Clinical Updates in Reproductive Health

Safety and effectiveness

Last reviewed: January 30, 2020

Key Information:

  • A combined regimen with mifepristone and misoprostol is recommended over a misoprostol-only regimen for medical abortion at or after 13 weeks gestation.
  • The combined regimen is safe and effective, with fetal expulsion rates of over 90% at 24 hours, median induction-to-abortion time of 6-10 hours and major complication rates of less than 1%.
  • Where mifepristone is not available, misoprostol-only medical abortion is safe and effective, with fetal expulsion rates of 72-91% at 24 hours, average induction-to-abortion time of around 10-15 hours and major complication rates of less than 1%.

Quality of evidence: High

Combined regimen with mifepristone and misoprostol

Expulsion rates

Studies using the recommended regimen of mifepristone and misoprostol show fetal expulsion rates of 94% at 24 hours and 97% at 48 hours (Abbas et al., 2016), and fetal and placental expulsion rates of 88% at 24 hours and 92% at 48 hours (Dabash et al., 2015). When women continue misoprostol until expulsion with no cut off time, 99% of women eventually have a successful abortion (Ashok, Templeton, Wagaarachchi, & Flett, 2004; Louie et al., 2017).

Induction-to-abortion interval

In studies using the recommended mifepristone and misoprostol regimen, the median times to fetal expulsion were from 6-10 hours, with a wide range of times until complete expulsion (Abbas et al., 2016; Dabash et al, 2015;Louie et al., 2017; Ngoc et al., 2011; Shaw, Topp, Shaw, & Blumenthal, 2013; Prodan et al, 2019). The induction-to-abortion interval is longer in nulliparous women, older women and women with pregnancies at a later gestational age (Abbas et al., 2016; Ashok et al., 2004; Dabash et al., 2015; Louie et al., 2017; Platais et al., 2019). The addition of mifepristone to a misoprostol medical abortion regimen consistently reduces the induction-to-abortion interval (Constant et al., 2016; Dabash et al., 2015; Kapp, Borgatta, Stubblefield, Vragovic, & Moreno, 2007; Ngoc et al., 2011; Prodan et al., 2019).

Complication rates

The rate of major complications from mifepristone and misoprostol medical abortion at or after 13 weeks gestation is low, although minor complications—such as needing a procedure for bleeding or retained products of conception—are more frequent than for dilatation and evacuation (Autry, Hayes, Jacobson, & Kirby, 2002). The largest related cohort study of medical abortion with mifepristone and misoprostol included 1,002 women between 13-21 weeks gestation (Ashok et al., 2004).  Eighty-one women (8.1%) needed a uterine evacuation procedure, the majority of which were needed for retained placenta; only two women needed an evacuation to terminate the pregnancy. In this study, serious complications such as hemorrhage, blood transfusion or unanticipated surgery occurred in eight women (less than 1%). In a 2017 cohort study in which 120 women between 13-22 weeks gestation received mifepristone followed by unlimited dosing of misoprostol until fetal and placental expulsion, 99% of women evacuated the uterus without any additional intervention (Louie et al., 2017). No serious adverse events were reported in this study and only one woman failed to abort with the combined regimen.

In a meta-analysis of data from medical abortion studies at or after 13 weeks gestation using either the combined regimen or a misoprostol-only regimen, the overall rate of uterine rupture was 0.08%, with a rate of 0.28% in women with a previous cesarean section (Goyal, 2009).

Subsequent perinatal outcomes

A Finnish register-based study of women who had a medical abortion up to 12 weeks gestation (3,427 women) or between 12-20 weeks gestation (416 women) compared incidence of several outcomes in subsequent pregnancies—preterm birth, low birth weight, small-for-gestational-age infants and placental complications (Mannisto et al., 2014). No differences were observed between the two groups, suggesting medical abortion at or after 13 weeks does not increase risk of these outcomes in subsequent pregnancies compared to earlier medical abortion.

Misoprostol-only regimen

Expulsion rates

The largest international randomized controlled trial of medical abortion at or after 13 weeks gestation with the recommended vaginal or sublingual misoprostol-only regimen included 681 women between 13-20 weeks gestation (von Hertzen et al., 2009). The fetal expulsion rate was 84.8% at 24 hours and 94.3% at 48 hours. Smaller randomized trials using vaginal or sublingual misoprostol every three hours showed fetal expulsion rates of 72-91% at 24 hours and 91-95% at 48 hours (Bhattacharjee, Saha, Ghoshroy, Bhowmik, & Barui, 2008; Tang, Lau, Chan, & Ho, 2004), and fetal and placental expulsion rates of 62-64% at 24 hours and 79-82% at 48 hours (Bhattacharjee et al., 2008). In nulliparous women, vaginal misoprostol has higher expulsion rates than sublingual misoprostol (von Hertzen et al., 2009).

Induction-to-abortion interval

In the von Hertzen trial cited above, the median time to fetal expulsion was 12 hours (range 4.1-61.8 hours), with parous women having faster induction-to-abortion times than nulliparous women (von Hertzen et al., 2009). In smaller randomized trials, time to expulsion ranges from 10-15 hours (Bhattacharjee et al., 2008; Tang et al., 2004). Lengthening the dosing interval of misoprostol from every three to every six hours increases the induction-to-abortion time (Wong, Ngai, Yeo, Tang, & Ho, 2000).

Complication rates

The rate of major complications from misoprostol-only abortion at or after 13 weeks is low. In the trial cited above, 12 adverse events (0.02%) were reported;  10 women required blood transfusions (von Hertzen et al., 2009).

References

Abbas, D.F., Blum, J. Ngoc, N.T.N, Nga, N. T. B., Chi, H. T. K, Martin, R. & Winikoff, B. (2016). Simultaneous administration compared with a 24-hour mifepristone-misoprostol interval in second-trimester abortion. Obstetrics & Gynecology, 128(5), 1077-1083.

Ashok, P., Templeton, A., Wagaarachchi, P., & Flett, G. (2004). Midtrimester medical termination of pregnancy: A review of 1002 consecutive cases. Contraception69(1), 51-58.

Autry, A. M., Hayes, E. C., Jacobson, G. F., & Kirby, R. S. (2002). A comparison of medical induction and dilation and evacuation for second-trimester abortion. American Journal of Obstetrics & Gynecology187(2), 393-397.

Bhattacharjee, N., Saha, S. P., Ghoshroy, S. C., Bhowmik, S., & Barui, G. (2008). A randomised comparative study on sublingual versus vaginal administration of misoprostol for termination of pregnancy between 13 to 20 weeks. Australian and New Zealand Journal of Obstetrics and Gynaecology48(2), 165-171.

Constant, D., Harries, J., Malaba, T., Myer, L., Patel, M., Petro, G., & Grossman, D. (2016). Clinical outcomes and women’s experiences before and after the introduction of mifepristone into second-trimester medical abortion services in South Africa. PLoS ONE, 11(9), e0161843. DOI: 10.1371/journal.pone.0161843.

Dabash, R., Chelli, H., Hajri, S., Shochet, T., Raghavan, S., & Winikoff, B. (2015). A double-blind randomized controlled trial of mifepristone or placebo before buccal misoprostol for abortion at 14-21 weeks of pregnancy. International Journal of Gynecology & Obstetrics130(1), 40-4.

Goyal, V. (2009). Uterine rupture in second-trimester misoprostol-induced abortion after cesarean delivery: A systematic review. Obstetrics & Gynecology113(5), 1117-1123.

Kapp, N., Borgatta, L., Stubblefield, P., Vragovic, O., & Moreno, N. (2007). Mifepristone in second-trimester medical abortion: A randomized controlled trial. Obstetrics & Gynecology, 110(6), 1304.

Louie, K. S., Chong, E., Tsereteli, T., Avagyan, G., Abrahamyan, R., & Winikoff, B. (2017). Second trimester medical abortion with mifepristone followed by unlimited dosing of buccal misoprostol in Armenia. European Journal of Contraception & Reproductive Health Care, 22(1), 76-80.

Mannisto, J., Mentula, M., Bloigu, A., Gissler, M., Niinimaki, M., & Heikinheimo, O. (2014). Medical termination of pregnancy during the second versus the first trimester and its effects on subsequent pregnancy. Contraception89(2), 109-115.

Ngoc, N. T. N., Shochet, T., Raghavan, S., Blum, J., Nga, N. T. B., Minh, N. T. H., & Winikoff, B. (2011). Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: A randomized controlled trial. Obstetrics & Gynecology118(3), 601-608.

Platais, I., Tsereteli, T., Maystruk, G., Kurbanbekova, D., & Winikoff, B. (2019). A prospective study of mifepristone and unlimited dosing of sublingual misoprostol for termination of second-trimester pregnancy in Uzbekistan and Ukraine. BMJ Sexual & Reproductive Health, 45, 177-182.

Prodan, N., Breisch, J., Hoopmann, M., Abele, H., Wagner, P., & Kagan, K.O. (2019). Dosing interval between mifepristone and misoprostol in second and third trimester termination. Archives of Gynecology and Obstetrics, 99(3), 675-679.

Shaw, K., Topp, N. J., Shaw, J. G., & Blumenthal, P. D. (2013). Mifepristone-misoprostol dosing interval and effect on induction abortion times: A systematic review. Obstetrics & Gynecology121(6), 1335-1347.

Tang, O. S., Lau, W. N. T., Chan, C. C. W., & Ho, P. C. (2004). A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy. BJOG: An International Journal of Obstetrics & Gynaecology111(9), 1001-1005.

Von Hertzen, H., Piaggio, G., Wojdyla, D., Huong, N. T. M., Marions, L., Okoev, G., & Nair, R. (2009). Comparison of vaginal and sublingual misoprostol for second trimester abortion: Randomized controlled equivalence trial. Human Reproduction24(1), 106-112.

Wong, K., Ngai, C., Yeo, E., Tang, L., & Ho, P. (2000). A comparison of two regimens of intravaginal misoprostol for termination of second trimester pregnancy: A randomized comparative trial. Human Reproduction15(3), 709-712.