Current trends in the management of ectopic pregnancy

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Current trends in the management ofectopic pregnancy

Introduction

Ectopic pregnancy is implantation of the fertilized ovumoutside the uterine cavity. The incidence of ectopic pregnancyhas been rising steadily in the last four decades. In the USA,it has steadily increased from 4.5/1000 in the 1970s to nearly20/1000 pregnancy in the 1990s.1 In the UK also, the incidenceof ectopic pregnancy has been reported to rise 3.8 fold from1966 to 1996. This is partly due to improved diagnosis.2

Incidence in India is reported 1 in 300 by ICMR in 1989.Hospital admissions due to ectopic pregnancy also increasedfour-fold from the early 1970s to the late 80s, but the late1990s saw a decline in admissions due to changes in practicebrought about by early diagnosis hence medical andconservative management without admission.3 Thus, despitean increasing incidence, both hospital admissions and maternaldeaths due to ectopic pregnancy are declining. Neverthelessit still remains a leading cause of maternal death in the firsttrimester.4 First successful surgical treatment of ectopicpregnancy was described by Tail in 1883. He performedsalpingectomy in 4 cases and all survived. In 1940 bloodbank facility developed and prognosis became better for thesecases. Availability of pregnancy test in 1960 and ultrasoundscan in 1970 were significant advances for early diagnosis ofectopic pregnancy.

With advent of serum βHCG measurement as marker forectopic pregnancy early and accurate diagnosis is possibleand it is the key for medical management of ectopicpregnancy.

Risk factors of tubal pregnancy

Various factors that increase the risk of ectopic pregnancyinclude tubal factors, zygote abnormalities, ovarian factors,intrauterine devices (IUDs), etc. Among tubal factors,salpingitis increases the risk of ectopic pregnancy 2-4fold,5 tubal ligation and recanalization by 9-10 fold6 andprevious tubal surgery by 20 fold.7 In a woman who hasalready had one tubal pregnancy the risk of havingrepeat ectopic pregnancy is 7 to 13 times greater than overallrisk.8

Infertility increases the risk of ectopic pregnancy moderately,mainly because of tubal factors. This is particularly true forpregnancies that occur during infertility treatment.In multiparas with a history of infertility for 14 years

there is a 2-3 fold increased risk of ectopic pregnancy. Theincidence of ectopic pregnancy following in vitro fertilization(IVF) procedures is reported in up to 28% of cases, i.e.,a six-fold risk.9 Some studies have reported increasedectopic pregnancy rates with use of clomiphene citrate too,probably due to altered tubal function from hormonefluctuations.10 Intrauterine devices prevent intrauterinepregnancy more effectively than tubal pregnancy and,therefore, if pregnancy occurs with an IUD in situ, it is morelikely to be ectopic.11 A higher proportion of ovarian ectopicpregnancies has been seen in IUD users (5.5% vs 0% innonusers).12,13

Natural history of tubal pregnancy

Spontaneous resolution, either by regression or tubal abortion,is expected in up to 60% of cases.14 Tubal abortion is commonwhen the ectopic pregnancy is situated at the ampullary orfimbrial region. Choriodecidual haemorrhage separates theovum from tube and thereafter one of the four things mayhappen. It may resolve completely, present withhaematosalpinx, or may keep trickling, resulting in persistentpain and the formation of a pelvic hematocele. Rarely, tubalabortion may result in secondary abdominal pregnancy. Acutetubal rupture is the classical course, which occurs morecommonly at the isthmic site. The patient develops acuteabdomen and hypovolaemia. Sometimes tubal rupture canhave a chronic course if bleeding at the site is not acute orsevere.

Clinical features

There is a wide spectrum of symptoms and signs, rangingfrom asymptomatic to the haemodynamically unstable. Earlyectopic pregnancy may be entirely asymptomatic. The most

Nutan Agarwal, Vidushi Kulshrestha, Alka KriplaniDepartment of Obstetrics and Gynaecology, AIIMS,

New Delhi, India

I N V I T E D A R T I C L E

Table 1. Symptoms and signs of ectopic pregnancy16

Symptoms and signs Approximate percentage

Abdominal pain 95%Amenorrhoea 85%Vaginal bleeding 75%Dizziness, fainting 25%Passage of tissues 10%Adnexal tenderness 80%Adnexal mass 50%Uterine enlargement 25%

correspondence:Prof. Alka Kriplani, Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India,email: [email protected]

N. J. Obstet. Gynaecol Vol. 1, No. 1, p. 4 - 12 May 2006

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commonly reported symptoms are lower abdominal pain,amenorrhoea and vaginal bleeding. The classical symptomsof ectopic pregnancy are found in 30% of cases and usuallypresent between 5-9 weeks of amenorrhoea.15

Abdominal pain has a wide spectrum ranging from mild tosevere, lower to upper abdomen, unilateral or bilateral,localized or generalized, continuous or intermittent. Half ofthe cases presenting with amenorrhoea may experiencespotting per vaginum at the time of the expected period.Vaginal bleeding occurs due to inadequate endocrine function.The failing trophoblast may lead to involution of the deciduaand occasionally the entire decidua is sequestrated or expelledthrough the cervical canal (decidual cast), mimicking passageof products of conception.

On examination, ipsilateral adnexal tenderness is frequentlyfound. Cervical excitation, i.e., tenderness on movement ofthe cervix, may be present in about two-thirds of cases. Anadnexal mass may be palpable if it is > 3cm in size.17 Caremust be taken while performing bimanual examination asvigorous manipulation may expedite rupture of the ectopicgestational mass. The patient may present with tachycardia,hypotension, abdominal distension, marked reboundtenderness and shoulder tip pain in cases of acute ruptured ectopic.

Early diagnosis

Nowadays, a larger number of pregnancies, especially thosereceiving infertility treatment, are monitored early and thediagnosis of ectopic pregnancy can be established before anysymptoms manifest. Early diagnosis is essential to preventmaternal mortality and preserve future fertility. To achievethis, it is important to ‘think’ ectopic. The diagnosis of ectopicpregnancy should be suspected in any sexually active womanof reproductive age who presents with symptoms of lowerabdominal pain and delayed menstruation, until provenotherwise. All women with a history of any of thepredisposing factors such as infertility, pelvic inflammatorydisease, previous ectopic pregnancy, tubal surgery, IUD use,or use of assisted reproductive techniques (ART) must bescreened for ectopic. This is done by a urine pregnancy test,ultrasound and follow up with serum β-hCG, if required.Screening has been shown to reduce the risk of rupture from2.1% to 0.6%.18

Diagnosis

The importance of symptoms and signs should not beunderestimated despite the powerful diagnosticarmamentarium. They not only help in diagnosing thecondition, but also influence the choice of treatment.A good history and physical examination can diagnoseectopic pregnancy with 60% accuracy.19 However, varioustests have become available over the last decade that haverevolutionized the diagnosis of ectopic pregnancy. Of these,serum β-hCG and ultrasound are the most important.

Diagnostic tests

1. Serum β-hCG2. Transabdominal and transvaginal ultrasound3. Uterine curettage

4. Serum progesterone5. Doppler6. Culdocentesis7. Laparoscopy

Serum β-hCG

Serum β-hCG is the principal endocrine marker of pregnancy.It can be detected in maternal serum as early as 10 days afterfertilization. β-hCG is positive in virtually all ectopicpregnancies. On very rare occasions ectopic pregnancy maybe found where β−hCG cannot be detected in serum. It maybe due to very small volume of trophoblastic tissue whichmay be progressively degenerating. As the β-hCG levels varyin pregnancy, a single measurement cannot distinguishbetween an ectopic and intrauterine pregnancy, but repeatingthe measurement within 48-72 hours is useful. This is thenormal doubling time of β-hCGin normal pregnancy. In 85%of normal intrauterine pregnancies, the β-hCG rises by 66%in 48 hours and 114% in 72 hours. In ectopic pregnancies onthe other hand, 85% of ectopic pregnancies have no or lessthan 66% rise in 48 hours and their doubling time is usually> 7 days.20

Drawbacks of β-hCG testing: β-hCG alone is unreliable forthe following reasons:1. In 15% of intrauterine pregnancies the rise is

subnormal, whereas in 15% of ectopic pregnanciesthere is a normal rise of serum β-hCG.

2. An abnormal pattern of serum β-hCG levels in ectopicpregnancy cannot be distinguished from the oneobserved in a failing intrauterine pregnancy.

3. Serum β-hCG levels cannot correlate with the size orsite of the ectopic.

Ultrasound

The introduction of ultrasonography has revolutionized thediagnosis and management of ectopic pregnancy. It can beused to evaluate the contents of endometrial cavity, identifyan adnexal mass as small as 10 mm and assess the amount offree peritoneal fluid.

Both transvaginal and transabdominal ultrasound are used toestablish the diagnosis of ectopic pregnancy. Usingtransvaginal ultrasound the diagnosis can be made one weekearlier, with better visualization and assessment of the fluidin Pouch of Douglas, whereas the transabdominal scanprovides a broader view of the pelvis, detection of unusualsites and assessment of peritoneal fluid.

The ultrasound picture can be very variable in ectopicpregnancy and correlation with clinical findings andserum β-hCG level is required to establish the correctdiagnosis.

1. Definite intrauterine pregnancy

If a definite intrauterine pregnancy is seen, the likelihood ofa coexisting ectopic pregnancy is extremely low. Thepossibility of heterotopic pregnancy should be kept in mindin pregnancy after IVF. An intrauterine gestation sac is locatedeccentrically in the intrauterine cavity with a double decidualsac sign (DDSS) (Fig.1).

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Figure 1:Intrauterine gestational sac showing doubledecidual sac sign (DDSS)

3. Abnormal intrauterine pregnancy

Various ultrasound features that can be seen at different stagesof decay of the embryo include: gestation sac with no fetalpole, no cardiac activity in the fetal pole, irregular crenatedborder of the gestation sac, larger sac with no DDSS or large,thin-walled yolk sac.

4. Probable ectopic

Presences of adnexal mass, tenderness on probe palpation orfluid in the cul-de-sac are signs that lead to a suspicion ofectopic pregnancy. Adnexal masses other than simple cystof varying sizes are found. Adnexal mass due to ectopicpregnancy are other than simple cyst. They are complexmasses with solid and cystic component. It is due to partiallycollapsed gestational sac and haemorrhagic and thromboliccomponents. These complex adnexal masses are separatefrom the ovary. The gestation SAC may be seen as a tubalring (Bagel’s ring) (Fig. 3), which is seen as a thick echogenicring with fluid filled sac.23

Figure 2: Pseudosac in case of ectopic gestation

DDSS is echogenic ring like structure around sac which hasthick 2 consecutive lines due to decidua capsularis-smoothchorion and peripherally located decidua pareitales andcontains the fetal pole and yolk sac. It has to be differentiatedfrom a pseudosac, which is seen in 10% of ectopicpregnancies.21 But pseudosacs are centrally located with noDDSS and no fetal pole (Fig.2).

Figure 3: Gestational sac as a tubal ring in the fallopian tube

5. Definite ectopic

Detection of an echogenic ring-like structure outside theuterine cavity with a fetal pole is diagnostic of definite ectopicpregnancy (Fig. 4).

2. No definite intrauterine pregnancy

The level of β-hCG at which an intrauterine pregnancy shouldbe detectable on ultrasound is termed the discriminating zoneof serum β-hCG. By transabdominal scanning, this is 6000IU/l, whereas by transvaginal scan this is 2000 IU/L.22 If theuterus is empty at the discriminating zone (DZ) of serumβ-hCG, ectopic pregnancy should be diagnosed, until andunless proven otherwise. In such a situation, there can be avery rare possibility of multiple pregnancy where higherserum β-hCG levels can be expected in earlier gestation. Ifserum β-hCG levels are low, the possibility of earlypregnancy has to be kept in mind.

Figure 4: Live ectopic with fetal pole

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Drawbacks of ultrasonography: Diagnosis byultrasonography may be difficult in the following situations:1. Differentiation between a pseudosac and a true

intrauterine gestation sac may be difficult.2. In the absence of an intrauterine pregnancy with low

serum b-hCG levels, the possibility of very early viableintrauterine pregnancy has to be kept in mind.

3. The absence of intrauterine pregnancy above DZ serumb-hCG level does not rule out abortion.

4. There is a remote possibility of heterotopic pregnancy,especially after ART.

5. Other adnexal masses and corpus luteum can bemisdiagnosed as ectopic.

Correlation with Serum βββββ-hCG andultrasonography

Proper evaluation, follow up ultrasonography and serum β-hCG may be required in certain situations to establish thediagnosis and plan the choice of treatment. If β-hCG levels arebelow the discriminating zone and no intrauterine sac is seen,follow up is required after 48 hours to assess rise in β-hCG aswell as appearance of a gestational sac once the DZ is reached.The DZ is considered 6000 IU for trans-abdominal and 2000IU for trans-vaginal ultrasound, but with the availability ofhigh resolution scanners, it is reported to be as low as 3000 IU/L for trans-abdominal and 1000 IU/l for trans-vaginalultrasound.24 An average gestational sac is detectable at 35days at β-hCG level of 1000 IU/L, the fetal poleis visible at40 days at β-hCG level of 3000 IU/L and cardiac activity isseen at 47 days at β-CG level of 3000 IU/ml.25

Other diagnostic modalities

Doppler ultrasound can be helpful to differentiate betweena true and pseudo-gestational sac. High velocity flow is seenin developing placentation, so it is seen at endometrium innormal or abnormal intrauterine pregnancy but not in ectopicpregnancy.

Dilatation and curettage (D&C) can differentiate ectopicfrom non-viable intrauterine pregnancy. Villi can be checkedimmediately in normal saline after curettage. Chorionic villifloat, dediduas settles. Histological findings consistent withpregnancy confirm the clinical diagnosis. This can be furtherfollowed up with bhCG, a fall of > 50% in 24 hours indicatingabortion. Caution should be taken to avoid disruption of anearly viable intrauterine pregnancy and D&C should beavoided as far as possible.

Serum progesterone testing takes only 2-3 hours and asingle measurement may be helpful in identifying normaldeveloping pregnancy. A level exceeding 25 ng/ml is associatedwith intrauterine viable pregnancy whereas a value <5 ng/mlis highly suggestive of non-viable pregnancy. However, levelsbetween 5-25 ng are inconclusive, so it has limited value.26

Culdocentesis : A significant amount of non-clotted blood isindicative of haemoperitoneum. In case of haemoperitoneumwith positive pregnancy test, ectopic pregnancy is thecommonest cause. Serous fluid or pus is a sign negative forectopic pregnancy. Dry tap is inconclusive. In cases of ectopicpregnancy with little or no intra-abdominal bleeding ororganized pelvic hematocele culdocentesis may be falsely

negative. Because of the widespread availability of sonography,it is rarely indicated nowadays.

Differential diagnosis of early tubalpregnancy

There are various conditions which can be confused withectopic pregnancy1. Abortion: Abortion also presents with amenorrhoea

and uterine bleeding. Pain may be accompanied butpain is not associated with fainting attacks. Adnexaltenderness is not a feature unless there is associatedsalpingitis.

2. Acute or subacute salpingitis – there may be irregularuterine bleeding with occurrence of lower abdominalpain. Amenorrhoea may not be there but patients havetenderness with or without adnexal mass, it is usuallya bilateral condition.

3. Early pregnancy with corpus luteum – sometimes apatient in early pregnancy may present with abdominalpain. If a corpus luteum is felt in adnexa. It can beconfined as adnexal mass due to ectopic pregnancy.But tenderness will be definitely less in such cases.

4. Torsion or rupture of ovarian cyst with sudden onsetof pain and fainting attack or collapse with findings ofadnexal mass may be confusing.

Treatment

Treatment options for ectopic pregnancy are surgery, medicalmanagement or expectant. Previously surgery was regardedmandatory because of risk of rupture of ectopic pregnancy.Now, with early diagnosis, medical management or expectantmanagement is also possible. Choice of treatment in theindividual case depends on the characteristics of the patient,desire for future fertility, facilities and expertise available atthe center, compliance, socioeconomic status and preferenceof the patient.

Surgery

Surgery is the mainstay of treatment. It is the preferred modeif the fallopian tube is already ruptured, pain is persisting for>24 hours or the patient is not suitable for medical management.Surgery may be conservative or radical. Conservative surgery,i.e., salpingostomy or fimbrial expression is the logical optionfor women who wish to preserve their fertility. The subsequentintrauterine pregnancy rate is greater but there is also a higherrecurrence risk of ectopic pregnancy.27 Radical surgery, i.e.,salpingectomy, is indicated in cases of ruptured ectopic,uncontrolled bleeding, extensive tubal damage, large tubalpregnancy (> 5 cm), recurrent ectopic on the same side orprevious reconstructive surgery.

Laparotomy is done for haemodynamically unstable patientswith a frank haemoperitoneum. Such patients are bestwheeled directly to the theatre without further ado. A wide-bore intravenous cannula is inserted and a sample obtained atthe same time so that adequate blood can be cross-matchedand obtained immediately. If there is any doubt about thesource of the bleeding, the abdomen is opened through avertical incision that can be extended as required, but if thereis no doubt about the diagnosis a Pfannenstiel incision may


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be preferable. On opening the rectus sheath, the peritoneumis seen bulging with bluish colour reflected through from thehaemoperitoneum. The peritoneal cavity is opened and, whilethe assistant suctions off the collected blood, the surgeonimmediately plunges a hand into the pelvis and feels for theuterine fundus and pulls it out of the collected pool. Pullingup the uterus immediately decreases the amount of bleeding.The tubes are rapidly inspected and the site of bleedingidentified and clamped. If the tube is grossly damaged, partialsalpingectomy is the treatment of choice. A series of clampsis applied at the base of the tube and ligated with 1-0 chromiccatgut or Vicryl. It used to be the practice to cover the stumpof the tube by the round ligament using the modified Coffeysuture but this practice has now been abandoned. If futurefertility is not desired, the contra-lateral tube is ligated byPomeroy’s technique. The peritoneal cavity is lavaged wellto wash out all collected blood.

Laparoscopic surgery is preferable in haemodynamically stablepatients as it is minimally invasive. Relative contraindicationincludes previous surgery, extensive pelvic adhesions, largeblood clots, insufficient laparoscopic facilities or inexperienceof the surgeon.

Linear salpingostomy

Linear salpingostomy is standard conservative surgery forectopic pregnancy. Ectopic pregnancy is identified and tubeis immobilized. A linear incision is made on the antimesosalpinxwall of the tube at the point where it is maximally distended.Incision is made by unipolar electro-cautery or laser. Theproducts of conception are flushed out with irrigating solutionat high pressure. A combination of blunt and hydrodissectionshould be used. Specimen is grasped with claw forceps andremoved. One should try to avoid removing the productspiecemeal. Bleeding points can be coagulated. Tube is irrigatedcarefully and inspection should be done for haemostasis underwater. The tubal incision is left open to heal by secondaryintention.

Fimbrial expression by “milking” the tube may be appropriatein cases of ampullary pregnancy if the pregnancy is aborting,trophoblastic tissues are expressed out by compressing thetube from proximal to distal side and further tube can bewashed with irrigating solution. Thin suction cannula can beinserted from fimbrial side and solution can be flushed inunder pressure. Tube should be thoroughly inspected forany retained products. Care should be taken by wash of allbits of trophoblastic tissue from the tube. Milking can leadto damage to the cilia. If there are large blood clots minilaparotomy is often indicated in such cases.

In cases of chronic ectopic, if there is hematocele it is suckedout cleared. Trophoblastic tissue may be in the pelvis andadhered to other organs like intestine. Trophoblastic tissuesas much as possible are removed. Badly adherent bits can beleft as there is risk of bleeding or injury to organs.Salpingectomy has to be done if there is badly rupturedfallopian tube and it is unrepairable condition or the futurefertility is not required. Pelvis and abdominal cavity isthoroughly irrigated.

Medical management

Where facilities for β-hCG estimation and ultrasound exist,there is timely diagnosis of ectopic pregnancy and the needfor surgical visualization is eliminated in many cases. Hencemedical treatment is effective and safe in carefully selectedcases, provided a definite diagnosis of ectopic pregnancy canbe made. The patient must be willing and eligible for medicalmanagement. All contraindications should be ruled out. Usingthe following criteria, about 40% of ectopic pregnancies arefound to be appropriate for medical management:28

Eligibility criteria for medical management

� Haemodynamically stable patient� Unruptured ectopic� Reliable and compliant patient, can return for follow

up� Ectopic pregnancy < 4 cm in size� No contraindication for methotrexate� Normal blood counts, liver and kidney function� No suspected heterotopic pregnancy� No history of prolonged pain (>24 hours)� Desirous of future fertility

Presence of cardiac activity in the ectopic embryo and serumβ-hCG levels >10000 mIU/ml are relative contraindicationsfor medical management, although reports have shownsuccessful outcome in such cases also.29 We have also usedmethotrexate successfully in 2 cases of live ectopic and in 2cases with the high β-hCG lvel of 28000 and 40,000 mIU/mlrespectively. But close supervision in hospital is essential inthese cases.

Treatment regimen

Methotrexate is the drug of choice. Both single and multipledose regimens have been described. In the multidose regimen,methotrexate is given in a dose of 1mg/kg IV or IM followedby leucovorin 0.1mg/kg orally 24 hours later and the doserepeated every alternate day up to a maximum of 4 dosesuntil bhCG level declines by 15%. Serum bhCG should beassessed at day 0, 3, 5 and 7 until hCG declines 15% fromprevious value.30 Not all patients need four doses. The second,third or fourth dose is administered only if the bhCG valuedoes not show response. After response is achieved, thepatient is monitored with weekly bhCG levels until these areundetectable. If there is no response even after 4 doses, thepatient is maintained drug-free for a week to decrease therisk of side effects.31

The single dose regimen is more commonly used as it haslesser side effects. Methotrexate is given in a dose of 50mg/m2 IV or IM. bhCG is measured on Day 0, 4 and 7. Thereshould be a fall of 15% between Day 4 and 7. A rise in levelis often seen on day 4 and does not indicate failure of response.In fact, an initial rise is sometimes caused by the release oftrophoblastic tissues into circulation. If the bhCG levels areincreased or plateau between day 4 and 7, a second weeklydose can be given.32 Although most of the reports showsadministration by methotrexate by intramuscular route, we

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personally feel intravernous route is a better option. In ourexperience in 2 cases where patient did not respond to IMinjection responded to intravenous injections. In one casewho received first intramuscular injection at nearly 10,000bhCG did not respond and β-hCG level raised upto 40,000at D7 and surprisingly responded to second intravenousinjection and did not require any surgery. Her β-hCG becamenegative in 10 weeks.

Monitoring and follow up

Most patients can be managed on an outpatient basis. Whilereceiving methotrexate, the patient should be instructed not totake folic acid, salicylates or alcohol, and should avoid exposureto sun and maintain abstinence. She should be observed forheavy bleeding, pain, especially severe and persistent (>12hours), any sign of rupture and haematocrit. The most difficultaspect is to distinguish between transient pain due to successof therapy from that of tubal rupture. Transient abdominalpain after 3 days for 4-12 hours is presumably due to tubalabortion.33 About 80% of cases who have pain after medicalmanagement do not require surgery.34 The patient can beadmitted if required. Ultrasonography is not of much help.35

The patient is followed with weekly β-hCG monitoring tilllevels are undetectable. Resolution usually takes 5 weeks anda maximum of 7 weeks.36 Medical management is notconsidered successful until β-hCG is no longer detectable inthe serum. There are cases of treatment failure even withβ-hCG value as low as < 50mIU/ml.37

Surgical intervention

Surgical intervention may be necessary if there is orthostatichypotension, decreasing haematocrit, persistent or severepain, any sign of tubal rupture or impending tubal rupture.Surgery is indicated if the patient no longer wants to continuewith medical therapy or if medical therapy fails.

Risk of tubal rupture

The risk of tubal rupture is greater with high levels of serumβ-hCG. The presence of cardiac activity is associated withhigher failure rate 14% vs 4.7% when cardiac activity isabsent.29 The tube is unlikely to rupture if the mass is < 2 cmand β-hCG is < 2000 mIU/ml, although cases of rupturehave been reported even with β-hCG of < 5 mIU/ml.38

Success rate

In review of 26 studies the overall success rate with themultiple dose regimen is greater than with the single doseregimen (95% vs 90%).39 In the single dose regimen, 15% ofcases need more than one dose. Multidose is less convenientand associated with more side effects 48% vs 29% in singledose. Comparison of medical management and conservativesurgery has shown that success rate and patency is the samein both, whereas resolution is faster with salpingostomy.40

Expectant management

The fact that some patients of ectopic pregnancy havespontaneous resolution, either through regression or throughtubal abortion, is the basis of expectant management of ectopicpregnancy. Selection of patients for expectant managementdepends on the initial serum β-hCG levels and size of theectopic gestation. It is a reasonable option in very carefullyselected patients. Stringent inclusion criteria include: ectopicmass < 3 cm, β-hCG < 1000mIU/ml and absence of cardiacactivity. Approximately 15-20% cases of ectopic pregnancymay be appropriate for expectant management. The patientis closely monitored with clinical symptoms, haematocritand weekly β-hCG till undetectable. Transvaginalultrasonography is performed if required. The overall successis approximately 70%. Complete resolution may take 4weeks. Patients with persistent or increasing β-hCG levelsshould be treated with medical or surgical therapy. The riskof tubal rupture on expectant management is reported to beabout 2.5%.41

Surgically assisted medical management

Patients diagnosed before tubal rupture can be treatedwith alternative treatment options. Besides systemicmedical management local injections of tropholytic agentsmay be alternative options. These local injections may beinjected either by ultrasound guidance or by laparoscopicguidance. Laparoscopically guided local injection does notseem to be logical option as once patient is exposed tolaparoscopy, it is ideal to remove the ectopic gestation at thesame sitting.

However, ultrasound guided salpingocentesis can be aoption in certain cases of unruptured ectopic pregnancy toavoid the side effects of systemic drug. It is limited tothose patients in whom ultrasound positively localizes atubal mass. Needle injection should be precisely and safelyguided into exact gestational target site. The most reliableultrasound finding for ectopic pregnancy is observationof live embryo outside of the uterus. Tubal ring is anotherhighly specific sonographic appearance. Salpingocentesis canbe performed in those patients with these specific findingsonly.

Variety of the treatment agents including methotrexate 10mg,hyperosmolar glucose and potassium chloride are used. Thereis lack of widespread acceptance of this technique. There aresome distinct potential advantages. One is avoidance of riskof laparoscopic surgery and secondly, its lack of systemictoxicity of methotrexate. There is delivery of high localconcentration of methotrexate with reduced incidence ofsystemic side effects. But, efficacy is considered same as IMinjection, there is need for experienced practitioner to performthis procedure. Other risks are infection, haemorrhage, tubaldamage at the site of injection. We gave KCl along with IVmethotrexate in two live ectopics and both responded to thetreatment.


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Persistent ectopic pregnancy

Conservative surgical management of ectopic pregnancy aswell as medical therapy may not entirely eradicate thetrophoblastic tissue. The remaining trophoblast may remainviable and continue to grow, leading to persistent ectopicpregnancy. The incidence of persistent ectopic has beenreported to vary from 2 to 20%,42 although in our practice itis very low.

Persistent ectopic pregnancy may result in sudden tubalrupture and haemorrhage. The diagnosis should be suspectedin a woman who has abdominal pain after conservativesurgical management. Sonographic identification of apersistent ectopic mass may not always be possible due tosmall size.

bhCG levels decrease rapidly after salpingostomy. Onpostoperative day 12, the level declines to less than 10% ofthe preoperative value.Increasing or plateauing bhCG levelsare obvious indications of persistent ectopic pregnancy.

Predictors of persistent ectopic

The fall in serum bhCG level on day 1 can be a predictor ofpersistent ectopic. More than 85% cases where there is a fallof > 50% in the bhCG level on the first postoperative daywill not develop a persistent ectopic, whereas if the fall is >75% on day 1, the risk is almost nil.43 An increased risk ofpersistent ectopic is seen in cases where the ectopic is smaller< 2 cm in diameter, bhCG is high > 3000 mIU/ml and rapidlyrising, the implantation site is medial to the salpingostomyincision or removal is done piecemeal. Weekly follow upwith bhCG is recommended following conservativesurgery.

Treatment of persistent ectopic

The treatment of persistent ectopic pregnancy is single dosemethotrexate. The role of prophylactic methotrexate toprevent persistent ectopic following conservative surgeryhas not yet been determined.

The pregnancy rate does not seem to decrease after persistentectopic and chances of recurrent ectopic are also not high.

Abdominal pregnancy

Abdominal pregnancy occurs in 1 in 8000 pregnancies andthe mortality is 8 times higher than other ectopics. Abdominalpregnancy can be primary or secondary. Primary abdominalpregnancy is implanted in peritoneal cavityitself. Diagnosisof primary abdominal ectopic pregnancy is made byStuddiford criteria which include :1. The presence of normal tube and ovary2. The absence of placental fistula3. Presence of pregnancy related to peritoneal surface.

Secondary abdominal pregnancy is more common. Herethe pregnancy is initially implanted in the ampullary or

fimbrial part of tube. It may be expelled from the tube andmay then get re-implanted onto any peritoneal area in theabdomen. The placenta grows anywhere in the abdominalcavity.

Medical management may be of little value in abdominalpregnancy. Advanced abdominal pregnancy is managed bylaparotomy. Preoperative diagnosis of abdominal pregnancyis difficult. The sonographic features as suggestive ofabdominal pregnancy are described as visualization of fetusas a part separate from the uterus, failure to visualize theuterine wall between the fetus and the urinary bladder, closeapproximation to the abdominal wall and visualization ofextra-uterine placental tissue.44 Diagnosis is often missed onultrasound. We also reported a case where diagnosis wasmissed on first ultrasound.45 When ultrasound findings areequivocal or inconclusive, magnetic resonance imaging shouldbe performed.

Surgery is indicated whenever the diagnosis is established.Intraoperative decision regarding removal or non-manipulation of placenta is an important management issue.In early abdominal pregnancy it may be possible to removeplacenta completely but in advanced cases it may be quitedifficult. In such circumstances, management includes ligationof umbilical cord close to the placenta and leaving it in situ. Itmay be followed up by ultrasound and bhCG for placentalinvolution. Methotrexate may be indicated in certain caseswith persistent bhCG level.

Interstitial pregnancy

The incidence of interstitial pregnancy is 1 in 5000pregnancies. Rupture is usually delayed to 9-12 weeksgestation because of myometrial distensibility. Previoussalpingectomy is a unique risk factor for interstitial pregnancyand is seen in 25% of cases. The diagnosis is made byultrasound. The gestation sac is located within themyometrium towards the site of the fallopian tube butdetached from the endometrial echo. A myometrium mantle,i.e., at least 5 mm myometrium between the gestation sacand endometrium, is seen. Traditionally, the treatment iscornual resection or hysterectomy. However, in cases wherean early diagnosis of interstitial pregnancy can be established,systemic or local methotrexate can be attempted first.

Ovarian pregnancy

The incidence of ovarian pregnancy is 1 in 40,000 pregnancies.The clinical features are the same as in ectopic tubalpregnancy, but 30% of cases are haemodynamically unstable.There is a high association with IUD use. Ovarian pregnanciesare mistaken for ruptured corpus luteum.

The diagnosis of ovarian pregnancy is made by Spiegelberg’scriteria1. Intact fallopian tubes2. Ovarian tissue in sac wall3. Ovarian connection to uterus with ligament4. Fetal sac in position of ovary.

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Both diagnosis and treatment can be done by laparoscopy.Removal of ectopic gestation, ovarian wedge resection oroophorectomy can be performed.

Cervical pregnancy

It occurs in 1 in 1200 pregnancies. As implantation occurs inthe cervical canal, it can be confused with partially expelledspontaneous abortion of an intrauterine pregnancy. Onultrasound, the gestation sac is seen below the level of theinternal os and located within the limits of the cervix, deeplypenetrating into one of the cervical walls. If the diagnosis isnot confirmed, CT or MRI may be valuable. Predisposingfactors include preexisting cervical pathology, cervical surgeryand Asherman’s syndrome.Treatment modalities include systemic or local methotrexate,arterial embolization, cervical curettage followed by balloontamponade, cervical curettage and, lastly, hysterectomy iffuture fertility is not a concern.

Heterotopic pregnancy

Heterotopic pregnancy, where pregnancy occurssimultaneously in intrauterine as well as at an ectopic site,has been reported in 1 in 30,000 pregnancies. It occurs in upto 1% of pregnancies after assisted reproductive techniques(ART). It should be suspected in a patient who has undergonecontrolled ovarian hyperstimulation, with or without ART.

There are several diagnostic pitfalls. Serial bhCG may not beuseful because of the concomittant intrauterine pregnancy.

There is no role of medical management in these cases. Surgicalmanagement is required to treat this type of ectopicpregnancy.

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Current trends in the management of ectopic pregnancy