Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.
OBJECTIVE
What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations?


CONCLUSIONS
In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX.


BACKGROUND
MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women.


METHODS
A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time.


METHODS
From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial.


RESULTS
We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations.


CONCLUSIONS
Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women.   BIAS, LIMITATION AND GENERALISABILITY:  A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX.


BACKGROUND
This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154).


BACKGROUND
ISRCTN 48210491.
Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. n.m.vanmello@amc.nl
N M
NM
van Mello
F
F
Mol
H R
HR
Verhoeve
M
M
van Wely
A H
AH
Adriaanse
E A
EA
Boss
A B
AB
Dijkman
N
N
Bayram
M H
MH
Emanuel
J
J
Friederich
L
L
van der Leeuw-Harmsen
J P
JP
Lips
M A
MA
Van Kessel
W M
WM
Ankum
F
F
van der Veen
B W
BW
Mol
P J
PJ
Hajenius
D000020:Abortifacient Agents, Nonsteroidal / Q000008:administration & dosage / Q000009:adverse effects; D000027:Abortion, Incomplete / Q000139:chemically induced / Q000601:surgery; D000022:Abortion, Spontaneous / Q000209:etiology*; D000032:Abortion, Therapeutic / Q000009:adverse effects; D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood*; D015536:Down-Regulation; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009426:Netherlands; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D016216:Ultrasonography, Prenatal
D000020:Abortifacient Agents, Nonsteroidal; D006063:Chorionic Gonadotropin; D008727:Methotrexate