1. Are we managing ectopic pregnancy appropiately? Professor Cindy Farquhar Fertility Plus National Women’s Hospital University of Auckland

2. 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

3. 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

4. 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

5. Patient No 1 - β-hCG results Day 0Day 4Day 7Day 11 β-hCG15600870056002600 SymptomsNo 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

6. 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

7. Patient no 2: β-hCG results Day05121922252627 β-hCG1309290210200240170180 Day 27 has repeat ultrasound – R sided mass 5x9x4cm and free fluid Laparoscopic R salpingectomy

8. What is the evidence for expectant management of ectopic pregnancy Cochrane Review (Hajenius 2009) Expectant management - 1 RCT only - 75% success rate

9. What is the evidence for medical management of ectopic pregnancy Cochrane review (Hajenius 2009) Variable doses of MTX versus laparosopic surgery

10. 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)

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

12. Trial Results Laparoscopy: 26 (93%) treated successfully Methotrexate: 22 (88%) treated successfully (more than one injection) (no statistical difference)

13. Trial Profile

14. 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)

15. Methotrexate was cheaper MethotrexateSurgical Direct costs$1470$3083 Indirect costs$1141$1899

16. 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

17. An audit of ectopic pregnancies at NWH: 6 years 1996-2001 673 women with discharge diagnosis of ectopic pregnancy Mean age 31 years

18. Initial management of ectopic pregnancy NWH 199619971998199920002001 Expectant management 62991123 Methotrexate6813121123 Surgery14082747610064 Total 1529298 122110

19. Use of Methotrexate NWH 1996-2001 (%)199619971998199920002001 MTX criteria present 35.529.336.738.834.444.1 MTX criteria and discussed (%) 24.144.485.144.750.091.8 MTX criteria and given (%) 11.129.641.731.626.949.6

20. 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

21. 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

22. Further audits by Trainee Interns

23. New Research ESEP study: European surgery in ectopic pregnancy: salpingotomy versus salpingectomy in tubal ectopic pregnancy: impact on future fertility (www.esepstudy.nl)www.esepstudy.nl METEX study; methotrexate versus expectant management in ectopic pregnancy (www.metexstudy.nl)www.metexstudy.nl