmopathy differentiates molar pregnancy from thyrotoxicosis due to Graves' disease.[40]
Women with unevacuated hydatidiform moles generally require stabilisation of associated comorbidities, including hyperthyroidism, before definitive treatment. Thyrotoxicosis in molar pregnancy is typically self-limited and best treated with supportive care. Beta-blockers should be given with the induction of anaesthesia at the time of surgical management, if the woman is clinically hyperthyroid. Carbimazole can be added, if a faster clinical response is needed or there is a thyrotoxic storm.[51]
Women may report earlier and more severe symptoms of pregnancy (as a result of abnormally high serum hCG levels) that include severe nausea and emesis (hyperemesis gravidarum).
The objectives of managing a woman with molar pregnancy complicated by hyperemesis revolve around symptomatic control of emesis with an anti-emetic and/or an H2 antagonist and intravenous hydration with electrolyte replacement, while moving towards prompt removal of the hydatidiform mole. Hyperemesis associated with a molar gestation resolves promptly after surgical management, roughly in parallel with the decline in hCG levels.
Complete hydatidiform mole, because it is accompanied by significantly higher levels of hCG, is more likely to be associated with these symptoms than partial hydatidiform mole.[23][24][25][26]
Anaemia, with symptoms of pallor, dizziness, and fatigue, may result from heavy or persistent vaginal bleeding and the dilutional effects of increased blood volume.
Bleeding can complicate hydatidiform mole as acute haemorrhage before treatment, during surgical management, or as a delayed haemorrhage during follow-up after evacuation of a molar pregnancy. There is a greater risk for serious bleeding at the time of evacuation for MP.
Women with unevacuated hydatidiform moles generally require stabilisation of associated comorbidities, including severe aaemia, before definitive treatment. Women with severe anaemia or haemodynamic instability, require transfusion.
Invasion of hydatidiform mole beyond the normal placentation site (into the myometrium with venous penetration) is followed by persistently elevated serum hCG levels after evacuation of molar pregnancy.[4][34][42]
Persistence is defined as a plateau in hCG levels for four measurements over a period of at least three consecutive weeks (on days 1, 7, 14, and 21) or a rise in hCG levels for three consecutive weekly measurements over a period of at least 2 weeks (on days 1, 7, and 14).[4]
The condition is treated with chemotherapy.[4]
Malignant transformation of molar tissue or a de novo carcinogenesis may evolve from an antecedent normal placenta. Although it is more common after MP, it can occur after any type of pregnancy (e.g., miscarriage, abortion, ectopic pregnancy, or preterm/term gestation).[34]
Histological findings include the presence of both cytotrophoblasts and syncytiotrophoblasts, but chorionic villi are absent (which differentiates the condition from an invasive mole).[4][42]
Dysfunctional vaginal bleeding after any pregnancy that does not respond to conventional therapy may indicate choriocarcinoma.[70]
Elevated hCG levels in this setting are suggestive of this condition. Pathology confirming the presence of choriocarcinoma is diagnostic, although biopsies are not ordinarily indicated because of the risk of haemorrhage.[4] The hormonal biochemical diagnosis is sufficient for the initiation of treatment.[3]
The condition is treated with chemotherapy.[4]
The placental site trophoblastic tumour (PSTT) is a rare type of malignant neoplasia derived from intermediate trophoblastic cells, with low-level production of hCG.[42][71]
These tumours most commonly arise months to years after a term gestation, but can occur after any pregnancy (e.g., a miscarriage, abortion, ectopic pregnancy, or MP).[71] Benign placental site nodules with or without atypical features (PSNs/ASPNs) can co-exist with or develop into PSTTs, but the association with GTN seems stronger for ASPNs.[72]
Women present with abnormal uterine bleeding, a mass in the endometrial cavity, or amenorrhoea.[71]
Serum hCG levels may only be mildly elevated.[71]
The condition is most often treated with surgery (usually hysterectomy) and occasionally with chemotherapy.[4][71] Although PSTTs are not resistant to chemotherapy, they are less sensitive than other types of GTN (e.g., invasive mole and choriocarcinoma).[3]
Epithelioid trophoblastic tumours (ETTs) are rare but can occur after a prior gestation.[42][71]
Most of these malignant tumours occur after a term gestation, but they may arise after any pregnancy (e.g., miscarriage, abortion, ectopic pregnancy, or MP).[71] ETTs arise from the intermediate trophoblast. Benign placental site nodules with or without atypical features (PSNs/ASPNs) can co-exist with or develop into ETTs, but the association with GTN seems stronger for ASPNs.[72]
Vaginal bleeding is the presenting symptom in two-thirds of women; about one third of women present with metastatic disease because normal or only mildly elevated levels of hCG and a lack of symptoms contribute to late diagnosis.[71]
The condition is most often treated with surgery (usually hysterectomy) and occasionally with chemotherapy.[4][71] Although ETTs are not resistant to chemotherapy, they are less sensitive than other types of GTN (e.g., invasive mole and choriocarcinoma).[3]
The incidence of complications after post-molar dilation and evacuation increases with uterine size. One of the most serious of these is post-evacuation respiratory distress syndrome. This may occur as a result of pulmonary embolisation of trophoblastic tissue, as well as a high-output cardiac failure secondary to hyperthyroidism, severe pre-eclampsia, and, less commonly, from anaemia.[50]
This condition is usually self-limiting, and resolves over time after complete evacuation of the MP. It is best treated with supportive care, including mechanical ventilation tailored to minimise barotrauma, central haemodynamic monitoring, and beta-blockade to control sequelae of thyrotoxicosis.
The presence of adhesions and/or fibrosis within the uterine cavity (intrauterine synechiae) due to scars is known as Asherman's syndrome and may form after dilation and evacuation (D&E). This risk is increased after sharp curettage.[73] However, the exact influence of hydatidiform mole itself on the appearance of intrauterine synechiae is unknown because they can occur even if molar evacuation is performed exclusively by suction evacuation and sharp curettage is not used.[53]
Asherman's syndrome may result in infertility, repeated miscarriages, pain from trapped blood, and future obstetric complications, although it can be successfully diagnosed and treated with hysteroscopy.[74]
Women with an established diagnosis of GTN should be evaluated with a pelvic examination and chest x-ray, as vaginal and lung metastases are the most common sites of metastatic disease.[3] If the chest x-ray is inconclusive, if there are metastases ≥1 cm, or the woman has a signs or symptoms of metastatic disease, computed tomography scans of the chest, abdomen, and pelvis should be performed and magnetic resonance imaging of the brain should be obtained to further evaluate and stage metastases.[3][4]
Management is determined by tumour stage and risk classification: low-risk GTN can be treated with single-agent chemotherapy, whereas high-risk GTN or recurrent disease is treated with multiple agent chemotherapy regimens.[4]
Surgery can be incorporated into primary management of women with low-risk disease who desire hysterectomy, as well as resection of isolated brain metastasis, or to resect isolated lesions in women with chemorefractory disease.[4][42] Radiation is occasionally used to treat high-risk brain metastases.[4]
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