Definition

The World Health Organisation (WHO) definition of miscarriage is ‘the expulsion or extraction from its mother of an embryo or fetus weighing 500 g or less’ (approximate gestational age of 20-22 weeks, which is considered pre-viable).

Incidence of miscarriage

  • ■ Spontaneous miscarriage occurs in 15-20 per cent of all clinically diagnosed pregnancies. However, the actual loss may be as high as 60 per cent of ‘chemical pregnancies’ diagnosed before the first missed period by estimation of the fi-human chorionic gonadotrophin level.
  • ■ Even after three or more consecutive losses, the chance of a successful pregnancy in the subsequent pregnancy is still at best 75 per cent and at worst about 50 per cent.

Threatened miscarriage

History is typically vaginal spotting or mild vaginal bleeding but with minimum pelvic or lower back pain without loss of any tissue vagi-nally. Threatened miscarriage complicates 15 per cent of pregnancies, and 20 per cent of these will progress to a miscarriage. Threatened miscarriage tends to be associated with a high likelihood of adverse subsequent perinatal outcome with complications including prematurity, small for gestational age, breech presentation, perinatal asphyxia, and increased risk of perinatal death. An ultrasound scan should be done weekly until bleeding has settled.

Inevitable miscarriage

The internal cervical os is dilated, usually preceded by lower abdominal pain and vaginal bleeding.

Septic miscarriage

Septic miscarriage presents with the patient febrile, with significant tenderness over the uterus and lower abdomen. The uterus should be evacuated as soon as the patient is stable. Swabs are taken to identify bacteria for sensitivity to antibiotics. Antibiotics should be commenced. Anaerobic organisms are common (anaerobic streptococci, bacteroides and clostridia). A broad-spectrum antibiotic such as co-amoxiclav 1.2mg i.v. 8-hourly is an ideal single agent for anaerobic and aerobic organisms as it is a potent fi-lactamase inhibitor. Alternative antibiotics include crystalline penicillin G (10 million units i.v. 4-hourly), ampicillin (2g4-hourly), and ofloxacin (400mg once-daily).

Table Features of septic shock syndrome.

Sepsis
Tachypnea (>20 breaths/min)
Tachycardia (>90 beats/min)
Hypotension
Hypothermia (<35°C) or hyperthermia (>38.3°C)
Evidence of inadequate organ perfusion
Hypoxaemia
Elevated plasma lactate
Oliguria (<0.5ml/kg body weight for at least 1 hour in patients with a catheter)
Positive blood cultures

Treatment of anaerobic organisms

Septic shock is caused by Gram-negative organisms in up to 80 per cent of cases and by Gram-positive organisms in up to 20 per cent of cases. It should be treated with metronidazole (500mg i.v. 8-hourly), clindamycin (300-600mg i.v. 6-hourly) or chloram-phenicol (lg in 100ml saline 6-hourly).

Early septic shock is responsive to conventional therapy (i.v. fluids and antibiotics). Refractory septic shock is treated with vasopressors such as dopamine (>6mg/kg/hour).

Complete miscarriage

The fetus, placenta and membranes are passed intact with minimal bleeding or pain. On pelvic examination the uterus is well contracted and the cervix is closed. Retained products of conception are diagnosed by ultrasound scan.

Incomplete miscarriage

Incomplete miscarriage presents with a history of increased vaginal bleeding with crampy lower abdominal pain and the passage of some products of conception. On vaginal examination, tissue may be seen coming through the dilated cervical os. It should be removed with sponge forceps to decrease the uterine bleeding and prevent cervical (vasovagal) shock. If there is profuse vaginal bleeding, 20 units oxytocin in 1000ml normal saline, 5% dextrose or Plasma-Lyte should be given to enhance uterine contractility. It should be run at 10-12 milliunits/min. Evacuation should be carried out as soon as the patient is stable, to reduce blood loss.

Missed miscarriage

Missed miscarriage is the failure to expel the products of conception after death of the embryo. It is clinically recognised by the uterus not being as large as expected for gestation. The symptoms of pregnancy may have disappeared. Ultrasound scanning identifies no fetal heartbeat. Often there is morphological abnormality of the gestation sac.

Management of first trimester miscarriage

1 Expectant

A randomised controlled trial at a gestation of less than 13 weeks has shown that surgical curettage may not be necessary for the resolution of miscarriage. Up to 80 per cent of women may be managed by expectant management. Expectant management results in no subsequent impairment in cumulative conception rates or pregnancy outcome.

2 Medical evacuation

Evacuation is performed with mifepristone and misoprostol.

3 Surgery

Surgical evacuation of the uterus may be preferred for those bleeding heavily with pain, or to avoid inconvenience of not knowing when a miscarriage will take place.

Products of conception

It is usual practice to send products of conception for histology.

Histological analysis of products of conception (histology, karyotype, culture)

The incidence of miscarriage overall is approximately 11.3 per cent, but for women aged 35-40 it is double at 21 per cent and for women over 40 it is double this at 41 per cent. There is a 70 per cent rate of successful outcome of subsequent pregnancies after many treatment regimens, attributable to chance than to specific therapy.

Causes of miscarriage

A diagnosis can be established in up to 50 per cent of cases.

Table Causes of recurrent miscarriage in 195 couples.

First trimester Second trimester Primary miscarriage Secondy miscarriary age Total
Causative factors No. % No. % No. % No. % No. %
Uterine defects 15 12.1 15 12.1 27 20.0 3 5.5 30 15
Cervical incompetence 4 3.2 21 29.6 17 12.6 8 13.3 25 12
Endocrine 9 7.3 1 1.4 9 6.7 1 1.7 10 5
Endometrial infection 20 16.1 9 12.7 21 15.6 8 13.3 29 14
Chromosomal 5 4.0 0 0 4 3.0 1 1.7 5 2
Systemic disorder 0 0 2 2.8 2 1.5 0 0 2 1
Oligospermia 7 5.6 1 1.4 8 5.9 0 0 8 4
Excessive smoking 1 0.8 0 0 1 0.7 0 0 1 0
Total known 61 49.2 49 69.0 89 65.9 21 35.0 110 56
Total unknown 63 50.8 22 31.0 46 34.1 39 65.0 85 43

Chromosomal abnormalities

Forty to sixty per cent of first trimester abortuses have chromosomal anomalies. Five per cent of abnormal karyotypes are abnormalities in the structure of individual chromosomes such as translocation. The majority are numerical abnormalities as a result of errors occurring during gametogenesis (chromosomal non-disjunction during meiosis), during fertilisation (triploidy as a result of disgyny or dispermy) or during the first division of a fertilised ovum (tetraploidy or mosaicism). Autosomal trisomy is the most common with chromosomes 13, 16, 18, 21 and 22 (50-60 per cent incidence).

Polyploidy is a deviation from the normal diploid number of chromosomes (2n = 46) in a cell by a multiple of the haploid number (n = 23). Polyploidy occurs in 10 per cent of abortuses. Triploidy and tetraploidy occur, triploidy most commonly. It originates by dispermy or by the failure of the first or second meiotic division of oocytes or spermatocytes, or less commonly through participation of the second polar body in fertilisation, or by defective segregation of one haploid set of chromosomes during the first zygotic division. Tetraploids originate from the suppression of the first cleavage division (cytokinesis) of a diploid zygote after the duplication of chromosomes. It is associated with hydropic degeneration that may occur as an incomplete hydatidiform mole. The karyotype 45 XO occurs in 7 per cent. Most fetuses with this karyotype are miscarried. In the few who survive (1 in 300) the karyotype is clinically recognisable as Turner Syndrome.

The prevalence of major chromosomal abnormalities in either parent is 3 per cent in those with two or more pregnancy losses. This is five to six times higher than in the general population. About half of all chromosomal abnormalities are balanced reciprocal transloca-tions; 25 per cent are Robertsonian translocations; 12 per cent are sex chromosome mosaicism in the female. The rest are inversions and other sporadic abnormalities. Therefore karyotype of both partners with two or more spontaneous miscarriages should be performed. If a translocation is found in one parent, about 80 per cent of their subsequent pregnancies will miscarry. If miscarriage does not occur in a subsequent pregnancy, fetal cytogenetic studies are indicated because there is about a 3-5 per cent incidence of unbalanced fetal karyotype in these pregnancies. Among couples with a history of both miscarriage and fetal anomalies, the frequency of a chromosomal abnormality in one parent is 23 per cent.

Anomalies of uterine development

Uterine abnormalities occur from 1 in 200 to 1 in 600 women. In women with anomalies of uterine fusion, 20-25 per cent have problems with reproduction. Surgical correction of bicornuate and septate uteri is possible by using transfundal metroplasty techniques or by transcervical hysteroscopic incision of the uterine septum. Hysteroscopic incision of a septate uterus can reduce the pregnancy loss from as high as 95 per cent to 10 per cent.

Other causes/associations with miscarriage

Infections:

  • ■ Toxoplasmosis
  • Ureaplasma uiealyticum (T-mycoplasma)
  • Cblamydia
  • ■ Cytomegalovirus
  • ■ Herpes simplex. Other:
  • ■ Severe congenital heart disease
  • ■ Renal disease with hypertension
  • ■ Maternal and paternal age.

Antiphospholipid syndrome

A recent consensus statement for the preliminary classification criteria for definite antiphospholipid syndrome has been formulated.

Lupus anticoagulant activity is measured by one of the phospholipid-dependent coagulation tests:

  • ■ The activated partial thromboplastin time
  • ■ The kaolin clotting time
  • ■ Dilute Russell’s viper venom time.

Presence of lupus anticoagulant is determined using dilute Russell’s viper venom time (DRWT).

Anticardiolipin antibody can be determined by specific solid phase or enzyme-linked immunoassays. Lupus anticoagulant is found in about 10 per cent of women with recurrent spontaneous miscarriage of undetermined aetiology. Prevalence of either lupus anticoagulant or anticardiolipin antibodies in a normal obstetric population is only about 1 per cent for each antibody. If one of these antibodies is present in women with recurrent miscarriage and no treatment given, spontaneous miscarriage occurs in 90 per cent of the next pregnancies.

Table Preliminary criteria for the classification of the antiphospholipid syndrome.

Clinical criteria:
(1) Vascular thrombosis
One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ, confirmed by imaging or Doppler studies or histopathology that does not identify significant inflammation in the vessel wall
(2) Pregnancy morbidity
(a) One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus; or
(b) One or more premature births of a morphologically normal neonate at or before the 34th week of gestation because of severe pre-eclampsia or eclampsia, or severe placental insufficiency; or
(c) Three or more unexplained consecutive spontaneous miscarriages before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded
Laboratory criteria:
(1) Anticardiolipin antibody of IgG and/or IgM isotype in blood, present in medium or high titre, on two or more occasions, at least 6 weeks apart, measured by a standardised ELISAfor p2-glycoprotein l-dependent anticardiolipin antibodies
(2) Lupus anticoagulant present in plasma, on two or more occasions at least 6 weeks apart, detected according to the guidelines of the International
Society on Thrombosis and Haemostasis in the following steps:
(a) Prolonged phospholipid-dependent coagulation demonstrated on a screening test, e.g. activated partial thromboplastin time, kaolin clotting time, dilute Russell’s viper venom time, dilute prothrombin time, Textarin time
(b) Failure to correct the prolonged coagulation time on the screening test by mixing with normal platelet-poor plasma
(c) Three or more unexplained consecutive miscarriages before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded
(d) Exclusion of other coagulopathies, e.g. factor VIII inhibitor or heparin, as appropriate
Definite antiphospholipid antibody syndrome is considered to be present if at least one of the clinical criteria and one of the laboratory criteria are met

In women with recurrent miscarriage without these antibodies present, miscarriage occurs in approximately 34 per cent of subsequent pregnancies.

Furthermore, fetal heart activity is detected in up to 90 per cent of these pregnancies. Thus, first trimester loss is embryonic, not anembryonic in those with antiphospholipid antibodies.

A recent randomised study in those with a history of three or more fetal losses and persistently positive for antiphospholipid antibodies (excluding those with systemic lupus erythematosus or a history of thrombosis) found that low-dose aspirin (75mg daily) gave a subsequent live birth rate of 80 per cent, compared to placebo who had an 85 per cent live birth rate, who otherwise received supportive care .

Recurrent miscarriage

  • ■ Three consecutive pregnancy losses before the 20th week of gestation.
  • ■ Recurrent miscarriage is infrequent, affecting 1 in 200 couples or 1 in 500 pregnancies.
  • ■ Only 30 per cent of all possible fertilisations result in a viable fetus.
  • ■ There is a lack of randomised treatment trials of sufficient power to demonstrate a significant effect of treatment. Therefore the use of a variety of treatments is often empirical.
  • ■ There is a high placebo response with treatment of miscarriage with ‘tender loving care.

Treatment

■ There is no general agreement about therapy for women with recurrent miscarriage in the presence of lupus anticoagulant or anti-cardiolipin antibodies, because in randomised control trials the birth rate is of the order of 75 per cent in the treatment regimen for women with a history of recurrent miscarriage in the presence of either anti-cardiolipin or antiphospholipid antibodies. The avoidance of stress and supportive care give very good results in randomised trials. Table 2.4 outlines ‘rules’ to achieve stress avoidance, not just coping skills, as based on empirical experience by observation of circumstances that may have contributed to recurrent pregnancy loss.

Table Empirical ‘rules’ – tender loving care or stress-reducing guidelines for management of recurrent pregnancy loss.

Listen lying down to relaxation tapes on a Walkman V2-I hour per day
Stop work for 9 weeks (sick leave)
Once fetal heart is seen, practise creative visualisation
60 per cent threaten miscarriage – treat any bleeding with bed rest for 1 week
No sexual intercourse until 13 weeks, or until 2 weeks after gestation of previous loss
No moving house. If house is on the market, take it off
No exercise except walking 10 minutes per day and swimming
No gym, no tennis
No driving until 13 weeks
No house guests
No dinner parties
No weddings
No funerals except immediate family
No natural herbs
5mg folic acid until 15 weeks
No hot baths, spa pools
Avoid chemicals and sprays
No housework, gardening, sweeping floors, vacuuming
No other children – to be minded for 3 days per week
No travel
Out for lunch 11.30a.m., home by 2.30p.m.
Out for dinner 6.30p.m., home by 9.00p.m. only, Sunday-Wednesday
Only go to the cinema during the day
Avoid crowds

■ Women with a history of recurrent miscarriage have a high perinatal mortality rate. They are particularly at risk of severe sepsis and life-threatening haemorrhage and should be cared for by a perinatal team.

■ A recent study has shown that in a recurrent miscarriage clinic, excluding those with known associations with recurrent miscarriage (antiphospholipid syndrome, oligomenorrhoea, mid-trimester loss, abnormal parental karyotype and other rare abnormalities), there was a 70 per cent conception rate and 75 per cent live birth rate. Of 55 miscarriages, 3 per cent occurred following detection of fetal cardiac activity. In women with a history of idiopathic recurrent miscarriage, the most perilous time is between 6 and 8 weeks’ gestation. Between these gestations, 78 per cent of the pregnancy losses occurred, with 89 per cent occur ring without the detection of fetal cardiac activity (this discriminates a pregnancy as ‘embryo loss’, rather than fetal loss).

Table Important gestational milestones for success and loss prediction.

Gestational age (weeks) Success rate (%) Miscarriage rate (%)
6 78 22
8 98 2
10 99.4 0.6

Therefore, identification of the fetal heartbeat by 8 weeks gives a chance of successful outcome in a subsequent pregnancy of 98 per cent, increasing to 99.4 per cent if a fetal heartbeat is seen at 10 weeks.

■ Where there is a history of thrombosis or Systemic lupus erythematosus, treatment consists of 80 mg aspirin daily throughout the pregnancy and heparin (10000 units subcutaneously) as soon as fetal heart activity is demonstrated by ultrasound, with or without steroids. Aspirin (70-80 mg) inhibits platelet aggregation. Heparin prevents thrombosis. Heparin requires parenteral administration and may cause osteoporosis and thrombo-cytopenia. Prednisone is associated with glucose intolerance, skin and bone changes and preterm rupture of the membranes.

■ Human leukocyte antigen testing or any alternative immune tests are reported. However, these studies remain controversial.

■ Maternal age has a profound effect on pregnancy outcome. A 20-year-old woman with two miscarriages has a 92 per cent (confidence internal 86-98) chance of success in a subsequent pregnancy compared to a 45-year-old woman, where the chance of success is 60 per cent (confidence internal 41-79) with two previous losses .

The psychological effects of miscarriage can be traumatic.

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