Clinical Updates in Reproductive Health

Treatment of incomplete and missed abortion for less than 13 weeks uterine size

Last reviewed: October 14, 2022

Recommendation:

  • Medical methods or vacuum aspiration may be offered for treatment of incomplete or missed abortion.
  • Recommended medication regimen:
    • Incomplete abortion: Misoprostol 600mcg orally in a single dose or 400mcg in a single dose buccally, sublingually or, in the absence of vaginal bleeding, vaginally.
    • Missed abortion: Misoprostol 800mcg buccally, sublingually or, in the absence of vaginal bleeding,  vaginally every three hours until pregnancy expulsion (generally 1-3 doses). Where available, add pretreatment with mifepristone 200mg orally 1-2 days before misoprostol.

In practice:

  • Uterine size, not gestational age, should be used to determine treatment for postabortion care.

Strength of recommendation: Strong

Quality of evidence: Moderate

Incomplete abortion

A 2021 systematic review and network meta-analysis examining methods for managing miscarriage before 13 weeks gestation included 26 randomized trails reporting on 5,735 women who were treated for incomplete abortion (Ghosh et al., 2021). Suction aspiration (RR 1.19, 95% confidence interval [CI] 1.09, 1.31) and misoprostol therapy (RR 1.14, 95%CI 1.03, 1.25) were slightly more effective than expectant management or placebo in achieving abortion completion, however success rates were similar for all management strategies. Reported completion rates range from 52-85% for expectant management, 80-99% for treatment with misoprostol, and 91-100% for surgical treatment (Kim et al., 2017). Oral, sublingual and vaginal misoprostol showed similar efficacy and side effect profiles; lengthening the time to follow-up assessment increased the success of misoprostol treatment (Kim et al., 2017). 

Missed abortion

A 2021 systematic review and network meta-analysis examining methods for managing miscarriage before 13 weeks gestation included 16 randomized trials reporting on 4,397 women who were treated for missed abortion (Ghosh et al., 2021). Suction aspiration (RR 2.43, 95%CI 1.69, 3.49), mifepristone plus misoprostol (RR 1.82, 95%CI 1.28, 2.58) and misoprostol alone (RR 1.67, 95%CI 1.18, 2.37) were all more effective in achieving a complete abortion than expectant management or placebo treatment. Three randomized controlled trials found that people with a missed abortion who received pretreatment with mifepristone before receiving misoprostol were more likely to successfully complete their abortion than those who received misoprostol only. In Schreiber et al. (2018), women received either mifepristone, followed 24 hours later by a single dose of 800mcg misoprostol vaginally, or misoprostol with no pretreatment. Abortion success, determined the day after misoprostol was used, was 84% in the mifepristone group compared to 67% in the misoprostol-only group. In another study (Sinha et al., 2018), women received either mifepristone or placebo, followed 48 hours later by identical multidose regimens of misoprostol. Abortion success rates were 87% and 58% respectively; more women in the mifepristone group than in the placebo group expelled the pregnancy after a single misoprostol dose (66% compared to 11%, respectively) and had a significantly shorter induction to abortion interval (4.7 hours compared to 8 hours, respectively). A third study of mifepristone or placebo, followed 48 hours later by misoprostol 800mcg, demonstrated successful expulsion in 83% and 76% of the 696 women in the trial, respectively, at seven days post-mifepristone (Chu et al., 2020). A meta-analysis, which included these three studies and one additional study accounting for 1,143 women, found a benefit for the addition of mifepristone in resolving missed abortion (RR 1.15, 95% CI 1.01-1.30) (Chu et al., 2020). In a prospective cohort study, risk of failure following mifepristone and misoprostol for missed abortion was increased among people with a uterine size of greater than nine weeks gestation (Ehrnsten et al., 2019). Despite the relatively high cost of mifepristone, two studies from the United States and one from the United Kingdom have shown that use of a combined mifepristone and misoprostol regimen for treatment of missed abortion is cost-effective, particularly in settings where surgical evacuation of the uterus is performed in an operating theater (Berkley, Greene, & Wittenberger, 2020; Nagendra et al., 2020; Okeke Ogwulu et al., 2021).

A 2017 systematic review and network meta-analysis of misoprostol management of missed abortion, which included 18 studies reporting on 1,802 women, concluded that misoprostol 800mcg vaginally or 600mcg sublingually are the most effective treatments (Wu et al., 2017). A single dose of misoprostol 800mcg vaginally results in successful uterine evacuation in 76 to 93% of women (Fernlund et al., 2017; Mizrachi et al., 2017; Ngoc et al., 2004). In two studies, when women were managed expectantly over seven days after a single dose of misoprostol, their abortion success rates increased over time (Ngoc et al., 2004) up to 88% at seven days compared with 72% at four days (Mizrachi, et al, 2019). Although a number of studies have reported an increase in abortion success when an additional dose of misoprostol is administered 24 (Barcelo et al., 2012; Graziosi, Mol, Ankum, & Bruinse, 2004; Muffley, Stitely, & Gherman, 2002), 48 (Lyra et al., 2017) or 72 hours after the initial dose (Gilles et al., 2004; Zhang et al., 2005), it has been unclear whether this is due to the additional medication or the increased time to evaluation. A 2017 trial which randomized women to receive a single dose of misoprostol 800mcg vaginally, or to receive an additional dose of misoprostol after four days, found that both groups had nearly identical success rates after seven days: 77 and 76% respectively (Mizrachi et al., 2017).

Misoprostol 600mcg sublingually repeated every three hours following the initial dose for a maximum of two more doses achieves abortion success rates of 88-92% (Tang et al., 2003; Tang et al., 2006). No studies have evaluated single doses of sublingual misoprostol for treatment of missed abortion.

 

Who can provide postabortion care for individuals with a uterine size less than 13 weeks gestation?

The World Health Organization (WHO) makes service delivery recommendations for the provision of postabortion care for individuals with a uterine size of less than 13 weeks gestation (WHO, 2022). Health workers with the skills to perform transcervical procedures, and a bimanual examination to diagnose pregnancy and determine gestational age based on uterine size, can be trained to perform vacuum aspiration for postabortion care. WHO advises that uterine aspiration is within the scope of practice for specialty and general medical practitioners, and recommends the provision of vacuum aspiration by associate and advanced associate clinicians, midwives, and nurses based on moderate certainty evidence of safety and effectiveness. Traditional and complementary medicine professionals are recommended to provide uterine aspiration based on low certainty evidence of safety and effectiveness, and WHO suggests that auxiliary nurses and auxiliary nurse midwives may be able to perform aspiration in settings where they provide basic emergency obstetric care (WHO, 2022). WHO advises that all cadres of health care workers (specialty and general medical practitioners, associate and advanced associate clinicians, midwives, nurses, auxiliary nurses and auxiliary nurse midwives, traditional and complementary medicine professionals, pharmacists and pharmacy workers, and community health workers) can safely and effectively provide medical management of uncomplicated incomplete abortion and missed abortion, based on a variety of evidence and the expected skills and knowledge for that type of health worker (WHO, 2022). For further information about health worker roles in abortion care, see Appendix C: World Health Organization recommendations for health worker roles in abortion care.

Resources

Protocols for Medical Abortion (dosage card)

Abortion Care Videos – Ipas: Caring for a Woman with a Miscarriage

References

Barcelo, F., De Paco, C., Lopez-Espin, J. J., Silva, Y., Abad, L., & Parrilla, J. J. (2012). The management of missed miscarriage in an outpatient setting: 800 versus 600 μg of vaginal misoprostol. Australian and New Zealand Journal of Obstetrics and Gynaecology, 52(1), 39-43.

Berkley, H.H., Greene, H.L., & Wittenberger, M.D. (2020). Mifepristone combination therapy compared with misoprostol monotherapy fo the management of miscarriage: A cost-effectiveness analysis. Obstetrics & Gynecology, 136(4), 774-781.

Chu, J.J., Devall, A.J., Beeson, L.E., Hardy, P., Cheed, V., Sun, Y., … & Commarasamy, A. (2020). Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial. Lancet, 396, 770-78.

Ehrnsten, L., Altman, D., Ljungblad, A., & Kopp Kallner, H. (2019). Efficacy of mifepristone and misoprostol for medical treatment of missed miscarriage in clinical practice: A cohort study. Acta Obstetricia et Gynecologica Scandinavica, 00, 1-6.

Fernlund, A., Jokubkiene, L., Sladkevicius, P., & Valentin, L. (2018). Misoprostol treatment vs expectant management in early non-viable pregnancy in women with vaginal bleeding: A pragmatic randomized controlled trial. Ultrasound in Obstetrics and Gynecology,51(1), 24-3232.

Ghosh, J., Papadopoulou, A., Devall, A.J., Jeffery, H.C., Beeson, L.E., Do, V., Price, M.J., Tobias, A., Tuncalp, O., Lavelanet, A., Gulmezoglu, A.M., Coomarasamy, A., & Gallos, I.D., (2021). Methods for managing miscarriage: A network meta-analysis. Cochrane Database of Systematic Reviews, 6(6), CD012602.

Gilles, J. M., Creinin, M. D., Barnhart, K., Westhoff, C., Frederick, M. M., & Zhang, J. (2004). A randomized trial of saline solution-moistened misoprostol versus dry misoprostol for first-trimester pregnancy failure. American Journal of Obstetrics & Gynecology, 190(2), 389-394.

Graziosi, G. C., Mol, B. W., Ankum, W. M., & Bruinse, H. W. (2004). Management of early pregnancy loss. International Journal of Gynecology & Obstetrics, 86(3), 337-346.

Kim, C., Barnard, S., Neilson, J. P., Hickey, M., Vazquez, J. C., & Dou L. (2017). Medical treatment for incomplete miscarriage. Cochrane Database of Systematic Reviews, 1:CD007223. DOI: 10.1002/14651858.CD007223.pub4.

Lyra, J., Cavaco-Gomes, J., Moucho, M., & Montenegro, N. (2017). Medical termination of delayed miscarriage: Four year experience with an outpatient protocol. Revista Brasiliera de Ginecologia e Obstetrica, 39(10), 529-533.

Mizrachi, Y., Tamayev, L., Shemer, O., Kleiner, I., Bar, J., & Sagiv, R. (2019). Early versus delayed follow-up aftermisoprostol treatment for early pregnancy loss. Reproductive Biomedicine Online, 39(1), 155-160.

Mizrachi, Y., Dekalo, A., Gluck, O., Miremberg, H., Dafna, L., Feldstein, O., … Sagiv, R. (2017). Single versus repeat doses of misoprostol for treatment of early pregnancy loss-a randomized clinical trial. Human Reproduction, 32(6), 1202-1207. Muffley, P. E., Stitely, M. L., & Gherman, R. B. (2002). Early intrauterine pregnancy failure: A randomized trial of medical versus surgical treatment. American Journal of Obstetrics & Gynecology, 187(2), 321-325.

Nagendra, D., Koelper, N., Loza-Avalos, S.E., Sonalkar, S., Chen, M., Atrio, J., … & Harvie, H.S. (2020). Cost-effectiveness of mifepristone pretreatment for the medical management of nonviable early pregnancy: Secondary analysis of a randomized trial. JAMA Nerwork Open, 3(3), e201594.

Ngoc, N. T., Blum, J., Westheimer, E., Quan, T. T., & Winikoff, B. (2004). Medical treatment of missed abortion using misoprostol. International Journal of Gynecology & Obstetrics, 87(2), 138-142.

Okeke Ogwulu, C.B.O., Williams, E.V., Chu, J.J., Devall, A.J., Beeson, L.E., Hardy, P., Cheed, V., Yongzhong, S., Jones, L.L., Papadopoulos, J.H.L., Bender-Atik, R., Brewin, J., Hinshar, K., Choudhary, M., Ahmed, A., Naftalin, J., Nunes, N., Oliver, A., Izzat, F., … Roberts, T.E. (2021). Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: An economic evaluation based on the MIfeMiso trial. BJOG: An International Journal of Obstetrics and Gynaecology, 128(9), 1534-1545.   

Schreiber, C. A., Creinin, M. D., Atrio, J., Sonalkar, S., Ratcliffe, S. J., & Barnhart, K. T. (2018). Mifepristone pretreatment for the medical management of early pregnancy loss. New England Journal of Medicine, 378(23), 2161-2170.

Sinha, P., Suneja, A., Guleria, K., Aggarwal, R., & Vaid, N. B. (2018). Comparison of mifepristone followed by misoprostol with misoprostol alone for treatment of early pregnancy failure: A randomized double-blind placebo-controlled trial. Journal of Obstetrics and Gynaecology of India, 68(1), 39-44.

Tang, O. S., Lau, W. N., Ng, E. H., Lee, S. W., & Ho, P. C. (2003). A prospective randomized study to compare the use of repeated doses of vaginal with sublingual misoprostol in the management of first trimester silent miscarriages. Human Reproduction, 18(1), 176-181.

Tang, O. S., Ong, C. Y., Tse, K. Y., Ng, E. H., Lee, S. W., & Ho, P. C. (2006). A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage. Human Reproduction, 21(1), 189-192.

Van den Berg, J., Gordon, B. B. M., Snijders, M. P. M. L., Vandenbussche, F. P. H. A., & Coppus, S. F. P. J. (2015). The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: A systematic review of the literature. European Journal of Obstetrics & Gynecology and Reproductive Biology, 195, 18-26.

Wu, H. L., Marwah, S., Wang, P., Wang, Q. M., & Chen, X. W. (2017). Misoprostol for medical treatment of missed abortion: A systematic review and network meta-analysis. Science Reports, 7(1), 1664.

Zhang, J., Gilles, J. M., Barnhart, K., Creinin, M. D., Westhoff, C., & Frederick, M. M. (2005). A comparison of medical management with misoprostol and surgical management for early pregnancy failure. The New England Journal of Medicine, 353(8), 761-769.

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