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Miscarriage

  1. TYPES
  2. THE INCIDENCE
  3. CAUSES
  4. INVESTIGATION
  5. TREATMENT

The occurrence of a miscarriage is a tragic loss for a couple trying to have a child and can be associated with significant psychological problems for the woman, their partner and family. Miscarriage is usually a single occurrence, and often followed by successful pregnancy. Recurrent miscarriage is defined as the loss of three or more consecutive pregnancies. Even after 3 consecutive losses, the chance of a successful pregnancy is over 60%. Most miscarriage occurs within the first 14 weeks of pregnancies. Maternal age and previous number of miscarriages are independent risk factors for a further miscarriage.

Vaginal bleeding is the most common symptom of a miscarriage; the bleeding may be slight spotting but sometimes very heavy with clots. The bleeding is usually followed by crampy lower abdominal pain.

Types of miscarriage (abortion)

When vaginal bleeding is slight, there is no or mild pain, the cervix is closed and the uterus feels the correct size for date. The diagnosis of "threatened miscarriage" is made. The woman is usually advised bed rest, bleeding and pain may settle down and pregnancy may proceed normally. However, if the bleeding become very heavy, the cervix opens up and the woman complains of intense cramping, the fetus will subsequently pass out; this is called "inevitable abortion". If the fetus and placenta pass out of the womb completely, this is called "complete abortion". If any bits remain inside the cavity of the uterus it is called "incomplete abortion". The patient will then undergo evacuation of retained products of conception (ERPC) under a general anesthetic. Should any tissue be left in the uterus there is a serious risk of infection. If infection intervenes the term "septic abortion" is used. 
Sometimes, the fetus dies in the womb but not expelled, and the term "missed abortion" is used.

The diagnosis of all these kinds of miscarriage is made by ultrasound scan, this may show an empty sac, viable pregnancy, retained pregnancy tissue or a dead baby. Although surgical management of miscarriage is the norm, medical evacuation with prostaglandin analogue, with or without antiprogesterone, is an effective alternative in selected cases. Expectant management (awaiting spontaneous resolution of the miscarriage) may also be offered as an alternative for certain cases provided that facilities for monitoring the patient are available. It should be noted that when miscarriage is managed expectantly resolution may take several weeks. If the woman blood group is Rhesus negative and she miscarry or experience bleeding in the pregnancy; it is important that she have Anti-D injection to prevent antibodies developing. In the vast majority of women, fertility is not impaired after miscarriage.

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The incidence of miscarriage

The risk of miscarriage is known to increase with age.

The overall percentage of pregnancies that end in miscarriage lies between 10-15%. Miscarriage accounts for about 50,000 in-patient admissions to hospitals in the UK annually. Recurrent miscarriage affects 1% of all women. This incidence is greater than that expected by chance alone (0.34%). The risk of miscarriage increases with advancing maternal age from about 9% at age 20 years to 80% at age 48 years. It is worth noting that this increase is observed irrespective of a woman's reproductive history.

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Causes of miscarriage

  1. CHROMOSOMAL
  2. HORMONAL
  3. IMMUNOLOGICAL
  4. UTERINE
  5. OTHERS
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Chromosomal abnormalities

Fetal chromosomal abnormalities are the commonest cause of sporadic miscarriage affecting more than half of all early miscarriages. This may be due to abnormalities in the egg, sperm or both. The usual chromosomal pattern is 46 chromosomes which are arranged in 23 pairs, one of these pairs is called sex chromosomes, females will have two X chromosomes and males will have one X chromosome and a Y chromosome. The genes we all have are lined up along the chromosomes. For each of these genes there are two copies. A person will inherit one copy of each gene and one of each pair of chromosome from each parent. The most common chromosomal defects are:

Trisomy
A trisomy is where there are three chromosomes of one type instead of the normal pair. This constitutes the largest group and is more common as maternal age increases. These faults are not very likely to recur and there is a good chance that the pregnancy will be right next time.

Monosomy
A monosomy is where there is one chromosome missing. Only 1% of pregnancies with one X chromosome will survive and the condition is called Turner's syndrome.

Polyploidy
A polyploidy is where one or more extra complete set of chromosomes are present, this may be the result of an egg being fertilized with more than one sperm.

Unbalanced translocation
This is a less common cause of miscarriage.

Some of these abnormalities are inherited from one or another of the parents who has what is called balanced translocation where one of the chromosome swapped bits of its genetic material with that of another chromosome. This usually causes no problem to the parent as all his or her genetic materials is present, it is just some of it is in unusual place. There would be a significant risk of a fetus inheriting what is called unbalanced form of this translocation, which may means the fetus would have either too much or too little genetic material. This situation may cause fetal death and miscarriage or fetal abnormalities.

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Hormonal problems

Several different problems may fall in this category including low progesterone levels, high LH levels, or thyroid abnormalities.

Low progesterone level
If too little progesterone is produced by the corpus luteum, the endometrium may not develop adequately to sustain the pregnancy. However, low progesterone levels in early pregnancy usually reflects a pregnancy that has already failed.

High LH levels
Elevated levels of luteinizing hormone is common in women with PCOS. High LH affects the quality of the eggs and hence the embryos, and may result in recurrent early miscarriages.

Thyroid abnormalities
Thyroid abnormalities may also cause miscarriage.

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Immunological

Antiphospholipid antibodies syndrome (APAS) are present in about 15% of women with recurrent miscarriage (compared with 2% normally). These antibodies circulate in the blood and can cause thrombosis of the placental vessels, and if this happen, the baby dies. The association between APAS and miscarriage is stronger for second trimester losses than for the first trimester losses. It is also possible that disorders of the protective mechanism that prevent the fetus from being rejected by the mother can cause miscarriage. This is more likely to happen if the mother and father have similar tissue types. The peripheral blood of women with recurrent miscarriages have been shown to have a higher proportion of activated NK cells than control groups.

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Uterine abnormalities

There are several uterine problems that may result in miscarriages. These include a misshapen uterus, fibroids, cervical impotence and adhesions.

Misshapen uterus
Some women with abnormally shaped uterus miscarry. The reason for this is not fully understood but it is possible that the uterus may not enlarge enough to accommodate the pregnancy. The miscarriage often occurs in the second trimester, but early losses may occur as well. Uterine abnormalities are present from birth and include a septate uterus (a uterus divided by a wall) and double uterus.

Fibroids
Fibroids sometimes distort the uterine cavity and prevent pregnancy from implanting properly.

Cervical incompetence
During pregnancy, the cervix (neck of the womb) should remain closed until labor begins. In some women, the cervix is weak and starts to open up quite painlessly with subsequent spontaneous rupture of membranes and expulsion of the fetus. Miscarriage caused by cervical incompetence is usually late in pregnancy, often after 16 weeks. This weakness of the cervix may be an inborn fault, or a result of a previous surgery such as cone biopsy, or previous childbirth.

Adhesions
Adhesions inside the womb cavity (Asherman's syndrome) may not only cause infertility but may also be associated with miscarriage possibly by restricting the implantation and growth of the fetus.

Endometrial causes
Miscarriages may be associated with retarded endometrial development (luteal phase defect).

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Infection

Any severe infection such as rubella, cytomegalovirus and listeria infection can cause sporadic miscarriage. Bacterial vaginosis also can cause late miscarriage, preterm labour and premature rupture of membranes. The role of infection in recurrent miscarriage is unclear.

Gene defects

Some gene defects may cause miscarriage, but most results in a more serious problem with the baby such as cystic fibrosis or Duchenne muscular dystrophy.

Chronic maternal illness

Some chronic diseases in the mother such as diabetes mellitus, very high blood pressure, kidney problems, systemic lupus may occasionally cause miscarriage. However, with all these diseases, normal pregnancy is the usual.

Environmental hazards

Any substance that result in toxicity in a pregnant woman may be implicated in miscarriage including, radiation, some insecticides, lead, toxic chemicals, smoking and alcohol.

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Investigation of recurrent pregnancy lossss

The specialist will take a full history, perform general and an internal examination, and order some investigations. The initiation of recurrent pregnancy loss investigation should be tailored to meet the couple's need based on woman's age, reproductive history and health rather than arbitrary number of pregnancy losses. A history of subfertility, particularly ovulation problems is present in 25%-30% of women with recurrent miscarriage and confers a poor prognosis for future pregnancy outcome. In a significant proportion of women the cause of the recurrent pregnancy loss remains unexplained after careful investigation.

The investigations the specialist may order include some or all of the following tests.

  • Blood test from both partners for karyotyping. About 3-5% of couples presenting with recurrent pregnancy losses carries chromosomal abnormalities, the wife being affected twice as frequently as the male partner.
  • Karyotyping of all fetal products.
  • Pelvic ultrasounds scan to diagnose polycystic ovaries and uterine abnormalities.
  • A hysterosalpingogram or hysteroscopy in order to assess the uterus and cervix. An ultrasound examination can suggest but usually can not provide a definitive diagnosis.  
  • Blood test to check for the presence of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies). Before a diagnosis of antiphospholipid syndrome is made it is mandatory that the patient has two positive tests at least six weeks apart for either lupus anticoagulant or anticardiolipin antibodies in medium or high titre.
  • Blood test to check the levels of FSH, LH and thyroid function tests.
  • Blood tests from the female partner to test her for thrombophilic defects (antithrombin III, protein C, protein S, hyperhomocysteinemia, activated protein C resistance).
  • High vaginal swab to check for infection.

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Treatment of recurrent pregnancy loss

The treatment of recurrent pregnancy loss depends on the results of the investigations taken to determine thecause of recurrent miscarriages. The treatment options include aspirin, heparin, drug treatment by progesterone or hCG, insertion of a purse-string suture around the cervix, myomectomy, hysteroscopic surgery or metroplasty. When the cause of recurrent miscarriage is unknown, regular ultrasound scans, and tender love and care provide adequate support.

  • If karyotyping showed chromosomal abnormalities, genetic counseling should be thought to give the couple enough information to decide whether to attempt another pregnancy, use donor sperm (if the male partner has the genetic problem), donated eggs (if the female partner has the genetic problem) and adoption.
  • Women with persistently positive tests for antiphospholipid antibodies are offered treatments with low dose aspirin together with low dose. heparin during pregnancy and both are discontinued at 34 weeks.
  • Metroplasty (corrective surgery of the uterus) is usually offered if it is thought that the uterine abnormalities is the prime cause of miscarriage. Open uterine surgery is associated with postoperative adhesions, infertility and carries the risk of uterine rupture during labor. These complications are less likely after hysteroscopic surgery.
  • If cervical incompetence is diagnosed, this is usually dealt with by inserting a purse-string suture around the cervix under general anesthetic at around 14 weeks. The stitch may then be removed at about 37-38 weeks or earlier if labor commences. The suture may be left in place and the baby is delivered by cesarean section. Some gynecologists advocate performing the operation before the woman conceive and through an abdominal cut.
  • Myomectomy should be performed if a fibroid distorts the cavity and the woman has at least one-second trimester miscarriage.
  • Adhesions inside the womb are best treated hysteroscopically.
  • Progesterone or hCG treatment may be offered to women with low progesterone levels. At present, there are no proven benefit of such treatments in women with recurrent pregnancy loss.
  • hCG treatment may improve pregnancy outcome in women with oligomenorrhoea and recurrent miscarriage.
  • Some specialists offer treatment with high dose steroids, immunoglobulins or tumour necrosis factor blocking agents for women that are found to have a high level of NK cells. However, no large randomized studies have confirmed such a benefit.

After a miscarriage the woman may feel very anxious about becoming pregnant again, but it is important to remember that the vast majority of women will have a healthy pregnancy next time without any treatment.

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