Miscarriage

Miscarriage is an unscientific term for an abortion that is the natural end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation. Abortion is the most common complication of early pregnancy. Spontaneous abortion is a frequently used clarification to distinguish this natural process from an induced abortion.

Terminology
Very early spontaneous abortions—those that occur before the sixth week LMP (since the woman's last menstrual period)—sometimes are termed early pregnancy loss or chemical pregnancy. Those that occur after the sixth week post-LMP are medically termed clinical spontaneous abortion.

In medical (and veterinary) contexts, the technical term "abortion" refers to any process by which a pregnancy ends with the death and removal or expulsion of the fetus, regardless of whether it is spontaneous or intentionally induced. Many women who have had miscarriages, however, object to the term "abortion" in connection with their experience, because in everyday English the word may be strongly associated with induced abortions. In recent years there has been discussion in the medical community about avoiding the use of this term in favor of the term, "miscarriage". In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate a revision of nomenclature used to describe early pregnancy events.

Labour resulting in live birth before the 37th week of pregnancy is termed "premature birth", even if the infant dies shortly afterward. The limit of viability at which 50% of fetuses survive longterm is around 24 weeks, with moderate or major neurological disability dropping to 50% only by 26 weeks. Although long-term survival has never been reported for infants born from pregnancy shorter than 21 weeks and 5 days, fetuses born as early as the 16th week of pregnancy may sometimes live for some minutes after birth.

A fetus that dies while in the uterus after about the 20–24th week of pregnancy may be termed, a "stillbirth"; the precise gestational age definition varies by country. Premature births or stillbirths are not generally considered "miscarriages", though usage of the terms and causes of these events may overlap. Another term for this has been coined, intrauterine fetal demise (IUFD).

Classification
The clinical presentation of a threatened abortion describes any bleeding seen during pregnancy prior to viability, that has yet to be assessed further. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems.

Alternatively the following terms are used to describe pregnancies that do not continue:
 * An empty sac is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. Other terms for this condition are blighted ovum and anembryonic pregnancy.
 * An inevitable abortion describes a condition in which the cervix has already dilated open, but the fetus has yet to be expelled. This usually will progress to a complete abortion. The fetal heart beat may have been shown to have stopped, but this is not part of the criteria.
 * A complete abortion is when all products of conception have been expelled. Products of conception may include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane.
 * An incomplete abortion occurs when tissue has been passed, but some remains in utero.
 * A missed abortion is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed or missed miscarriage.

The following two terms consider wider complications or implications of a miscarriage:
 * A septic abortion occurs when the tissue from a missed or incomplete abortion becomes infected. The infection of the uterus carries risk of spreading infection (septicaemia) and is a grave risk to the life of the woman.
 * Recurrent pregnancy loss (RPL) or recurrent miscarriage (medically termed habitual abortion) is the occurrence of three consecutive miscarriages. If the proportion of pregnancies ending in miscarriage is 15%, then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%. A large majority (85%) of women who have had two miscarriages will conceive and carry normally afterward.

The physical symptoms of a spontaneous abortion vary according to the length of pregnancy:
 * At up to six weeks only small blood clots may be present, possibly accompanied by mild cramping or period pain.
 * At 6 to 13 weeks a clot will form around the embryo or fetus, and the placenta, with many clots up to 5 cm in size being expelled prior to completion of the process. The process may take a few hours or be on and off for a few days. Symptoms vary widely and may include vomiting and loose bowels, possibly due to physical discomfort.
 * At more than 13 weeks the fetus may be passed easily from the uterus, however the placenta is more likely to be fully or partially retained in the uterus, resulting in an incomplete abortion. The physical signs of bleeding, cramping, and pain may be similar to an early stage abortion, but sometimes more severe and labour-like.

Signs and symptoms
The most common symptom of a spontaneous abortion is bleeding; bleeding during pregnancy may be referred to as a threatened abortion. Of women who seek clinical treatment for bleeding during pregnancy, about half will abort. Symptoms other than bleeding are not statistically related.

Spontaneous abortion may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Women pregnant from ART methods, and women with a history of aborting, may be monitored closely and so detection is sooner than women without such monitoring.

Several medical options exist for managing documented nonviable pregnancies that have not been expelled naturally.

Psychological
Although a woman physically recovers from a spontaneous abortion quickly, in general, psychological recovery for parents may take a long time. People differ greatly in this regard: some are able to move on after a few months, but others take more than a year. Still others may feel relief or other less negative emotions. A questionnaire (GHQ-12 General Health Questionnaire) study following women having aborted showed that half (55%) of them presented with significant psychological distress immediately, 25% at 3 months; 18% at 6 months, and 11% at 1 year after miscarriage.

Besides the feeling of loss, a lack of understanding by others is often important. People who have not experienced it themselves may find it difficult to empathize with what has occurred, and how upsetting it may be. This may lead to unrealistic expectations of the parents' recovery. The pregnancy and the abortion cease to be mentioned in conversations, often because the subject is too painful. This may make the woman feel particularly isolated. Inappropriate or insensitive responses from the medical professionals can add to the distress and trauma experienced, so in some cases attempts have been made to draw up a standard code of practice.

Often interaction with pregnant women and newborn children is painful for parents who have experienced spontaneous abortion. Sometimes this makes interaction with friends, acquaintances, and family very difficult.

Causes
Abortions may occur for many reasons, not all of which can be identified. Some of these causes include genetic, uterine, or hormonal abnormalities, reproductive tract infections, and tissue rejection.

First trimester
Most clinically apparent spontaneous abortions (two thirds to three-quarters in various studies) occur during the first trimester.

Chromosomal abnormalities are found in more than half of embryos aborted in the first 13 weeks. An embryro with a genetic problem has a 95% probability of being aborted. Most chromosomal problems happen by chance, have nothing to do with the parents, and are unlikely to recur. Chromosomal problems due to a parent's genes are, however, a possibility. This is more likely to have been the cause in the case of a woman suffering repeated spontaneous abortions, or if one of the parents has a child or other relatives with birth defects. Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.

Progesterone deficiency may be another cause. Women diagnosed with low progesterone levels in the second half of their menstrual cycle (luteal phase) may be prescribed progesterone supplements, to be taken for the first trimester of pregnancy. No study has shown that general first-trimester progesterone supplements reduce the risk however, (when a mother might already be losing her baby), and even the identification of problems with the luteal phase as a contributing factor has been questioned.

Second trimester
Up to 15% of pregnancy losses in the second trimester may be due to uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions also may contribute to premature birth.

One study found that 19% of second trimester losses were caused by problems with the umbilical cord. Problems with the placenta also may account for a significant number of later-term miscarriages.

Risk factors
Pregnancies involving more than one fetus are considered at increased risk.

Uncontrolled diabetes greatly increases the risk also. Because diabetes may develop during pregnancy (gestational diabetes), an important part of prenatal care is to monitor for signs of the disease.

Polycystic ovary syndrome is a risk factor, with 30–50% of pregnancies in women with PCOS being aborted during the first trimester. Two studies have shown treatment with the drug metformin significantly lowers the rate of abortion in women with PCOS (the metformin-treated groups experienced approximately one-third the miscarriage rates of the control groups). A 2006 review of metformin treatment in pregnancy found insufficient evidence of safety, however, and did not recommend routine treatment with the drug.

High blood pressure during pregnancy, known as preeclampsia, is sometimes caused by an inappropriate immune reaction (paternal tolerance) to the developing fetus, and is associated with the risk of spontaneous abortion. Similarly, women with a history of recurrent spontaneous abortions are at risk of developing preeclampsia.

Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. The presence of certain immune conditions such as autoimmune diseases is associated with a greatly increased risk. The presence of anti-thyroid autoantibodies is associated with an increased risk with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6.

Certain illnesses (such as rubella, chlamydia and others) increase the risk.

Tobacco (cigarette) smokers have an increased risk of spontaneous abortion. An increase in the rates also is associated with the father being a cigarette smoker. The husband study observed a 4% increased risk for husbands who smoke fewer than 20 cigarettes/day, and an 81% increased risk for husbands who smoke 20 or more cigarettes/day.

Cocaine use increases the rates. Physical trauma, exposure to environmental toxins, and use of an IUD during the time of conception have also been linked to increased risk.

Antidepressants specially paroxetine and venlafaxine can lead to spontaneous abortion.

The age of the mother is a significant risk factor. Spontaneous abortion rates increase steadily with age, with more substantial increases after age 35.

Several other factors have been correlated with higher rates in some research, but whether they cause the abortions is debated. No causal mechanism may be known, the studies showing a correlation may have been retrospective (beginning the study after the abortions occurred, which may introduce bias) rather than prospective (beginning the study before the women became pregnant), or both. A greater correlation has been shown in the following categories, however.

Autoimmune disease
Some research suggests autoimmunity as a possible cause of recurrent or late-term abortions. Autoimmune disease occurs when the body's own immune system acts against itself. Therefore, in the case of an autoimmune-induced abortions the woman's body attacks the growing fetus or prevents normal pregnancy progression. Further research also has suggested that autoimmune disease may cause genetic abnormalities in embryos which in turn may lead to spontaneous abortion.

Morning sickness
Nausea and vomiting of pregnancy (NVP, or morning sickness) are associated with a decreased risk. Several mechanisms have been proposed for this relationship, but none are widely agreed upon. Because NVP may alter a woman's food intake and other activities during pregnancy, it may be a confounding factor when investigating possible causes of spontaneous abortion.

Exercise
Another factor is exercise. A study of more than 92,000 pregnant women found that most types of exercise (with the exception of swimming) correlated with a higher risk of aborting prior to 18 weeks. Increasing time spent on exercise was associated with a greater risk: an approximately 10% increased risk was seen with up to 1.5 hours per week of exercise, and a 200% increased risk was seen with more than 7 hours per week of exercise. High-impact exercise was especially associated with the increased risk. No relationship was found between exercise rates after the 18th week of pregnancy. The majority of abortions had already occurred at the time women were recruited for the study, and no information on nausea during pregnancy or exercise habits prior to pregnancy was collected.

Caffeine
Caffeine consumption also has been correlated to spontaneous abortion rates, at least at higher levels of intake. A 2007 study of more than 1,000 pregnant women found that those who reported consuming 200 mg or more of caffeine per day experienced a 25% rate, compared to 13% among women who reported no caffeine consumption. 200 mg of caffeine is present in 10 oz (300 mL) of coffee or 25 oz (740 mL) of tea. This study controlled for pregnancy-associated nausea and vomiting (NVP or morning sickness): the increased rate for heavy caffeine users was seen regardless of how NVP affected the women. About half of the abortions had already occurred at the time women were recruited for the study. A second 2007 study of approximately 2,400 pregnant women found that caffeine intake up to 200 mg per day was not associated with increased rates (the study did not include women who drank more than 200 mg per day past early pregnancy). A prospective cohort study in 2009 showed no increased risk.

Diagnosis
A spontaneous abortion may be confirmed via ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. Genetic tests also may be performed to look for abnormal chromosome arrangements.

Management
Bleeding during early pregnancy is the most common symptom of both impending abortion and of ectopic pregnancy. Pain does not strongly correlate with the former, but is a common symptom of ectopic pregnancy. Typically, in the case of blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, serial βHCG tests should be performed to rule out ectopic pregnancy, which is a life-threatening situation.

If the bleeding is light, making an appointment to see one's doctor is recommended. If bleeding is heavy, there is considerable pain, or there is a fever, then seeking emergency medical attention is recommended.

Whilst bed rest has been advocated in the past to help ensure that a threatened pregnancy might continue, and in one study possibly helped when small subchorionic hematoma had been found on ultrasound scans, the prevailing opinion is that this is of no proven benefit.

No treatment is necessary for a diagnosis of complete abortion (so long as ectopic pregnancy is ruled out). In cases of an incomplete abortion, empty sac, or missed abortion there are three treatment options:
 * With no treatment (watchful waiting), most of these cases (65–80%) will pass naturally within two to six weeks. This path avoids the side effects and complications possible from medications and surgery, but increases the risk of of mild bleeding, need for unplanned surgical treatment, and incomplete abortion.
 * Medical management usually consists of using misoprostol (a prostaglandin, brand name Cytotec) to encourage completion of the natural process. About 95% of cases treated with misoprostol will complete within a few days.
 * Surgical treatment (most commonly vacuum aspiration, sometimes referred to as a D&C or D&E) is the fastest way to complete the process. It also shortens the duration and heaviness of bleeding, and avoids the physical pain associated with the abortion. In cases of repeated spontaneous abortions, D&C is also the most convenient way to obtain tissue samples for karyotype analysis (cytogenetic or molecular), although it is also possible to do with expectant and medical management. D&C, however, has a higher risk of complications, including risk of injury to the cervix (e.g. cervical incompetence) and uterus, perforation of the uterus, and potential scarring of the intrauterine lining (Asherman's syndrome). This is an important consideration for women who would like to have children in the future and want to preserve their fertility and reduce the chance of future obstetric complications.

Prevention
Currently there is no known way to prevent an impending abortion, however, fertility experts believe that identifying the cause of the miscarriage may help prevent it from happening again in a future pregnancy. In one study, researchers found that use of the supplement dehydroepiandrosterone before and during pregnancy reduced the risk of pregnancy losses.

Epidemiology
Determining the prevalence of spontaneous abortions is difficult. Many happen very early in the pregnancy, before a woman may know she is pregnant. Treatment of women without hospitalization means medical statistics misses many cases. Prospective studies using very sensitive early pregnancy tests have found that 25% of pregnancies abort by the sixth week LMP (since the woman's last menstrual period), however, other reports suggest higher rates. One fact sheet from the University of Ottawa states, "The incidence of spontaneous abortion is estimated to be 50% of all pregnancies, based on the assumption that many pregnancies abort spontaneously with no clinical recognition." The NIH reports, "It is estimated that up to half of all fertilized eggs die and are lost (aborted) spontaneously, usually before the woman knows she is pregnant. Among those women who know they are pregnant, the miscarriage rate is about 15–20%." Clinical abortions (those occurring after the sixth week LMP) occur in 8% of pregnancies.

The risk of aborting decreases sharply after the 10th week LMP, i.e., when the fetal stage begins. The loss rate between 8.5 weeks LMP and birth is about two percent; loss is “virtually complete by the end of the embryonic period."

The prevalence increases considerably with age of the parents. One study found that pregnancies from men younger than 25 years are 40% less likely to end in spontaneous abortion than pregnancies from men 25–29 years. The same study found that pregnancies from men older than 40 years are 60% more likely to end in spontaneous abortion than the 25–29-year age group. Another study found that the increased risk in pregnancies from older men is mainly seen in the first trimester. Yet another study found an increased risk in women, by the age of 45, on the order of 800% (compared to the 20–24 age group in that study), 75% of pregnancies ended in spontaneous abortion.

In other animals
Abortion occurs in all animals that experience pregnancy. There are a variety of known risk factors for it in non-human animals. For example, in sheep, it may be caused by crowding through doors, or being chased by dogs. In cows, spontaneous abortion may be caused by contagious disease, such as Brucellosis or Campylobacter, but often can be controlled by vaccination. Other diseases are also known to make animals susceptible. Spontaneous abortion occurs in pregnant Prairie Voles when their mate is removed and they are exposed to a new male, an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory. Female mice who had spontaneous abortions showed a sharp rise in the amount of time spent with unfamiliar males preceding the abortion than those who did not abort.