What you need to know about pregnancy complications
Gynaecologists Dr Roy Farquharson, Dr Cecilia Bottomley and Dr Emma Kirk answer GP Dr Mandy Fry’s questions on aspirin in recurrent miscarriage, the risks associated with exercise and toxoplasmosis
Gynaecologists Dr Roy Farquharson, Dr Cecilia Bottomley and Dr Emma Kirk answer GP Dr Mandy Fry's questions on aspirin in recurrent miscarriage, the risks associated with exercise and toxoplasmosis
1 Is it true that strenuous exercise increases the risk of miscarriage? How would you define strenuous exercise? Are any forms of exercise likely to be more harmful than others?
Few sports are absolutely contraindicated, but these include:
• contact sports – risk of abdominal trauma
• scuba diving – risks of decompression on the foetus
• skiing/waterskiing – risks from falls
In fact exercise should be promoted and pregnancy provides a unique opportunity for behaviour modification. It improves energy, mood and posture and reduces backache, constipation and bloating.
Exercise also decreases the risk of gestational diabetes, especially in women who are obese.
The American College of Obstetricians and Gynecologists recommends that women with uncomplicated pregnancies follow the same exercise guidelines in pregnancy as for non-pregnant women, that is at least 30 minutes of moderate exercise (equivalent to walking at 3-4mph) on most days. Walking, swimming, running and cycling are all safe.
2 What can we tell women who are worried that sexual intercourse can increase the risk of miscarriage?
Sexual intercourse is safe in pregnancy and is associated with earlier onset of labour and reduced requirement for postdates induction, with an estimated five couples needing to have sexual intercourse at 39 weeks gestation to avoid one postdates induction of labour.
There is no evidence that sexual intercourse causes miscarriage. But it can be pragmatic to advise women with threatened miscarriage to avoid intercourse until after the bleeding has completely resolved so, if miscarriage does occur, the couple does not feel that they may have triggered or exacerbated events.
3 Women tend to be investigated for recurrent miscarriages after three events but they often present to us in distress after two. What advice should we give them? Are there any simple relevant investigations that we could carry out in primary care?
Significant distress is provoked by two losses especially when foetal heart action was seen on scan before the loss. This can trigger a full bereavement process. With two foetal losses like this there is a substantial possibility of background maternal thrombophilia as a causal factor such as antiphospholipid syndrome (APS) so at this stage referral to a specialist miscarriage clinic is worthwhile1.
Although quality control problems have bedevilled APS testing, there is no reason primary care screening shouldn't include a thrombophilia screen although particular attention must be paid to sample delivery time and laboratory control processes.
When very early loss occurs – such as biochemical loss and empty sac loss – then deferring referral until three consecutive losses is probably more appropriate.
Success rates for subsequent pregnancies is high – about 72% for a 32-year-old woman with three early losses2. Also, the number of women who suffer three very early losses is about 3-5% so referral of such high numbers would place too high a burden on current capacity.
4 What is the role of aspirin in preventing miscarriage? I know of its importance in APS but it increasingly seems to be used in other women, including those undergoing IVF.
There is still considerable controversy over the role of aspirin in recurrent miscarriage, although many believe it has an important role in providing support for women at a very difficult time in early pregnancy. Regular ultrasound – fortnightly from six weeks – and surveillance by the same team, low-dose aspirin (75mg daily) along with folic acid (5mg daily) can be of benefit to patients – although no clear RCT evidence exists for this approach. Many women self- medicate as they wish to ‘help' a potentially successful process.
IVF protocols, particularly involving single embryo transfer, may use aspirin but there is no published work to support this.
The addition of heparin compared to aspirin alone seems not to offer added value to women with recurring miscarriage and thrombophilia3.
5 Is there any quantifiable risk of infection from infections such as toxoplasmosis during pregnancy? Should we continue to advise women to avoid contact with cat faeces, for example?
Several infections during pregnancy are associated with known and significant adverse outcomes. These include rubella, chickenpox, listeriosis, cytomegalovirus and parvovirus as well as toxoplasmosis.
Toxoplasmosis causes either no or minimal symptoms of sore throat or fever in the mother but is associated with severe adverse outcome for a foetus. About 30% of people acquire the infection during their lifetime, although it is rare in pregnancy at 2-2.6 per thousand. The transplacental transmission rate is reported to range from 0% to 40%.
Transmission to the foetus occurs only in women who develop their primary infection during pregnancy. It may result in visual and hearing deficit, mental and psychomotor retardation, seizures, haematological abnormalities or death. Although there is little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis the evidence from observational studies suggests it is. The National Screening Committee has advised that the current evidence does not support screening.
The infection can be acquired through ingestion of infected, undercooked meat or contaminated food or water. A common source of infection is handling soil that has been contaminated with cat faeces. So women should not be advised to avoid all contact with cats but to avoid the main risk factors of undercooked meat, gardening without gloves and handling cat litter.
6 Why is PCOS associated with a higher rate of miscarriage?
Polycystic ovarian morphology is probably not associated with miscarriage but PCOS is associated with a higher miscarriage rate although the pathophysiology is unclear.
Initially it was thought that raised LH led to premature maturation of the oocyte and development of a nonviable embryo but more recent studies have not confirmed the association. Miscarriage in these women may be due to endometrial ‘dysynchrony', whereby an embryo attempts to implant in an endometrium that is not fully prepared.
There are conflicting results about whether raised androgens are associated with miscarriage and, if so, whether this is independent of polycystic ovarian morphology.
Women with PCOS are often obese and this is in itself a risk factor for miscarriage. Hyperinsulinaemia and insulin resistance may be the key factor, possibly via deficient endometrial development or because of excessive glucose transport into the embryonic environment.
A review of the role of PCOS in recurrent miscarriage was published last year4.
7 What role does metformin play for these patients? Would you use it routinely in women with PCOS or only in those who have experienced miscarriage? Are there any risks to the foetus associated with its use?
No congenital abnormalities or developmental problems have been found with use of metformin in pregnancy.
Non-randomised trials have suggested a significant reduction in the miscarriage rate with metformin in women with PCOS. In two randomised studies, there was no benefit from adding metformin to clomifene for improving live birth rate and preventing miscarriage. But metformin is not licensed for use in pregnancy or for the prevention of miscarriage, and therefore its use should still be reserved for women taking part in clinical trials. There is no evidence to support use of metformin in women who have not had a miscarriage.
8 What would make you suspect cervical incompetence as a cause of miscarriage?
First, it's worth pointing out that incompetence is a term that has rather fallen out of favour, to be replaced with cervical weakness.
A detailed clinical event history of mid-trimester loss between 12 and 24 weeks is very worthwhile. Description of silent cervical dilatation in the presence of foetal heart action and absence of vaginal bleeding is strongly suggestive of cervical weakness – as is rupture of membranes immediately prior to loss.
It is important to exclude bacterial vaginosis (BV) and thrombophilia (such as APS) as causal factors as about 10% of women will have two causal factors operating independently.
The patient should be referred to a specialist miscarriage clinic for standardised investigation protocol. After this, treatment by elective vaginal cervical cerclage may be undertaken with an average success rate of 70-80%. If this fails then resort to the highly successful (90% success) transabdominal cerclage technique can be considered5.
9 Following a miscarriage women often ask how soon they can start trying to conceive again. Often they seem to have been advised to wait until they have had a normal menses. What is the rationale behind this advice? Is it accurate?
As long as the woman feels psychologically prepared for the next pregnancy the time interval from last loss is arbitrary and has no evidence base. It is simply a matter of certain dates that promotes this advice. But the availability of high resolution transvaginal ultrasound has improved the accuracy of dating an early pregnancy.
Couple vary enormously in how they cope with loss so this time frame should be flexible for them.
10 What extra precautions do women with Factor V Leiden mutation need to take to maximise their chance of a successful pregnancy outcome?
Some 4% of the population carry this gene mutation but it remains unknown how active this mutation is for an individual. They may have no lifelong risk yet others will have thrombosis or late pregnancy loss as first presentation.
In maximising pregnancy success the evidence still remains uncertain. Most clinicians would consider LDA during pregnancy with a past history of miscarriage. Heparin with added risk factor - such as caesarean section, obesity, advanced maternal age - should be considered. Recent evidence suggests no added value with heparin compared to aspirin alone3.
Dr Roy Farquharson is consultant gynaecologist at Liverpool Women's NHS Foundation Trust
Dr Cecilia Bottomley is clinical lecturer in obstetrics and gynaecology at St George's University of London
Dr Emma Kirk is a specialist trainee in O&G at St George's Hospital, London
Competing interests None declared
What I will do now What I will do now
Dr Mandy Fry considers the responses to her questions
I found the advice on exercise helpful, particularly the idea that in many ways
pregnant women should be exercising as much as non-pregnant women. It was also good to know exactly which sports might be contraindicated.
Although I was obviously aware of how toxoplasmosis was transmitted, I hadn't made the link between cat faeces and gardening without gloves so I will add that to the advice that I give women in early pregnancy.
It was also heartening to know that specialist services would consider seeing women after only two miscarriages if these are later in the pregnancy, as this may help alleviate some patients' distress.
The discussion around metformin and aspirin was also interesting as often these women come armed with advice from a variety of sources, including the internet, and I shall now feel more able to discuss the relative lack of an evidence base for these interventions and signpost them to trials if appropriate.
Dr Mandy Fry is a GP in Cirencester, Gloucestershire, and senior primary care lecturer at Oxford Brookes University