Miscarriage- Definition and Introduction
A miscarriage (also known as abortion) is a pregnancy that ends before the baby can survive outside the womb because it has not yet reached viability. A miscarriage may be early - during the first 14 weeks of pregnancy, or late. The vast majority are early - only about 1% of miscarriages are late.
The definition of a miscarriage is a spontaneous loss of a pregnancy before 24 weeks: in the UK we calculate the duration of a pregnancy from the first day of the last period (LMP). A miscarriage - the medical term for an early pregnancy loss is abortion - tends to start with bleeding, and pain may then develop. Sometimes there may be bleeding early in the pregnancy but the pregnancy continues (threatened abortion). An inevitable abortion means that the pregnancy cannot be salvaged. It may be incomplete, with pregnancy products still in the cavity of the womb or complete with nothing remaining.on
The combination of modern pregnancy tests and ultrasound will usually determine the situation quite quickly. Pregnancy tests these days should become positive within ten days of conception (i.e. even before the first missed period). Ultrasound begins to show a pregnancy within the uterus by five or six weeks (a week or two after the first missed period). On occasion, it may be too early to diagnose the situation accurately and tests may need to be repeated to see what changes occur.
Prevalence Of Miscarriage
It is thought that between 10 and 20% of pregnancies miscarry. Most miscarriages occur in the early weeks of pregnancy. Ultrasound screening for fetal anomaly has shown the incidence of non-viable pregnancy at 10-13 weeks to be 2.8%
- The prevalence of non-viable pregnancy at 10-13 weeks of gestation. (1996-01)
- Incidence of early loss of pregnancy (1988)
- Unsuspected pregnancy loss in healthy women (1983)
Cause of Miscarriage
Often the cause of a miscarriage remains unknown. The most common cause for miscarriage is a blighted ovum - the afterbirth type tissues develop but there is no baby. Another common cause is a genetic defect and nature decides not to allow the pregnancy to continue. Smoking and obesity may contribute to miscarriage but do not cause miscarriage by themselves. Similarly, stress may play a role in pregnancy loss, but it hasn't been shown to cause miscarriage on its own. Cause for recurrent miscarriages is discussed Q12.16 to Q12.21.
The first miscarriage symptom is vaginal bleeding, which can range from spotting to being heavier than a period. A little spotting may be an early sign of miscarriage although fortunately this may amount to no more than a threatened miscarriage and the pregnancy continues. The second miscarriage symptom is pelvic pain. The third miscarriage symptom is cessation of pregnancy symptoms including breast tenderness, morning sickness and having to pass urine more frequently than usual. Some women have no miscarriage symptom and the discovery is made at ultrasound examination.
Types of miscarriage
Table 12.1 indicates the various terms most frequently associated with miscarriage.
|Types of Miscarriage||Description|
|Spontaneous Miscarriage||This is when the miscarriage occurs naturally as opposed to being induced.|
|Induced Miscarriage||The pregnancy is terminated artificially.|
|Threatened Miscarriage||There is bleeding and sometimes pelvic pain but the cervix is closed and ultrasound indicates an ongoing pregnancy within the uterus.|
|Inevitable Miscarriage||The pregnancy is not continuing.|
|Complete Miscarriage||An inevitable miscarriage and the uterus has completely emptied itself.|
|Incomplete Miscarriage||An inevitable miscarriage with products of the pregnancy still present in the uterus.|
|Missed Miscarriage||There are no reasons to have suspected that the pregnancy is not going to continue but the embryo has died.|
|Septic Miscarriage||The miscarriage has been complicated by infection.|
|Recurrent or Habitual Miscarriage||Most authorities recommend that these terms should be used only for three or more consecutive miscarriages although there is a tendency towards two.|
|Early Miscarriage||Miscarriage in the first few weeks of the pregnancy.|
|Late Miscarriage||Miscarriage after the first few weeks.|
|First trimester Miscarriage||Miscarriage before thirteen weeks of pregnancy.|
|Second trimester Miscarriage||Miscarriage after thirteen weeks and before twenty four weeks.|
Sometimes there may be no sign or symptom to suggest miscarriage and pregnancy symptoms continue, and the miscarriage is only discovered in a routine scan. This is a missed miscarriage. A threatened miscarriage occurs when there is vaginal bleeding but ultrasound confirms a viable pregnancy.
Normally the fertilised egg divides and part becomes the embryo (future baby) and part becomes the afterbirth type tissue (trophoblast) and the membranes that form a fluid filled bag around the baby. When there is a blighted ovum, the afterbirth tissues develop alone without the development of the baby. Blighted ovum hasalso been referred to as an 'anembryonic pregnancy'. Nearly half of early miscarriages are associated with a blighted ovum. It is likely that abnormal chromosomes are more prevalent.
This is a benign tumour of the trophoblast (afterbirth tissues) characterised by vesicles which look like small grapes. Usually a hydatidiform mole develops without an embryo but this is not always the case. As hydatidiform moles produce a relatively high level of the pregnancy hormone HCG, there tends to be an increased incidence of excessive vomiting in early pregnancy. The diagnosis is usually made from the typical ultrasound picture. The womb will need to be carefully emptied by suction. Very rarely, there is subsequently evidence of malignancy (choriocarcinoma). It is therefore essential that you are carefully monitored for a few months by hormone tests on your urine. These days choriocarcinoma can be treated successfully by chemotherapy (Q32.33).
Pictures of a hydatidiform mole from www.hmole-chorio.org.uk
Picture of Hydatidiform Mole
- Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy. (2005-01)
- Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53. (2004-01)
- Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy. (2004-02)
Pregnancy tests are designed to determine the presence of the pregnancy hormone HCG. Until twenty years ago, pregnancy tests were biological, relying on the affects of the hormone on animals. There could be a cross-reaction with other hormones, notably LH. Many women reaching the menopause could have a false alarm as LH levels rise at the menopause and when they missed their periods their pregnancy tests could be falsely positive. Modern pregnancy tests are monoclonal they react only with the specific hormone they are designed to detect. In the early weeks of pregnancy, the HCG level doubles every two days. Whereas the old pregnancy tests would become positive with a concentration of 3,000 IU (about two weeks after the missed period) the monoclonal tests show a positive result at between 25 and 50 IU and these levels are reached before a period is missed.
The accuracy of modern pregnancy tests are not only useful in the early detection of pregnancy but also in assisting in the management of early pregnancy problems such as threatened miscarriage or possible ectopic pregnancy.
A lady presented with vaginal bleeding and left sided pelvic pain. Her pregnancy test was positive and ultrasound did not show any sign of a pregnancy either within or outside the uterus (ectopic pregnancy). Her beta HCG level was 365 units suggesting a very early pregnancy at most. Two days later the level had fallen to 180 units which indicated that the pregnancy was not continuing. We could not say for certain whether this had been an intra-uterine pregnancy that miscarried or a possible ectopic pregnancy that was being resolved by nature but no operative intervention was required.
Treatment of Miscarriage
The options for managing miscarriages are outlined in Figure 12.1. If miscarriage is threatened, you will usually be advised to rest for a few days and a repeat scan will confirm whether the pregnancy is continuing. There have been several important developments in the management of miscarriage in recent years. The combination of highly sensitive pregnancy tests and ultrasound will usually assist in providing an accurate diagnosis. Many hospitals now have an early pregnancy assessment unit that specialise in these problems. This should allow you to see an expert in a dedicated area where you can receive sympathetic assistance away from busy, and often fraught, accident and emergency departments.
Flowchart showing a flowchart for the treatment management for miscarriage.
At one time, we believed that if you miscarried between seven and thirteen weeks, there were likely to be retained products of pregnancy and an ERPC (evacuation of retained products of conception) was indicated to reduced the risk of infection and bleeding. In the days before legal termination of pregnancy (Chapter 19) infection with induced abortion was relatively common. These septic abortions could be life threatening. Current opinion is that the risk of infection and bleeding has been overstated and a conservative approach now seems safe. From your point of view, this means that you may not need an operation which, as always, carries an element of risk (surgery risks) and furthermore delays waiting for an operation slot are avoided. A repeat scan about ten days after the diagnosis of incomplete abortion will usually confirm that nature has solved the problem for you and the womb has completely emptied itself. If a miscarriage is incomplete, oral misoprostol 600 micrograms may be as safe as surgical evacuation.
If you are Rhesus negative you should be offered an injection of Anti-D to reduce the chance of rhesus problems in a future pregnancy. Guidelines for the administration of Anti-D are currently under review.
The emotional aspects of miscarriage can be difficult to deal with particularly if you have had difficulty conceiving or if this is not your first miscarriage. There is inevitably a time of grieving. A trained counsellor with a special interest in miscarriage can provide support and help you come to terms with your loss.
What is meant by recurrent miscarriage?
Miscarriage is an emotionally challenging ordeal accompanied by all the feelings of bereavement. When it occurs more than once it may, understandably, be a devastating experience. Most experts suggest that investigations to detect the cause of recurring miscarriage should begin after three consecutive pregnancy losses. Regional centres have difficulty coping with referrals even for women who have miscarried three times. For those who have miscarried twice, this seems harsh. If we are pedantic, when something recurs it has happened more than once so the second miscarriage is obviously a recurrence. Some departments, have revised their criteria so that consultation and some investigations can commence after two consecutive miscarriages.
As the majority of pregnancies, even after three miscarriages, are likely to be successful, it is particularly difficult to scientifically prove that a particular treatment is effective. The one cause of miscarriage that can be detected and for which there is effective treatment is increased levels of antiphospholipid antibodies. The blood tests are for lupus anticoagulant and anticardiolipin. If these prove to be positive, Aspirin (75mg daily) particularly in combination with heparin, significantly reduces the likelihood of miscarriage.
The incidence of early pregnancy loss doubles from the age of 20 to 40 years and evidence from IVF with egg donation suggests that increased miscarriage problems in older women may be partly attributable to the state of the uterus. A recent study in Bologna, Italy compared implantation and pregnancy rates in an oocyte donation programme with women of different ages sharing oocytes from the same donor: clinical pregnancy rates and ongoing pregnancy rates were twice as likely in recipients of less than forty years old compared to older recipients.
(A guide to pregnancy after suffering the loss of an infant, miscarriage, or stillbirth. Issues discussed include: the facts about pregnancy loss and neonatal death; how to determine if you're ready for another pregnancy; common fertility myths; support after you've decided to tell people you're pregnant again; and prenatal testing risks and benefits. The book offers a helping hand to women coping with their loss and at the same time contemplating future pregnancies.)
Can miscarriage and recurrent miscarriage result in symptoms of anxiety and depression?
It is more than understandable that miscarriage is frequently associated with depression and anxiety for both the female and male partners. A miscarriage can be associated with all the symptoms associated with bereavement and reactive depression is a common feature. There may be anxiety that there may be difficulty achieving a family particularly if miscarriage has occurred before.(Q12.20).
- Is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care? Results from a randomised trial in Burkina Faso, West Africa.(2007-01)
- Economic evaluation of alternative management methods of first-trimester miscarriage based on results from the MIST trial. (2006-01)
- Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). (2006-02)
- Expectant care versus surgical treatment for miscarriage. (2006-03)
- Expectant, medical, or surgical management of first-trimester miscarriage: a meta-analysis. (2005-01)
- A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage. (2005-02)
- A randomized controlled trial comparing medical and expectant management of first trimester miscarriage. (2004-01)
- Expectant management of early pregnancies of unknown location: A prospective evaluation of methods to predict spontaneous resolution of pregnancy (2001)
- The treatment of incomplete miscarriage with oral misoprostol (2001)Randomised trial comparing expectant with medical management for first trimester miscarriages. (1999)
- Early pregnancy assessment; A role for the gynaecology nurse-practitioner. (1999)Expectant management of missed miscarriage. (1998)
- Randomised trial of expectant versus surgical management of spontaneous miscarriage (1997)
- Expectant management versus elective curettage for the treatment of spontaneous abortion (1997)
- The spontaneous pregnancy prognosis in untreated subfertile couples: The Walcheren primary care study. (1997)
- Expectant management versus elective curettage for the treatment of spontaneous abortion. (1997)
Pregnancy after Miscarriage.
If you are pregnant after miscarriage, the chances are that the pregnancy will be successful. Even after three miscarriages, your chance of a successful pregnancy is 55%.
Usually nature has detected some problem such as a chromosome abnormality (genes - chromosomes) and decides that it is in your interests to discontinue this pregnancy and give you an early chance to start a successful one. A blighted ovum (Q12.4), or an embryo with an abnormality would be reasons for spontaneous miscarriage. Occasionally there may be a different and perhaps remedial cause which would need consideration if you have three miscarriages.
There is some evidence that an initial miscarriage is associated with a higher risk of obstetric complications in the next continuing pregnancy.0801
- Maternal smoking predicts the risk of spontaneous abortion. (2006-01)
- Obesity in pregnancy. (2006-02)
- Paternal age and spontaneous abortion. (2006-03)
- Cocaine and tobacco use and the risk of spontaneous abortion (1999)
- The role of consanguinity and inbreeding as a determinant of spontaneous abortion in Karachi, Pakistan (1998)
- Determinants of risk of spontaneous abortions in the first trimester of pregnancy. (1997)
- A prospective study of work-related physical exertion and spontaneous abortion. (1997)
- Caffeinated beverages, decaffeinated coffee, and spontaneous abortion (1997)
- Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion (1996)
- Tree-based, two-stage risk factor analysis for spontaneous abortion (1996)
- Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception.(1988)
- Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome (1988)
- Risk factors for spontaneous abortion and its recurrence. (1988-03)
- Drinking during pregnancy and spontaneous abortion. (1980-01)
What is the chance of a successful pregnancy after recurrent miscarriage?
This depends on the number of consecutive miscarriages that you have had (Table 12.2).
Table 12.2 The chance of subsequent miscarriage related to previous number of consecutive miscarriages.
|Number of Previous Miscarriages||% Future Successful Pregnancies|
Whilst this is to some extent reassuring, it means that the potential value of a new treatment is difficult to determine as a healthy baby could be as much due to chance as to the treatment. Large numbers of patients are required in controlled trials to demonstrate any true benef
Why do I keep miscarrying?
It is sad enough to lose one pregnancy but it is particularly devastating when this problem recurs; you will have the sympathies of all concerned.
Pregnancy may fail at any time from implantation to
childbirth. The majority of unsuccessful pregnancies will
fail in the first four months first trimester. About one
pregnancy in five or six will result in a first trimester
pregnancy loss about the same chance as rolling a 1 with a
dice. When a miscarriage occurs the question to be answered
is Was this just chance?
. If you roll the dice once and get a 1 it seems reasonable to assume this is chance. A second 1 may still be chance but by the third consecutive 1 there is more than a suspicion that the dice is weighted. The investigation of recurrent miscarriage is really designed to check in the first instance whether the dice has been weighted and whether it is possible to get a new and fairer dice (Q12.6).
A successful pregnancy requires a healthy egg and a healthy sperm. The resulting embryo must be perfect and the womb capable of sustaining the pregnancy. There is a requirement for a series of appropriate changes in hormone production. When evaluating the potential value of the numerous tests that can be considered we need to determine how relevant the result may be to determining the likelihood of a further miscarriage and particularly whether the result would influence treatment. During investigation, observations may be made that are incidental and not necessarily the cause of recurrent miscarriage (Q4.3). We are looking for a cause for which there is evidence based effective treatment (Q33.24).
Before considering the possible causes of recurrent miscarriage it should be emphasised at the outset that there is only one investigation that may identify a problem for which there is effective treatment, the antiphospholipid antibody tests (Q12.17). A diagnosis of polycystic ovary syndrome may lead to treatment with metformin which looks promising but it will take time before controlled trials have been undertaken to determine whether it is effective in reducing recurrent miscarriage.
The causation of a clinical problem may be reviewed under the headings identified in Q3.2. In Table 12.3 this grouping has been applied to recurrent miscarriage. Recurrent miscarriage is one of the most difficult clinical problems to identify the cause as it involves eggs, sperm, embryos, uterus and hormones.
'TORCH' infections; Endometrial Infection; Syphilis.
Hormone deficiency; LH excess (PCOS)
Anxiety / depression
Congenital uterine abnormality; Fetal abnormality
'TORCH' infections; Endometrial Infection; Syphilis.
Hormone deficiency; LH excess (PCOS)
Anxiety / depression
- An informative protocol for the investigation of recurrent miscarriage: Preliminary experience of 500 consecutive cases (1994)
Could A Congenital Abnormality Cause Recurrent Miscarriage?
It is now recognised that some inherited defects in the normal anticoagulant mechanism of the blood may be related to recurrent miscarriage. When tissues are cut they bleed and the blood should clot (coagulation) to stop the bleeding. There is a cascade of chemical changes in the blood that lead to this coagulation. The body also produces a set of chemicals that prevent the blood clotting inappropriately - these are anticoagulants. There is increasing interest in a number of inherited defects in these anticoagulants including activated protein C resistance, which is usually due to Factor V Leiden gene mutation, deficiencies of Protein C or S, antithrombin III, hyperhomocystinaemia, and prothrombin gene mutation. About 10% of women with recurrent miscarriages will prove to have inherited thrombophilia compared to 3% of controls. It is believed that anticoagulation treatment with aspirin 75 mg daily or injections of heparin may improve the prognosis but more research is required in this area.
Congenital structural abnormality may relate to the uterus or the fetus. Congenital uterine abnormalities are discussed in Q3.3 . It is not uncommon to find evidence of a congenital uterine abnormality during investigation of recurrent miscarriage. Many women with congenital uterine abnormality seem to have uneventful pregnancies. It is not certain whether there is an increased incidence of congenital uterine abnormality in association with recurrent miscarriage. There have been many women who have conceived whilst awaiting corrective uterine surgery and these pregnancies have proceeded uneventfully suggesting that the abnormality was not preventing a successful outcome. Controlled studies (placebo & controlled trials) are awaited to determine whether surgery reduces recurrent miscarriage.
Genetic evaluation of the embryo or placental tissue is only possible in about 60% of cases even in dedicated university departments. It would appear that in 50-60% of miscarriages there is evidence of chromosome defects. Recent developments in DNA analysis may indicate that an even higher proportion of miscarriages may be genetic. At this time there is no known treatment that would reduce the incidence of genetic disorders.
Parental chromosome abnormalities may be found in about 6% of couples with three miscarriages or more. These families require counselling from geneticists (doctors who specialise in gene disorders). Advice can be given on the chance of successful pregnancy and the risk of producing a child with a genetic disorder. On rare occasions, it may be appropriate to consider donated gametes, i.e. donor insemination (23) if the problem is with the male partner and IVF/ donated ova (IVF - egg donation) if the problem is with the woman.
A woman of 30 was investigated for recurrent miscarriage and was found to have a balanced translocation between chromosomes 8 and 14 (genes - chromosomes). This causes no difficulties for the lady as she has all the required genetic material, albeit in an incorrect order. The problem is that her gametes (eggs) may contain an incorrect amount of chromosomes 8 and 14, which almost certainly accounts for recurrent miscarriage. A pregnancy could continue with a 5% risk of physical or intellectual problems for the baby. The options open to this couple were to continue trying for a pregnancy and in the event of success to accept CVS or amniocentesis (Q19.3) to check the baby's chromosomes. A second option would be IVF with donated eggs (IVF - egg donation).
Preimplantation genetic diagnosis can be beneficial for three major subgroups of patients with recurrent pregnancy loss:
- couples carrying chromosomal translocations
- women more than 35 years of age
- women of any age whose previous miscarriages were due to fetal aneuploidy.
It is likely that the rate of miscarriage will be further reduced with the new advances in methods of performing preimplantation genetic diagnosis for more chromosomes.0801
- Can preimplantation genetic diagnosis overcome recurrent pregnancy failure?(2008-01)
- Embryonic karyotype in recurrent miscarriage with parental karyotypic aberrations. (2006-01)
- Parental karyotype and subsequent live births in recurrent miscarriage. (2004-01)
- Female genital anomalies affecting reproduction. (2002)information?
- Clinical implications of uterine malformations and hysteroscopic treatment results (2001)
- Karyotype of the abortus in recurrent miscarriage (2001)?
- Ultrasound screening for congenital uterine anomalies (1997)
- Chromosomal analysis in Japanese couples with repeated spontaneous abortions (1990)
What traumatic conditions might be associated with miscarriages?
The cervix (neck of the womb) should remain closed through pregnancy but in labour it must stretch to allow the baby through. Cervical incompetence is characterised by weakness of the cervix allowing it to open without the typical labour pains, expelling the fetus during the middle weeks of pregnancy (mid-trimester miscarriage). For the cervix to be incompetent the internal os (top end of the cervix) must be weak. It is possible for the cervix to be weak from the outset particularly in association with congenital uterine abnormality. Cervical incompetence can result from outmoded traumatic obstetric delivery but we now resort to Caesarean section rather than difficult forceps delivery. Stretching the cervix beyond 10mm to terminate pregnancy may be a factor in cervical incompetence and every care is taken to avoid damage to the cervix during these procedures. Cone biopsy of the cervix (Q12.14) could theoretically damage the cervix but again care is taken to avoid the internal os and studies of the outcome of pregnancy following the modern loop cone procedures provide reassurance.
The diagnosis of cervical incompetence is not easy. Painless miscarriage may occur when there was no apparent reason to predict that this would occur. Serial ultrasound assessment of the cervix looking for evidence of the internal os opening may be a reasonable approach. The treatment of cervical incompetence is a special stitch (cervical cerclage), which acts as a purse-string. No operation is without complication (surgery risks). Controlled studies (Q33.24) have not demonstrated that cervical cerclage is as beneficial as we originally believed. An interesting recently published concept is that the stitch may work by preventing bacteria ascending from the vagina into the uterus rather than as a mechanical barrier stopping the cervix from opening.
Can Infection Cause Recurrent Miscarriage?
Any acute infection in pregnancy can sometimes result in miscarriage.
Listeriosis is caused by the Listeria bacterium which has the unusual ability to grow over a wide range of temperatures. Some miscarriages have been associated with this infection which can be acquired from undercooked foods and soft cheeses. Appropriate care with food preparation is particularly important during pregnancy.
The 'TORCH' infections (Toxoplasmosis, Rubella, Cytomegalovirus and Herpes may be associated with miscarriage. Each of these infections, however, can occur on one occasion only as immunity is then acquired. It is, therefore, not possible for any one of these infections to be responsible for recurrent miscarriage. Toxoplasmosis is an infection acquired from the domestic cat. It has been shown that one woman in five in the UK has evidence of infection prior to pregnancy and this compares to 80% in France. The incidence of infection during pregnancy in the UK is low. Rubella is also known as German measles. Rubella infection can be prevented by immunisation. Cytomegalovirus can produce a flu-like illness. About 50% of women will have had this infection before pregnancy. Herpes infection is discussed in 3.
There has recently been increasing interest in the role of bacterial infection in relation to miscarriage and premature labour. Bacterial vaginosis (Q 22.7) has been implicated in some studies but not all. The difficult question that remains to be answered is whether the bacteria that may be found in association with some miscarriages are the cause of the problem or whether they are opportunistic and proliferate as a result of the miscarriage.
- Ureaplasma urealyticum in semen: Is there any effect on in vitro fertilization outcome? (1999)information?
- Pre-implantation endometrial leukocytes in women with recurrent miscarriage. (1999)information?
- Influence of bacterial vaginosis on conception and miscarriage in the first trimester: Cohort study. (1999)information?
- Association of bacterial vaginosis with a history of second trimester miscarriage (1996)information?
- Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. (1994)information?
- Outcome of subsequent pregnancies following antibiotic therapy after primary or multiple spontaneous abortions (1986)information?
- Efficacy of antibiotic therapy in preventing spontaneous pregnancy loss among couples colonized with genital mycoplasmas. (1983)
Can a Metabolic condition cause recurrent miscarriage?
There has been a suggestion that deficiencies of minerals such as zinc may be a cause of miscarriage but there are no controlled trials to demonstrate the efficacy of supplements.
Obesity has been shown to increase the risk of recurrent miscarriage but it is not known whether it is a direct effect or if PCOS underlies the obesity and recurrent miscarriage. Smoking increases the risk of miscarriage but it is not known how the body chemistry is affected. One study in Italy found that the risk of miscarriage is increased by 40% in smokers.
- Recurrent miscarriage - An aspirin a day? (2000)
- Association of reduced selenium status in the aetiology of recurrent miscarriage. (1999)
- Risk of recurrent spontaneous abortion, cigarette smoking, and genetic polymorphisms in NAT2 and GSTM1. (1998)
- Spontaneous abortion in a hospital population Are tobacco and coffee intake risk factors? (1994)
Can a hormonal problem cause recurrent miscarriage?
It is tempting to assume that administration of the pregnancy hormones HCG and progesterone would increase the chance of a successful outcome but there is no definite evidence to demonstrate that these treatments are effective. Some women have heard anecdotal stories of hormones being successful. Most IVF centres advocate hormone supplements in pregnancy and there is no evidence of any adverse effects. Gestone (progesterone) 100 mg injections, HCG 5000 units by injection, Crinone (progesterone) 4 or 8% on alternate days and Cyclogest pessaries 400mg each night until about 14 weeks are typical regimens.
An elevated FAI appears to be a prognostic factor for a subsequent miscarriage in women with recurrent miscarriage and is a more significant predictor of subsequent miscarriage than an advanced maternal age (> or =40 years) or a high number (> or =6) of previous miscarriages in this study.0801
PCOS (Q7.2) and high levels of LH are thought to be associated with miscarriage. It may be that metformin will prove to be effective, if there is evidence of such problems, but it will be some while before we have evidence.
- Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage?(2008-01)
- Recurrent pregnancy loss and inappropriate local immune response to sex hormones. (2007-01)
- Polycystic ovaries and recurrent miscarriage - A reappraisal (2000)
- Endocrine abnormalities during the follicular phase in women with recurrent spontaneous abortion. (1999)
- Hyperprolactinemic recurrent miscarriage and results of randomised bromocriptine treatment trials (1998)
- Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial (1996)
- Human chorionic gonadotropin supplementation in recurring pregnancy loss: A controlled trial (1994)
- Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: Prospective study in 50 women (1993)
- Luteinizing hormone: Its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase (1993)
- Human chorionic gonadotrophin (hCG) in the management of recurrent abortion; results of a multi-centre placebo-controlled study (1992)
- Hypersecretion of luteinising hormone, infertility, and miscarriage (1990)
Can an autoimmune problem cause recurrent miscarriage?
An autoimmune disease is an illness that occurs when the body tissues are attacked by its own immune system. The immune system is a complex organization within the body that is designed normally to "seek and destroy" invaders of the body, including infectious agents. Patients with autoimmune diseases frequently have unusual antibodies circulating in their blood that target their own body tissues. Examples of autoimmune diseases include:-
- systemic lupus erythematosus,
- Sjogren syndrome,
- Hashimoto thyroiditis,
- rheumatoid arthritis,
- juvenile (type 1) diabetes,
- Addison disease,
- pernicious anemia,
- glomerulonephritis, and
- pulmonary fibrosis.
There are two issues to consider in the context of a possible autoimmune causation of recurrent pregnancy loss the antiphospholipid antibodies and alloimune pregnancy loss.
Lupus anticoagulant and anticardiolipin are two antiphospholipid antibodies that have been associated with miscarriage. They increase the chance of the blood clotting (throbophilia - Q12-12) and this may damage the placenta . When they are present, and not treated, a live birth can only be expected in 25-50% of subsequent pregnancies. Scientifically controlled trials have demonstrated that low-dose aspirin in combination with heparin will increase the chance of a live birth in women with antiphospholipid antibodies. Many women have taken low dose aspirin in pregnancy apparently without problems. There is no evidence so far that low dose aspirin treatment will improve the outcome if there is no increased antiphospholipid antibodies although in one study involving IVF, low dose aspirin enhanced treatment outcome even in the absence of these antibodies.
In the era of blood transfusion and organ transplantation, we have all become aware of the importance of tissue typing and the problems of the immune response, which limits our choice of donors. In general, tissue typing is likely to show that a child could not donate an organ to its mother. In this context, it is remarkable that during pregnancy the baby is not rejected by the immune system even though the baby's blood comes into direct contact with maternal tissue in the placenta (afterbirth). The immune system is known to change in pregnancy and there must be some adaptation to allow the majority of pregnancies to continue. It has been suggested that some women who recurrently miscarry have a defect in this normal immune adaptation (alloimune pregnancy loss).
One method of treating women with recurrent miscarriage seeks to alter their immune response by immunising them with white blood cells obtained from their partners. It is still uncertain whether this treatment increases the live birth rate. One meta-analysis (Q33.23) suggests that there may be a 10% improvement. If it has a benefit it may be appropriate only for those who are deficient in the relevant antibody (APCA) and also those with a relatively high number of pregnancy losses.
- Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss.(2007-01)
- Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages. (2005-01)
- Factor V leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage (2001-01)
- Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage (2001-02)
- Recurrent miscarriage - An aspirin a day? (2000-01)
- A population-based case-control teratologic study of acetylsalicylic acid treatments during pregnancy (2000-02)
- Primary habitual abortions are associated with high Frequency of Factor V Leiden mutation (2000-03)
- Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. (1999-01)
- The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion. (1999-02)
- Habitual abortions in 678 healthy patients: investigation and prevention. (1999-03)
- Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage. (1999-04)
- Antiphospholipid antibodies in infertile couples with two consecutive miscarriages after in-vitro fertilization and embryo transfer (1999-05)
- Lack of association between antiphospholipid antibodies and first- trimester spontaneous abortion: Prospective study of pregnancies detected within 21 days of conception (1998-01)
- Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospolipid antibodies (or antiphospholipid antibodies) (1997-01)
- Chromosome analysis of aborted conceptuses of recurrent aborters positive for anticardiolipin antibody (1997-02)
- Allogenic leukocyte immunization after five or more miscarriages (1997-03)
- Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: Effect on prostacyclin and thromboxane A2 production (1997-04)
- Adverse pregnancy outcome in the antiphospholipid syndrome: Focus for future research. (1997-05)
- Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. (1997-06)
- Intravenous immunoglobulin treatment of pregnant patients with unexplained recurrent abortions (1996-01)
- Antiphospholipid antibodies in women with habitual abortions. Treatment with prednisone and acetylsalicylic acid during pregnancy (1995-01)
- The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages (1994-01)
- Immunotherapy and recurrent abortion: A randomized clinical trial (1994-02)
- The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages (1994-03)
- Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: Results of a controlled trial. (1993-01)
- Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: Results of a controlled trial (1993-01)
- Lupus anticoagulant: Significance in habitual first-trimester abortion (1993-02)
- Antiphospholipid antibodies in pregnancy: Prevalence and clinical associations. (1993-03)
Could a tumour cause recurrent miscarriage?
fibroids) are extremely common and it follows that one or more fibroids are frequently found during investigation of recurrent miscarriage, although this does not prove that a fibroid is the cause (Q4.3).
Submucosal fibroids may be a factor because they distort the cavity of the womb. Furthermore, as they are amenable to hysteroscopic surgery (Q 24.8) treatment is worthy of consideration. There have been numerous anecdotes of live births after myomectomy (surgical removal of fibroids - 17) but equally there have also been stories of live births in pregnancies that have occurred before planned myomectomy was undertaken. There are no controlled trials (placebo & controlled trials) to demonstrate that myomectomy improves the outcome.
What degenerative process might cause recurrent miscarriage?
There is no doubt that miscarriage occurs more frequently in older women. This may be partly because of the effect of age on the eggs and partly due to reduced function of the uterus.
- Paternal age and spontaneous abortion. (2006-01)
- Impact of maternal age on obstetric outcome. (2005-01)
Could depression cause recurrent miscarriage?
It is natural to feel very low after any loss and a miscarriage is associated with all the feelings of bereavement. Pregnancy can continue unaffected by other bereavements, even the loss of a partner. One study in Japan suggested a relationship between depression and early pregnancy loss.
- Anxiety following miscarriage and the subsequent pregnancy: a review of the literature and future directions. (2004-01)
- Psychiatric morbidity among patients with recurrent miscarriage. (2002-01)
- Depression as a potential causal factor in subsequent miscarriage in recurrent spontaneous aborters. (2002-02)
- Investigation of the cause of miscarriage and its influence on women's psychological distress. (1999)
- Does miscarriage affect the father? (1996)
Is it always possible to explain recurrent miscarriage?
There are many times when we really have no answer we call this idiopathic.
The prognosis for those with unexplained recurrent miscarriage is good.
There have been tremendous advances in our knowledge in recent years. A
paper in 1994 demonstrates how little was known just a short time ago.9401
How can we ensure that I will not miscarry again?
It is an understandable cry from the heart from couples who experience the devastation of recurrent pregnancy loss that there must be one explanation and one perfect treatment. Even if a cause is identified we are unlikely to achieve success rates better than 75% within the foreseeable future. Half of the fifteen percent of pregnancies that miscarry can be attributed to a genetic problem of the embryo and we do not have a remedy for this. It is only in the last ten years that we have begun to find some treatable explanations for recurrent miscarriages.
For those with identified antiphospholipid antibody problems aspirin alone or in combination with heparin has been shown to be beneficial. Twenty percent of women have PCOS (Q7.2) and this syndrome may perhaps account for a greater proportion of recurrent miscarriages. Metformin looks promising on theoretical grounds but we still lack the scientific proof that is required. The role of bacterial infection and the possible benefit of antibiotics is an example of a new area that is being investigated. There is a suggestion that 'tender loving care', with frequent assessment during pregnancy, may help. There is no evidence that hormone support in pregnancy or low-dose aspirin for those without evidence of antiphospholipid antibody problems improves the outcome.
There is some evidence that metformin treatment for PCOS may be beneficial but more robust research is required before it can be implemented in routine clinical care.
- Metformin reduces abortion in pregnant women with polycystic ovary syndrome. (2006-01)
- A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. (2006-02)
- Anticoagulants for the treatment of recurrent pregnancy loss in women without antiphospholipid syndrome. (2005-01)
- Recurrent miscarriage: pathophysiology and outcome. (2005-02)
- Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. (2005-03)
- Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update. (2005-04)
- Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin.(2004-01)
- Pregnancy outcome in patients with a history of recurrent spontaneous miscarriages and documented thrombophilias. (2004-02)
- Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study.(2001-01)
- Guides for practitioners. Recurrent miscarriage: Principles of management. (1998)
- The outcome of in vitro fertilization in unexplained habitual aborters concurrent with secondary infertility (1997)
- Oocyte donation in women with recurrent pregnancy loss (1996)
Recurrent spontaneous miscarriage - Current trends and management (1996)