Introduction

Molar pregnancy is a rare complication of pregnancy resulting from problems during fertilisation. This results in abnormal growth of the cells in the developing placenta. It is also called hydatidiform mole. It is part of a group of related tumours called Gestational Trophoblastic Disease (GTD). Other diseases in the spectrum include invasive mole, placental site trophoblastic tumour and choriocarcinoma.

Molar pregnancy is a benign (non-cancerous) condition. However it may persist and develop into a cancerous condition. It is diagnosed by taking patient's history, physical examination and findings from imaging and laboratory tests. It consists of two types, the complete and partial mole and the type determines the course of the disease. It is treatable by a simple surgical procedure and treatment is complemented by a period of follow-up. When promptly and effectively managed, it has no negative effect on future pregnancies. 

How molar pregnancy develops

Molar pregnancy results from abnormal fertilisation. This results in abnormal cells presenting as clusters of water-filled sacs (grape-like sacs) in the womb.^1,2

The normal human cell contains 46 chromosomes (thread-like part of the cell that contains genetic material), with 23 derived from each parent. This can either be 46XX, if female and 46XY if male. In a molar pregnancy, this arrangement is altered.

In molar pregnancy, there are two different types, the complete mole and the partial mole. The complete mole results from the fertilisation of an empty egg by either two sperm or a single sperm that duplicates itself. The embryo has 46 chromosomes and the entire genetic material is from the father.³

In partial mole, there is the fertilisation of a normal ovum by a single sperm that later duplicates or by two sperm. The resultant embryo has 69 chromosomes. Because it contains genetic material from both parents, a fetus(unborn baby) may be present in association with the molar tissue.⁴

The course of the diseases is determined by the type of molar pregnancy; the risk of persistence is higher in complete moles (20-30%) than in partial moles (<5%).

The molar tissues elaborate a high level of Human Chorionic Gonadotropin (HCG) hormone, and the analysis of this hormone is very critical in the diagnosis and follow-up of patients.⁵

Risk factors for molar pregnancy

There are no known causative factors but some conditions are known to increase the risk. These include:^1.2.3

• Native of an Asian region
• Maternal age less than 20 or greater than 40
• Women with previous molar pregnancies
• People with a deficiency of folic acid, protein and carotene
• Women who have never given birth
• Women with blood A impregnated by men with blood group O

Clinical Presentation and Diagnosis of molar pregnancy

The diagnosis of molar pregnancy is made by the assessment of the:

• Patient's history
• Physical examination
• Investigation findings

The typical presentation described here is no longer common because of the increased availability of ultrasound which has enabled the diagnosis of molar pregnancies at early gestational ages.⁶

History

The patients will usually report a few months of absence of menses with a positive pregnancy test, in addition to:

• Vaginal bleeding: this may be associated with the passage of grape-like tissues (vesicles)
• Exaggerated nausea and vomiting

Uncommon forms of presentation include:

• Features of hyperthyroidism: This is because the HCG has a similar structure to the thyroid hormone and can produce a thyroid hormone-like effect
• Difficulty breathing because it has spread to the lungs
• Anaemia

Physical examination

Some of the findings on examination include:

• Paleness due to excessive loss of blood
• Uterine (womb) size greater than the age of the pregnancy
• The uterus feels doughy (resembling the consistency of dough) on palpation
• Pre-eclampsia (elevated blood pressure with protein in the urine) in the first trimester (this is an uncommon finding in normal pregnancies)
• Tachycardia (increased heart rate)
• Warm extremities 
• Tremors due to hyperthyroidism

Investigation findings

The suspicion of molar pregnancy from history and examination is confirmed by investigation findings.

The principal marker of molar pregnancies is their ability to elaborate high levels of HCG, one of the hormones of pregnancy. The levels of HCG can be up to hundreds or thousands, especially in complete moles. This hormone can be detected in the urine or blood as well as in normal pregnancies. To confirm the diagnosis, the exact levels of this hormone in the blood are assessed. The levels of the hormone correspond to the quantity of tumour cells available. Therefore,  it is a useful marker for the diagnosis of the disease. It also aids in the monitoring of the progression of the disease.⁶

The confirmation of  the diagnosis would require:

• Detection of excessively high levels of HCG in the blood compared to a normal pregnancy
• ‘Snowstorm’ appearance on pelvic ultrasound. This is due to the presence of vesicles. There may be the presence of a fetus(unborn baby) in partial moles, in addition to the vesicles. Because of the presence of fetal parts, Partial mole is more difficult to diagnose^7,8

The presence of ovarian cysts can be on both ovaries. These are called Theca lutein cysts and results from overstimulation of the ovaries by the HCG.

Because molar pregnancy is part of the spectrum that may include other diseases, therefore further tests need to be done to rule out the presence of other types of tumours. They include:

• Complete blood count
• Blood group
• Kidney function test
• Liver function test
• Thyroid function test: if there are symptoms of hyperthyroidism
• Clotting profile: molar pregnancy could cause abnormalities in blood clotting
• Chest X-rays: spread to the lungs can be seen as ‘canon ball’ (round whitish) lesions in the lungs
• Higher forms of imaging like Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan if spread is suspected

Treatment and follow-up of molar pregnancy

Treatment

Suction evacuation

If you have a molar pregnancy, it will be good for you to be managed by a specialist. The major form of treatment of molar pregnancy is through the evacuation of the products of conception. This is done under anaesthesia through a procedure called ‘suction curettage’. In this procedure, the surgeon uses a tube connected to a machine to suck out the molar tissue from the womb.⁹ The tissue removed from you would be sent to the laboratory to further establish the diagnosis. It will also help to exclude the diagnosis of other severe forms of gestational trophoblastic disease.

Hysterectomy

If you have completed childbearing or you are more than 40, hysterectomy (removal of the womb) may be the preferred management option.¹⁰ Emergency hysterectomy may also be done if there is excessive bleeding during the process of evacuation.

Prophylactic chemotherapy

There is emerging evidence that prophylactic administration of chemotherapeutic drugs like methotrexate or actinomycin D at the time of procedure or immediately after molar evacuation, is associated with a reduction in the incidence of transformation to cancer by 3%–8%.⁶ This practice is reserved for cases at high risk of persistence, like complete moles.

Follow-up

Irrespective of the mode of treatment, surveillance for the progression of the disease is needed. The goal of follow-up is to confirm successful treatment and identify those with persistent GTD.⁷ Your healthcare provider will have a follow-up plan to evaluate the levels of βHCG in your blood.⁹ This follow-up is usually between 6 months to a year. During the time of follow-up, you are to be on a temporary method of contraception. This is because the presence of a new pregnancy may cause an increase in HCG levels and this may lead to confusion in monitoring.

Decreasing levels up to normal indicates the resolution of the disease. If the levels plateau or increase, it signifies persistent GTD. This would require further evaluation and treatment with chemotherapy with or without further surgical therapy. 

Various HCG criteria have been used to diagnose chronic gestational trophoblastic disease. Recently, the International Federation of Gynecologists and Obstetricians (FIGO) published the following HCG criteria for the diagnosis of persistent gestational trophoblastic disease:

• An HCG level plateau of four values ±10% is recorded over a 3-week duration (days 1, 7, 14, and 21)
• An HCG level increase of more than 10% of three values is recorded over a 2-week duration (days 1, 7, and 14)
• If HCG is still detectable for more than six months after molar evacuation

Prognosis of the disease

Molar pregnancy does not usually result in complications if treated early and well. However, on occasion, there may be complications like:

• Persistence as a cancerous lesion (invasive mole and choriocarcinoma)
• Excessive bleeding leading to shock
• Clotting abnormalities
• Infection (if not evacuated on time)
• Emotional and psychological trauma

Summary

Though molar pregnancy is usually benign, it can lead to a cancerous condition. As a result, detecting and treating molar pregnancy early is more effective. The follow-up period is key, thus ensuring compliance is very essential.

FAQs

When should I get pregnant after a molar pregnancy?

You can only start trying for a pregnancy after your follow-up period.

How do I ensure that I do not get pregnant during follow-up?

To avoid pregnancy, you will need to use any effective temporary method of contraception like hormonal contraception. Avoid  Intrauterine contraceptives because of the increased risk of perforation.

What is my risk of having another molar pregnancy?

The risk of recurrence in a later pregnancy is low (0.6%–2%) after one molar pregnancy, although the risk increases after consecutive molar pregnancies.