Contraception xx (2017) xxx–xxx Original research article Serial multilevel urine pregnancy testing to assess medical abortion outcome: a meta-analysis☆,☆☆ ⁎ Elizabeth G. Raymonda, , Tara Shocheta, Jennifer Bluma, Wendy R. Sheldona, Ingrida Plataisa, Hillary Brackena, Rasha Dabasha, Mark A. Weaverb, Nguyen Thi Nhu Ngocc, Paul D. Blumenthald, Beverly Winikoffa aGynuity Health Projects, 15 E 26th Street, Suite 801, New York, NY, 10010, USA bUniversity of North Carolina at Chapel Hill, Departments of Medicine and Biostatistics, Chapel Hill, NC, USA cCenter for Research and Consultancy in Reproductive Health, Ho Chi Minh City, Vietnam dStanford University Medical Center, 300 Pasteur Drive, Stanford, CA, USA Received 27 September 2016; revised 20 December 2016; accepted 22 December 2016 Abstract Objectives: To summarize data on the accuracy of a strategy designed to exclude ongoing pregnancy after medical abortion treatment by observing a decline in urine human chorionic gonadotropin (hCG) concentration as estimated by multilevel urine pregnancy tests (MLPTs) performed before and after treatment. Study design: We collated original data from seven studies performed by our organization that evaluated the accuracy of the MLPT strategy for assessment of outcome of medical abortion. Our first analysis included data from the five studies in which each participant was evaluated both with the MLPT strategy and with ultrasound or other clinical assessment. Our second analysis combined data from two randomized trials that compared the MLPT strategy to assessment by ultrasound. Both analyses included only participants treated at ≤63 days of gestation. Results: In the first analysis, 1482 (93%) of 1599 participants had a decline in hCG concentration after treatment. Twenty-one (1.3%) had an ongoing pregnancy, none of whom had a decline (predictive value 100%, 95% CI 93.3%, 100%). The remaining 96 women (6.0%) had no decline without an ongoing pregnancy. The second analysis, which included 3762 participants with follow-up, found no significant difference in the rates of ongoing pregnancy ascertained in the randomized groups (RR 0.88; 95% CI 0.50, 1.54). Nearly all of the post-treatment MLPTs in the seven studies (3484/3535; 99%) were performed by the participants themselves. Conclusions: Serial multilevel urine pregnancy testing is a highly reliable and efficient strategy for excluding ongoing pregnancy after medical abortion at≤63 days of gestation. Implications statement: Serial urine testing using MLPTs can obviate the need for routine ultrasound or examination after medical abortion treatment and can allow most women to avoid an in-person follow-up visit to the abortion facility. © 2017 Elsevier Inc. All rights reserved. Keywords: Medical abortion; Diagnostic accuracy; Multilevel pregnancy test; Follow-up; Semiquantitative pregnancy test; Human chorionic gonadotropin 1. Introduction examination, or serum pregnancy testing. These tests are costly and may be inconvenient, particularly for women who Medical abortion providers commonly ask women to live far away or have competing commitments, and they return one or two weeks after taking the abortifacient drugs must be performed by specially trained personnel. Moreover, to confirm pregnancy termination with ultrasound, pelvic they provide no clinical benefit to the vast majority of women who have successful uncomplicated abortions [1]. Over the past decade, Gynuity Health Projects has ☆ investigated an alternative strategy for follow-up after early Disclosure of interests: Authors report no conflicts of interest. ☆☆ Funding: This research was funded by an anonymous charitable donor. medical abortion. In this strategy, a semiquantitative multilevel ⁎ Corresponding author. Tel.: +1 212 448 1230; fax: +1 212 448 1260. pregnancy test (MLPT) that measures the approximate E-mail address: [email protected] (E.G. Raymond). concentration of human chorionic gonadotropin (hCG) in http://dx.doi.org/10.1016/j.contraception.2016.12.004 0010-7824/© 2017 Elsevier Inc. All rights reserved. 2 E.G. Raymond et al. / Contraception xx (2017) xxx–xxx urine is performed before and after the woman takes the abortifacient drugs. A decline in concentration is interpreted to indicate that no ongoing pregnancy exists, whereas a stable or [7] rising concentration indicates need for further evaluation. The 2012 strategy is not intended to identify persistent non-viable sacs or – Study G 63 2010 Group 1: MLPT plus ultrasound if indicated Group 2: exam, ultrasound if indicated Uzbekistan, Moldova incomplete abortions. The primary aim of our research was to 2 weeks evaluate the accuracy of this strategy using a specific MLPT, dBest® (AmeriTek, Seattle WA, USA), which estimates the urinary hCG concentration asb25, 25–99, 100–499, 500–1999, – ≥ 2000 9999, or 10,000 mIU/ml. Here we summarize the [6] 2011 resultsofthiswork. – Study F 63 Group 1: MLPT plus ultrasound if indicated Group 2: ultrasound Vietnam 2. Material and methods Gynuity Health Projects has completed eight studies that [5] 2014 2010 evaluated the MLPT strategy using the dBest test for – Study E 63 2013 Group 1: MLPT plus ultrasound Group 2: HSPT plus ultrasound Vietnam assessment of medical abortion outcome, six of which have 3, 7, 14 days 2 weeks been published [2–7]. We excluded one unpublished study from this report because it was not designed to ascertain ongoing pregnancy as a specific reason for intervention after abortifacient treatment. The other seven studies enrolled women in six countries who presented for outpatient medical [4] 2014 abortion with mifepristone and misoprostol between 2010 – 14 days and 2014 (Table 1). – 400 mcg sublingual 800 mcg buccal 800 mcg buccal 400 mcg sublingual 70 2013 and/or exam Tunisia 10 Studies A–D were non-comparative studies designed to assess the diagnostic accuracy of the strategy. Each participant had an MLPT before ingesting mifepristone and was given a second test to perform at home 1 week (study A [2]) or 2 weeks (studies B [3], C (unpublished study), and D [4]) later. She reported the result at a scheduled in-person clinic visit. If a participant had not done the test at home, a test was performed at the clinic. The provider then assessed Study C (unpublished data) Study D 70 Not specified 2013 MLPT plus ultrasound MLPT plus ultrasound Mexico the abortion outcome using ultrasound and/or examination 2 weeks and determined whether the participant needed further treatment for ongoing pregnancy or another reason. Study E was a randomized trial designed to assess the effect of the timing of the post-treatment test on the diagnostic [3] accuracy of the strategy [5]. In one group, each participant had 2010 an MLPT before the abortion and was then asked to perform – Study B 63 Not specified 2009 and/or exam Vietnam additional tests at home 3, 7 and 14 days later. She was told to 2 weeks return to the clinic for assessment with ultrasound if any follow-up MLPT showed either a rise or a decline in urine hCG concentration or at 14 days regardless of the result. In the comparison group, each participant had a highly sensitive ≥ [2] urine pregnancy test able to detect 25 mIU hCG/ml on Days 2011 3, 7 and 14, and was evaluated by the clinician on the day the – Study A United States result was negative or 14 days after enrollment, whichever MLPT plus ultrasound MLPT plus ultrasound 1 week was earlier. Studies F [6] and G [7] were randomized trials that compared the MLPT strategy to standard clinical follow-up after medical abortion. Participants assigned to the MLPT groups performed the post-treatment MLPTs at home 2 weeks after taking the mifepristone and were instructed to return to the clinic for ultrasound only if the urine hCG concentration for ongoing pregnancy after treatment N enrolledStudy designYears of enrollment 2010 490 CS 300 CS 400 CS 403 CS 300 RCT 1433 RCT 2400 RCT Table 1 Gynuity Health Projects studies evaluating urine MLPT included in this analysis Country Maximum GA (days) doseMisoprostol and routePosttreatment assessment Not specified 63 Timing of assessment did not decline or specified symptoms occurred; otherwise, Abbreviations: CS, case-series study; RCT,Note: randomized All clinical studies trial; included MLPT, women multilevel obtaining pregnancy outpatient test. medical abortion with mifepristone and misoprostol. E.G. Raymond et al. / Contraception xx (2017) xxx–xxx 3 they were considered to have had complete abortions and were 3. Results dismissed from the study. In the comparison groups, all participants returned to the clinic at two weeks for evaluation Across all seven studies, we identified no ectopic with exam and/or ultrasound. pregnancies among women who used the MLPT strategy for We used the primary data from the seven studies to perform medical abortion follow-up. Ongoing pregnancies diagnosed two main analyses. The purpose of the first analysis was to among study participants were treated with surgical abortion, estimate the diagnostic accuracy of the strategy for identifying additional abortifacient medication, or expectant management. ongoing pregnancy, focusing on its sensitivity (proportion of The first analysis included data from Studies A-E. These participants with known ongoing pregnancies who did not studies enrolled a total of 1893 participants assigned to use the have a decline in hCG concentration as measured by the MLPT for assessment of abortion outcome, of whom 1847 MLPT) and negative predictive value (proportion of partici- (97.6%) were ≤63 days of gestation (Table 2). Of these, 248 pants with a decline in hCG concentration who had no ongoing (13%) were excluded from the analysis because they did not pregnancy) [8]. This analysis included all studies designed to have both a follow-up MLPT test and definitive assessment of evaluate each participant for ongoing pregnancy using both the abortion outcome. Thus, the analysis population consisted of MLPT strategy and a clinical reference standard (ultrasound or 1599 participants. For 1442 (90%) of these participants, the exam), which were studies A-D and the MLPT group of study post-abortion evaluation included ultrasound; in the rest, the E.