Are we managing ectopic pregnancy appropiately?

Professor Cindy FarquharFertility Plus

National Women’s HospitalUniversity of Auckland

Outline

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

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)

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 Day 4 Day 7 Day 11β-hCG 15600 8700 5600 2600Symptoms No pain No pain No pain 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

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 12 19 22 25 26 27β-hCG 130 92 90 210 200 240 170 180

Day 27 has repeat ultrasound – R sided mass 5x9x4cm and free fluid

Laparoscopic R salpingectomy

What is the evidence for expectant management of ectopic pregnancy

Cochrane Review (Hajenius 2009) 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

Pragmatic open randomised trial

(computer generated, numbered sealed envelopes)

Ultrasound diagnosis (no diagnostic laparoscopy)

Recruitment from 3 hospitals (NWH, NSH, MMH)

Entry Criteria

Unruptured ectopic pregnancy hCG < 5000 IU/l Adnexal mass ≤3.5 cm diameter No fetal heart in adnexae Normal FBC, LFT, RFT

Trial Results

Laparoscopy: 26 (93%) treated successfully

Methotrexate: 22 (88%) treated successfully (more than one injection)

(no statistical difference)

Trial Profile

Tube conservation and need for further surgery

17 (61%) conserved ipsilateral tube with surgery

and 31 (91%) with MTX

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 salpingectomiesBUT 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

An audit of ectopic pregnancies at NWH: 6 years

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 management

6 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 and discussed (%)

24.1 44.4 85.1 44.7 50.0 91.8

MTX criteria and given (%)

11.1 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 66 ectopics over 6 month period

12% expectant management 33% medical management 55% surgical management

Of medical management – 36% rate of failure 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

ESEP study: European surgery in ectopic pregnancy: salpingotomy versus salpingectomy in tubal ectopic pregnancy: impact on future fertility (www.esepstudy.nl)

METEX study; methotrexate versus expectant management in ectopic pregnancy (www.metexstudy.nl)