Discussion
Ectopic pregnancy can be a life-threatening condition and still remains
a cause of up to 4.9 % of all maternal deaths in developed countries
with almost 80% of all maternal deaths occurring during the first
trimester of pregnancy 6,7,8.
Ectopic pregnancies pose an increased diagnostic challenge and to an
even greater extent. It is possible that due to the low index of
suspicion in spontaneous HP with the false reassurance of the presence
of an intrauterine pregnancy, the diagnosis can be delayed and a good
number of women will thus present with serious clinical presentations as
tubal rupture, acute abdomen, shock and hemoperitoneum5.
In HP, the clinical picture may not be significant in asymptomatic
patients, and seeing an intrauterine pregnancy by ultrasound may lower
the vigilance of looking into the adnexa for another gestational sac or
‘thinking ectopic’. A presentation of vaginal spotting or lower
abdominal or adnexal pain and tenderness may be attributed erroneously
to a threatened miscarriage especially with a low index of suspicion
after seeing an intrauterine pregnancy 9.
In a review of the world literature on 589 combined intrauterine and
extrauterine pregnancies, a combination of signs and symptoms including
abdominal pain, peritoneal irritation and enlarged uterus were the most
significant findings, with the pelvic inflammatory disease a significant
risk factor 4. The early diagnosis of an ectopic
pregnancy is possible due to a combination of ultrasound and serum
measurements β-hCG. A doubling time of serum β-hCG of 66% was initially
used in the early 80s 10. Following that a doubling
time of 53% 11 and more recently 35% or more, over a
2 day period, was suggested 12. A doubling time of
more than 35% over a period of 2 days suggests the diagnosis of a
viable intrauterine pregnancy, thus excluding an ectopic pregnancy in
many (not all) cases. Another concept in the early diagnosis of ectopic
pregnancies is the discriminatory zone. Seeing an intrauterine pregnancy
by transvaginal ultrasound should be possible with a serum β-hCG level
of 1500-2000 iu/ml 13, or more recently a conservative
level 3500 iu/ml was suggested 14. Above that level,
nearly all viable intrauterine pregnancies should be visualized using
transvaginal ultrasound. Failing to see an intrauterine pregnancy at
such a level would raise the probability of an ectopic pregnancy.
Unfortunately, in HP pregnancies, both concepts; the doubling time and
discriminatory zones, commonly used in early diagnosis of ectopic
pregnancy, are unlikely to be helpful, thus posing an increased risk of
misdiagnosis, with a third to half of HP cases thus presenting late and
already ruptured before a diagnosis was made 5,15. The
level of serum β-hCG in HP represents the combined contribution of both
the intrauterine (mainly) and extrauterine pregnancy. These confusing
levels are unlikely to be of clinical use for the diagnosis of a HP.
Visualizing both an intrauterine and extrauterine gestational sac, yolk
sac, fetal pole, or fetal heart activity is understandably diagnostic of
a HP. Unfortunately visualizing both intrauterine and extrauterine fetal
heart activity is rare 9.
To add to the diagnostic challenge, an HP can be misdiagnosed as a
corpus luteum cyst with the low vigilance of having already confirmed an
intrauterine pregnancy. When seeing what could be a corpus luteum in the
adnexa using greyscale ultrasound, a Doppler ultrasound can be very
useful in such cases, and determining the location of blood flow and
‘ring of fire’ sign, can improve the sensitivity of diagnosing an
ectopic pregnancy over a corpus luteum cyst 16. This
is what we performed in our case and seeing a ‘ring of fire’ sign on
Doppler ultrasound, raised our suspicion towards the presence of a HP.
Although ultrasound remains the main imaging modality in ectopic and HP
pregnancies, a subset of patients may need further imaging to provide
additional information. These patients are a minority who for example
need a precise diagnosis where the required information could not be
obtained by ultrasound. This further imaging can be undertaken using
MRI, which can provide images with high soft-tissue contrast without the
use of intravenous contrast agents.
In a review of 1737 patients exposed to first trimester MRI exposure, as
compared with non-exposure, was not associated with increased risk of
harm to the fetus or in early childhood of up to 4 years of age, this
includes the risk of stillbirth or neonatal death within 28 days of
birth and any congenital anomaly, neoplasm, and hearing or vision loss
from birth to age 4 years. In contrast, Gadolinium MRI at any time
during pregnancy was associated with an increased risk of a broad set of
rheumatological, inflammatory, or infiltrative skin conditions and for
stillbirth or neonatal death 17.
Ultrasound remains the imaging modality of choice in pregnancy. MRI –
in selected patients where a diagnosis cannot be made by ultrasound –
has another advantage due to its excellent soft-tissue contrast without
the use of ionizing radiation. We found it useful to review the findings
suggestive of ectopic pregnancy on MRI and we feel it is important we
are familiar with them. Findings on MRI include tubal dilation and wall
enhancement, tubal hematoma, adnexal hematoma, and a gestational
sac-like structure18. In our patient, an MRI revealed
an adnexal rounded mass lesion with a thick wall showing a high T2
signal.
It should be emphasized that despite the evidence of reported safety of
MRI, and the ability to gain valuable information without the resort to
intravenous contrast agents as Gadolinium, a conservative approach
should still be adopted, and MRI should only be used in very selected
cases and ultrasound remains the main imaging modality in pregnant women
with suspected HP or ectopic pregnancy.
Any treatment for HP should aim to target the ectopic pregnancy,
selectively, without harmful effects on the ongoing intrauterine
pregnancy.
With this in mind, systemic methotrexate is contraindicated with a
viable intrauterine pregnancy 19 and local treatment
modalities have thus been suggested to avoid the use of systemic agents
in HP, as local injection of potassium chloride 20 or
hyperosmolar glucose in the ectopic pregnancy in the tube. Local
injection of 50% glucose after aspiration of the tubal gestational sac
fluid under transvaginal ultrasonographic guidance seemed effective in
resolving the ectopic pregnancy without adversely affecting the
concurrent intrauterine pregnancy 21.
Although local injections of these agents avoid surgery – at least
initially – the risk of failure of such treatments and subsequent
surgery and salpingectomy is high, reaching 55%, making them not an
attractive or advisable modality in the context of HP with the other
pregnancy in the tube 22. These modalities, however,
may have a place in ectopic pregnancies with no concomitant intrauterine
pregnancy, scar pregnancies, or in HP where the extrauterine sac is in
an unusual location for example cervical or cornual23.
Realistic and practical approaches in HP with one of the pregnancies in
the tube are performing a laparoscopy (preferred option) or laparotomy
(depending on the clinical condition and expertise) and undertaking a
salpingectomy (usually if the other tube is normal) or salpingotomy19. Another advantage of the surgical approach is that
laparoscopy (or laparotomy) can confirm the diagnosis in addition to
providing a definitive treatment.
We do however feel that although salphingotomy for a ‘sole’ ectopic
pregnancy (without concurrent intrauterine pregnancy) is an established
modality in selected cases especially with a damaged contralateral tube,
a salphingotomy in cases of HP is not similar for two reasons.
Firstly, there is a risk of around 21% of a repeat operation via
salpingectomy due to persistent tubal bleeding 24 and
this risk should not be taken lightly in a woman with HP and ongoing
remaining intrauterine pregnancy already subjected to a salphingotomy.
A second reason is that, as opposed to a radical surgery as a
salpingectomy, a salpingotomy carries the additional risk of persistent
trophoblasts of around 7% 25 which cannot be followed
up by β-hCG due to the concurrent intrauterine pregnancy nor treated
with systemic methotrexate for the same reason.
We thus feel it is thus appropriate to perform a salpingectomy rather
than a salpingotomy in most HP cases when dealing with the tubal element
of pregnancy as it minimizes the risks at, and after the procedure, that
is inherently associated with salpingotomy.