Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy

Abstract

ObjectivesThis study evaluates the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have high risk of underlying ectopic pregnancy (EP) and to investigate whether this would result in inadvertent exposure of MTX to viable intra‐uterine pregnancy (IUP).MethodsA retrospective observational study was conducted on clinically stable women who were classified PUL at Early Pregnancy Unit, Nepean Hospital, between 2007 and 2021. PUL is defined as when a woman presents with a positive pregnancy test but has no signs of IUP or EP on the transvaginal ultrasound (TVS). If patients with a PUL behave biochemically like an EP but the location is not confirmed on ultrasound, these women are eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of American College of Obstetricians and Gynaecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians & Gynaecologists (RCOG) and National Institute for Health Care Excellence (NICE) were applied to the collected PUL database. The number of patients eligible to receive MTX and the number of women with underlying viable IUP who would be inadvertently given MTX were calculated.ResultsA total of 816 consecutive women with PUL were reviewed, and 724 had complete data and were included in the final analysis. 6 patients were persistent PULs, and 718 fell among outcomes of 4 subgroups: viable IUP, non‐viable IUP, EP, failed PUL. According to the ACOG, ASRM, RCOG and NICE, the rate of possible MTX administration among patients with a PUL is 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no single persistent‐PUL would have received MTX according to the above protocols, and majority of the MTX treatment were unnecessary because those patients were classified as NVIUP or FPUL later. More importantly, ACOG and ASRM could theoretically result in inadvertent MTX administration to women with an underlying IVUP at rates of 4.1/1000 (3/724).ConclusionsCurrent guidelines used to predict high risk of EP among PUL population are not safe enough to avoid inadvertent MTX administration to women with an underlying viable IUP. These guidelines need to be wisely used to ensure that no wanted pregnancy is exposed to MTX. Women with PULs should be carefully monitored and MTX should be used with judicious care when the location of pregnancy is yet to be confirmed.This article is protected by copyright. All rights reserved.