Recurrent Miscarriage - Causes, Symptoms & Signs
One of the most frustrating situations in Infertility Treatment is recurring abortions. These are women who conceive but cannot carry a pregnancy to term - women who have repeated miscarriages. Since it is not fully understood yet, it raises a lot of questions that do not have the answers.
How are abortions classified medically ?
How often do abortions occur ?
What are some of the myths about abortions ?
What are the causes of repeated abortions ?
How do chromosomal abnormalities cause miscarriages ?
How do hormonal imbalances cause miscarriages ?
Which illnesses can cause repeated abortions ?
How does PCOD cause repeated miscarriages ?
How do immune problems cause repeated abortions ?
How do antiphospholipid antibodies cause repeated abortions ?
How do uterine problems cause repeated abortions ?
Can lifestyle factors cause repeated abortions ?
What about the emotional aspects of dealing with repeated abortions ?
What should you know about planning your next pregnancy after you have had an abortion ?
What are the treatment options for women who have had repeated abortions ?
What are the chances of having a healthy baby after repeated abortions ?
An extended definition of infertility includes women who conceive but cannot carry a pregnancy to term - women who have repeated miscarriages. The technical term for this is recurrent pregnancy loss. This is one of the most frustrating problems in reproductive medicine medicine today , because we still do not understand it well. Patients with repeated miscarriages have hundreds of questions - and we still do not have the answers !
The medical term for a miscarriage is an abortion. Most miscarriages start with vaginal bleeding which is initially slight and painless. This is called a threatened abortion, because the pregnancy is threatened by the bleeding. This bleeding is from the mother, and is not fetal blood. About half the time this stops spontaneously and results in no harm to the pregnancy. At this stage, the most useful test is an ultrasound scan (usually done with a vaginal probe). If a fetal heartbeat can be seen, this means that there is a 95 % chance that the pregnancy will proceed normally. On the other hand, if the ultrasound scan shows that the fetus has not developed properly ("blighted ovum " or anembryonic pregnancy when no fetus can be seen; or a missed abortion or intrauterine fetal death when the fetus is seen but the heart is not beating, then nothing can be done to save the pregnancy.
In such cases, the bleeding progresses, and the uterus starts contracting. This is felt as painful cramps, and the mouth of the uterus ( the cervix) opens. This is called an inevitable abortion (because it cannot be stopped). If some of the pregnancy has already been pushed out by the contractions, this is called an incomplete abortion.
In patients with a blighted ovum, missed abortion, inevitable or incomplete abortion, the treatment is a uterine curettage (D&C) - a short surgical procedure which is performed to empty the uterus and remove the pregnant tissue.
Abortions which occur in the first twelve weeks of pregnancy are called first trimester abortions. Those which occur between the 13th to 20th weeks are called second trimester abortions.
The magnitude of the problem
Perhaps 20-30% of all women spot, bleed or suffer cramps during their first twelve weeks of pregnancy, and about 10% miscarry. This figure may be an underestimate, because there are a number of women who miscarry unknowingly, thinking that their period was late or heavy. It is very common for women to have one miscarriage during the first twelve weeks of their pregnancy . The commonest reason for a first trimester miscarriage is a genetic defect in the embryo. This is actually Nature's defense mechanism, to prevent the birth of a baby with a birth defect. The genetic error is a random event which happens by chance , and occurs because a genetically abnormal egg or sperm gets fertilised. This is not a sign that they have a health problem, because most of them will probably have a healthy baby the next time they get pregnant without any treatment. This is why most doctors will not do any testing for couples who have had a single first trimester miscarriage - the testing is usually not cost effective, and rarely provides any useful information.
If however, a patient has had two or more miscarriages consecutively, this is called repeated or habitual abortion. Now although the risk of miscarrying again does increase, this risk is still quite small, and increases from the 15% risk a normal woman has to 35% - which still means there is a 65% chance that they will not have a miscarriage again.
Most women who miscarry do so only once. Their risk for miscarrying again is not increased and is the same as that of a normal woman's - about 15%
Women who are over thirty five are no more liable to miscarry
Travelling, lifting weights and sex does not threaten a healthy pregnancy. As the old saying goes, " You cannot shake a good apple off a tree."
If you've had a previous miscarriage, it is very normal to be frightened and worried during your next pregnancy. It is important to understand that exercise, working and intercourse do not increase the risk of pregnancy loss. Likewise, staying at home and resting in bed probably do not prevent miscarriage.
Repeated miscarriages can happen because of any of the following:
- Chromosomal abnormalities
- Hormone imbalance
- Physical Illness
- Polycystic Ovary Syndrome
- Immune problems
- Antiphospholipid antibodies
- Problems in the uterus
- Life style of the woman
At least 60% of spontaneous miscarriages occur because of a chromosomal abnormality at conception. This means that a genetically (chromosomally) defective sperm or ovum gives rise to a genetically abnormal fetus. The miscarriage is Nature's defense mechanism, which aborts a defective fetus, rather than giving birth to a defective baby. Since most of these genetic defects are chance occurrences, the risk of it being repeated again in the next pregnancy is very small.
In order to establish the diagnosis of a genetic cause for repeated pregnancy loss, a karyotye (study of the chromosomes) of the fetal tissue (if available) may be done. It is expensive, and often the cells fail to grow in culture, so that the study may not be possible. Moreover, since little can be done even if a defect is detected, it has little impact on patient management. However, it does provide an explanation for some patients with recurrent pregnancy loss.
In about 5 % of couples, a chromosome abnormality found in one of the parents explains recurrent miscarriage. This is detected by doing a chromosomal study on the parent's blood. The commonest problem is a structural defect (break or loss of a piece of the chromosome, called a deletion; a rearrangement of a bit of a chromosome, called a translocation ) .
If the karyotype is normal, then the patient can be reassured that the miscarriages were a chance genetic event, and they can feel comfortable continuing with their efforts to have a baby. However, if the karyotypes are abnormal, this is a permanent situation, which indicates an increased risk of miscarriage. Genetic counselling should be sought to discuss the degree of risk. Depending upon the individual problem, this risk may be anywhere from 25% to 100%. Since chromosomal rearrangement at conception (when the sperm fertilises the egg) is a random event, there is little which can be done to treat this. Options may include: continuing to try to conceive a baby naturally; adoption; donor eggs (if you have the genetic problem) or donor sperms (if the husband has the genetic problem).
Patients may miscarry because they have a luteal phase defect - that is, the amount of progesterone hormone produced after the egg is released is reduced. Progesterone is the hormone which supports the pregnancy. It helps implantation of the embryo in the uterus and if this is deficient, there can be a problem with the embryo lodging itself in the uterine lining.
A luteal phase defect is suspected if the menstrual cycles are short - especially if the luteal phase (the time of the menstrual cycle between ovulation and the next menstruation) is shorter than 12 days.
This diagnosis can be confirmed by a blood test (a serum progesterone level done one week after ovulation is low) and an endometrial biopsy (which will show that the endometrium is "out of phase").
The doctor can help provide luteal support by prescribing progesterone during the last two weeks of the menstrual cycle after ovulation. If the woman is already pregnant, treatment may be with vaginal suppositories of natural progesterone for the first twelve weeks of the pregnancy; or progesterone injections intramuscularly. However, this treatment is controversial.
Health problems that can cause repeated miscarriages are:
- Uncontrolled thyroid disease, especially hypothyroidism
- Severe heart, liver or kidney disease
- Systemic lupus erythematosus an illness in which the woman produces antibodies against her own body tissues.
What about TORCH Infections? Certain infections called TORCH ( which stands for TOxoplasmosis, Rubella, Cytomegalovirus and Herpes) , may be a cause for a single miscarriage, but are NOT a cause for repeated miscarriages. While a number of specialists will do these tests, and even start treatment based on the results, these tests are not worthwhile for patients who undergo habitual abortion. They just waste a lot of the patient's time and money.
A positive TORCH test simply means the patient has positive antibody levels against that particular infection. Thus, a positive Toxo IgG test means that the patient has anti-toxoplasmosis antibodies which protect her against a repeat toxoplasmosis infection. This means a positive test is actually a good sign and suggests that the patient is protected against that infection because she has been exposed to that infection in the past. Unfortunately, many doctors do not know how to interpret these results and scare the patient into thinking that the positive test result means she has an active infection which can cause her to miscarry again. In fact, some doctors will even attempt to "treat" the "infection" ! This wastes time and causes needless distress. If your doctor asks you do a TORCH test after a miscarriage, you should refuse and find a better doctor !
Although infections of the uterine cavity (for example, due to mycoplasma) are frequently thought to be a cause of recurrent pregnancy loss, substantial proof of this is lacking. Studies have in fact failed to indicate a greater incidence of infection in women with a history of miscarriage when compared to normal fertile women.
Polycystic Ovary Syndrome
Exciting research done recently by Dr Howard Jacobs at the Middlesex Hospital, London, shows that polycystic ovary syndrome can also be a cause of recurrent miscarriages. In PCOS, the ovaries produce a large amount of the LH hormone. PCOS patients also have insulin resistance, and the high LH levels and high insulin levels have a detrimental effect on the egg, so that at the time of ovulation, the egg which is released is overripe and unhealthy. If such an egg is fertilised, the embryo is also likely to be unhealthy, and is consequently rejected by the body after 6-8 weeks as a miscarriage. Treating the abnormal insulin resistance in PCOD patients who have had repeated miscarriages with metformin helps many of them to have healthy babies . The interesting point of these studies is that it tells us that we should also be focussing on what is happening at the time of fertilisation - and not just what goes on after the pregnancy. Problems with the eggs and sperms at the time of fertilisation will manifest themselves as a miscarriage later on, but these are often neglected by the doctor.
The immune system plays an important protective role in maintaining health throughout life, by defending against infection. It "rejects " the foreign invaders (bacteria, viruses) which are recognised by the body as being "outsiders". It is now becoming evident that inappropriate activation of the mother's immune system may cause early first trimester miscarriages.
Current theory suggests that during a normal pregnancy, the fetus, which carries the father's foreign genes (and is therefore immunologically foreign to the mother) can nevertheless survive in the mother' uterus because of a special protection from the mother's immune system - the uterus is a "privileged" site. This is why it is not "rejected" like other foreign tissues (such as kidney transplants) are. This means that in the normal course of events, the fertilised egg somehow stimulates a protective maternal immune response which allows implantation and growth. For certain couples, this protective response does not occur, and the maternal immune system rejects the father's foreign material in the fetus, resulting in miscarriage. Tests are available to check for this, but these are still in the experimental stage. Treatment is in the research phase too, and includes sensitising the mother to the father's genes, by injecting his blood cells into her skin, the theory being that exposure to the foreign cells will stimulate her immune system to provide the normal protective immune response when she gets pregnant.
Some women produce antibodies against the circulating substances that cause blood clotting. These are called lupus anticoagulant or anticardiolipin or antiphospholipid antibodies. They severely inhibit fetal development (by blocking off the blood supply to the fetus by causing clots in the maternal-fetal circulation) and cause miscarriages. Their presence can be detected by a blood test. Treatment is possible, either with low doses of aspirin (which decreases the clot formation); or with a steroid (prednisone) which suppresses the mother's abnormal immune system.
Problems in the Uterus
Miscarriages because of uterine problems usually occur after the twelfth week. These could be because of :
- A congenital abnormality of the uterus, which the woman is born with, but which does not cause any problems, until she gets pregnant . The common types of uterine anomalies include: a septate uterus ( in which a wall divides the uterine cavity); a unicornuate uterus, in which the uterus has only one horn , because only one half has developed properly; and a bicornuate uterus, in which the uterus has two halves or horns, because the two did not fuse normally during their development in utero). This abnormal uterus cannot grow normally to hold and retain the pregnancy and this is consequently expelled. In women with a septate uterus , if the embryo implants on the abnormal tissue of the septum, the pregnancy may miscarry because the septum cannot support a pregnancy.
- Fibroids, which are growths of smooth muscle tissue inside the uterus. While most fibroids will not mar a pregnancy, if the fibroid is very close to the lining of the uterus ( submucous fibroid), it will interfere with the implantation of the embryo in the uterus, and will cause its expulsion.
- Intrauterine adhesions ( Ashermann's syndrome). These are uncommon, and are fibrous bands of scar tissue in the uterus, which interfere with implantation of the embryo. They may be formed after a uterine curettage (after an abortion) and can be diagnosed by hysteroscopy or hysterosalpingography. They can be removed by hysteroscopic surgery, allowing uneventful pregnancies in the future.
- Incompetent os, in which the cervix (mouth of the womb) is weakened. When the growing fetus presses on it, the weakened cervix opens, leading to expulsion of the growing foetus. This condition may be congenital; or because of a cervical tear or injury during previous pregnancy or miscarriage; or could be a result of over enthusiastic surgical dilatation of the cervix during previous surgery. The insertion of a cervical stitch, called the Shirodkar stitch after the Indian doctor who discovered this condition and invented the surgical operation to correct it, can be very effective. The cervical stitch is a simple surgical operation, usually done after 12 weeks of pregnancy after an ultrasound shows that the baby is healthy ; and it helps by strengthening the weakened cervix. The stitch is removed two weeks before the baby is due, or when labor starts, whichever is first.
Diagnosis of these anatomic defects can be made by hysteroscopy or hysterosalpingography. An ultrasound examination can suggest a problem exists, but usually cannot provide a definitive diagnosis. Newer imaging techniques such as 3-D ultrasound or MRI scanning can also provide useful diagnostic information.
If patients are regularly exposed to toxic fumes and chemicals (example, workers in chemical factories ; or nurses and anesthetists in operating rooms) these could damage the developing fetus (which is very sensitive to poisons) and cause a miscarriage. Recent studies show that even men exposed to environmental toxins can cause their partner to miscarry a fetus (presumably because their sperms are damaged by the toxins). Smokers, alcoholics and drug abusers also have an increased incidence of miscarriages.
Abnormal sperm do not cause miscarriages !
Since sperm provide 50% of the genes of the embryo, it is logical to assume that 50% of the time the reason for genetically abnormal embryos ( and thus recurrent miscarriages) would be genetically abnormal sperm !
However, what is logical is not always true ! In reality, studies have shown that there is no correlation between abnormal sperm and failed IVF or miscarriages.
Let's look at a very common reason for infertility. This is the problem of abnormal sperm morphology, known medically as teratozoospermia. These are men who have a very large proportion of abnormally shaped sperm - more than 95% abnormal forms. The standard treatment for these men is ICSI, in which a single sperm is injected into an egg to fertilise it.
Now one would logically expect that many of these embryos would be abnormal, as a result of which the risk of a miscarriage in these men would be increased. Surprisingly, this is not true - and the fertilisation and pregnancy rate in these men is exactly the same as it is in men with normal sperm. This means that abnormal sperm do not create abnormal babies ! This is one of the reasons why all the new sperm tests which check for sperm DNA integrity are of such little clinical value in patients with recurrent miscarriages.
A large group of women who experience recurrent pregnancy loss, who are often not diagnosed correctly , are those with poor ovarian reserve. This is called oopause; and the reason for the miscarriage is poor egg quality, since these eggs are often genetically abnormal ( leading to genetically abnormal embryos, which are then aborted).
The emotional aspects
Human society still tends to dismiss miscarriage complacently; it is a subject which is rarely discussed. A foetus for most people is a non-person and a miscarriage is a non-event. But, to the would be parents, the developing fetus is a baby with an identity, especially if you have seen it on the ultrasound screen and heard its heart throbbing with a Doppler. When the child is lost, it is a bereavement and your sense of loss, tinged with pain, anger, isolation and depression, can be profound - especially when it follows a long period of infertility.
After a miscarriage, it is normal to experience a period of grief. Find support from each other; and from others who have had a similar experience. Healing does happen in time. Focus on getting through the grieving rather than on the suffering.
Your next pregnancy
After a miscarriage, making the decision to go in for another pregnancy is difficult. Collect as much information as possible to try to find out the possible causes of the loss and whether they might influence a future pregnancy.
If you have had 2 or more miscarriages, then tests are usually done to try to find a cause. These include the following:
- Hysterosalpingogram or hysteroscopy to make sure there are no defects in your uterus (womb)
- Blood tests, such as serum progesterone, to rule out a luteal phase defect
- Blood tests for antiphospholipid antibodies (lupus anticoagulant)
- The VDRL (Venereal Diseases Reach Laboratory) blood test, for sexually transmitted diseases
- Karyotype, for you and your husband, to rule out chromosomal abnormalities.
The doctor may also want to send the aborted tissue for chromosomal study, to find out if the fetus was chromosomally normal or not.
Often many doctors will do what is called a "TORCH" test - but this is a a waste of money for most patients, since it provides little useful information.
When to start the testing depends upon you. While few doctors would do anything after one miscarriage (since your chance of having a healthy pregnancy even without tests and treatment is better that 85%), most would start a workup after two miscarriages. Often, nothing is found, and this can be very frustrating to the doctor and patient. But do remember that medical technology has it's limitations, and we still do not know a lot about the early embryo and its development.
What about treatment? Sometimes it is possible to treat the underlying problem - for example, by taking a cervical stitch to treat an incompetent os; or removing a uterine septum by hysteroscopic surgery.
In our experience, we have found that many women with recurrent pregnancy loss have occult PCOD ( polycystic ovarian disease) , which is usually not diagnosed correctly. Because of their abnormal insulin resistance, many of these women ovulate abnormal eggs, which are genetically abnormal, leading to genetically abnormal embryos which then miscarry. We have found that the following empiric treatment, based on experience, helps treat many women who have experienced recurrent early pregnancy losses: Metformin, 1500 mg daily; folic acid, 5 mg daily; and low dose aspirin, 50 mg daily. This needs to be started at least one month prior to conception, and continued till 16 weeks of pregnancy. When they conceive, we continue all the above; and also add 600 mg vaginal progesterone suppositories daily till 20 weeks.
Another group of women who experience recurrent pregnancy loss, who are often not diagnosed correctly , are those with poor ovarian reserve. This is called oopause; and the reason for the miscarriage is poor egg quality, since these eggs are often genetically abnormal ( leading to genetically abnormal embryos, which are then aborted). For these women, one option is to try to improve egg quality using DHEA , Vit D and wheat germ and doing IVF with aggressive superovulation; Plan B would be to use donor eggs , which is a very effective treatment option with a high success rate.
Often the only option for many women ( especially when there is no clear diagnosis) is to try again. Remember, even if you have had 3 or more miscarriages, your chance of carrying the next baby to term is still more than 50 % - even with no specific treatment, and just tender loving care!
Deciding when to start the next pregnancy is a decision only you can make. It takes a lot of courage and both of you need to be ready.
Your next pregnancy probably won't be as joyful as you would like. Insist that your pregnancy be monitored carefully. Whenever the slightest problem occurs, you'll feel vulnerable and terrified - but don't panic.
Everyone will make suggestions about what you should do to make your pregnancy successful. This can be annoying - but remember they are doing it because they care! The easiest way to handle this is to listen, and then do what you and your doctor feel is best for you.
Your child birth experience can be bittersweet - memories surface about your loss, especially if you are at the same hospital. You probably will need to do some grieving in addition to celebrating the new life.
The experience of miscarriage will also affect your parenting. Bonding with your child may also be delayed because you feel the need to protect yourself from more sorrow - so you wait till you are certain that all is safe and sure with your baby. Moments of panic will occur when the baby is ill or too quiet or with someone else. You are also likely to treat your children as "extra special" - and be less objective than other parents.
If you've experienced recurrent miscarriage, you may feel hopeless and confused regarding a positive pregnancy outcome. Remember that miscarriage is not an uncommon event. Your testing will focus on trying to find out the known causes of recurrent miscarriage. But knowledge of this problem is still limited, and no obvious cause is detected in upto 50% of couples with repeated pregnancy loss. This can be very frustrating - both to the patient and the doctor. The encouraging news is that the spontaneous cure rate is very high; and successful treatment is available for treating certain uterine and endocrine causes. So even if your evaluation does not reveal a treatable cause and you do not undergo treatment, your chance of achieving a healthy pregnancy despite having had several miscarriages in the past is still better than 50% - and the only "treatment " you need is tender loving care !
Often the best treatment is Information Therapy ! I would advise you to read the book, Coming to Term. This is one of the wisest books I have ever read. It is written by a skilled author, who is not only a scientist, but who has also experienced the trauma of multiple miscarriages firsthand.
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