Download Miscarriage: frequently asked questions

There is so much we don't know in medicine that could make a difference,
and often we focus on the big things, and the little things get forgotten. To
highlight some smaller but important issues, we've put together a series of
pearls that the Red Whale found at the bottom of the ocean of knowledge!
Miscarriage: frequently asked questions
What is the best method for managing miscarriage?
The MIST trial (BMJ 2006;332:1235) compared medical, surgical and expectant management in a UK-based RCT of 1200 women.
It found no difference in the rate of gynaecological infection.
There were more unplanned hospital admissions in the expectant and medical management groups compared with the
surgical group (49% vs. 18% vs. 8% respectively).
Bleeding stopped sooner in surgical management, but this did not affect Hb levels.
Unplanned surgical intervention was required in:
6% (missed), 2% (incomplete) managed surgically.
38% (missed), 29% (incomplete) managed medically.
50% (missed), 25% (incomplete) managed expectantly.
Based on this study, the RCOG concluded that:
Women who were at high risk of bleeding/infection or molar pregnancy should be offered surgical treatment.
All other women should be allowed to choose which option they prefer.
NICE has recommended expectant management first line, medical second line and surgery third line on the basis of costeffectiveness.
Does choice of method affect future fertility?
No! ...
Long-term follow-up of the women from the MIST trial showed that the method of miscarriage management does not affect
subsequent pregnancy rates (BMJ 2009;339:b3827).
Of the initial 1200 women, 762 replied to 5y follow-up, and live birth rates were approximately 80% in all three groups within
5y of the index miscarriage.
Older women (>35y) and those with previous miscarriages were less likely to give birth.
1 previous miscarriage – 74% had a live birth at 5y.
2 previous miscarriages – 67% had a live birth at 5y.
3 previous miscarriages – 58% had a live birth at 5y.
In view of the number of women who did not respond to the follow-up survey, it is possible that these figures may be overly
optimistic.
How soon can we try again?
I always say as soon as you feel emotionally ready on the basis of common sense and practicality!
This large Scottish retrospective cohort study found that women who conceive again within 6m were significantly less likely to have
another miscarriage, termination, ectopic pregnancy or complications in pregnancy, compared with women with longer
interpregnancy intervals. The worst outcomes were seen with delays of >24m (BMJ 2010;341: c3967 and c4181 (editorial)).
As with all retrospective studies, confounding may be a significant factor in the result, e.g. women who take longer to conceive may
be more likely to have adverse pregnancy outcomes owing to factors which contribute to fertility itself, rather than interpregnancy
duration. Causation cannot be determined.
It appears safe to recommend trying again for pregnancy as soon as the woman is ready, and the best outcomes are seen
if conception occurs within 6m of the first miscarriage.
What can I do to reduce the chance of miscarriage?
This article in the NEJM focuses on the causes and management of recurrent miscarriage (NEJM 2010;363:1740). The most
common cause of early spontaneous miscarriage is chromosomal aneuploidy (having more or less genetic material than normal).
This is a spontaneous event which is more common under the age of 18y and over the age of 35y. There is little that an individual
woman can do to prevent it.
Poorly controlled diabetes and thyroid disease are associated with increased risk of miscarriage, but well controlled chronic
diseases are not.
Offer patients with diabetes and thyroid disease a pre-conception review to ensure they are optimally managed prior
to becoming pregnant.
Do not screen for diabetes and thyroid disease in women who have had a miscarriage, unless there are other clinical
indicators for doing so.
In the case of recurrent miscarriage (three or more consecutive miscarriages), women should be referred for further investigation,
although this review openly acknowledges that the evidence base for these investigations and interventions is poor.
With no intervention, 65% of couples with recurrent miscarriage will achieve a future live birth.
The role of antithrombotics is controversial and is considered below.
Screening for uterine abnormalities, e.g. septate and bicornate uterus, is commonly undertaken, and many experts
recommend correction before trying for future pregnancy – but RCT data to support this is lacking.
Genetic screening and IVF with pre-implantation genetics does not improve live birth rate compared with spontaneous
conception.
Lifestyle issues associated with an increased risk of miscarriage include:
Obesity.
Cigarette smoking.
Alcohol use.
Moderate to heavy caffeine intake.
There is no evidence that sexual activity has any impact on miscarriage.
This very large observational study published in the BJOG looked at nine established risk factors for miscarriage in pregnancies
included in the Danish National Birth cohort from 1996 to 2002 (BJOG 2014;DOI 10.1111/1471-0528.12694).
It found that being underweight or obese prior to conception and age >29y at time of conception increased the risk of
miscarriage. During pregnancy, drinking coffee or alcohol, lifting >20kg in weight on a daily basis, and night shift work
compared with daytime non-shift work, also increased the miscarriage risk.
It concluded that a quarter of miscarriages could be prevented if all women conceived between the ages of 25 and 29y, were a
normal weight, did not drink alcohol, did not lift >20kg on a daily basis and only did daytime work.
However, the miscarriage rate in the population studied was much lower than expected. This suggests early miscarriages may
have been missed, as women were recruited from their first antenatal clinic appointment.
There is also a risk of recall bias because 77% of the miscarriages had taken place by the time the woman was interviewed.
The study provides further evidence for the increased risk of miscarriage with the lifestyle factors listed above, but more
research is needed to determine whether there is a causal link with heavy lifting or night shift work.
Antithrombotics and miscarriage
Recurrent miscarriage is defined as 3 or more consecutive pregnancy losses before 24w gestation, and affects 1% of women of
reproductive age. Women with recurrent miscarriage should be referred to a specialist clinic for further investigation (RCOG green
top guideline 17). Identifiable causes include:
Antiphospholipid syndrome.
Acquired thrombophilia.
Heritable thrombophilia, e.g. Factor V Leiden.
The risk of miscarriage due to antiphospholipid syndrome has been shown to be reduced by the use of antithrombotic treatment.
This has led to speculation that antithrombotic treatment may be helpful in all recurrent miscarriages.
This small RCT in the NEJM randomised women with two or more miscarriages to receive placebo, aspirin alone, or aspirin and low
molecular weight heparin (NEJM 2010;362:1586). Women entered the trial if they were planning to conceive or were less than 6w
pregnant. The outcome was live birth rate.
The trial was terminated early because there was no difference in live birth rate between the three groups. Live birth rates were
between 50 and 57% across the groups. There were no significant harms, but bruising and swelling at injection sites were reported.
The authors concluded that, in unexplained recurrent miscarriage, neither aspirin alone nor aspirin combined with low
molecular weight heparin improved live birth rates compared with placebo.
The linked editorial (NEJM 2010;362:1630) comments that it is still possible that some groups may benefit more than others, e.g.
those with three or more pregnancy losses or heritable thrombophilias, but this study was not powered to detect these sub-group
differences. There are ongoing trials specifically focusing on women with heritable thrombophilia.
This RCT in America compared pre-conception use of 81mg aspirin daily with placebo during 6 menstrual cycles while trying to
conceive and continued until 36w gestation. It included women with one or two previous miscarriages who had no major medical
problems (Lancet 2014;384:29). The majority of women had one previous miscarriage, and more than half had one or two previous
live births.
Live birth rates were higher in the low dose aspirin group (58% vs. 53%), but the difference was not significant.
There was no significant difference between groups in pregnancy loss (13% aspirin group vs. 12% placebo group) or other
pregnancy complications.
Vaginal bleeding was significantly more common in women taking low dose aspirin, but this was not associated with
increased pregnancy loss.
The authors conclude that low dose aspirin is not indicated for the prevention of pregnancy loss in women with one or two
previous miscarriages.
Management of miscarriage
Method of miscarriage management does not seem to affect future fertility, with 80% of
women achieving a live birth within 5y of their first miscarriage.
Women aged >35y and with previous miscarriages had lower live birth rates.
After one miscarriage, it is safe and desirable to try for a further pregnancy as soon as a
woman feels ready. The best pregnancy outcomes are seen in those conceiving within
6m of the initial miscarriage.
Maintaining a normal BMI, stopping smoking, cutting out alcohol and reducing caffeine
all reduce the risk of miscarriage. There is no evidence that sexual activity has any
effect. Lifting >20kg/d and working night shifts may increase the risk of miscarriage, but
further research is needed.
Ensure diabetes and thyroid disease are well controlled prior to conception.
Do not prescribe aspirin and/or low molecular weight heparin to women with recurrent
unexplained miscarriage as there is no evidence it improves live birth rates.
We make every effort to ensure the information in these pages is accurate and correct at the date of
publication, but it is of necessity of a brief and general nature, and this should not replace your own good
clinical judgement, or be regarded as a substitute for taking professional advice in appropriate circumstances.
In particular check drug doses, side effects and interactions with the British National Formulary. Save insofar as
any such liability cannot be excluded at law, we do not accept any liability for loss of any type caused by
reliance on the information in these pages.
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