WRITE UPS - CRITICAL ISSUES - Ectopic Pregnancy : New Horizons


Ectopic pregnancies continue to prove to be quagmirish for an average clinician. Many nuances have influxed into the diagnosis and management. What seemed to be a gospel truth and final word uttered on ectopic pregnancy just a decade ago seems to be  obsolete today.  It is therefore  worth while seeing the new horizons of ectopic pregnancies.


There is a general belief amongst those working in this field that there seems to be a rise in incidence of ectopic pregnancy.  This rise is both real as well as apparent. The real rise seems to be due to increased incidence of P.I.D. in general  and contributing  sexually transmitted disease in particular.  However increasing operative interventions in pelvic pathologies, some contraceptive methods like progesterone only pills and modern methods of infertility treatment like  ART, have been implicated at some times or the other for increasing the incidence of ectopic pregnancies. The extent to which these factors do contribute in actuality is indeed debatable. The apparent rise could be  because of better diagnostic facilities. Easy access to high resolution ultrasonography and B HCG estimation picks up ectopic more readily than previously.

Current incidence of ectopic pregnancy has been placed between  0.25%  to  1 % of all pregnancies. By all pregnancies, it is meant as the sum of reported live births, legal induced abortions and ectopic pregnancies.  ( I. Stabile :  1994).  Presently, ectopic pregnancy is reported to be accounting for  11.5 % of all maternal deaths in UK ( DHSS  Report ;  1990 ).

Etiology of Ectopic  Pregnancy  :-

As mentioned in the previous section, P.I.D. is now considered to be the most important  causative factor ( Beral : 1975 ).  It is however interesting to note that a promptly and correctly treated  PID does not add to the incidence of ectopic pregnancy. Chlamydial infections are currently thought to be most important cause of  PID contributing to ectopic pregnancy.

In 1989  Palkkinen and Jaakola  showed that progesterone  levels less than  20 nmol/ L    were associated with primarily ovarian  directed electrical activity of the fimbrial end of the tube.  If these levels exceeded 20 n mol/ L  the electrical activity was exactly reversed. This could explain albeit  theoretically the association between late ovulation and short luteal phase ( Iffy,  1960 ).

Assisted reproductive techniques have also been suggested to have increased the incidence of ectopic pregnancy recently ( Rizk : 1991  ).

Abnormal embryogenesis is currently thought to be a major factor in causation of ectopic pregnancy.  However the validity of the same and the extent to which  it contributes is being  extensively investigated,  Verhoge  ( 1988) and Buhi ( 1989)  have identified two proteins uniquely synthesized by the fallopian tube.  These may hold a key to the explanation of etiology of  ectopic  pregnancy.


The importance of early diagnosis of ectopic pregnancy need not be overstressed. It has been found that the morbidity and  even mortality in cases of ectopic  pregnancy is directly influenced by the appearance of clinical features and initiation of treatment. With the advent of high resolution endosonography and serum  HCG level estimation early diagnosis of ectopic pregnancy is very much  a reality. Indeed the diagnosis is now possible even before the actual appearance of  symptoms.  With such precise and non- invasive methods becoming popular,  the erstwhile used methods like culdocentesis or D & C are no more used.  These have been found to lack precision with poor specificity and sensitivity.

Attempts are now on to establish the correlation between circulating HCG levels and appearance of intrauterine gestational sac. It is found that following transabdominal sonography (  TAS ) intrauterine gestational sac  should be visible  at serum HCG levels of  6000  I.U./ L in more than  90 % of cases ( Kadar- 1981 ).  Recently  Cacciatore ( 1990)  has shown that one should strongly suspect ectopic pregnancy if serum HCG levels are more than  1000 I.U. and no intrauterine gestational sac is visible on Transvaginal Sonography ( TVS).  Single value estimations have their own limitations and therefore a serial estimation is desirable.

On a serial estimation of  HCG levels alone as a diagnostic parameter for ectopic pregnancy, the concept of “ doubling time ” becomes very  important. It is recommended by Kadar &  Colleagues  ( 1981)  that if  HCG  increased  by less than  66 %  over  48 hrs. in a given case than laparoscopy should be performed to rule out ectopic pregnancy. Thus  48 hrs. is considered as a  “ doubling time “” for HCG  levels in a given case wherein the pregnancy is  intrauterine. Level of  HCG  in intrauterine  pregnancy are depicted in Table I.  Lindblom & Colleagues (  1989)  have made this concept more refined by plotting the initial values to the rate of change. By using this correlation one can  be further accurate in early diagnosis of ectopic  pregnancy.


 HCG levels versus days of conception  in  intrauterine pregnancy

              Days  from  conception                            HCG levels


                          15                                                      200

                          18                                                      400

                          21                                                      800

                          24                                                     1600

                          27                                                     3000

                          30                                                     6000

                          42                                                     50000

Currently however, HCG  levels and  TVS  are used in combination for the purpose rather than using either of them alone.

Other markers used for early diagnosis of ectopic pregnancy are enumerated in Table  II. These have more or less  remained experimental and their use in clinical  practice is limited.


 Some newer biochemical tests used for  detecting ectopic pregnancy

Human placental lactogen ( HPL )

Schwangerschafts  protein ( SP-1)

Pregnancy  associated plasma  protein A ( PAPP -A )

Progesterone  dependent endometrial protein ( P.E.P )

Insulin like  growth factor binding protein  ( IGF - bp).

Active renin  assay

 Alpha  Fetoprotein ( AFP  )  

The importance of early diagnosis of ectopic pregnancy stems from the fact that for newer treatment modalities like medical management or expectant management it is imperative to pick up ectopic pregnancies as early as possible.

In this endeavor of early diagnosis of ectopic pregnancy,  transvaginal colour doppler can help to characterize the nature of the adnexal mass thus permitting preoperative  diagnosis when the ectopic embryo and its characteristic heartbeat can not be seen. Ectopic pregnancy in such cases is seen as an ectopic colour flow, usually very prominent and randomly dispersed inside the solid part of the adnexal mass and clearly separated from ovarian tissue and corpus luteum.  Pulsed doppler wave form analysis shows a very low impedance signal and calculated R.I.  is below  0.4  due to increased end diastolic flow.  The brightness of the colour is usually high, indicating high velocity of ectopic flow  ( Taylor, 1993 and Kurjak A.  1991 ).


Laparotomy followed by salpingectomy of the affected side has been a standard modality of treatment of ectopic  pregnancy for many years. However with the influx of endoscopic techniques and better understanding of the pathology of the disease - the face of treatment of ectopic pregnancy is changing very fast.

The policy of expectant management of ectopic pregnancy has become popular  in some specific situations.  The basis of expectant management rests on the fact that many ectopic pregnancies are now diagnosed very early. In due course of  evolution of the disease many of these are expected to resolve spontaneously ( Land J : 1955.)  With the advent of high  resolution ultrasound it is now possible to keep these pregnancies under close surveillance without intervention.  However this treatment is limited to those subgroup of patients who have minimal symptoms,   have falling  HCG levels and over a period of time shows diminishing  size of the sac on  TVS.  Besides  a frequent  TVS  in these cases, it is also necessary to estimate HCG levels atleast twice at a 2 day interval  ( Ylastolo et al    1992 ).  It is estimated that with modern diagnostic methods described above  35 % of ectopic  pregnancies can be  managed conservatively.

Medical management of ectopic pregnancy has also been fascinating as it obliviates the need of surgical intervention.  Drugs like methotrexate, actinomycin D,  Mifepristone, etc.  alone or in combination are used. Many routes have been tried like IM, intragestational sac, transcervical tubal cannulation and the like. They key to successful  treatment of conservative therapy is a proper selection of cases. It is recommended that size of the gestational sac should be less than  3 CMS., the tube should be unruptured and without active  bleeding, Serum HCG  levels should be less than  1500 IU/L  and on  TVS it should be a nonviable pregnancy. Even single dose of methotrexate  of  75  mgm.  intramuscularly has been found to be effective in medically managing such ectopic pregnancies.  However the final choice of drug and dose remains many a times with the gynecologist’s preference and practical skills, until such time as controlled randomized prospective studies indicate which technique  is superior in terms of adverse reactions and future fertility ( I. Stabile,  1994 ).

Surgery still remains the treatment of choice for most cases  However  laparoscopic surgery  remains the line of choice.  With less morbidity and equally good results  laparoscopic approach to ectopic pregnancies is now the approach of; choice.  However the debate now rests at the choice of technique -  salpingectomy or salpingostomy  ?  Salpingostomy was long since preferred as  it was thought to be conservative surgery, promising better fertility rates subsequently. However, the opinion based on current literature states that irrespective of the surgical technique used, the condition of contralatteral tube is the most significant factor in terms of future fertility ( Vermesh M. Et al 1992 ), besides the woman’s own fertility potential. Thus current thinking is for doing a salpingectomy rather than a salpingostomy in management of ectopic pregnancy.


Increasing incidence of  PID and modern methods of infertility treatment have caused a rise ectopic  pregnancies. Influx of endosonography and endocrinal assays of  HCG have helped in very early diagnosis of ectopic pregnancy. Nearly 25 % of  ectopics so diagnosed can be  managed conservatively.  Medical management gives good results in carefully selected cases. Laparoscopic surgical intervention is now the method of choice.  Days have returned wherein salpingectomy is preferred over salpingostomy.


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