Last reviewed: February 14, 2021
Recommendation:
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Medical methods or vacuum aspiration may be offered for treatment of incomplete or missed abortion.
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Incomplete abortion: Misoprostol 600mcg orally in a single dose or 400mcg in a single dose sublingually or, in the absence of vaginal bleeding, vaginally.
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Missed abortion: Misoprostol 600mcg sublingually or, in the absence of vaginal bleeding, 800mcg vaginally every three hours until pregnancy expulsion (generally 1-3 doses). Where available, add pretreatment with mifepristone 200mg orally 1-2 days before misoprostol.
Strength of recommendation: Strong
Quality of evidence: Moderate
Incomplete abortion
In a Cochrane review of 24 studies which included 5,577 women presenting with incomplete abortion under 13 weeks, management with misoprostol was as effective as expectant care to complete the abortion (relative risk [RR] 1.23, 95% confidence interval [CI] 0.72, 2.10), and was less effective than surgical treatment (RR 0.96, 95% CI 0.94, 0.98); success rates were high for all management strategies (Kim et al., 2017). Completion rates were 52-85% for expectant management, 80-99% for treatment with misoprostol, and 91-100% for surgical treatment (Kim et al., 2017). In the analysis, 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. A randomized controlled trial comparing a single dose of misoprostol to MVA demonstrated higher success of MVA for abortion completion (RR 0.84, 95% CI 0.77-0.92) (Ibeyemi, Ijaiya & Adesina, 2019).
Missed abortion
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, Marwah, Wang, Wang & Chen, 2017). A single dose of misoprostol 800mcg vaginally results in successful uterine evacuation in 76 to 93% of women (Fernlund, Jokubkiene, Sladkevicius, & Valentin, 2017; Mizrachi et al., 2017; Ngoc, Blum, Westheimer, Quan, & Winikoff, 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, Cavaco-Gomes, Moucho, & Montenegro, 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, Lau, Ng, Lee, & Ho, 2003; Tang et al., 2006). No studies have evaluated single doses of sublingual misoprostol for treatment of missed abortion.
Three randomized controlled trials found that women with missed abortion who received pretreatment with mifepristone before receiving misoprostol were more likely to successfully complete their abortion than women 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 in the same year (Sinha, Suneja, Guleria, Aggarwal & Waid, 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 benenfit for the addition of mifepristone in resolving missed abortion (RR1.15, 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 women with uterine size of greater than nine weeks gestation (Ehrnsten, Altman, Ljungblad, & Kopp, 2019). Despite the relatively high cost of mifepristone, two studies from the United States 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).
Resources
Protocols for Medical Abortion (dosage card)
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.
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.
Ibiyemi, K.F., Ijaiya, M.A., & Adesina, K.T. (2019). Randomised trial of oral misoprostol versus manual vacuum aspiration for the treatment of incomplete abortion at a Nigerian tertiary hospital. Sultan Qaboos University Medical Journal, 19(1), e38-e43.
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.
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.
