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INTRODUCTION:
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.
INCIDENCE :-
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.
DIAGNOSIS :-
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.
TABLE
- I
HCG
levels versus days of conception in intrauterine
pregnancy
Days from conception
HCG levels
[I.U./L]
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.
TABLE
- II
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 ).
MANAGEMENT OF ECTOPIC PREGNANCY :-
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.
CONCLUSIONS :-
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.
REFERENCES :-
1)
Beral V. : An epidemiological study of recent trends in ectopic
pregnancy. Br. J. Obstet. Gynecol : 1975 : 82 : 755- 782.
2)
Buhi W.C., Van Wert J.W., Alwarex J.M. : Synthesis and secretion
of proteins by post partum human oviductal
tissue in culture : Fertil Steril : 1989 : 51 : 75- 80.
3)
Cacciatore B., Tiitinen A, Stenman D.H. : Normal early
pregnancy :Serum HCG levels and vaginal USG findings
: Br. J. Obstet. Gynecol : 1990 : 97 : 899- 903.
4)
Department of Health and Social Security :Report on confidential
inquiries into maternal death in UK : 1985 - 87 : London :
HMSO : 1990.
5)
Iffy L. : The role of premenstrual post midcycle
conception in the etiology of ectopic gestation : An
evaluation of reflex theory : J. Obstet. Gynecol. Br.
Commonwealth : 1963: 70 : 996- 1000.
6)
Kadar N., De Vore G., Romero R. : Discriminatory HCG Zone
: Its use in the sonographic evaluation of ectopic pregnancy :
Obstet. Gynecol. : 1981 : 58 : 156 - 161.
7)
Kurjak A, Zalud I and Schulman H. : Ectopic preg. Transvaginal
colour Doppler identifies trophoblastic flow in suspicious
adnexal mass : J. Ultrasound Med. 1991 : 10 : 685.
8)
Lindblom B, Nahlin M., Kallfelt B. : Local PGF-2
injection for termination of ectopic pregnancy :
Lancet : 1987 : 1 : 776- 777.
9)
Lund J. : Early ectopic pregnancy : Comments on conservative
treatment ; J. Obstet. Gynecol. Br. Emp. : 1955 : 62
: 70-76.
10)
Stabile I. Grudzinskas J.G. : Ectopic pregnancy : What is new ?
Progress in Obst. & Gynecol : Vol. II : 1994 :
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11)
Taylor K.J.W. Ramos IM, Feyock A.L. : Ectopic pregnancy duplex
doppler evaluation : Radiology : 1989: 173 : 93.
12)
Verhage H.G. Fazeleabas A.T. : The in vitro synthesis and
release of proteins by the human oviduct : Endocrinology :
1988 : 122 : 1639 - 1645.
13)
Vermesh M., Presser S.C. : Reproductive outcome after linear
salpingostomy for ectopic pregnancy : Fertil Steril : 1992 :
57 : 682- 684.
14)
Ylastalo P., Cacciatore B., Sjoberg J. : Expectant
management of ectopic preg. : Obst. Gynecol : 1992 :
80 : 345 - 348 .
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