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Management of miscarriage

In this series a GP interviews an expert to get first-hand information that goes beyond the textbook on a topic of current clinical interest

Dr Linden Ruckert interviews

Mr Raj Rai on the commonest complication

in pregnancy

What's in this article

 · Defining miscarriage and infertility

 · Factors causing early miscarriage

 · Problems occurring later in pregnancy

 · Dealing with antiphospholipid syndrome

Defining miscarriage and infertility

How common is miscarriage?

Miscarriage itself is the commonest complication of pregnancy. The prevalence of miscarriage depends upon its definition. Miscarriage may be described as being either preclinical, with loss of pregnancy occurring after conception but before a missed period, or clinical, when pregnancy loss occurs after a missed period. If you stick to the latter definition, 15 per cent or one in seven pregnancies miscarry.

But this represents only the tip of the iceberg; if preclinical miscarriages are included, the true miscarriage rate is in the region of 70-80 per cent. Indeed, we are beginning to appreciate that many couples who are labelled as infertile are in fact having repeated preclinical miscarriages rather than failing to conceive.

What effect does maternal age have?

The miscarriage rate gently increases until age 37 or 38 but after this there is a sharp increase, mainly owing to a rise in the rate of chromosomal abnormalities in the fetus.

However, age is only an indirect correlate of miscarriage and a more direct relationship is between miscarriage rate and early follicular phase FSH level, which reflects oocyte quality. If a woman of 40 or 42 has a significantly lower early follicular phase FSH level than a woman of 35, she will have a lower miscarriage rate than the 35-year-old, despite her age.

If a woman has had one, two or three miscarriages, what do you say about her risk of miscarriage next time?

Epidemiological data reported in the late 1980s reports that a woman's future reproductive performance is directly related to her previous reproductive history. A woman pregnant for the first time has a

15 per cent risk of miscarriage. If her first pregnancy miscarries, the risk of her second pregnancy also miscarrying is slightly higher at 20 per cent.

If her first two pregnancies have ended in miscarriage, the chance of her next pregnancy also miscarrying is 28 per cent. But even after three first trimester miscarriages, a woman still has about a

60 per cent chance of future successful pregnancy.

What basic tests should be done?

Peripheral blood karyotyping on both partners, early follicular phase FSH and a pelvic ultrasound can be requested by GPs. Screening for phospholipid antibodies and the various thrombophilic abnormalities are best performed after specialist referral. We do not routinely screen for infection unless there has been a late miscarriage.

Future miscarriage rates

After 1 miscarriage 20 per cent

After 2 miscarriages 28 per cent

After 3 miscarriages 43 per cent

Dealing with antiphospholipid syndrome

Antiphospholipid syndrome has had a lot of publicity. What should we know about it in this context?

Antiphospholipid syndrome has emerged over the last 15 years as the most important treatable cause not only of recurrent miscarriage but also late pregnancy complications, such as preterm labour IUGR and pre-eclampsia.

Diagnosis of the syndrome is difficult as the natural history of the antibodies is that they fluctuate over time and laboratory assays for these antibodies have not kept pace with the explosion of clinical interest in the subject.

National and international surveys have repeatedly reported widespread inter-laboratory variation in phosphpolipid testing. Sample collection is crucial: the sample should be venous, uncuffed and reach the lab and be centrifuged within an hour, otherwise there will be false negatives. Transient positive levels are not significant and can be drug induced or secondary

to infection at the time of collection.

Our own data, confirmed by others, reports that 15 per cent of women with recurrent miscarriage have antiphospholipid syndrome and prospective studies report that untreated the miscarriage rate is up to 90 per cent.

The mainstay of treatment is aspirin and heparin. The live birth rate is transformed to 70 per cent. But these pregnancies are at significant risk; one-third will develop pre-eclampsia or IUGR or deliver prematurely. Our most recent data shows there is a cohort of women with the syndrome who are resistant to therapy, which forces us to reconsider the mechanisms of pregnancy loss with these antibodies.

Although thrombosis is central to pregnancy loss these antibodies have other effects such as adversely affecting implantation.

At St Mary's, women are advised to start low-dose 75mg aspirin as soon as a pregnancy test is positive. They are then invited for a transvaginal ultrasound scan at five to six weeks of amenorrhoea to confirm the pregnancy is intrauterine. Then we start low molecular weight heparin for the rest of the pregnancy.

Is there any place for progesterone?

There is no evidence for the use of progesterone.

What about the effectiveness of

supportive management?

If no cause can be found the most effective intervention that can be offered by a GP or hospital is supportive care. We have reported on a large cohort at St Mary's that with supportive care the miscarriage rate is decreased from 75 per cent to 42 per cent. Work in Scandinavia and Australia also supports our findings.

More recently, data from animal models reported that stress is associated with pregnancy loss and provide a scientific basis for supportive care.

Problems occurring later in pregnancy

What about second trimester miscarriage?

The miscarriage rate in the second trimester is still one in 100. The causes of early and late miscarriage overlap and a concept we are developing is the implantation spectrum of pregnancy failure. At one end of this spectrum there is infertility, then first and second trimester miscarriage, followed by intra-uterine growth retardation and some cases of pre-eclampsia and, rarely, stillbirth. Many pregnancy complications can be considered to be due to defective implantation ­ a process that remains poorly understood.

I believe all women with a pregnancy failure at over 10 weeks which has been ultrasonically proven should be investigated.

How important is bacterial vaginosis?

The prevalence is similar among women with recurrent early miscarriage compared with a control population. But with late miscarriage the prevalence of bacterial vaginosis is significantly higher and it is our practice to screen women with a history of late miscarriage or preterm labour for bacterial vaginosis every two weeks using a high vaginal swab, which the woman can take herself, and if it is found we treat it aggressively with antibiotics.

Factors causing early miscarriage

Is there any evidence to support the belief that eight-week miscarriages are due to hormonal imbalance and those at 10-12 weeks are due to chromosomal abnormalities?

In fact most chromosomally abnormal fetuses miscarry before eight weeks of pregnancy ­ the miscarriage may not present until after eight weeks of pregnancy but the pregnancy failed much earlier.

We have traditionally divided pregnancies into trimesters but this does not accurately reflect the development of an embryo or a fetus. The growth and development of an embryo before eight weeks is quite different to that after this time. Before eight weeks, the embryo needs a hypoxic environment and there is no physical contact between the embryo and the maternal circulation.

Intervillous blood flow develops after eight weeks, so it is more useful to divide pregnancies into before and after eight weeks' gestation. While a variety of endocrine disturbances have been stated to be causal of pregnancy losses, no treatment of endocrine disturbance has been shown to improve the subsequent live birth rate.

It is important to differentiate between polycystic ovaries, an ultrasound diagnosis, and polycystic ovarian syndrome (PCOS), where the woman must have polycystic morphology together with another feature, such as anovulation or hirsutism. While it is true the prevalence of polycystic ovaries is significantly higher in women with miscarriage ­ in the region of 40 per cent compared with 22 per cent among controls ­ ovarian morphology per se is not predictive of pregnancy outcome. On the other hand, PCOS is associated with a number of endocrine changes, such as hypersecretion of LH and increased testosterone levels. In the late 1980s and early 1990s, data from IVF units and from women attempting to conceive spontaneously suggested hypersecretion of LH was associated with infertility and increased risk of miscarriage.

But the ' LH hypothesis' has now turned a full circle; we reported that suppressing endogenous LH production in women with high LH and recurrent miscarriage does not improve pregnancy outcome.

In fact those with high LH levels had an excellent 60-70 per cent live birth rate without suppression. IVF unit data shows that complete suppression of LH is deleterious to the outcome of an IVF cycle. Women with PCOS who are given clomiphene or gonadotrophins to ovulate do have a higher rate of miscarriage than those who conceive spontaneously.

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