Pregnancy outside the uterine cavity- ectopic pregnancy: types, diagnosis and management

 When the fertilized ovum gets implanted and develops in a site other than normal uterine cavity that pregnancy  is called ectopic pregnancy.

Incidence

It is seen in > 1 in 100 pregnancies.  Recent evidence indicates that the incidence of ectopic

pregnancy has been rising in many countries.

In India  ectopic pregnancy  is seen in  <b>1 in 100 deliveries</b> as per the records.

In USA there is rise in the incidence of ectopic pregnancy to about 5 folds.

In UK , 2 folds increase is seen in the incidence of ectopic pregnancy.

In France the ectopic pregnancy is seen in  15 cases of 1000 pregnancies.

In Nigeria  2-3% of gynecological emergencies are ectopic pregnancies.

 Recurrence rate  is  15% after  first ectopic pregnancy,  25% after  two  ectopic pregnancies.

History of ectopic pregnancy:

 Albucasis first described the ectopic pregnancy in  963 AD.

After so many years in 1884 Robert Lawson Tait of Birmingham performed the first successful salpingectomy operation.

 later in  1953,  Stromme  first did the  salpingostomy which is a conservative surgery .

After invention of laparoscopic technology in 1973 Shapiro & Adller  did the  laparoscopic salpingectomy  and in 1991, Young et al  did the laparoscopic salpingotomy.

AETIOLOGY:

 The  factors  which cause delayed transport of the fertilized ovum through the fallopian tube favor  implantation in the tubal mucosa,  giving rise to a tubal ectopic pregnancy.

These factors may be congenital or acquired.

Congeital factors leading to ectopic pregnancy: 

Fallopian tubal hypolasia,  tortuosity of the tube,  congenital diverticuli of the tube, accessory ostia at the fimbrial end, partial stenosis of the fimbrial or uterine end.

Acquired factors leading to ectopic pregnancy :

Inflammatory conditions like : PID(pelvic inflammatory disease)- by leading to occlusion of tubes, septic abortion, puerperal sepsis, MTP(medical termination of pregnancy)-  by leading to Intra luminal adhesions may cause ectopic pregnancy.

Surgical causes like: tubal reconstructive surgery, recanalisation of tubes- by leading to intra luminal adhesions in the tube may cause ectopic pregnancy.

Neoplastic conditions like: broad ligament myoma, ovarian tumour by obstructing the fimbrial or uterine orifices or lumen of the fallopian tube can lead to ectopic pregnancy.

Miscellaneous causes like : IUCD(intra uterine contraceptive devices), endometriosis,

ART(artificial reproductive techniques) like  IVF(in vitro fertilisation) &  GIFT(gammate intra fallopian tube transfer) or  previous ectopic pregnancy may also lead to ectopic pregnancy.

Sites of ectopic pregnancy:

 In the fimbrial end of fallopian tube ectopic pregnancy is seen in 1% of cases.

In the ampullary region of fallopian tube ectopic pregnancy is seen in > 85% of cases.

In the isthmic region of fallopian tube ectopic pregnancy seen in 8% of cases.

In the interstitial part of fallopian tube ectopic pregnancy seen in 4% of cases.

Ovarian ectopic pregnancy seen in <2% of cases. https://srsree.blogspot.com/2019/03/ovarian-ectopic-pregnancy-at-34-weeks.html?m=1

Cervical ectopic pregnancy seen in <2% of cases.

Cornual rudimentary horn ectopic pregnancy seen in <2% of cases.

Secondary abdominal ectopic pregnancy seen in <1% of cases.

Broad ligament ectopic pregnancy seen in <1% of cases

Primary abdominal ectopic pregnancy seen in <1% of cases

Clinical presentation of ectopic pregnancy:

Normally ectopic  pregnancy remains asymptotic until it ruptures.

 When it ruptures it  can present in two variations – acute and chronic forms.

Symptoms will be like – amenorrhea, abdominal pain, syncope, vaginal bleeding or pelvic mass.o

Diagnosis of ectopic pregnancy:

Though the diagnosis of ectopic pregnancy is difficult it can be overcome by careful history taking,  examination and investigations.

 In recent years, in spite of an increase in the incidence of ectopic pregnancy, there has been a fall in the case fatality rate.

This is due to the widespread introduction of diagnostic tests and an increased awareness of the serious nature of this disease. This has resulted in early diagnosis and effective treatment.

With this now the rate of tubal rupture is as low as 20 %.

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Methods of early diagnosis:

 Immunoassy  utilising monoclonal antibodies to β-HCG(beta-human chorionic gonadotrophin) which will be elevated in pregnancy.

Ultrasound scanning : abdominal & vaginal including colour Doppler – to know the position and status of ectopic sac.

 Laparoscopy: for direct visualisation of the ectopic sac.

 A combination of these methods have to be employed for accurate diagnosis than any single method.

TVS(trans vaginal ultrasound) can visualise a gestational sac as early as 4 – 5 weeks from LMP(last menstrual period). During this time, the lowest serum β HCG level is 2000 IU/L.

When β HCG level is greater than this and there is an empty uterine cavity on TVS, ectopic pregnancy can be suspected.

 In such a situation, when the value of β HCG does not double in 48 hours ectopic pregnancy will be confirmed.

Ultrasound features of ectopic pregnancy after 5 weeks can be any of the following:

1. The gestational sac may be demonstrated  with or without a live embryo, which  is called the Begel’s sign.  By 6 weeks the gestational sac  appears as an intact well defined tubal ring when it measures 5 mm in diameter. Afterwards it can be seen as a complete sonolucent sac with the yolk sac and the embryonic pole with or without heart activity inside.

2. Or the gestational sac can also be seen as poorly defined tubal ring possibly containing echogenic  structure and POD(pouch of douglas) containing fluid or blood.

3.In case of  ruptured ectopic,  fluid may be seen in  the POD with an empty uterus.

4. In colour doppler, the vascular colour in a characteritic placental shape, the so-called fire pattern, can be seen outside the uterine cavity while the uterine cavity is not having good blood flow as in normal pregnancy.

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Management:

 Depends on the stage of the disease and the condition of the patient at the time of diagnosis.

  Options:

Surgical treatment – laparotomy / laparoscopy.

Medical  management– administration of trophotoxics at the site or systemically.

Management of acute ectopic pregnancy:

Once  patient  suspected of having acute ectopic pregnancy, she should be hospitalised and resuscitation to be done.
If patient is in shock :  patient should lie flat with the leg end raised, this will improve blood supply to heart.  Immediately   intravenous lines to be  secured, fluids to be started.  Blood  to be sent for cross matching and typing.

 Analgesics to be given if needed.

 Blood transfusion should be started once cross matching is ready.  More  blood bags to be kept ready if needed.

Mean while ultrasound can be done to confirm the ectopic pregnancy.

Culdocentesis:  is highly specific to diagnose ectopic pregnancy if performed and interpreted correctly,  presence of free  flowing, non-clotting blood in the pouch of douglas suggests ectopic pregnancy.

Negative tap  in culdocentesis is  inconclusive and  remains controversial as it can not rule out ectopic pregnancy.

 Laparotomy should be done at the earliest.  Salpingectomy is the definitive treatment.

But there will be no benefit from removing ovary along with the tube if it is not involved in ectopic pregnancy.

Blood Transfusion:  if needed during surgery,  autotransfusion of patient blood can be done under strict aseptic precautions.

 Management of chronic  ectopic pregnancy:

Investigations:

Laboratory tests: 

Measuring serial quantitative β HCG level by RIA(radio immuno assay) is the main test to be performed in follow up of ectopic pregnancy. Constant elevated levels will suggest persistence of disease.

Estimating serum progesterone level , which is the hormone of pregnancy is also useful test, normally < 5 mg/ml is seen in  ectopic pregnancy.

 Trophoblastic proteins such as SPI and PAPP- Placental Protein 14 & 12  will be in low levels in ectopic pregnancy as compared to normal pregnancy.

Ultrasonography:

 In ectopic pregnancy when ultrasound is performed usually haematocele will be seen. Ultrasonography will be useful in detecting the site of ectopic pregnancy and also the condition of surrounding structures.

Laparoscopy:

Through laparoscopy we can directly visualise the ectopic sac and surrounding structures. It is both diagnostic and therapeutic.

Treatment:

 Treatment  of chronic ectopic pregnancy is always surgical.

 Preocedure normally performed is salpingectomy, that is removal of the offending tube is to be done.

 If pelvic haematocele is infected, posterior colpotomy is to be done to drain the prelvic abcess.

 Salpingo-oophorectomy should be done in some cases like,  ovarian ectopic pregnancy, or with excessive adhesions between ovary and fallopian tube.

Management of unruptured ectopic pregnancy:

Options:

1. Surgical treatment

2. Surgically administered medical  (SAM) treatment

3. Medical treatment

 4.Expectant management

1.Surgical treatment:

 Surgical treatment of unruptured ectopic pregnancy can be carried out either by laparotomy  or

by  laparoscopy.

The procedures are:  salpingectomy  or  cornual resection  or excision.  These to be choosed depending  on the site of ectopic pregnancy.

 Conservative surgery  can be planned in cases of infertility &  patient desiring  for pregnancy.

This can be done by linear salpingostomy or  linear salpingotomy or segmental resection and anastomosis or milking out the tube depending on the feasibility.

 Now a day  laparoscopy is becoming  more popular than laparatomy because of hospital stay is less, post operative adhesions  are less with laparoscopy and risk of future ectopic  pregnancy  and future fertility are same as laparatomy.

 But for laparoscopy experience of surgeon,  trained assistants and special equipement are needed.

Normally  all tubal pregnancies can be treated by partial or total salpingectomy but salpingostomy or salpingostomy is only indicated when:

1. The patient want to conserve her fertility. In infertile woman removal of one tube may affect the fertility to some extent.

2. If the patient is haemodynamically stable, we can go for time consume surgeries like salpingostomy  or salpingostomy. In unstable patients quick entry and exit  from abdomen is needed that time salpingectomy is preferred.

3. When tubal pregnancy is accessible salpingostomy  or salpingostomy can be done, if not better to remove the tube.

4. To perform salpingostomy  or salpingostomy, ectopic sac  should be  unruputed and < 5 cm in size.

5. In case when contra lateral tube is absent or damaged, to conserve the remaining tube better to go for salpingostomy  or salpingostomy.

Normally the choice of surgical treatment does not influence the post treatment fertily,  but prior history of infertility is associated with a marked reduction in fertility after treatment.

For making the choice between salpingostomy /salpingotomy and salpingectomy  a scoring system is used which was described by  Chapron  in 1993. It is  based on the patient's previous gynaecological history and the appearance of the pelvic organs.
Fertility reducing factor score by Chapron:

Antecedent one ectopic pregnancy – 2

 Antecedent each further ectopic pregnancy – 1

Antecedent adhesiolysis - 1

Antecedent tubal micro surgery  - 2

 Solitary tube - 2

Antecedent salpingitis - 1

Homolateral  adhesions - 1

The main aim of the scoring system is to decide the risk of recurrent ectopic pregnancy.

Conservative surgery is indicated with a score of less than 5, while radical treatment is to be performed if the score is 5 or more.

Laparoscopic  salpingectomy:

 Laparoscopic  salpingectomy  is carried out by laparoscopic scissors and diathermy or endo-loop.

 After passing a loop of no. 1 catgut over the ectopic pregnancy, the stitch is tightened and then the tubal pregnancy is cut distal to the loop stitch.

 The excised tissue is removed piece meal or in a tissue removal bag and sent for histo pathological examination to confirm the ectopic pregnancy.

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Laparoscopic salpingotomy:

In this procedure  to reduce blood loss,  first 10 – 40 IU of vasopressin diluted in 10 ml of normal

saline is injected into the mesosalpinx.

 Then the tube is opened through an anitmesenteric longitudinal incision over the tubal pregnancy by a Co2 laser or  argon laser or laparoscopic scissors or fine diathermy knife and ablating the bleeding points with bipolar diathermy.

The tubal pregnancy is then evacuated by suction irrigation.

 Hemostasis of the trophoblastic bed is to be ensured before closing.

 If the tubal incision is left open it is called salpingostomy and if the incision line is closed in two layers it is called salpingotomy.

Persistent ectopic pregnancy (PEP):

 This is a complication of salpingotomy or salpingostomy when residual trophoblastic continues to survive because of incomplete evacuation of the ectopic pregnancy.

 Diagnosis is made because of a <b>raised postoperative serum β HCG</b> levels.

 If untreated, it can cause life threatening hemorrhage.

Treatment  is by:  Reoperation and futher evacuation or  salpingectomy or administration of IM / oral  Methotrexate in a single dose of 50 mg/m2 of body surface.

2. Surgically administered medical  (SAM) treatment:

 The aim of the surgically administered medical  (SAM) treatment is  trophoblastic destruction but avoiding the systemic side effects.

Technique is , injection of trophotoxic substance into the ectopic pregnancy sac or into the affected tube by- laparoscopy or ultrasonographically guided  (transabdominal  or transvaginal) or with falloposcopic control or with  hysteroscopic control or with hysterosalpingographic control.

Trophotoxic substances commonly used are: Methotrexate,  Potassium Chloride, Mifepristone, PGF2a, Hyper osmolar glucose solution or Actinomycin D.

3.Medical treatment with Methotrexate:

 Tanaka  in 1982 first described the resolution of tubal preganancy by systemic administration of Methotrexate .

 Methotrexate is mostly used for early resolution of placental tissure in abdominal pregnancy. Can be used for tubal pregnancy as well.

 Mechanism of action-  Methotrexate  Interferes with the DNA synthesis by inhibiting the synthesis of pyrimidines leading to trophoblasic cell death. Auto enzymes and maternal tissues then absorb the trophoblast.

To use Methotrexate ectopic pregnancy size should be <3.5 cm.

 Methotrexate  can be given  IV(intra venous) /IM (intra muscular) /Oral,  usually along with folinic acid.

 Now a day  Methotrexate is given in  a  IM  single dose of 50mg/m2 without folinicacid.  If serum HCG does not fall to 15% within 4 to 7 days, then a second dose of Methotrexate is given and resolution is confirmed by serum HCG estimation.

 Advantages:  Minimal hospitalisation. Usually outpatient treatment is enough  and it will  reduce the cost. Quick recovery and  90% success if cases are properly selected.

 Disadvantages:  Side effects like gastrointestinal disturbances & skin allergies can occur.

 Monitoring  of total blood count, LFT(liver function tests)  to be done. Estimation of  serum HCG once weekly till it becomes negative is essential.

4.Expectant treatment:

 Tubal pregnancies are known to abort or resolve, so expectant treatment works sometimes.

 Before the advent of salpingectomy in 1884, ectopic pregnancies were being treated expectanly with 70% mortality. And the diagnosis  was made at postmartum.

 Today only selected cases are managed expectantly: like cases which are  screened and identified by high relolution ultrasound scanner and monitored by serial serum β HCG assay.

 Identification criteria for expectant treatment:

Serum β HCG  levels at 2 day intervals  should be falling, they  will indicate absence  of intrauterine pregnancy.

To do expectant treatment the  diameter of ectopic pregnancy should be < 4 cm.

And there should be  no signs of rupture or of acute bleeding in TVS.

 If any deviation from the above criteria occurs, then emergency treatment is needed.

 Spontaneous resolution occurs in 72%, while 28% will need laparoscopic salpingostomy.

  In spontaneous resolution, it may take 4 to 67 days (mean 20 days) for the serum HCG to return to non pregnant level.

 The percentage  of fall in serum HCG by day 7 is a better indicator than the percentage fall by day 2.

But we have to remember during  expectant treatment that tubal pregnancies have been

known to rupture when  serum HCG levels are low.
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