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March 2008: Prompt diagnosis vital in ectopic pregnancy

How can ectopic pregnancy be recognised?

Is surgery always required?

What are the implications for future fertility?

How can ectopic pregnancy be recognised?

Is surgery always required?

What are the implications for future fertility?

Pregnancy and having a baby is a happy and rewarding experience and nowadays a safe one for most women in the UK.

Nevertheless, some mothers do still die and these deaths are all the more shocking because they occur so rarely. Deaths in early pregnancy, particularly from a ruptured ectopic pregnancy, account for a significant proportion of all maternal deaths.

The Confidential Enquiry into Maternal and Child Health (CEMACH) has recently published its seventh report on maternal deaths. Whereas previous reports were published under the title Why Mothers Die, the current one, which covers the period 2003–2005, is entitled Saving Mothers' Lives to reflect its aim to make motherhood safer.1

The report estimates the number of pregnancies that occurred in the UK during 2003-2005 at 2.8 million, and the number of ectopic pregnancies at 32,100, giving a rate of 11.1 ectopic pregnancies per 1,000 pregnancies. This is an increase from 24,775 ectopic pregnancies in 1988. During the same time, the number of pregnancies has remained approximately the same.1

The increase in ectopic pregnancies may result from increased effectiveness of screening for ectopic pregnancy and the increase in prevalence of STIs, particularly chlamydia.

41182052During the three-year period reported, 10 deaths resulted from a ruptured ectopic pregnancy and one woman died during anaesthesia for treatment of an ectopic pregnancy. Four of these women presented with diarrhoea and vomiting, three of whom were misdiagnosed, as illustrated in the case history in box 1,left.


Causes of ectopic pregnancy

Ectopic pregnancy results when the fertilised egg is implanted outside the uterus. The most common site is the fallopian tube, but other sites include the ovary, caesarean section scar, interstitial part of the tube, rudimentary horn, abdomen and cervix.2 Heterotopic pregnancy occurs rarely, when an ectopic pregnancy co-exists with an intrauterine pregnancy, although ovulation induction and in-vitro fertilisation treatment has meant an increase in incidence.

41182053Damage to the fallopian tube is the most common reason for ectopic pregnancy, and although it can occur in women without pre-existing risk factors, a history that includes any of the factors in box 2, left, suggests an increased risk.

Presentation

GPs play a vital role in the diagnosis and referral of women with suspected ectopic pregnancy. In women of reproductive age who present with diarrhoea and vomiting and/or fainting, the possibility of ectopic pregnancy should be considered. GPs should refer all women with a positive pregnancy test and a suspected ectopic pregnancy urgently.

41182054The classic presentation is at six weeks' gestation with unilateral pain and bleeding (usually dark like prune juice). The pain is worse than the bleeding. However, ectopic pregnancy is difficult to diagnose because it can present in many different ways (see box 3,left).

Interstitial pregnancies present classically at 12-14 weeks and abdominal and rudimentary horn pregnancies at 20 weeks.

Ectopic pregnancy remains the differential diagnosis of an acute abdomen and collapse throughout pregnancy. Pregnancy plus fainting points to ectopic pregnancy until proved otherwise. The vital signs, particularly tachycardia, hypotension and tachypnoea, are all important indicators.

During telephone consultations with or concerning women who are or who may be pregnant, GPs should carry out a careful risk assessment. If there is any doubt, they should see the woman or arrange for her referral.1

It is important to bear in mind that easier access to egg donation and fertility treatment has extended reproductive age.

Women with suspected ectopic pregnancy should be referred through the on-call system for urgent review. It may be appropriate to refer women to an emergency early pregnancy clinic, which will accept women on next-day referral.

Pregnancy tests

Pregnancy can be confirmed by urine test or biochemical measurements. Urine pregnancy tests are highly sensitive and specific. A test will normally be positive two weeks after fertilisation, at around the time of the first missed period, and occasionally before this. There is little cross-reaction and a positive pregnancy test usually indicates a pregnancy.

Women are usually advised to test an early morning urine specimen because the urine is more concentrated then, but human chorionic gonadotrophin (hCG) can be detected at any time of day. Serum hCG is useful when the urine is very dilute.

A positive pregnancy test two weeks after a ‘complete miscarriage' requires further investigation.

Biochemical measurements

In a normally developing intrauterine pregnancy, hCG levels double every 1.4 days before five weeks and every 2.4 days between five and seven weeks.

A prolonged hCG doubling time can indicate an abnormal pregnancy, but does not distinguish between intrauterine and ectopic pregnancy. In about 10% of ectopic pregnancies, hCG increases at a normal rate. However, a normally developing intrauterine pregnancy would usually be visible at a level of 1,000 IU.

An assay of progesterone, produced by the corpus luteum, is an assay of the viability of the pregnancy. A serum progesterone of less than 20 nmol/l may indicate a failing ectopic pregnancy and those more likely to resolve spontaneously. A level greater than 60 nmol/l indicates a highly viable pregnancy, but does not distinguish between intrauterine or ectopic pregnancy. A high progesterone level may therefore indicate a viable and highly dangerous ectopic pregnancy.

Ultrasound

Introduction of transvaginal ultrasound and increased resolution has resulted in increased detection of ectopic pregnancies. The sensitivity of detection will depend on the skill of the operator.

Treatment

Surgery is the gold standard for treatment of ectopic pregnancy. However, with the advent of transvaginal ultrasound and increased resolution, conservative management with methotrexate treatment is possible in selected cases.

Laparoscopic surgery

The advantages of laparoscopic surgery over open surgery are that there is less post-operative pain, a shorter hospital stay and quicker recovery.2

In laparoscopic salpingotomy an incision is made in the fallopian tube over the site of the ectopic pregnancy, which is then eased out. This method enables the tube to be conserved; however, it carries a greater risk of intraoperative and postoperative bleeding from the tube and it is unclear whether it has advantages over salpingectomy. There is a 10-15% risk of persistent trophoblast following salpingotomy, and further surgery or medical treatment may be required.

Vaginal bleeding after surgical treatment is normal, and the passage of decidua can be mistaken for miscarriage.

Current guidance is that salpingectomy may be performed with consent if the other tube appears healthy. Salpingotomy should be attempted if the other tube appears damaged and the woman wishes to attempt another pregnancy.3 Cumulative intrauterine pregnancy rates at seven years are significantly higher following salpingotomy (89%) than after salpingectomy (66%).4

Medical treatment

Treatment of ectopic pregnancy with methotrexate has grown in popularity, and success rates in excess of 90% with a single dose of intramuscular methotrexate have been reported.5 However, some cases of intrauterine miscarriage may have been diagnosed as ectopic pregnancies, inflating the success rate.

Treatment and follow-up can be prolonged, with an average length of follow-up of five weeks, and the fallopian tube may rupture despite a decline in hCG level and apparently successful treatment.

Nearly 75% of women will experience abdominal pain following injection. Side-effects are common and include nausea and anorexia, and hepatic and renal function may also be temporarily disturbed. Close monitoring is therefore essential. The hospital and often the early pregnancy clinic will monitor treatment, but women may present to the GP with complications of treatment.

Methotrexate treatment is most suitable for the highly motivated woman with a small unruptured ectopic pregnancy, a serum hCG level of less than 4,000 IU/l and good access to emergency medical care.

Methotrexate carries a possible teratogenic risk and women should avoid conception until one month after the injection.

Anti-D immunoglobulin

The RCOG guideline recommends giving anti-D immunoglobulin at a dose of 250 IU to all nonsensitised rhesus negative women with confirmed or suspected ectopic pregnancy, whether treated surgically or with methotrexate.

Management following an ectopic pregnancy

Treatment is often as an emergency, with laparoscopic surgery and discharge home within 24 hours. The expression of feelings, grief and loss may occur later, and GPs are increasingly in a position to provide support and counselling.

There is no ‘correct time' to start trying for another pregnancy. Periods will resume 4-6 weeks after the ectopic pregnancy and conception is possible within this time. For some women and their families, psychological recovery takes longer, hence the advice to wait three months before trying again.

The subsequent pregnancy rate following ectopic pregnancy is approximately 66%.

Each woman must be judged individually. In any future pregnancy, there is a 10% risk of ectopic pregnancy and ultrasound scan at 6-7 weeks to confirm an intrauterine gestation is advised. Once confirmed, previous ectopic pregnancy should not affect pregnancy or delivery.

Prompt diagnosis vital in ectopic pregnancy ectopiccase box2ect Box3ect Key points Author

Mrs Caroline Overton
MBBS MD FRCOG FHEA
consultant obstetrician & gynaecologist, specialist in reproductive medicine & laparoscopic surgery, senior clinical lecturer, University of Bristol

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