Are we managing ectopic
pregnancy appropiately?
Professor Cindy Farquhar
Fertility Plus
National Women’s Hospital
University of Auckland
Outline
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Two cases from past 12 months
Evidence from RCTs for medical management
of ectopic pregnancies
What has happened at NWH over the last 15
years?
Protocols
NWH protocol: suitable patients for
MTX therapy
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Diagnosis of ectopic pregnancy
-HCG <5000
Adnexal mass ≤ 3.5 cm (confirmed on NWH scan)
Minimal free fluid on US (confirmed on NWH scan)
Haemodynamically stable
Normal FBC, LFTs, creatinine
UpToDate supports this -HCG threshold
Similar to RCOG but -HCG <3000
Patient no 1 22 years old P0G4 (2M,
1T)
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Seen in WAU with 1 wk spotting
β-hCG = 11100 Labtest, 15600 Labplus
US 38mm L ectopic pregnancy
Offered MTX as one of the options
Consented and had treatment same day
Discharged home with follow up arranged in 4
days
Patient No 1 - β-hCG results
Day 0
β-hCG
15600
Symptoms No pain
Day 4
8700
No pain
Day 7
5600
No pain
Day 11
2600
Pain and
collapse
Admitted to NWG with collapse and pain and
required emergency laparotomy, left
salpingectomy and sustained bladder injury
requiring further laparotomy 2 days later
Patient No 2 – 27 years old P0G1
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Presented to GP with 3 weeks of bleeding
GP measured β-hCG = 130, 5 days later 92, 7
days later 90
US - no IUP
Referred to EPAU on day 12
Patient no 2: β-hCG results
Day
0
5
β-hCG 130 92
12
90
19
210
22
200
25
240
26
170
Day 27 has repeat ultrasound –
R sided mass 5x9x4cm and free fluid
Laparoscopic R salpingectomy
27
180
What is the evidence for expectant
management of ectopic pregnancy
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Cochrane Review (Hajenius 2009)
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Expectant management - 1 RCT only - 75%
success rate
What is the evidence for medical
management of ectopic pregnancy
Cochrane review (Hajenius 2009)
• Variable doses of MTX versus laparosopic surgery
An RCT of laparoscopic management of
ectopic pregnancy compared with methotrexate
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Pragmatic open randomised trial
(computer generated, numbered sealed envelopes)
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Ultrasound diagnosis (no diagnostic laparoscopy)
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Recruitment from 3 hospitals (NWH, NSH, MMH)
Entry Criteria
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Unruptured ectopic pregnancy
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hCG < 5000 IU/l
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Adnexal mass ≤3.5 cm diameter
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No fetal heart in adnexae
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Normal FBC, LFT, RFT
Trial Results
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Laparoscopy: 26 (93%) treated successfully
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Methotrexate: 22 (88%) treated successfully
(more than one injection)
(no statistical difference)
Trial Profile
Tube conservation and need for
further surgery
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17 (61%) conserved ipsilateral tube with surgery
and 31 (91%) with MTX
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2 patients with persistent trophoblast in surgical
group and 5 (12%) required surgery in the MTX
group (3 had tubal rupture)
Methotrexate was cheaper
Methotrexate
Surgical
Direct costs
$1470
$3083
Indirect costs
$1141
$1899
Conclusions
MTX well tolerated by patients
 MTX cheaper than laparoscopy
 MTX associated with fewer salpingectomies
BUT
 MTX only effective at relatively low hCG levels
 Less than 30% of ectopic pregnancies likely to be
suitable for MTX
 Multiple doses may be needed
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An audit of ectopic pregnancies at
NWH: 6 years
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1996-2001
673 women with discharge diagnosis of ectopic
pregnancy
Mean age 31 years
Initial management of ectopic
pregnancy NWH
1996
1997
1998
1999
2000 2001
Expectant
6
management
2
9
9
11
23
Methotrexate 6
8
13
12
11
23
Surgery
140
82
74
76
100
64
Total
152
92
98
98
122
110
Use of Methotrexate NWH 1996-2001
(%)
1996 1997
1998
1999
2000
2001
MTX criteria
present
35.5
29.3
36.7
38.8
34.4
44.1
MTX criteria
24.1
and discussed
(%)
MTX criteria
11.1
and given (%)
44.4
85.1
44.7
50.0
91.8
29.6
41.7
31.6
26.9
49.6
Methotrexate
Over the six year period:
74/673 (11%) women given MTX
14/74 (18.9%) failed & required surgery
8 % given MTX who did not met criteria
(hCG > 5000 IU/L) but included cornual &
cervical pregnancy
Audit at NWH in 2010
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66 ectopics over 6 month period
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Of medical management – 36% rate of failure
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12% expectant management
33% medical management
55% surgical management
43% had breach of the protocol with 75%
presenting as ruptured ectopics
Common breaches of the protocol were relying
on community scan, significant free fluid in the
POD
Further audits by Trainee Interns
New Research
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ESEP study: European surgery in ectopic
pregnancy: salpingotomy versus salpingectomy
in tubal ectopic pregnancy: impact on future
fertility (www.esepstudy.nl)
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METEX study; methotrexate versus expectant
management in ectopic pregnancy
(www.metexstudy.nl)