Clinical Updates in Reproductive Health

Safety and effectiveness

Last reviewed: January 29, 2021

Key Information:

  • A combined regimen of mifepristone and misoprostol is effective and safe with success rates over 95%, continuing pregnancy rates of less than 2% and complication rates of less than 1% up to 10 weeks gestation.
  • Between 10 and 13 weeks, the success rate of mifepristone combined with misoprostol is over 95%, with a continuing pregnancy rate around 2% and complication rate of 3%.
  • A combined regimen of mifepristone and misoprostol is recommended for medical abortion; where mifepristone is not available, the misoprostol-only regimen may be used.
  • A misoprostol-only regimen has lower success rates of about 80-85%, with continuing pregnancy rates of 3-10% and complication rates of 1-4% up to 13 weeks gestation.

Quality of evidence: High

Background

A combined regimen of mifepristone and misoprostol is recommended for medical abortion as it is more effective than misoprostol only (Abubeker, Lavelanet, Rodriguez, & Kim, 2020; Blum et al., 2012; Kapp, Eckersberger, Lavelanet, & Rodriguez, 2018; Kulier et al., 2011; Ngoc et al., 2011; Raymond, Harrison, & Weaver, 2019; World Health Organization [WHO], 2018). Where mifepristone is unavailable, the misoprostol-only regimen may be used.

Mifepristone and misoprostol

Effectiveness

Medical abortion success is defined as a complete abortion that needs no further intervention. A 2015 systematic review reported data from 20 studies that included a total of 33,846 women undergoing medical abortion with mifepristone and buccal misoprostol through 70 days gestation (Chen & Creinin, 2015). The overall success rate was 96.6% and the continuing pregnancy rate was 0.8%. Two prospective cohort studies have examined mifepristone combined with either 400mcg or 600mcg of sublingual misoprostol through 70 days gestation, finding success rates of 93-99% and ongoing pregnancy rates of less than 2% (Bracken et al., 2014; Platais, Tsereteli, Grebennikova, Lotarevich, & Winikoff, 2016). One prospective cohort study (Gouk et al., 1999) and one retrospective case series (Hsia, Lohr, Taylor, & Creinin, 2020) have examined mifepristone combined with 800mcg vaginal misoprostol from 63-70 days gestation, both finding a success rate of 95%; one additionally reported a continuing pregnancy rate of 3.4% (Hsia et al., 2020). Comparable effectiveness has been found in diverse settings; a systematic review of medical abortion with 200mg mifepristone and 800mcg misoprostol up to 9 weeks’ gestation in low- and middle-income countries included 52 studies and found an average  abortion success rate of 95% (Fergeson & Scott, 2020).

Between 10 and 13 weeks gestation only one available study, a retrospective cohort study of 1,076 women, has used the currently recommended regimen of 200mg mifepristone followed 36-48 hours later by misoprostol (800mcg vaginally or 600mcg sublingually), and then repeated doses of 400mcg misoprostol vaginally or sublingually every three hours for two additional doses (Hamoda, Ashok, Flett, & Templeton, 2005). The success rate for this regimen was 95.8%, with an ongoing pregnancy rate of 1.5%. A smaller prospective cohort study which included 254 women used a similar regimen and reported a success rate of 91.7% and an ongoing pregnancy rate of less than 1% (Lokeland et al., 2010).

Three large cohort studies, including a total of 260,256 women who had mifepristone and misoprostol medical abortions up to nine weeks gestation (Cleland et al., 2013; Gatter, Cleland, & Nucatola, 2015; Goldstone, Walker, & Hawtin, 2017), found rates of incomplete abortion treated with uterine aspiration of 2.3-4.8%. Between 10 and 13 weeks, reported rates of uterine aspiration for any reason range from 4-8% (Hamoda et al., 2005; Lokeland et al., 2010). A Danish cohort study which included 86,437 mifepristone and misoprostol medical abortions before nine weeks concluded that increasing gestational age was most strongly associated with requiring surgical intervention (Meaidi, Friedrich, Gerds, & Lidegaard, 2019).

Safety

In the three cohort studies referenced above, rates of complications observed during medical abortion with mifepristone and misoprostol up to nine weeks gestation were less than 1% (Cleland et al., 2013; Gatter, Cleland, & Nucatola, 2015; Goldstone, Walker, & Hawtin, 2017). Between 10 and 13 weeks gestation, complication rates are around 3% (Hamoda et al., 2005). A large retrospective cohort study of 11,319 first-trimester medical abortions evaluated all complications from abortions provided in the state of California in the United States from 2009-2010 (Upadhyay et al., 2015). Researchers assessed complications arising at the time of the abortion, as well as complications diagnosed when patients sought additional care from sites other than the site where the abortion was provided, such as emergency departments. The overall rate of complications during the six weeks following medical abortion was 5.2%; only 0.3% were major complications—defined as requiring hospitalization, surgery or blood transfusion. Complications included incomplete abortion (0.87%), failed abortion (0.13%), hemorrhage (0.14%), infection (0.23%) and undetermined/other (3.82%).

Complications by study

  Goldstone, 2017 Cleland, 2013 Gatter, 2015
Number of women included 13,078 233,805 13,373
Gestational Age ≤ 63 days ≤ 63 days ≤ 63 days
Location/organization MSI Australia Planned Parenthood USA Planned Parenthood USA
Time period 2013-2015 2009-2010 2006-2011
Incomplete abortion requiring aspiration 4.84% Not reported 2.3%
Unrecognized ectopic pregnancy Not reported 0.007% Not reported
Ongoing pregnancy 0.76% 0.5% 0.5%
Transfusion 0.13% 0.05% 0.03%
Infection 0.11% 0.02% 0.01%
Death <0.01% (1 death from pneumonia, likely unrelated) 0.0004% (1 death from unrecognized ectopic pregnancy) No deaths

 

Misoprostol only

Safety and effectiveness data for medical abortion with misoprostol only are more limited. Large retrospective case series documenting success and complication rates are not available. Disparate regimens, gestational age ranges, timeframes to measure abortion success and reporting of complications makes comparison of success and complication rates across studies of misoprostol-only medical abortion difficult.

Effectiveness

The largest randomized trial using the recommended misoprostol-only regimen, repeated doses of 800mcg of misoprostol by either the vaginal or sublingual route, included 2,046 women with gestations of seven weeks or less (von Hertzen et al., 2007). Success of misoprostol-only abortion was 84%. Smaller studies using similar regimens have reported success rates of 92% for gestations up to eight weeks (Fekih, 2010), 89-91% up to nine weeks (Salakos et al., 2005; Velazco et al., 2000), and from 84-87% from 9-13 weeks (Carbonell, Varela, Velazco, Tanda & Sanchez, 1999; Carbonell Esteve et al., 1998, Carbonell et al., 2001). A 2019 systematic review assessed effectiveness of misoprostol alone by reviewing 42 studies where at least one group of women received misoprostol alone to induce abortion; however, the misoprostol regimens differed across the studies. The review, which included 12,829 women, found an overall abortion success rate of 78%; 20% underwent subsequent surgical uterine evacuation for any reason (Raymond et al, 2019). Criteria to determine when surgical evacuation was required were heterogeneous across the studies. The ongoing pregnancy rate, available for only half of the women undergoing surgical uterine evacuation, was 6%. In studies that used the recommended misoprostol-only regimen or similar regimens, the rate of subsequent uterine aspiration for any reason ranges from 12-17%, with ongoing pregnancy rates of 3-10% (Carbonell et al., 1999; Carbonell et al., 2001; Velazco et al., 2000; von Hertzen et al., 2007).

In general, higher rates of success with misoprostol-only regimens are associated with a gestational age of less than 7 weeks (von Hertzen et al., 2007; Zikopoulos et al., 2002), higher number of repeat doses of misoprostol (Carbonell et al., 1999; Jain, Dutton, Harwood, Meckstroth, & Mishell, 2002), higher initial doses of misoprostol (Raymond et al, 2019), non-oral routes of misoprostol administration (Raymond et al., 2019), and a longer time period before provider follow-up to confirm abortion success (Bugalho, Mocumbi, Faundes, & David, 2000). However, women’s satisfaction decreases the longer the abortion process lasts (Ngai, Tang, Chan, & Ho, 2000).

Safety

Complications are infrequently reported: bleeding requiring aspiration occurs in 1-4% of women (Velazco et al., 2000; Salakos et al., 2005; Carbonell et al., 1999; Carbonell Esteve et al., 1998), transfusion is required in less than 1% of women (von Hertzen, et al., 2007; Carbonell et al., 1999), and infection is reported in 1-4% of women (Velazco et al., 2000; Carbonell et al., 2001; von Hertzen et al., 2007; Carbonell et al., 1999).

References

Abubeker, F. A., Lavelanet, A., Rodriguez, M.I. &  Kim, C. (2020). Medical termination for pregnany in early first timester (≤63 days) using combination of mifepristone and misoprostol alone: a systematic review. BMC Women’s Health, 20, 142.

Blum, J., Raghavan, S., Dabash, R., Ngoc, N. T., Chelli, H., Hajri, S., & Winikoff, B. (2012). Comparison of misoprostol-only and combined mifepristone-misoprostol regimens for home-based early medical abortion in Tunisia and Vietnam. International Journal of Gynecology & Obstetrics, 118, 166-171.

Bracken, H., Dabash, R., Tsertsvadze, G., Posohova, S., Shah, M., Hajri, S., … Winikoff, B. (2014). A two-pill sublingual misoprostol outpatient regimen following mifepristone for medical abortion through 70 days’ LMP: A prospective comparative open-label trial. Contraception, 89(3):181-186.

Bugalho, A., Mocumbi, S., Faundes, A., & David, E. (2000). Termination of pregnancies of <6 weeks gestation with a single dose of 800 microg of vaginal misoprostol. Contraception, 61(1), 47-50.

Carbonell Esteve, J. L., Varela, L., Velazco, A., Cabezas, E., Tanda, R., & Sanchez, C. (1998). Vaginal misoprostol for late first trimester abortion. Contraception, 57(5), 329-333.

Carbonell, J. L., Varela, L., Velazco, A., Tanda, R., & Sanchez, C. (1999). Vaginal misoprostol for abortion at 10-13 weeks’ gestation. The European Journal of Contraception and Reproductive Health Care, 4(1), 35-40.

Carbonell, J. L., Velazco, A., Varela, L., Tanda, R., Sanchez, C., Barambio, S., & Mari, J. (2001). Misoprostol for abortion at 9-12 weeks’ gestation in adolescents. The European Journal of Contraception and Reproductive Health Care, 6(1), 39-45.

Chen, M. J., & Creinin, M. D. (2015). Mifepristone with buccal misoprostol for medical abortion: A systematic review. Obstetrics & Gynecology, 126(1), 12-21.

Cleland, K., Creinin, M. D., Nucatola, D., Nshom, M., & Trussell, J. (2013). Significant adverse events and outcomes after medical abortion. Obstetrics & Gynecology, 121(1), 166-171.

Fekih, M., Fathallah, K., Regaya, L. B., Bouguizane, S., Chaieb, A., Bibi, M., & Khairi, H. (2010). Sublingual misoprostol for first trimester termination of pregnancy. International Journal of Gynecology & Obstetrics, 109, 67-70.

Ferguson, I., &  Scott, H. (2020). Systematic review of the effectiveness, safety, and acceptability of mifepristone and misoprostol for medical abortion in low-and middle-income countries. Journal of Obstetrics and Gynaecology Canada, 42(12), 1532-1542.

Gatter, M., Cleland, K., & Nucatola, D. L. (2015). Efficacy and safety of medical abortion using mifepristone and buccal misoprostol through 63 days. Contraception, 91(4), 269-73.

Goldstone, P., Walker, C., & Hawtin, K. (2017). Efficacy and safety of mifepristone-buccal misoprostol for early medical abortion in an Australian setting. Australian and New Zealand Journal of Obstetrics and Gynaecology, 57, 366-371.

Gouk, E. V., Lincoln, K., Khair, A., Haslock, J., Knight, J., & Cruickshank, D. J. (1999). Medical termination of pregnancy at 63-83 days gestation. BJOG: An International Journal of Obstetrics & Gynaecology, 106, 535-539.

Hamoda, H., Ashok, P. W., Flett, G. M., & Templeton, A. (2005). Medical abortion at 9-13 weeks’ gestation: A review of 1076 consecutive cases. Contraception, 71(5), 327-332.

Hsia, J.K., Lohr, P.A., Taylor, J., & Creinin, M.D. (2019). Medical abortion with mifepristone and vaginal misoprostol between 64-70 days’ gestation. Contraception, 100(3), 178-181.

Jain, J. K., Dutton, C., Harwood, B., Meckstroth, K. R., & Mishell, D. (2002). A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of pregnancy. Human Reproduction, 17(6), 1477-1482.

Kapp, N., Eckersberger, E., Lavelanet, A., & Rodriguez, M. I. (2018). Medical abortion in the late first trimester: a systematic review. Contraception, ePub ahead of print.

Kulier, R., Kapp, N., Gulmezoglu, A. M., Hofmeyr, G. J., Cheng, L., & Campana, A. (2011). Medical methods for first trimester abortion. Cochrane Database of Systematic Reviews, 11, Art No.: CD002855. DOI: 10.1002/14651858.CD002855.pub4.

Lokeland, M., Iverson, O. E., Dahle, G. S., Nappen, M. H., Ertzeid, L., & Bjorge, L. (2010). Medical abortion at 63 to 90 days of gestation. Obstetrics & Gynecology, 115(2), 962-968.

Meaidi, A., Friedrich, S., Gerds, T. A, & Lidegaard, O. (2019). Risk factors for surgical intervention of early medical abortion. American Journal of Obstetrics and Gynecology, 220, 478.e1-478.e15.

Ngai, S. W., Tang, O. S., Chan, Y. M., & Ho, P. C. (2000). Vaginal misoprostol alone for medical abortion up to 9 weeks of gestation: Efficacy and acceptability. Human Reproduction, 15(5), 1159-1162.

Ngoc, N. T., Blum, J., Raghavan, S., Nga, N. T., Dabash, R., Diop, A., & Winikoff, B. (2011). Comparing two early medical abortion regimens: Mifepristone+misoprostol vs. misoprostol alone. Contraception, 83, 410-417.

Platais, I., Tsereteli, T., Grebennikova, G., Lotarevich, T., & Winikoff, B. (2016). Prospective study of home use of mifepristone and misoprostol for medical abortion up to 10 weeks of pregnancy in Kazakhstan. International Journal of Gynecology & Obstetrics, 134(3), 268-271.

Raymond, E., Harrison, M, & Weaver, M. (2019). Efficacy of misoprostol alone for first-trimester medical abortion: A systematic review. Obstetrics & Gynecology, 133, 137-147.

Salakos, N., Kountouris, A., Botsis, D., Rizos, D., Gregoriou, O., Detsis, G., & Creatsas, G. (2005). First-trimester pregnancy termination with 800mcg of vaginal misoprostol every 12 h. The European Journal of Contraception and Reproductive Health Care, 10(4), 249-254.

Upadhyay, U. D., Desai, S., Zlidar, V., Weitz, T. A., Grossman, D., Anderson, P., & Taylor, D. (2015). Incidence of emergency department visits and complications after abortion. Obstetrics & Gynecology, 125(1), 175-183.

Velazco, A., Varela, L., Tanda, R., Sanchez, C., Barambio, S., Chami, S., … Carbonell, J. L. L. (2000). Misoprostol for abortion up to 9 weeks’ gestation in adolescents. The European Journal of Contraception and Reproductive Health Care, 5, 227-233.

von Hertzen, H., Piaggio, G., Huong, N. T., Arustamyan, K., Cabezas, E., Gomez, M., & Peregoudov, A. (2007). Efficacy of two intervals and two routes of administration of misoprostol for termination of early pregnancy: A randomised controlled equivalence trial. The Lancet, 369(9577), 1938-1946.

World Health Organization. (2018). Management of Medical Abortion. Geneva: World Health Organization.

Zikopoulos, K. A., Papanikolaou, E. G., Kalantaridou, S. N., Tsanadis, G. D., Plachouras, N. I., Dalkalitsis, N. A., & Paraskevaidis, E. A. (2002). Early pregnancy termination with vaginal misoprostol before and after 42 days gestation. Human Reproduction, 17(12), 3079-3083.