Medical treatment of ectopic pregnancy

LETTER TO THE EDITOR Medical treatment of ectopic pregnancy TO THE EDITOR: We welcome the recently published article by the Practice Committee of the American Society for Reproductive Medicine on the medical treatment of ectopic pregnancy (EP) (1). In selected patients methotrexate (MTX) is an effective treatment for unruptured EP and helps to avoid surgical intervention. We are, however, concerned about some aspects of the committee’s opinion. The document advocates the use of single measurements of serum hCG as a discriminatory zone to separate abnormal from normal gestations at the first presentation, if a transvaginal ultrasound scan (TVS) fails to identify the location of a pregnancy. This approach is not without risk. For example, it does not take into account the possibility of a multiple pregnancy, whereby for a given gestational age serum hCG levels are higher than in a singleton. Consequently, hCG levels in multiple pregnancies are usually much higher before the pregnancy reaches a size that may be visualized on TVS (2). This could result in the administration of MTX to a woman with a pregnancy of unknown location (PUL) who has a developing twin pregnancy rather than an underlying EP. Such an outcome would in all likelihood lead to major congenital abnormalities in the developing fetuses. We recommend that the diagnosis of EP be based on the positive identification of an EP mass if inappropriate use of MTX is to be avoided. In the event of a PUL, waiting 48 hours to determine the hCG ratio has been shown to be a safe management approach, which offers further reassurance if the ratio is incompatible with a viable intrauterine pregnancy (IUP) (3). Different discriminatory zone cutoff values are not helpful for the diagnosis of EP (4), because many EPs have serum hCG levels below 1,000 IU/L. In the event that the serum hCG is above the discriminatory zone, classifying a PUL as a ‘‘presumed EP’’ can again be misleading. Even at serum hCG levels of R2,400 IU/L there remains the possibility that an ongoing viable IUP may have been missed, particularly in the event the uterus is axial or in the presence of fibroids (4). The pregnancy should remain classified as a PUL until serial serum hCG levels show the pregnancy is failed or the location of the pregnancy has been identified using follow-up ultrasound examinations. Single serum hCG measurements should not be used in isolation to diagnose EP and certainly should not dictate immediate intervention. It is the behavior of the serum hCG over time that is most helpful in guiding diagnosis and management in women with a PUL. A further concern is the continued recommendation that uterine curettage be used as a diagnostic tool when a pregnancy has been classified as a PUL and when the hCG level is above a set discriminatory zone, or if the serum hCG

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fails to rise at a set rate over time (usually 48 hours). Use of uterine curettage risks disrupting ongoing viable IUPs. We have previously examined protocols with different definitions of pregnancy nonviability using an hCG discriminatory zone or the hCG ratio (0/48 hours). This study showed that the use of these protocols was associated with a rate of potential inadvertent termination of pregnancy of 12% (number of potential terminations of pregnancy/total number of potential curettages performed) (5). Both the use of MTX and curettage have the potential to cause harm to a normally developing IUP. Methotrexate should not be used unless a positive diagnosis of an EP has been made using TVS carried out by an experienced examiner. An exception is a PUL with plateauing serum hCG levels that fail to resolve. In this circumstance the correct management is not known, and a randomized trial comparing curettage, MTX, and no intervention is needed to answer this question. For uncomplicated PUL, provided the initial TVS is performed by an experienced operator, a ‘‘watch and wait’’ approach for the management of a PUL should be outpatient based and has been shown to be safe and reduce the need for unnecessary intervention. Fernando Infante, M.B.B.S., M.P.H.a Uche Menakaya, M.B.B.S., M.C.E.a George Condous, M.B.B.S., M.D.a,b a Acute Gynaecology, Early Pregnancy and Advanced Endosurgery Unit, Sydney Medical School Nepean, University of Sydney, Nepean Hospital; and b OMNI Gynaecological Care, Centre for Women’s Ultrasound and Early Pregnancy, St. Leonards, Sydney, New South Wales, Australia November 11, 2013 http://dx.doi.org/10.1016/j.fertnstert.2013.12.013

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Practice Committee of the American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril 2013; 100:638–44. Jurkovic D. hCG as a patient. Ultrasound Obstet Gynaecol 2010;36:395–9. Condous G, Kirk E, Van Calster B, Van Huffel S, Timmerman D, Bourne T. Failing pregnancies of unknown location: a prospective evaluation of the human chorionic gonadotrophin ratio. BJOG 2006;113:521–7. Condous G, Kirk E, Lu C, Van Huffel S, Gevaert O, De Moor B, et al. Diagnostic accuracy of varying discriminatory zones for prediction of ectopic pregnancy in women with a pregnancy of unknown location. Ultrasound Obstet Gynaecol 2005;26:770–5. Condous G, Kirk E, Lu C, Van Calster B, Van Huffel S, Timmerman D, et al. There is no role for uterine curettage in the contemporary diagnostic workup of women with a pregnancy of unknown location. Hum Reprod 2006;21: 2706–10.

VOL. 101 NO. 3 / MARCH 2014