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SYMPOSIUMWOMEN'S

HEAL.I

Prompt diagnosis vitai in ectopic pregnancy

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

lean ectopic pregnancy be recognised?

IS surgery always required?

one, which covers the period 2003-2005, is entitled Saving Mothers'Lives to reflect its aim to make motherhood safer' 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 1 1 . 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.' The increase in ectopic pregnancies may result from increased effectiveness of screening for ectopic pregnancy and the increase in prevalence of STIs, particularly chlamydia.

are the implications for future fertility?

During 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, p35.

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

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,

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Case history^ A woman who had diarrhoea and vomiting also had vaginal bleeding, fainting and severe abdominal pain. She was known to be pregnant and was diagnosed as having gastroenteritis by a very junior gynaecologist in an emergency department and discharged. She returned to the emergency department the following day with increased pain, having collapsed at home. She was found to be hypotensive and tachycardie by the nursing staff, given a very targe amount of intravenous fluid for what was thought to be dehydration from 'gastroenteritis' and again discharged. Her haemoglobin was not checked. She was tachycardie throughout. She returned a few hours later in extremis. Autopsy revealed a large haemoperitoneum from a ruptured tubal pregnancy.

rudimentary horn, abdomen and cervix.^ Heterotopic pregnancy occurs rarely, when an ectopic pregnancy co-exists with an intrauterine pregnancy, although ovulation induction and in-vttro fertilisation treatment has meant an increase in incidence. Damage 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.

Risk factors for ectopic pregnancy Pelvic infection, because of its association with fallopian tube damage Endometriosis Previous abdominal or pelvic surgery, because of its association with adhesions The presence of a coil. The coil is so effective at preventing intrauterine pregnancy that any pregnancy that occurs is more likely to be ectopic The progestogen-only contraceptive pill, because it affects tubal motility Infertility, because of its association with fallopian tube damage

Signs and symptoms of ectopic pregnancy A late, or missed, period Abnormal bleeding and a positive pregnancy test followed by a negative and then another positive test Suboptimal human chorionic gonadotrophin (hCG) change Evidence from ultrasound scan Decidua only on histology after surgical curettage Lower abdominal pain v^/ithout bleeding Heavy bleeding and stomach cramps suggesting miscarriage. Passage of a decidual cast, which is mistaken for products of conception Pain when passing urine Diarrhoea and vomiting, particularly painful defaecation because of haemoperitoneum Chest pain, because of haemoperitoneum, and referred pain in the chest and shoulder tip Tachycardia, hypotension Tachypnoea (air hunger) as a result of massive blood loss Collapse

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-react ion 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 PRESENTATION very dilute. GPs play a vital role in the diagnosis and referral of women with suspected A positive pregnancy test two ectopic pregnancy. In women of weeks after a 'complete miscarriage' reproductive age who present with requires further investigation. diarrhoea and vomiting and/or Biochemical measurements fainting, the possibility of ectopic In a normally developing intrauterine pregnancy should be considered. GPs pregnancy. hCG ievels double every should refer all women with a positive 1.4 days before five weeks and every pregnancy test and a suspected 2.4 days between five and seven ectopic pregnancy urgently. weeks. The classic presentation is at six A prolonged hCG doubling time can weeks' gestation with unilateral pain indicate an abnormal pregnancy, but and bleeding (usually dark like prune does not distinguish between juice). The pain is worse than the intrauterine and ectopic pregnancy. In bleeding. However, ectopic pregnancy about 10% of ectopic pregnancies, is difficult to diagnose because It can hCG increases at a normal rate. present in many different ways (see However, a normally developing box 3, left). intrauterine pregnancy would usually be visible at a level of 1.000 lU. Interstitial pregnancies present classically at 12-14 weeks and An assay of progesterone, produced abdominal and rudimentary horn by the corpus luteum, is an assay of pregnancies at 20 weeks. the viability of the pregnancy. A serum Ectopic pregnancy remains the progesterone of less than 20 nmo!/l differential diagnosis of an acute may indicate a failing ectopic abdomen and collapse throughout pregnancy and those more likely to pregnancy. Pregnancy plus fainting resolve spontaneously. A level greater points to ectopic pregnancy until than 60 nmol/l indicates a highly proved otherwise. The vital signs, viable pregnancy, but does not particularly tachycardia, hypotension distinguish between intrauterine or and tachypnoea, are all important ectopic pregnancy. A high indicators. progesterone level may therefore During telephone consultations with indicate a viable and highly dangerous or concerning women who are or who ectopic pregnancy. may be pregnant, GPs should carry Ultrasound out a careful risk assessment. If there is Introduction of transvagina! any doubt, they should see the woman ultrasound and increased resolution or arrange for her referral.^ has resulted in increased detection of It is important to bear in mind that ectopic pregnancies. The sensitivity easier access to egg donation and of detection will depend on the skill fertility treatment has extended of the operator reproductive age. Women with suspected ectopic TREATMENT pregnancy should be referred through Surgery is the gold standard for the on-call system for urgent review. It treatment of ectopic pregnancy. may be appropriate to refer women to However, with the advent of an emergency early pregnancy clinic, transvaginal ultrasound and increased which will accept women on next-day resolution, conservative management referral. with methotrexate treatment is possible in selected cases.

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Laparoscopic surgery The advantages of laparoscopic surgery over open surgery are that there is less post-operative pain, a Dr Peter Saul shorter hospital stay and quicker recovery.^ In laparoscopic salpingotomy an Ectopic pregnancy is relatively common with a rate incision is made in the fallopian tube of 1 1 . 1 per 1,000 pregnancies. over the site of the ectopic pregnancy, which is then eased out. This method Ectopic pregnancy results when the fertilised egg is enables the tube to be conserved; implanted outside the uterus. Damage to the fallopian however, it carries a greater risk of tube is the most common reason for ectopic pregnancy. intraoperative and postoperative A history of peivic infection, endometriosis, previous bleeding from the tube and it is abdominal or pelvic surgery, the presence of a coil, the progestogen-only pill and infertility are all associated with unclear whether it has advantages over salpingectomy. There is a 10-15% ectopic pregnancy. However, it can occur in women risk of persistent trophoblast following without pre-existing risk factors. salpingotomy, and further surgery or medical treatment may be required. The classic presentation is at six weeks' gestation, with Vaginal bleeding after surgical unilateral pain and bleeding, but symptoms may be variable. In women of reproductive age who present with treatment is normal, and the passage of decidua can be mistaken for diarrhoea and vomiting and/or fainting, the possibility of miscarriage. ectopic pregnancy should be considered. Tachycardia, hypotension and tachypnoea are all important indicators. Current guidance is that salpingectomy may be performed with consent if the other tube appears Urine pregnancy tests will normally be positive two weeks after fertilisation, at around the time of the first healthy. Salpingotomy should be missed period, and occasionally before this. If there is any attempted if the other tube appears damaged and the woman wishes to doubt, a serum hCG may be useful. attempt another pregnancy.^ Cumulative intrauterine pregnancy Close monitoring and Immediate access to hospital rates at seven years are significantly is required after medical treatment of ectopic pregnancy higher following salpingotomy (89%) with methotrexate. than after salpingectomy (66%).'* Medical treatment The RCOG guideline recommends giving anti-D Treatment of ectopic pregnancy with immunogiobulin at a dose of 250 lU to all nonsensitised methotrexate has grown in popularity, rhesus negative women with confirmed or suspected and success rates in excess of 90% ectopic pregnancy, whether treated surgically or with with a single dose of intramuscular methotrexate. methotrexate have been reported.^ However, some cases of intrauterine Current guidance is that salpingectomy may be performed with consent if the other tube appears healthy miscarriage may have been diagnosed as ectopic pregnancies, inflating the Salpingotomy should be attempted if the other tube success rate. appears damaged and the woman wishes to attempt Treatment and follow-up can be another pregnancy. 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 lU/l and good

key points

access to emergency medical care. Methotrexate carries a possible teratogenic risk and women should avoid conception until one month after the injection, Anti-D immunogiobulin The RCOG guideline recommends giving anti-D immunogiobulin at a dose of 250 lU 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.

Useful information
The Association of Early Pregnancy Units website gives information about local clinics and opening hours www..earlypregnancy.org.uk
REFERENCES
1 Lewis G (Gd), The ConMentiat Enquiry into Maternal antj Child Health (CBMACH). Saving Mothers'Lives: reviewing maternal deaths to make motherhood safer 2003-2005. The Seventh Report on Confidential Enquies into Matemai Deaths in the United Kingdom. London: GEMACH 2007 2 Royal College of Obstetricians and Gynaecologists. The management of tubal pregnancy. RCOG Guideline No 21 London: RCOG 2004 3 Bangsgaard N. Lund CO. Ottesen B et at. Improved fertility following conservative surgical treatrrvent of ectopic pregnancy. BJOG 2003:110 765-70 4 Strobelt N. Manani E. Fetran L et ai. Fertility after ectopic pregiiancy. Effects of surgery and expectant management. Jfleprod Med 2000,45:803-7 5 Stovail TG. and Ling FW. Single-dose methotrexate; an expanded clinical trial. Am J Obstet Gynecol 1993:168:1759-68

'Expression of feelings, grief and loss may occur later, and GPs are increasingly in a position to provide support and counselling'

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