Letters to the Editors
org
confirm significantly better success rate with MTX (especially
if b-hCG is not already declining and certainly with 2 doses).
Recently, concerns have arisen regarding inadvertent
administration of MTX to viable intrauterine pregnancy
causing major fetal malformations and multimillion dollar
compensation claims.3 Contrary to belief,4 strict protocols
should prevent these mishaps. The protocol introduced by
the author over the last 10 years requires at least 3 b-hCG
results showing suboptimal rise (<62% every 48 hours) and
absence of intrauterine pregnancy on transvaginal ultra-
sound scan. MTX should not be administered based on 1 or
2 b-hCG results (even when >1500 IU/mL) because of
about 10% false-positive and false-negative results and
rarely very early multiple pregnancy. On the other hand,
increased liberal expectant management may risk excessively
prolonged follow-ups, more tubal ruptures (with no reliable
way to predict), and chronic EPs. - medical therapy is administered are becoming a true option,
Shashikant L. Sholapurkar, MD, DNB, MRCOG
Department of Obstetrics and Gynecology
Royal United Hospital Bath National Health Service Trust
Bath, United Kingdom
s.sholapurkar@nhs.net
The author reports no conflict of interest.
REFERENCES
1. Cohen A, Zakar L, Gil Y, et al. Methotrexate success rates in pro-
gressing ectopic pregnancies: a reappraisal. Am J Obstet Gynecol
2014;211:128.e1-5.
2. van Mello NM, Mol F, Verhoeve HR, et al. Methotrexate or expectant
management in women with an ectopic pregnancy or pregnancy of un-
known location and low serum hCG concentrations? A randomized
comparison. Hum Reprod 2013;28:60-7.
3. Nurmohamed L, Moretti ME, Schechter T, et al. Outcome following
high-dose methotrexate in pregnancies misdiagnosed as ectopic. Am
J Obstet Gynecol 2011;205:533.e1-3.
4. Moretti ME, Finkelstein Y. Reply. Am J Obstet Gynecol 2012;206:e13.
ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.
2014.09.038
REPLY
Concerns about methotrexate embryopathy should preclude
its use when the possibility of an intrauterine pregnancy
exists. In his letter to the editor, Dr Sholapurkar suggests a
b-hCG follow-up of 3 repeat measurements, 48 hours apart,
to prevent inadvertent methotrexate administration in viable
intrauterine pregnancies.
As previously reported, there are no guidelines regarding
the timing of methotrexate therapy so that prompt adminis-
tration before b-hCG follow-up may have serious conse-
quences.1 Medical therapy with methotrexate is dangerous
in cases of an intrauterine viable pregnancy but it is also
redundant in cases of a spontaneously resolving ectopic
pregnancy or pregnancy of unknown location. A recent
publication points out the risks and suggests caution and
122 American Journal of Obstetrics & Gynecology JANUARY 2015
ajog.
tips with methotrexate administration.2 These issues were
our major concerns and the basis behind the design of our
protocol.3,4 Methotrexate therapy was avoided in cases
where an intrauterine pregnancy was suspected based on
rising b-hCG levels and an inconclusive ultrasound report.
An important contraindication for methotrexate therapy was
the presence on an intrauterine pregnancy, but more impor-
tantly, all of the patients with rising b-hCG levels had ultra-
sound scans performed and measurement of the ectopic
mass documented. Using the combination of b-hCG follow-
up and ultrasound scans documenting extrauterine pregnan-
cies we were able to prevent inadvertent use of methotrexate.
It follows that in our series of patients we treated patients
with ectopic pregnancies rather than patients with pregnan-
cies of unknown location.
In asymptomatic patients longer periods of follow-up before
thereby obviating the use of toxic agents such as methotrexate
in misdiagnosed cases of evolving intrauterine pregnancies.
In our large series of patients, we did not report a single
case of inadvertent administration of methotrexate where an
intrauterine viable pregnancy was later diagnosed. -
Ishai Levin, MD
Department of Gynecology
Lis Maternity Hospital
Tel Aviv Sourasky Medical Center
affiliated with Sackler School of Medicine
Tel Aviv University
Tel Aviv, Israel
ilevin@post.tau.ac.il
Aviad Cohen, MD
Benny Almog, MD
Department of Gynecology
Lis Maternity Hospital
Tel Aviv Sourasky Medical Center
affiliated with Sackler School of Medicine
Tel Aviv University
Tel Aviv, Israel
The authors report no conflict of interest.
REFERENCES
1. Practice Committee of the American Society for Reproductive
Medicine. Medical treatment of ectopic pregnancy. Fertil Steril 2006;86:
S96-102.
2. Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for
nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:
1443-51.
3. Levin I, Tsafrir Z, Sa’ar N, et al. “Watchful waiting” in ectopic preg-
nancies: a balance between reduced success rates and less metho-
trexate. Fertil Steril 2011;95:1159-60.
4. Cohen A, Zakar L, Gil Y, et al. Methotrexate success rates in pro-
gressing ectopic pregnancies: a reappraisal. Am J Obstet Gynecol
2014;211:128.e1-5.
ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.
2014.09.039