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Day 1 to day 4 serum hCG change in predicting single-dose methotrexate treatment failure for tubal ectopic pregnancies

  • Amy Goh
    Correspondence
    Corresponding author at: Department of Obstetrics and Gynaecology, Westmead Hospital, Hawkesbury Rd, Westmead, New South Wales, 2145, Australia.
    Affiliations
    Department of Obstetrics and Gynaecology, Westmead Hospital, Hawkesbury Rd, Westmead, New South Wales, 2145, Australia

    Sydney West Advanced Pelvic Surgery Unit, 6 Kempsey St, Blacktown, New South Wales, 2148, Australia
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  • Priyanka Karine
    Affiliations
    Department of Obstetrics and Gynaecology, Westmead Hospital, Hawkesbury Rd, Westmead, New South Wales, 2145, Australia
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  • Adrienne Kirby
    Affiliations
    NHMRC Clinical Trials Centre at The University of Sydney, The University of Sydney, Sydney, New South Wales, 2006, Australia
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  • Corey Williams
    Affiliations
    Department of Obstetrics and Gynaecology, Westmead Hospital, Hawkesbury Rd, Westmead, New South Wales, 2145, Australia
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  • Supuni Kapurubandara
    Affiliations
    Department of Obstetrics and Gynaecology, Westmead Hospital, Hawkesbury Rd, Westmead, New South Wales, 2145, Australia

    Sydney West Advanced Pelvic Surgery Unit, 6 Kempsey St, Blacktown, New South Wales, 2148, Australia

    The University of Sydney School of Medicine, Sydney, New South Wales, 2006, Australia
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Published:October 17, 2020DOI:https://doi.org/10.1016/j.ejogrb.2020.10.036

      Abstract

      Objective

      To determine if changes in Day 1 to Day 4 serum human chorionic gonadotropin (hCG) levels can predict treatment failure of single-dose methotrexate (MTX) in medical management of tubal ectopic pregnancies (EP).

      Study Design

      This retrospective cohort study was conducted at a tertiary level hospital. Files were reviewed for all women who received at least one dose of 50 mg/m2 intramuscular MTX for treatment of ultrasound-confirmed tubal EPs between 2013 and 2018. “Treatment failure” is defined as needing additional MTX or surgery to manage the EP. The primary purpose is to establish a threshold percentage change in Day 1 to Day 4 (Day 1/4) hCG that best predicts treatment failure, with clinically and statistically significant sensitivity and specificity, based on receiver-operator characteristic (ROC) analysis.

      Results

      252 files were reviewed, with 108 included for final analysis. 17% of cases required a second dose of MTX and 12% required surgery to manage the EP. Women in the treatment failure group had significantly higher median hCG levels on Day 1, 4 and 7, but were otherwise similar to women who were successful in age, parity, history of previous EP, and EP size. ROC curve analysis of Day 1/4 hCG demonstrates that ≥5% rise best predicts treatment failure with sensitivity 68% (95% confidence interval [CI] 49–83%), specificity 69% (95%CI 56–78%), and AUC 0.77 (95%CI 0.68–0.86, p < 0.001). The positive predictive value is 46% (95%CI 36–56%) and negative predictive value is 84% (95%CI 75–90%). In comparison, ROC analysis of Day 4 to Day 7 hCG demonstrates that a drop of ≤17% best predicted failure, with sensitivity 83% (95%CI 64–94%), specificity 82% (95%CI 71–90%), and AUC 0.90 (95%CI 0.84–0.96), p < 0.001.

      Conclusion

      This study suggests that ≥5% rise in Day 1/4 serum hCG levels could potentially predict treatment failure of single-dose MTX for tubal EPs, and that conversely, <5% rise or any drop in Day 1/4 hCG levels can reliably predict treatment success. Clinicians could consider factoring-in Day 1/4 hCG changes during the course of medically managing patients. They must bear in mind, however, that acting on the Day 1/4 hCG change would lead to increased interventions.

      Keywords

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      Biography

      Dr Amy Goh is a specialist Obstetrician and Gynaecologist in Sydney, Australia, and an Advanced Gynaecological Surgeon as endorsed by the Australasian Gynaecological Endoscopy Surgery Society. She achieved her Fellowship with the Royal Australia and New Zealand College of Obstetricians and Gynaecologists in 2019. Dr Goh did her undergraduate degree in Biomedical Engineering at The Johns Hopkins University (USA). She obtained her MBBS(Honours), followed by a MPhil(Medicine), from The University of Sydney Medical School. Dr Goh is actively involved in research and medical education and is a published researcher who has won awards and scholarships for research in women’s health.

      Biography

      Dr Priyanka Karine is a trainee in Obstetrics and Gynaecology at Westmead Hospital, Sydney, Australia. Dr Karine completed her MBBS in 2009 in India and after successfully completing Australian Medical Council exams, worked for 2 years in the Northern Territory, Australia. Dr Karine has also completed her Master in Public Health from Western Sydney University. Dr Karine’s interest in Women’s Health is deeply rooted from her enriching experiences in India and rural Australia, and aims to contribute to improving healthcare outcomes for women fromunderprivileged communities.

      Biography

      Adrienne Kirby is a senior research fellow at the NHMRC Clinical Trials Centre, University of Sydney. She has more than 20 years’ experience in analysing data from clinical trials and other clinical research. She also coordinates a Master’s Degree in Clinical Trial Methods in the Faculty of Medicine and Health, University of Sydney.

      Biography

      Dr Corey Williams currently works as a senior resident medical officer (SRMO) in Obstetrics and Gynaecology at a large tertiary hospital in Sydney, NSW, Australia. He qualified as a medical doctor in 2017 – graduating with Doctor of Medicine (MD) from University of New South Wales. He has ongoing involvement in education for medical students, with frequent involvement in teaching and as an examiner. He also has a special interest in improving outcomes in the Aboriginal and Torres Strait Islander women – particularly in improving antenatal outcomes and reducing the burden of gynaecological malignancies in this high-risk population.

      Biography

      Dr Supuni Kapurubandara is a consultant Obstetrician and Gynaecologist currently working in both Public and Private hospitals in NSW, Australia. She qualified as a medical doctor in 2008 and has pursued speciality training focussing on gynaecological endoscopic surgery by means of a 2-year endoscopic fellowship recognised by the Australian Gynaecological Endoscopic Society (AGES). She has served as a board member for the AGES and was a member of the NSW RANZCOG regional committee. She remains a committee member of the Australian Colposcopic Society and is an Associate Clinical Lecturer for University of Sydney where she continues to be involved in ongoing gynaecological surgical research and education.