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DIAGNOSTIC DILEMAS AND NEWER THERAPEUTIC APPROACH TO ECTOPIC GESTATION

Ectopic pregnancy remains a significant contributor to maternal mortality and morbidity. Despite the obstetrician’s awareness of the problems, ectopic pregnancy in many cases still remains a difficult diagnosis.

As ectopic pregnancy can present as abnormal uterine bleeding with or without missing a menstrual period it has been included in this book.

Definition: A pregnancy in which the fertilized ovum implants in any tissue other than the endometrial lining of the uterus.

  • 95% are tubal
  • 1.5% are abdominal
  • 0.5% ovarian
  • 0.3cervical

Incidence: There is a 3 to 5 fold increase in the incidence of ectopic pregnancy mainly attributable to increase in pelvic inflammatory disease and assisted reproductive technology.

It occurs in:

  • 16.9 per 1000 reported pregnancies USA
  • 12.5 per 1000 deliveries in UK
  • 3.86 per 1000 live births in India (ICMR study 1990)

Ectopics are responsible for 11.5% of all maternal deaths in the UK. It has decreased from 1.8 to 0.6 deaths per 1000 ectopic pregnancies.

The clinical diagnosis of ectopic pregnancy is not at all straight forward. The classic clinic triad pain abnormal uterine bleeding and amenorrhea is not commonly present. In a clinical review of 154 patients with ectopic, pain was present in 97% and abnormal bleeding was noted in 86%. Only 61% reported missing a menstrual period. A pelvic mass was palpated in 41% and equivocally present in 25%. No mass was felt in the remaining patients. The risk group of women include:

  1. Women with a documented history of pelvic inflammatory disease.
  2. Women who are pregnant with an IUCD in place.
  3. Women undergoing infertility treatment with HRT.

The other contributory factors for the increase in ectopics are poor socio economic status, race of the patient and improved methods of diagnosis and reporting.

Heteroptopic pregnancy once thought to occur 1 in 30,000 pregnancies are known to occur 1 in 4000 especially in patients undergoing infertility treatment. Therefore there is a need for increased surveillance in this group.

It is useful to remember that all women of childbearing groups are at risk for an ectopic. If this is borne in mind subtle presentations with slight abnormal uterine bleeding with or without history of missed periods with mild pain can be observed carefully to arrive at a definitive diagnosis.

Clinical diagnosis: Patients symptoms may be divided into 3 groups:

1st group “Emergency Group”: They present with acute shock and haemoperitoneum.
2nd group “Subacute presentations”: These women have mild pain irregular bleeding, may or may not have missed the period. Symptoms are less dramatic and diagnosis can be missed.

Diagnosis:

The clinicians dilemma: What should they do first? Urine or serum β hcg estimation? How soon can the pregnancy be detected by measuring β hcg? And then the problem of locating the site of midation.

The suggested protocol:

  1. First do a urine pregnancy test.
    Eliza tests which are done today are sensitive to 25miu/ml.
    False negative rate is only 2%
  2. If positive perform TVS.
  3. If intrauterine sac is seen also look at the adnexa.
  4. If no sac is seen do a serum β hcg.

Serum β hcg.

R/A assays: Can detect 1-2 miu/ml of β hcg. This detects both the whole and free β hcg. Different international standards are used for reporting. The first international standard is equivalent to two times the second international standard.

Later a purer standard was defined – the International Reference preparation (IRP). 1 mg/ml – 5-6 iu/ml (2nd IS)= 10-12 miu/ml IRP.

The discriminatory zone of β hcg is a concept introduced by Kadar and co-workers to improve clinical management of ectopics. They stated that above a critical level of β hcg; an intrauterine sac should be visible.

Today for abdominal scan this is 1500 miu/ml.
For TVS the cut off is 1000 miu/ml.

The discriminatory zone is well established for a normal intrauterine pregnancyl this is not true for an ectopic. Not seeing an ectopic on scan doesnot exclude it.

Doubling β hcg :

Normal intrauterine pregnancies tend to double their β hcg titres after 48 hours whereas abnormal pregnancies namely falling intrauterine and ectopics exhibit a decreasing or plateauing value. If β hcg value increases to <66% over 48 hours a diagnosis of an abnormal pregnancy is made.

If half life is <1.4 day an abortion is likely; if >7 day an ectopic is likely.

TVS:

  1. Demonstration of live embryo in the tube.
  2. Tubal ring.
  3. Extra uterine mass.
  4. Fluid in POD
  5. Pseudo gestational sac.
  6. Doppler

Doppler in ectopic pregnancy:

Increases confidence of diagnosis rather than the sensitivity:

a. colour flow- intense ring of vasularity.
b. Peritrophoblastic flow – low resistance type.
c. Doppler of the tubal branch of uterine artery RI difference > 8% between both sides.
Ectopic side lower resistance.
85% sensitivity and 96% specificity for diagnosis of ectopic in the absence of adnexal mass.

Surgical intervention should be undertaken if β hcg increases or clinical condition deteriorates.

Medical treatment:

Drugs used:

  1. Methotrexate
  2. Actinomycin D
  3. Mifepristine
  4. PG E2 and PG/2α

Of the above only Methotrexate is widely used.

This has been given in a single and multiple dose regimen. Given intramuscularly 1mg/m²/ body surface.

Methotrexate has been successfully used in unruptured ectopic, interstitial and cervical pregnancies.

Occasionally multiple doses are required with folinic acid rescue.

Criteria used for medial management.

  1. Ectopic mass < 3cms
  2. β hcg M 3000 iu/
  3. Non viable
  4. Unruptured

About 15% of medically treated women will require more than one dose of Methotrexate and of these 7% will experience rupture during follow up. 75% will experience pain following treatment. There are reports of fluoroscopic guided embolisation of hypogastric arteries.

Surgical management:

Laparoscopy vs Laparotomy:

There are no stric guidelines to determine which method is to be used.

Relative contraindications for laparoscopic management are:

  1. Massive intraperioneal bleeding with patient in shock.
  2. β hcg > 15, 000 iu/ml
  3. Extensive adhesions
  4. Mass greater than 4cms
  5. Live ectopic gestation

It also depends on facilities available and expertise available for laparoscopy.

Laparoscopy:

  1. Salpingostomy
  2. Segmental resection
  3. Salpinjectomy

Salpingostomy:

3 port entry is used. One 10mm intraumbilical and 2 accessory 5mm ports.

An incision is made on the antimesentric border of the tube at the point of maximal bulge and products are removed. The ectopic bed is thoroughly irrigated to remove as much of trophoblastic tissue as possible. No suture is placed. Healing takes place by secondary intention. Leaving residual trophoblastic tissue is a matter of concern.

Persistent ectopic is about 10%/ Wherever conservative surgery is performed, serial β hcg estimations should be done till the value becomes less than 20 iu/ml.

Segmental resection:

The ishtmial pregnancy linear salpingostomy can be difficult and can lead to tubal occlusion and recurrent ectopic. Here segmental resection and reanastomosis later is a good option.

Salpingectomy:

This is the procedure of choice if the woman has completed her family or if the tube is irreparably damaged. The tube is removed using bipolar forceps or using an endoloop. Chapron et al in 1993 described a scoring system based on patients previous history and appearance of pelvic organs to decide which methods salpingectomy or salpingostomy would be preferred for the patient.

Pregnancy outcome following surgical Management of Ectopic Pregnancy:

There are four recent cohorot studies that specifically compare laparoscopic conservative and radical treatments of ectopic pregnancy.

IUP Recurrent Ectopic

Points to Remember:

  1. In reproductive age group think ectopic when patients present with abnormal uterine bleeding.
  2. They need not be married and they need not miss a period.
  3. Serum β hcg and TVS have made early diagnosis possible. Sometimes this has to be repeated twice a week for definitive diagnosis to be made.
  4. Methotrexate used in medical management.
  5. Laparoscopic has replaced laparotomy in the surgical management.

REFERENCES

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    Chistica CD, Ectopic pregnancy – a new surgical epidemic
    Obstet Gynaecol 1983;61:698-701
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    A 15 year experience with ectopic pregnancy.
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    Risk of intrauterine contraceptive devices (Letter) Br. Med. J. 1984 288: 1919
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    Ectopic Pregnancy: Changes in Serum Choronic Gonadotrophin Contravention.
    Obstet Gynaecol 1984 63:76-80
  6. Canturight PS, Victory DF
    Wong SW et al, Evaluation of a new generation of Urinary Pregnancy tests.
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    The effect of different human chorionic gonadotrophin assay sensitivity on screening for ectopic pregnancy.
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    Discrimatory hCG zone: Its use in the sonographic evaluation for ectopic pregnancy.
    Obstet Gynaecol 58:156, 1981
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    Obstet Gynaecol 58: 162, 1981
  11. Robero R, Kadar N, Lopel JA et al
    The value of serial human chorionic gonadotrophin testing as a diagnostic tool in ectopic pregnancy.
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    Review of literature and Repeat of a case treated by single dose Methotrexate Therapy- Obstetrical and Gynaecological Surgery 1990, Vol. 45 No. 7 405-411
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