Gestational Trophoblastic Disease molar pregnancy

How a normal pregnancy develops

Once ovulation occurs, the ovum (egg) is fertilized by the sperm in the fallopian tube and begins to divide forming an embryo. The embryo moves into the womb where it attaches to the lining of the uterus, the endometrium. The part of the fertilized egg that forms the placenta is called the trophoblast, which invades the lining of the womb to anchor the pregnancy and allow it to grow. This is called implantation. The placenta forms and so does the embryo. The placenta produces the pregnancy hormone, human chorionic gonadotropin (hCG).

Gestational trophoblastic disease, often termed “GTD” is the name given to some rare tumours arising from the placental tissues. There are different types of GTD. They are usually diagnosed early and the most common is called a hydatidiform mole or “molar pregnancy”. There are two types of molar pregnancies, termed “complete” and “partial” moles. Typically, molar pregnancies can be managed conservatively following evacuation of the uterine contents (with a dilatation and curettage, or D&C) and most women go on to have normal pregnancies subsequently.

Sometimes the abnormal placental tissue persists. These cases of “persistent” GTD are often referred to as gestational trophoblastic neoplasia or “GTN”. In those rare cases, management by doctors and nurses with special expertise is required but, even in this situation, most patients can be effectively treated and cured of their disease.

What causes molar pregnancies?

Although some studies have linked molar pregnancy with dietary or genetic factors, the real cause of molar pregnancy is still unknown. As compared to a normal pregnancy, where two sets of genes are inherited from the mother and the father and result in a potentially viable foetus, in a complete molar pregnancy the genetic material is inherited solely from the father. The original nucleus containing the mother’s genetic material is lost at the time of conception. As a result, complete molar pregnancies form a mass of rapidly growing cells but do not contain a foetus and cannot develop into a baby.

In a partial molar pregnancy there is typically genetic material from both the father and the mother, but there is an imbalance as there are two sets from the father. In a partial molar pregnancy there may be a foetus visible on an early ultrasound, but it is always abnormal and does not survive beyond the first 3 months of the pregnancy. After the evacuation, most partial molar pregnancies do not require any additional treatment.

Who is at risk of developing a molar pregnancy?

Molar pregnancies appear to be more common at the beginning and end of the reproductive age group. Compared to women aged between 20 and 40 the risk for girls under 15 who become pregnant is approximately 1.5 times higher and for women aged over 45 the risk is 20-50 times higher than for younger women. The other groups who are at higher risk of having a molar pregnancy are women who have had one before. Here the risk is about 5 times higher than normal which works out as about a 1 in 100 chance of having a second molar pregnancy. Some studies also suggest that some ethnic groups, such as Asian women, are at higher risk than non-Asian women.

How common are molar pregnancies?

Accurate numbers are very hard to come by. Most studies have reported a range from 1 in 500 to 1 in 2000.

What is hCG and how is it measured?

In cases of molar pregnancy and the other forms of trophoblastic disease the hCG level is important for making the diagnosis and for monitoring treatment. The abbreviation hCG is short for human Chorionic Gonadotrophin, the pregnancy test hormone that is detected in home pregnancy tests. In pregnancy (normal and molar) when the egg is fertilized it starts to make hCG and then as the pregnancy develops the trophoblastic/ placental cells take over making hCG. After a molar pregnancy the level of the hCG gives an accurate measure of the number of abnormal cells left and a plateauing or rising hCG level after the evacuation is a pointer that further treatment is likely to be needed.

What are the symptoms of a molar pregnancy?

Most of the symptoms of a molar pregnancy are caused by the excessive amount of hCG produced by the overgrown trophoblast. The most common symptoms include irregular bleeding from the vagina with symptoms like those of a miscarriage. The blood may contain small fluid-filled cysts. Some women describe an absence of menses like a normal pregnancy. Severe nausea and vomiting can also occur. If left untreated or diagnosed late, a molar pregnancy can cause other problems but these rarely occur nowadays given that these are generally diagnosed and treated early.

Why is it important that the diagnosis of a molar pregnancy is correctly made?

The main concern following a molar pregnancy is that there is the risk of developing persistent trophoblastic disease which may need further treatment, most commonly chemotherapy. Overall the risk of needing treatment is about 1 in 10 after a complete mole and 1 in 100 after a partial molar pregnancy. Apart from careful follow-up, there is no accurate way of predicting which women will require treatment and which will not, emphasizing the importance of careful follow-up.

Is molar pregnancy a type of cancer?

If you have had a molar pregnancy, in the majority of cases you will need no further treatment beyond a curettage. A molar pregnancy on its own is not a form of cancer. For approximately 10-15% of patients who have had a complete molar pregnancy and 1% of partial mole patients the situation is different. We refer to these patients as having persistent trophoblastic disease or gestational trophoblastic neoplasia (GTN). This new situation can be considered a type of cancer. However, this type of cancer is completely different from the normal types of cancer and the cure rate for patients is over 80-90% even in the presence of metastatic disease.

How is a molar pregnancy diagnosed and treated?

The diagnosis of a molar pregnancy is most commonly suspected after an ultrasound is performed which shows an abnormality. Typically, a complete molar pregnancy shows a mass of cells without the presence of a foetus and a partial mole shows a non-viable foetus and placenta. After the ultrasound, you will undergo a dilatation and curettage (D&C), where the placental tissue will be removed from your uterus. This is a minor operation that is often carried out after miscarriages and involves a suction instrument being passed through the neck of the womb (cervix) while you are asleep under a general anaesthetic. The tissue removed will be sent to the laboratory for examination. In other cases when a miscarriage is diagnosed or a termination is performed for some other reason, the tissue is sent to the laboratory and may demonstrate that a molar pregnancy has occurred even when it was not suspected.

It is important to understand that this procedure is not a ‘termination of pregnancy’ or ‘abortion’. It is common to feel sad at the loss of your pregnancy, but in most cases there never was an embryo. Even in the case of a partial mole where an embryo is sometimes present, it would never develop normally. Furthermore, not undergoing this procedure could place you at increased risk

How is the decision made on who needs further treatment after the evacuation?

After the D&C you will require a weekly hCG test and assessment by your doctor until normal levels have been obtained. The results from your blood test are measured in IU/L (International Units of hCG/Litre). The ‘normal’ serum level is less than 5 IU/L. In most patients no further treatment is needed after the evacuation and the hCG level will fall back to normal and stay there. The normal fall in hCG levels after the evacuation of a molar pregnancy is shown below. The duration of monitoring varies depending on the type of molar pregnancy and when the hCG levels reach normal.

GTDcurve

If the hCG level falls satisfactorily, how will I be followed up?

Women who were diagnosed with a complete mole will have an hCG drawn monthly for at least six months. If the hCG level returns to normal (i.e. < 5) within 56 days of the evacuation then the monitoring continues for a total of 6 months from the day of the evacuation. In those patients where the hCG level takes more than 56 days to get to normal the monitoring continues for 6 months from the date of the first normal sample. For partial hydatidiform mole patients, follow is with blood tests every two weeks until hCG levels are normal. Follow-up is completed once three weekly hCG levels are reported as normal. In both situations it is advised that a further pregnancy is deferred until the end of the follow-up period, as a new pregnancy may mask any evidence of disease relapse.

How soon may I try to become pregnant again after a molar pregnancy?

For women who do not require additional treatment beyond uterine evacuation, it is recommended that you do not become pregnant until you have completed follow up. This means at least 6 months if you have had a complete mole. Patients who have had a partial moles are followed for shorter periods of time given that they very rarely persist or become malignant.

Why do I need to follow my hCG levels if everything is normal?

Follow-up is necessary so that we can be certain that any rise in your hCG is due to your pregnancy and not any remaining mole cells starting to grow again. The hCG produced during a normal pregnancy is similar to that produced during a molar pregnancy and there is no way to distinguish one from the other. For this reason it is recommended that you use a reliable method of contraception. The preferred method of contraception is the oral contraceptive pill. Given the risk of uterine perforation, the intra-uterine device is not recommended.

Do I need to be followed more closely if I become pregnant again?

Yes. Once you become pregnant it is recommended that you have an early ultrasound scan at about 8 weeks to confirm that your pregnancy is progressing normally. In addition, at the completion of that pregnancy, whether it ends in a miscarriage or a live-born baby, your obstetrician or midwife should check the placenta and measure your hCG level about 6 weeks after delivery.

If the hCG level does not fall what treatment will I require?

In about 10% of patients who have had a complete molar pregnancy and 1% of patients with partial molar pregnancies, extra treatment is needed. The decision to start additional treatment is generally made on the pattern of the hCG levels following the evacuation. To date, there is no definitive way, apart from careful follow-up, to determine who will require additional treatment. Additional treatment may involve chemotherapy, either a single drug or a combination of drugs, to destroy the remaining molar cells. Treatment is very effective and will not affect your ability to have more children. Another potential option to treat a molar pregnancy confined to the uterus may be performing a hysterectomy. Prior to the introduction of chemotherapy treatment this was the only treatment available and can be curative in many cases. It is important to note that even after a hysterectomy a number of women will need chemotherapy treatment in addition to the surgery, highlighting the importance of follow-up. We rarely recommend hysterectomy as the main treatment after a molar pregnancy. However some women may feel that hysterectomy is the right treatment for them due to their age, family plans being completed or other pre-existing gynaecological problems. In these cases we would recommend that patients are thoroughly counseled prior to undergoing surgery.

What are the other types of trophoblastic diseases?

Invasive Mole

In a normal pregnancy the trophoblast invades into and through the lining of the womb. This is necessary to make the placenta and hold it in the womb. Sometimes the trophoblast of a molar pregnancy invades much more deeply into the womb than it should. Rarely it can spread outside. Partial and complete moles are described as precancerous tissue but doctors sometimes disagree as to whether an invasive mole is cancer. What is important is that all molar pregnancies are recognised and managed properly.

Choriocarcinoma

In this very rare cancer, the trophoblast cells become totally disorganised and can invade and spread. Some choriocarcinomas follow a molar pregnancy but it can follow a normal pregnancy, ectopic pregnancy, miscarriage or termination of pregnancy. Choriocarcinomas are highly malignant cancers and need prompt diagnosis and treatment. The illness can become apparent occasionally during the last few weeks of pregnancy, but more commonly in the first few months after delivery. The most frequent problems are persistent bleeding or problems from the disease spreading or metastasizing. The illness can sometimes take a while to diagnose as it can mimic other diseases. The treatment for choriocarcinoma is generally with combination chemotherapy. Fortunately choriocarcinoma is a highly sensitive to chemotherapy, with a very high expectation of cure if diagnosed early.

Placental Site Trophoblast Tumour (PSTT)

Placental site trophoblastic tumour is a very rare diagnosis. This is also a form of cancer that arises after a pregnancy and is generally diagnosed months or years after the pregnancy. The most common symptoms are either abnormal bleeding or the periods stopping altogether. PSTT is also a highly curable illness, although the treatment can be more complicated than the other forms of GTT. All patients with PSTT should be seen and assessed and their individualised treatment worked out.

What happens in chemotherapy treatment?

Chemotherapy is drug treatment, which is used to kill the trophoblastic cells that are still trying to grow. The type of chemotherapy needed will depend upon the hCG hormone level at the time of treatment and the results of other tests. The majority of patients who need treatment after a documented molar pregnancy fall into the low risk treatment group and will receive treatment with a combination of drugs called methotrexate and folinic acid.

Overall, this treatment is relatively mild and it doesn’t cause hair loss or sickness. The side effects that can occur with methotrexate chemotherapy are generally quite mild, but can include sore eyes, mouth ulcers and occasionally abdominal or chest discomfort. The best way to minimise the chance of getting side effects or to minimise their severity is to take lots of fluids during treatment and to take the folinic acid tablets on time.

How long does treatment with chemotherapy last?

For patients that need treatment after the evacuation of a molar pregnancy the chemotherapy treatment usually continues for about 3 to 5 months. The exact duration of treatment is determined by the fall in hCG level. Our general policy is to continue treatment until the hCG has reached normal and then to have a further 3 cycles (i.e. six weeks) of treatment after this.

What happens after the chemotherapy treatment is competed?

Once a patient is in remission, meaning the hCG level has returned to normal, it is most likely that you have been cured; however, there is a 1-3% chance that it may flare up again. Normal life can be restarted and further hospital follow-up is not usually required. We suggest that any future pregnancy is deferred for a minimum of 12 months and to avoid excess sun exposure as it can produce patchy pigmentation in the skin.

Will my fertility be affected?

For most women, a molar pregnancy does not affect your fertility. Most women go on to have normal pregnancies and healthy babies following a molar pregnancy. Even women who receive chemotherapy are able to conceive successfully after a period of close observation.

Will I have another molar pregnancy?

It is possible but very unlikely. The odds of a repeat molar pregnancy are about 1 in 100. The risk increases further if a woman develops a second molar pregnancy. Recent data indicates that in rare cases, women may have a hereditary predisposition to recurrent molar pregnancies, but most women will have a perfectly normal pregnancy after a molar pregnancy.

Is it normal for me to feel upset?

The experience of a hydatidiform mole can be very distressing. This may mean a period of anxiety or may make you feel that you are in limbo as you cannot move on after the pregnancy and have to delay trying again. You may feel that your family and friends don’t understand what you are going through and this can make you feel quite isolated. If you are experiencing this, we encourage you to discuss this with our medical team in order to identify ways in which this anxiety or stress can be best managed.

The ovum (egg) is fertilised by the sperm in the fallopian tube and a couple of days later the fertilised egg moves to the womb where it attaches to the inner wall. The part of the fertilised egg that forms the placenta is called the trophoblast. The trophoblast invades into the lining of the womb to anchor the pregnancy and allow it to grow. This is called implantation. The placenta forms and so does the embryo. It is the placenta which produces the pregnancy hormone – human chorionic gonadotrophin (hCG) which is responsible for the symptoms of pregnancy.

What is a Hydatidiform Mole?

In a hydatidiform mole pregnancy, the baby does not develop and only the placenta forms. This placenta is abnormal, larger and contains many cysts (sacs of fluid). The name stems from the Greek hydatis, meaning droplet, thus the term hydatidiform. These structures appear to burrow into the wall of the womb, thus the term mole. Hydatidiform mole occurs in approximately one in 1,500 pregnancies.

There are two types of molar pregnancy, a complete and a partial hydatidiform mole. Occasionally the mole tissue persists and may start to grow and spread; this is an invasive mole. Choriocarcinoma is a very rare complication of hydatidiform mole.

Complete Mole

Generally when the egg and sperm fuse genetic material is shared. Sometimes the egg does not carry any genetic material (empty) so that when fertilisation occurs no sharing takes place. Usually the fertilised egg dies at this point but occasionally it goes on to implant in the womb. When it does, no embryo grows, only the trophoblast, and it grows in a disorganised way. This produces a complete hydatidiform mole.

Partial Mole

In this situation the egg is fertilised by two sperm. There is too much genetic material and as a result the pregnancy develops abnormally, with the placenta outgrowing the baby. A foetus may or may not be present and even if it is present it does not develop properly.

Invasive Mole

In a normal pregnancy the trophoblast invades into and through the lining of the womb. This is necessary to make the placenta and hold it in the womb. Sometimes the trophoblast of a molar pregnancy invades much more deeply into the womb than it should. Rarely it can spread outside. Partial and complete moles are described as precancerous tissue but doctors sometimes disagree as to whether an invasive mole is cancer. Equally unless a pathology specimen includes a section of the womb lining, the diagnosis of invasive mole cannot always be made. What is important is that all molar pregnancies are recognised and managed properly.

Choriocarcinoma

In this very rare tumour the trophoblast cells become totally disorganised and can invade and spread. Some choriocarcinomas follow a molar pregnancy but it can follow a normal pregnancy, ectopic pregnancy, miscarriage or termination of pregnancy. Choriocarcinomas are highly malignant tumours and need prompt diagnosis and treatment.

How do I feel if I am carrying a molar pregnancy?

One of the functions of hCG is to make the ovary produce hormones which allow the pregnancy to develop. Most of the symptoms of a molar pregnancy are caused by the excessive amount of hCG produced by the overgrown trophoblast.

Symptoms include:

  • No periods
  • Severe nausea and vomiting
  • Irregular bleeding from the vagina. The blood may contain small fluid-filled cysts.
  • Symptoms like those of a miscarriage between 8 and 16 weeks.
  • The womb is often larger than is expected from dates and sometimes the hCG causes the ovaries to be enlarged.
  • In very rare cases a mole can cause a serious condition called pre-eclampsia. Women with this condition will have high blood pressure and protein in the urine

How is a molar pregnancy diagnosed and treated?

After a molar pregnancy has been diagnosed by ultrasound, you will undergo a dilatation and curettage (D&C), where the placenta will be removed from your uterus. This is a minor operation that is often carried out after miscarriages and involves a suction instrument being passed through the neck of the womb (cervix) while you are asleep under a general anaesthetic. The tissue removed will be sent to the laboratory for examination.

It is important to understand that this is not a ‘termination of pregnancy’ or ‘abortion’. In most cases there was never an embryo and even in the case of a partial mole it would not develop. You may well still feel sad at the loss of your pregnancy.

This operation is normally all that is required as treatment for a hydatidiform mole. To ensure no molar tissue remains hCG levels are monitored until they reach the normal range.

In a small number of women who have a molar pregnancy it continues to grow despite the D&C. This is easily detected by the hCG levels which stop falling and either stay the same or rise. Further treatment will then be required.

If the hCG level does not fall what treatment will I require?

Additional treatment involves chemotherapy. You will be given a drug or combination of drugs to destroy the remaining molar cells. Treatment is very effective and will not affect your ability to have more children.

If the hCG level falls satisfactorily, how will I be followed up?

After the D&C you will require a weekly hCG test and assessment by your doctor until three normal levels have been obtained. The results from your blood test are measured in IU/L (International Units of hCG/Litre). The ‘normal’ serum level is less than 5 IU/L. Women who were diagnosed with a partial mole will then be reviewed monthly for at least six months. Women diagnosed with a complete molar pregnancy will require monthly assessment for one year. In selected patients who are at low risk of developing persistent disease this period of follow-up may be shortened to 6 months if the serum hCG returns to normal within 8 weeks of a curettage. This is based on recent research which noted a very low risk of recurrent disease in these patients. A copy of the graph used by your doctor to follow the hCG level is included at the end of this booklet.

How soon may I try to become pregnant again?

It is recommended that you do not try to become pregnant until you have completed follow up. This means at least 6 months if you have had a partial mole and 12 months if you have had a complete mole. This is so that we can be certain that any rise in your hCG is due to your pregnancy and not any remaining mole cells starting to grow again. For this reason it is recommended that you use a reliable method of contraception immediately as your periods may take some time to return. The preferred method of contraception is hormonal such as the oral contraceptive pill. Once you become pregnant it is recommended that you have an early ultrasound scan at about 8 weeks to confirm that your pregnancy is progressing normally. At the completion of that pregnancy, whether it ends in a miscarriage or a baby, your obstetrician should check the placenta and measure your hCG level after delivery.

Will my fertility be affected?

A molar pregnancy does not affect your fertility at all. Many women go on to have babies following a molar pregnancy. For those patients who have chemotherapy, fertility may be affected by the use of the drugs.

Will I have another hydatidiform mole?

It is possible but very unlikely. The odds of a woman who has never had a molar pregnancy having one are about 1 in 1500. If you have had a molar pregnancy this increases to about 1 in 80. If you have already had two molar pregnancies the risk of a third is approximately 1 in 6. It is important to remember that the chances are still high that you will have a perfectly normal pregnancy.

Is it normal for me to feel upset?

The experience of a hydatidiform mole can be very distressing. Not only have you lost your baby but you are required to have lengthy follow up and blood tests. This may mean a period of anxiety or may make you feel that you are in limbo as you cannot move on after the pregnancy and have to delay trying again. You may feel that your family and friends don’t understand what you are going through and this can make you feel quite isolated.

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