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MOLAR PREGNANCY

About one in every two thousand pregnancies is a so-called `molar` pregnancy. To begin with, a woman may have every reason to believe that she is expecting a baby. She will have missed one period or more, the pregnancy test will have been very strongly positive, and she may be experiencing all the classic signs of pregnancy. In addition she may be having particularly bad morning sickness.

However, when the woman is examined no fetal heartbeat can be heard and no heartbeat or indeed any fetal parts can be seen on scan. The scan may just have a white `snowstorm` appearance. A blood test may reveal exceptional levels of the pregnancy hormone, human chorionic gonadotrophin (hCG), and the woman will be told that that she has a hydatidiform (pronounced hyda-tidi-form) mole. Mole in this context has nothing to do with a mole on your skin, nor a garden mole, it just means a mass. `Hydatid` is a clear, fluid-filled cyst and taken together the term refers to a mass consisting of fluid-filled cysts-think of something looking like a bunch of fluid-filled grapes. The reason why hydatidiform mole is of special concern is because, depending on the type of mole, there is a risk of developing a type of cancer known as a gestational trophoblastic tumour (GTT).It used to be that these types of cancer had a very poor outlook indeed. Today, thanks to intensive medical research and diligent monitoring, this situation has been transformed, with an almost 100per cent cure rate for the most frequently encountered type of mole.

CAUSES

Why does a mole develop and what on earth does trophoblastic mean? To answer both questions, Soon after conception, rapid division of the fertilised egg takes place, so that very soon a ball of cells is formed. The outer layer of these cells is called the trophoblast and is initially responsible for the early nutrition of the embryo, but its principle job is to form the placenta. It rapidly forms, with other cells, into a sort of the placenta. It rapidly forms, with other cells, into a sort of double envelope which surrounds the inner cluster of cells which is to become the embryo. The outer layer of this envelop is called the chorion. Bits of the trophoblast chorion sandwich are then pushed out, forming little finger-like projections of cells called chorionic villi. At this stage, the embryo looks a bit like a sputnik. Once in contact with the wall of the womb, these little fingers of trophoblast, by enzyme action, burrow into the womb’s muscular wall, thus gaining an anchorage point and forming the placenta. Of course, only some of the projections on the `sputnik’ those in contact with the womb wall, will develop into the placenta. All the others, which point into uterine cavity, will gradually waste away. Trophoblast is potentially very invasive stuff, and from one point of view this is good because it favours as large a developing of placental tissue as possible. However, how does it know when to stop doing its invasive bit? A mole is formed when part or all of the trophoblast gets out of control and undergoes degenerative changes. Sometimes, for reasons we’ll go into later, no fetal development is possible and the conception remains as an undifferentiated ball of cells sometimes there is enough proper placental tissue to nourish an embryo through its very early stage, but almost invariably the embryo fails to develop properly, dies, and is soon reabsorbed. Depending on how much of the trophoblast is involved, the mole is classified either as complete or partial. In a complete mole, there never was a baby. In a partial mole there was a baby at the very beginning, although almost invariably there will be n baby by the time the mole is diagnosed. Although this sounds fairly clear-cut, in practice distinguishing between the two is not always and detailed pathological investigation is required to determine the status of the mole. The majority of molar pregnancies are complete moles, with about 20 per cent being partial moles. But how do they happen?

You will remember that in every cell in your body you have 23 pairs of chromosomes, the microscopic structures that are repositories for the instruction manual that are your genes. There is one exception to this rule. In sperm and egg, there are not 23 pairs, but 23 single chromosomes, so that when sperm and egg join up, there are once again 23 pairs of chromosomes. Part of the sperm manufacturing process that goes on in the testicle includes the so- called reduction division (meiosis) that ensures a chromosomal half measure in each sperm. However, in women, the reduction division occurs not in the ovary, but as the egg is moving down the fallopian tube. The half set of chromosomes that are excess to requirements are packaged up in something called a polar boy which is pushed out of the egg whilst it is still on the move. Sometimes the packing up and pushing out is a bit over-enthusiastic, and as a consequence some egg have no genetic material in them at all. Thus it is that a sperm can fertilise an empty egg. The resultant ball of cells will have a 46XX chromosomes pattern, because subsequent cell division just leads to duplication of the sperm’s genetic material. This material contains sufficient information to allow for the growth of the placenta (and it is the placenta, formed by trophoblast, that manufactures HCG, hence the positive pregnancy test), but there is not enough genetic material for a baby to be formed. Occasionally the chromosome pattern may be 46XY, because two sperm have fertilised an empty egg. Both these scenarios result in a complete hydatidiform mole.

The plot that results in a partial hydatidiform mole is a little different. Two sperm fertilise an apparently normal egg, resulting in a chromosome pattern which is triploid (three elements), one being maternal I origin and two paternal, either 69XXY, 69XXX or 69XYY. Here a baby can be formed, but because of the chromosome configuration It will have multiple congenital anomalies and will quickly die. Triploid chromosome patterns are not that uncommon, and by no means all of them result in molar pregnancy; they are a common finding following miscarriage.

It is possible for there to be a normal baby in association with a mole, if the pregnancy is a non-identical twin one, in which only one of the sacs is affected by molar changes. This is rare.
The common strand in both complete and partial mole is a double complement of paternal chromosomes. This is clearly abnormal, so it can be seen that a molar pregnancy is dictated right from the moment of conception and is not caused or influenced by any other factor that occurred between conception and diagnosis.

There are several theories as to why this should happen. A defect in the egg is a possibility, and this theory is strengthened by the fact that molar pregnancy is a progressive risk with age, a woman of 50 having a 400 times greater chance of having one than a woman of 25. It is also more common in teenage pregnancy.

There are many striking features connected to the incidence of molar pregnancy across the world which may give some clues as to its cause. The incidence is about 1 in 2,000 in Britain, but in Asian countries this may rise to 1 in 200 pregnancies. It is now thought that this difference may have been exaggerated by different diagnostic practices, especially since immigrant Filipino women in America are known to have a similar incidence to the rest of the American population. But molar pregnancy is only half as frequently in black women, leading to the conclusion that there is a genetic element as well, perhaps, as an environmental element. Since you can do nothing about your race, or your age, or the country you live in, it follows that there is nothing you can do to prevent having another molar pregnancy. Actually the risks of having another are very slight-just 2 per cent-so the odds are heavily stacked in favour of normal pregnancy.

SYMPTOMS

Symptoms for complete and partial mole are the same, although a partial mole are the same, although a partial mole may not show the symptoms as often. The most common `alerting` symptom is bleeding from the womb, which is usually not profuse and which is often brownish. The womb may be bigger than might be expected (or sometimes smaller with a partial mole). There may be abdominal pain because the abdominal levels of HCG have caused cysts to form temporarily in the ovaries. Sickness is a very common complaint, with 25 per cent of women having the type of excessive nausea and vomiting called hyperemesis. About half of women will pass some of the grapelike vesicles present in the womb through the vagina. For reasons which are not clear, 30 per cent of women with molar pregnancy will develop pre-eclampsia (see Chapter 11) before 24 weeks of pregnancy. A small number of women may develop signs of their thyroid having affected, with symptoms such as sweating, increased heart rate, intolerance to heat, etc.

DIAGNOSIS

Ultrasound is the most valuable tool for diagnosing the presence of a mole, resulting in a very characteristic pattern of multiple diffuse echoes, almost as if you had a black and white television on the blink. In a normal pregnancy, HCG levels gradually increase until around day 70-100 o pregnancy and then drop sharply. In a molar pregnancy, HCG levels are persistently high, or, earlier in pregnancy, are much higher than might be expected, particularly with complete mole. Partial mole levels of HCG in early pregnancy may be more or less normal.

Sometimes symptoms of molar pregnancy prompt diagnostic procedures. But it is having a miscarriage, usually of the missed abortion type (see Chapter 8) and only after she has had a D & C is she told that it as a molar pregnancy.

TREATMENT

Once the mole has been diagnosed, immediate surgery to remove it from the womb is indicated. Under general anaesthetic, the womb is very carefully evacuated, using a suction technique, and the inside of the womb scraped hard (curettage). Because trophoblast is so well supplied with blood vessels, haemorrhage is always a risk and access to appropriate transfusion services is essential. With specialist services, however, evacuating a mole is nearly always accomplished without problems.

FOLLOW-UP

In the vast majority of cases molar pregnancy has no more immediate consequences than any other failed pregnancy. Nevertheless you may feel devastated by it, partly perhaps because you may have felt so ill beforehand, but also because of concerns about future pregnancies and indeed concern for yourself. Nobody can even pronounce `hydatidiform`; very few people have heard of the condition, let alone written about it for the layman, and it’s all too easy for you and your partner and family to hear the word `cancer` and just shut off, hearing nothing further. Stop right there; this is not a horror story.
There are two types of cancer that can develop following a molar pregnancy: choriocarcinoma and invasive mole (actually this latter isn’t a true cancer). The risk of a choriocarcinoma after a complete mole is not more than 3 per cent; that of invasive mole about 10 per cent. Only 5 per cent of women who have had a complete mole pregnancy will require treatment. It is very treatable type of cancer (with a virtually 100 per cent cure rate if detected before it spread out of the womb), but this excellent prognosis depends on meticulous follow-up. The risk of either type of tumour following partial mole is much smaller.

The point of surgical evacuation following molar pregnancy is to remove all the trophoblast tissue; but it is difficult to be sure that It has all been removed. Thirty years ago one just had to guess and hope. Today, the story is different. After surgery, blood levels of HCG fall to non-pregnant levels quite quickly-for nearly half of cases, within a couple of months. If HCG fails to fall, or even rises during this time, it must mean that some trophoblast remains, either in the womb or perhaps in another site outside the womb, like the pelvis or lungs, to which it has escape via the bloodstream. Thus it is that weekly, and later monthly and then two-monthly blood checks for HCG, are essential for follow-up. Because pregnancy would mask any sinister rise in HCG levels, women must use effective contraception ( usually a low dose oestrogen pill) during the follow-up period, and avoid pregnancy.
It is important to stress that 90 per cent of women will have nothing but negative results. For cases where there has been partial mole and HCG levels have fallen to normal 56 days later, follow-up may only be necessary for six months at most, before trying again for a baby. The standard follow-up time, however, is two years, and no case of GTT has been identified after completing a two years follow-up. For the majority of women, not getting pregnant for two years is probably no hardship. But some, especially those who are older, this wait may feel like sentence. Enough is known, however, for obstetricians to be flexible, providing women know the risks. For instance, women whose HCG levels only fall to then remain normal for a subsequent six months, still have a risk of 1 in 286 of developing GTT. In these cases if women want to go ahead with pregnancy the choice is theirs; the odds are heavily in their favour. In comparison, a woman aged 36 and 9 months at the time of delivery, has the same risk of having a baby with Down’s Syndrome. It might make a 36 year-old woman stop and think, and have appropriate testing, but would it stop her having a baby? I might add that 1 in 200 is the risk of death at the same age if you smoke more than 20 cigarettes a day and you may know a lot of women who run this sort of risk without concern.

Because trophoblast tissue can get into the mother’s bloodstream, it can spread, as I have said, to other sites in the body (metastasis), usually the lungs or pelvis. If is in these sites it is very amenable to treatment with specialist drugs which will be given different combinations, depending on whether a woman is low, medium or high risk.

Very high HCG levels at the time of evacuation or in the subsequent four weeks will prompt chemotherapy. Low risk therapy is short, will not cause hair loss and has a cure rate of virtually 100 per cent. Medium risk therapy involves a short cycle of treatment (3-4weeks) and there may be some hair loss. High risk treatment is for those for whom previous treatment has failed.

COPING

If you have a complete mole, and know that there never was a baby, it can be very difficult; you have been pregnant, and yet you weren’t-at least not in the conventional sense. Nevertheless, pregnancy and a baby were what you were expecting and these expectations have suddenly been removed in a dramatic, and at first, an incomprehensible way. And now, to make things worse, you have been told that you may not get pregnant for some time yet. Molar pregnancy is so hard to explain that you may be justified in saying to people that you simply had a miscarriage and don’t feel like trying again for a while. But you have been fortunate to escape a condition which used to be a killer.

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