What Is Molar Pregnancy?

Overview

Molar pregnancies are a type of gestational trophoblastic disease (GTD), a pregnancy-related condition where the pregnancy does not develop normally and is characterised by the abnormal proliferation of the supporting pregnancy tissue called the trophoblastic tissue and swollen chorionic villi (finger-like projections from the placenta).¹ Molar pregnancies can be categorised into partial and complete hydatidiform moles, both of which differ in parental chromosome composition and whether or not a viable foetus is present. 

The abnormal growth process and the subsequent hormonal dysregulation mean that molar pregnancies are always non-viable. There is no single causative factor behind molar pregnancies however, it is a consequence of altered genetic expression and hormonal imbalances. There are certain risk factors associated with molar pregnancies, such as maternal age, ethnicity and a history of trophoblastic disease.

Treatment of molar pregnancies usually involves surgical procedures that can be undertaken to remove the non-viable tissue whilst still preserving the fertility of patients and their ability to sustain future pregnancies.

What is a molar pregnancy?

Gestational Trophoblastic Disease (GTD) is the name given to a rare group of tumours which can form during the early stages of abnormal pregnancies. During a normal pregnancy, a newly fertilised egg will be surrounded by a layer of cells called trophoblast. The trophoblast has two main functions:

1. Enables the egg to implant itself into the uterine wall.
2. Forms a large part of the placental tissue.

During  GTD, abnormal changes/ growth of the trophoblast layer induces tumour formation. Though the majority are benign (noncancerous), they can potentially become malignant (cancerous). 

Molar pregnancies are the most common type of GTD and are caused by hydatidiform moles. Hydatidiform comes from the Greek words ‘hydatisia’-drop of water, and ‘mola’-false conception.⁸ There are two types of molar pregnancies:

Partial molar pregnancy

Occurs when an egg containing half the maternal DNA is fertilised by two sperms. Though both maternal and paternal DNA is present, the abnormal total chromosome number leads to the formation of a hydatidiform mole. The foetus partially develops but is not able to become a viable foetus .⁷

Complete molar pregnancy

This is the most common form of molar pregnancy and occurs when an egg, which contains no maternal DNA, is fertilised by two sperms. Loss of the maternal DNA and gain of only paternal DNA results in an abnormal gene expression which results in abnormal trophoblast development, before there is differentiation into embryonic tissue. A foetus therefore does not form. Complete moles account for the majority of hydatidiform moles.³ 

Hydatidiform moles are characterised by overgrown trophoblast with swollen villi. Microscopically, they have a marked morphology of chorionic villi containing stromal fluid and an immature vascular network.² 

Causes of molar pregnancy

Genetic factors

The recurrence of molar pregnancies within the same patients indicates that some patients with molar pregnancies may have a genetic predisposition. Particular focus has been paid to the ‘NLRP7’ gene, which is mutated in 48-80% of patients with at least two hydatidiform moles.⁵ Its maladaptive response plays a role in downregulating maternal inflammation, promoting cellular proliferation and differentiation of trophoblastic tissue. The ‘KHDC3L’ gene is the second recessive gene responsible for recurrent hydatidiform moles.

Hormonal imbalances

Hormonal imbalances, particularly involving the hormone hCG (human chorionic gonadotropin), play a crucial role in the development of molar pregnancies. HCG is the hormone produced by the developing placenta during pregnancy, and in a normal pregnancy, hCG levels rise steadily and peak around the end of the first trimester before declining. However, in molar pregnancies, there is an overproduction of hCG, leading to significantly higher levels than in a typical pregnancy. This hormonal imbalance can be caused by various factors, including:

1. Genetic abnormalities–Molar pregnancies usually occur due to genetic errors during fertilisation, resulting in an abnormal placenta and as a result an abnormal hCG production.
2. Abnormal foetal development–In partial molar pregnancies, some foetal tissue may be present, but it is nonviable. The imbalance in hormonal signalling between the foetus and the placenta contributes to the growth of abnormal tissue.
3. Hormonal regulation issues–There might be issues with the body's ability to regulate hCG production, leading to excessive secretion by the placental tissue.

Risk factors 

Some of the most common risk factors for molar pregnancies include:

Maternal age 

Compared to average-age women, adolescents were 7 times as likely to develop complete molar pregnancies, and women with advanced maternal age (>35) were twice as likely.⁷

Ethnicity 

Hydatidiform molar pregnancies occur in about 1 in every 600 pregnancies in Western countries but at higher rates in the Middle East, Latin America, Africa and the Far East.⁵ It is important to note, however, this is not necessarily due to biological differences but rather the lifestyle and socioeconomic differences between the regions. 

History of trophoblastic disease 

Trophoblastic disease encompasses a group of diseases which cause abnormal proliferation of the trophoblast tissue. Having a history of trophoblast disease could be considered a risk factor for molar pregnancies due to the following reasons:

• Genetic predisposition–As mentioned above, abnormal proliferation finds its roots in abnormal gene expression. Some individuals may have a genetic predisposition to trophoblastic diseases. If there is a history of trophoblastic disease in a person's family or previous pregnancies, it may increase their susceptibility to experiencing a molar pregnancy in a subsequent pregnancy.
• Residual trophoblastic tissue– In certain cases of trophoblastic disease, especially when the moles become malignant or are invasive, the abnormal trophoblastic tissue can persist and continue to grow even after the initial treatment. If not adequately removed or treated, this residual trophoblastic tissue can give rise to a molar pregnancy in future pregnancies.
• Hormonal imbalances–The dysregulation of the hCG hormone is common in other trophoblastic diseases as well as molar pregnancies. This hormonal imbalance may create an environment conducive to the development of molar pregnancies

It is important to note however whilst the risk of repeat molar pregnancies is about 1 in 60, over 98% of women who become pregnant following a molar conception will not have a further hydatidiform mole.⁶

Signs and symptoms

Symptoms of Molar pregnancies/hydatidiform moles include:

1. Vaginal bleeding –Due to molar tissues separating from the decidua resulting in bleeding
2. Severe morning sickness –Due to high levels of hCG hormones circulating in the bloodstream.
3. Stomach cramps.
4. High blood pressure.
5. Severe respiratory distress –This is only observed in very severe cases when there is trophoblastic tissue in the lungs causing an embolism.

Diagnosis of molar pregnancy

In a pregnant woman with vaginal bleeding, the following steps may be taken to make a diagnosis of molar pregnancy:

1. Blood tests and hCG monitoring–A serum of hCG level and the patient’s blood type should be obtained.⁴ Complete moles have high serum hCG, greater than 100,000, whereas partial moles may be within the normal range for gestational age or slightly lower.³
2. Pelvic ultrasound – In complete molar pregnancies, a heterogeneous mass in the uterine cavity is found. There are cystic spaces of the villi, the absence of an embryo and no amniotic fluid. In a partial mole, this is a foetus with some amniotic fluid; however, the placenta has enlarged cystic spaces. If a molar pregnancy is suspected, then a CT/PET scan will be undertaken to determine the stage of the disease.
3. Medical history– Understanding a person’s medical history, whether or not they have a familial history of molar pregnancies or trophoblastic disease, though not deterministic as a diagnosis tool, can help to inform the diagnosis.

Treatment options

Surgical procedures

A molar pregnancy will never be able to survive, so the treatment options are based around the removal of the abnormal tissue. The type of procedure which is used can be differential based on the individual’s fertility plans/desires.

• Suction curettage – This procedure is preferred in patients who desire to preserve fertility. A tube that is attached to a suction device is inserted into the uterus and sucks out the pregnancy tissue.
• Total abdominal hysterectomy – Undertaken by patients who do not wish to preserve their fertility.³ In this procedure, the uterus and cervix are completely removed, reducing the subsequent risk of persistent trophoblastic disease by up to 50%.

Follow-up

This is to confirm a successful treatment or to identify women with persistent/malignant GTD. In very rare cases metastasis post-surgery can occur in which case chemotherapy will be required.

Chemotherapy

Complete molar pregnancies have the potential for local spread. After suction curettage, local uterine invasion occurs in about 15% of patients and metastases to other regions of the body in 4% of cases.³ Unfortunately, there are no clinical or pathologic features for predicting persistence after molar pregnancy. Several appropriate and case-dependent chemotherapy regimes are used to treat the disease.

Genetic counselling/family planning

For individuals who are aware of a familial history of gestational trophoblastic diseases or molar pregnancies, genetic counselling may be a good way to determine their own genetic predisposition and risk factors when wanting to start a family. 

Summary

Molar pregnancies can be distinguished between complete and partial moles, both of which lead to abnormal trophoblast tissue proliferation, which ultimately ends in non-viable pregnancies. The symptoms of molar pregnancies most commonly include vaginal bleeding and nausea. Consequential diagnosis of molar pregnancies is followed by analysis of serum hCG levels, blood tests, and pelvic ultrasounds. 

The heterogeneous clinical manifestations of molar pregnancies mean that a range of treatment options are available; from suction curettages which preserve fertility, to total abdominal hysterectomies to more advanced treatments such as chemotherapy in rare cases where moles become malignant and metastatic.