1. bHCG monitoring after single dose methotrexate treatment of tubal ectopic pregnancy : is the Day 4 bHCG necessary? A retrospective cohort study
Dr Monique Atkinson, Dr Sarika Gupta, Dr Therese McGee
Westmead Hospital

3. Background
Observing a minimum 15% fall in bHCG between Day 4-7 is the most commonly employed monitoring regime
overall success rate with one dose is 70-75%
Success improves to 90% with 2 doses but only 15-20% of women require a second dose

4. The Question Is.....
Why perform the Day 4 blood test if no decisions to give a second dose of MTX are made until Day 7? Is there an alternative?

5. UpToDate says a 25% fall in bHCG Day 1-7 is as good as 15% fall Day 4-7 in predicting the need for additional doses of MTX Would be great if it were true, but is it?

6. The Answer Is..... Truthfully, no data exists (even in UpToDate) to
evaluate this
So we decided to investigate.....

7. Aims
To determine the optimal monitoring regime after single dose methotrexate therapy in tubal ectopic pregnancy management
Compare traditional monitoring regimen (i.e. 15% fall bHCG day 4-7 after treatment) with other regimens previously described in the literature
25% fall bHCG day 0/1-7
Any fall bHCG day 0/1-4
20% fall bHCG day 0/1-4
Any fall bHCG day 0/1-7 (a novel regimen proposed by Westmead Hospital)

8. Methods Retrospective cohort study
Data collected on all women who received MTX in EPAC from 1st January th October based on pharmacy records
Medical file and hospital electronic results were reviewed

9. Methods Inclusion Criteria Exclusion Criteria US diagnosed EP
Pre treatment bHCG <6000
IU/L
Pregnancy of unknown
location (PUL)
Missing critical bHCG levels
Women whose EP may
reasonably have resolved
with expectant management*
*bHCG fallen by >10% prior to therapy OR
*Solitary low bHCG <1000 IU/L prior to MTX administration
with no plateau or rise in level

10. Methods
Note...
Prior to August 2012 day of administration at our institution was designated Day 0
Thereafter it was designated Day 1 in keeping with most published regimens
This degree of variation in nomenclature of the day of administration exists in the literature, hence both groups of women were included in our analysis

11. METHODS What we reviewed bHCG on Day 0/1, Day 4, Day 7
Other bloods pre-treatment and Day 7
Hemoglobin
Platelets
Neutrophils
liver function tests

12. Methods Incidence of treatment success* for each regime
Study Outcomes
*EP resolved without requiring surgical intervention
EP resolved with either one or two doses of MTX
Incidence of treatment success* for each regime
Comparison of treatment success incidence between regimes
Ability of each regime to appropriately select women for second doses of MTX

13. Methods
Statistical analyses performed using McNemar’s test

14. Results Pharmacy records identified 142 eligible files
After exclusions (mostly PULs), 88 files remained for review
In terms of methotrexate administration
55 women were designated Day 0
33 women were designated Day 1
In terms of follow up bloods
80 were collected on Day 4/7
8 were collected +/- 1 day either side

15. Results Outcome 1: Incidence of treatment success
92% of all cases (n=81/88) resolved without surgery
8% (7/88) progressed to surgery
1 case of significant hemoperitoneum (tubal rupture Day 17)
6 cases with no rupture or significant hemoperitonem
Indications for surgery: rising bHCG (2), severe pain after 2 doses MTX, anxiety (2), mis-diagnosis (E Coli pyelopehritis)
Complications
No cases of clinically significant toxicity
6/88 (7%) had >2 x elevations in LFTs, all spontaneously resolved

16. Results
Outcome 2: Relative efficacy of various regimes in predicting treatment success with MTX

17. Results
Outcome 3: comparison of how regimes inform prescription of second MTX doses

18. What Does This Mean?

19. Firstly
All regimens appropriately predict cases that don’t require surgery (positive predictive value) and correctly identify those women who require surgery (specificity)

20. Secondly Some regimes overselected women for
second doses of MTX including:
Day 0/1-7 25% fall (yes, the UpToDate one)
Day 0/1-4 falls (any fall and 20% fall)

21. Any fall Day 0/1-7 and 15% fall Day 4-7 regimes are significantly more selective so that fewer women need additional MTX

22. However
15% fall Day 4-7 regime requires women to have an additional blood test on Day 4

23. But
The novel regime ‘any fall bHCG between Day 0/1-7’ effectively predicts treatment success and avoids the extra blood test on Day 4 So we propose it gets a gold medal.

24. Why You Should Believe Us
Study strengths
Large sample size (other studies only persons)
Only US proven ectopics with plateaued or rising bHCG were included
Study limitations
Retrospective analysis (can’t measure pt anxiety)
Using surgery as an endpoint to define treatment success can be problematic as some indications for surgery vary between institutions such as patient anxiety and consultant response to borderline bHCG reductions

25. Conclusion
All regimes have good PPV (predict surgery avoidance) and specificity (don’t miss the need for surgery)
Some regimes overselect women for 2nd dose MTX
Of the two best regimes that correctly select women for surgery without overselecting them for additional doses of MTX, the Day 0-7 regime provides convenience and cost advantages by eliminating the need for Day 4 bHCG testing

26. References
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28. Questions