Clinical Updates in Reproductive Health

Misoprostol only: Recommended regimen

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Last reviewed: October 1, 2022

Recommendation

  • Misoprostol 800mcg buccally, sublingually or vaginally every three hours until expulsion.
  • A misoprostol-only regimen has success rates of 84-93%, with continuing pregnancy rates of 3-10% and complication rates of 1-4%.

In practice

  • A combined mifepristone and misoprostol regimen is more effective than misoprostol used alone and is recommended for medical abortion before 13 weeks; where mifepristone is unavailable the misoprostol-only regimen can be used.]
  • Additional doses of misoprostol can be used if bleeding, cramping, or pregnancy expulsion have not occurred and at least 3 hours have passed since the previous misoprostol dose.
  • Individuals undergoing misoprostol-only medical abortion outside of a health facility should be provided with 3-4 doses of misoprostol depending on the scenario. An extra dose of misoprostol, and information describing when to use additional doses, should be provided to be used if needed.

    Strength of recommendation: Strong

    Quality of evidence:

    • Up to nine weeks gestation: Moderate
    • 9-13 weeks gestation: Low

    Background

    Medical abortion success is defined as a complete abortion that needs no further intervention. A combined regimen of mifepristone and misoprostol is recommended for medical abortion, as it is more effective than misoprostol alone (Abubeker et al., 2020; Blum et al., 2012; Kapp et al., 2019; Kulier at al., 2011; Ngoc et al., 2011; Raymond, Harrison, & Weaver, 2019; World Health Organization [WHO], 2022). Where mifepristone is unavailable, the misoprostol-only regimen may be used.

    Misoprostol-only abortion regimen

    A 2019 systematic review assessed effectiveness of misoprostol alone by reviewing 42 studies where at least one group of participants received misoprostol alone to induce abortion. The misoprostol regimens differed across the included studies. The review, which included 12,829 women, found an overall abortion success rate of 78%. Twenty percent of participants underwent subsequent surgical uterine evacuation for any reason (Raymond et al., 2019); criteria to determine when surgical evacuation was required were heterogeneous across the included studies. The ongoing pregnancy rate, available for only half of those undergoing surgical uterine evacuation, was 6%. The largest randomized trial using the recommended misoprostol-only regimen of 3 doses of 800mcg of misoprostol by either the vaginal or sublingual route, included 2,046 participants  with gestations of seven weeks or less (von Hertzen et al., 2007). Success of misoprostol-only abortion was 84%.  A more recent study randomized 390 people with pregnancies up to 10 weeks of gestation to receive 3 doses of misoprostol 800mcg by either the buccal or sublingual route, with the option for an additional dose of misoprostol if the abortion was not complete at the time of follow up (Sheldon et al., 2019). At initial follow up, the ongoing pregnancy rate for both groups combined was 3%, and abortion success rate was 86%. After offering an additional dose of misoprostol to any participants who did not have a successful abortion, success rates increased to 93%. 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 et al., 1999; Carbonell Esteve et al., 1998, Carbonell et al., 2001). In studies that used the recommended misoprostol-only regimen or similar regimens, the rate of subsequent uterine aspiration for any reason ranges from 7-17%, with ongoing pregnancy rates of 3-10% (Carbonell et al., 1999; Carbonell et al., 2001; Sheldon et al., 2019; Velazco et al., 2000; von Hertzen et al., 2007).

    Studies examining strategies to support safe and effective abortion outside the clinical setting, such as those exploring abortion accompaniment or community-based distribution of misoprostol for medical abortion self-management, have reported abortion success rates for misoprostol-only abortion that exceed those for facility based care (Moseson et al., 2020b). In the SAFE study, which documents effectiveness of abortion self-management with accompaniment support, 99% of the misoprostol-only users reported a successful abortion without surgical intervention (Moseson et al., 2022). Two studies have documented the safety and effectiveness of misoprostol-only, self-managed abortion, accessed through community-based distribution up to either 9 or 10 weeks gestation; abortion success rates were 94-96% with no serious adverse events recorded (Foster, Arnott, & Hobstetter, 2017; Foster et al., 2022). One prospective cohort study conducted in Nigeria assessed success rates in pregnant individuals who purchased misoprostol from drug sellers to self-manage their medical abortion (Stillman et al., 2020). Despite receiving inadequate information about the drugs, what to expect, or where and when to seek additional care, 94% of the sample reported a complete abortion without surgical intervention. Of the sample, one participant required a blood transfusion.

    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 et al., 2002; Kapp et al., 2018), higher initial doses of misoprostol (Raymond et al., 2019), non-oral routes of misoprostol administration (Kapp et al., 2018; Raymond et al., 2019; Zhang et al., 2022), and a longer time period before provider follow-up to confirm abortion success (Bugalho et al., 2000; Sheldon et al., 2019). However, individual’s satisfaction decreases the longer the abortion process lasts (Ngai et al., 2000).

    The addition of letrozole

    One high quality, randomized controlled trial has assessed if the addition of letrozole-a third generation aromatase inhibitor that decreases estrogen levels and leads to pregnancy loss-to a misoprostol-only regimen improves success of medical abortion up to 9 weeks gestation (Lee et al., 2011a). One hundred and sixty-eight participants were randomized to a three day course of letrozole (10mg orally each day followed, by a single dose of vaginal misoprostol on day three), or to placebo, followed by misoprostol. Complete abortion was more likely in the letrozole group (87%), than the placebo group (73%, p=0.021); there were no statistically significant differences in continuing pregnancies between the two groups (8% compared to 11%, p=0.6). An earlier pilot study conducted in 20 participants with gestations up to 9 weeks examined a two dose letrozole regimen (10mg orally for two days, followed by a single dose of 800mcg of misoprostol administered vaginally on day three), finding a lower success rate of 80% (Lee et al., 2011b). A subsequent pilot study, including 20 participants with gestations up to 9 weeks, found a higher abortion completion rate (95%), comparable to that seen with the mifepristone and misoprostol regimen, when a seven-day course of letrozole 10mg was administered before a single dose of misoprostol 800mcg vaginally on day 7 (Yeung et al., 2021).

    One randomized controlled trial has examined the addition of letrozole to misoprostol compared to placebo and misoprostol in 46 participants with an average gestational age of 11 to 13 weeks (Javanmanesh, Kashanian, & Mirpangi, 2018). The letrozole group, which took 10mg of letrozole daily for three days, followed by repeated doses of sublingual misoprostol, had a 78% success rate, compared to 13% in the placebo group (p=0.0001), with no differences in side effects and no complications reported. These findings must be interpreted with caution given the very low quality of the study, the small sample size, the discrepancy in mean gestational age between the two groups (11.2 ± 4 weeks in the letrozole group compared to 13.2 ± 3 weeks in the placebo group), and the markedly low success rate reported for the placebo group, which is not in alignment with other studies’ reported success rates with misoprostol-only abortion regimens. Two additional randomized trials, conducted in participants with gestations after 13 weeks, have compared letrozole and misoprostol to placebo and misoprostol (Lee et al., 2011b; Naghshineh, Allame, & Farhat, 2015). Naghsineh, Allame, & Farhat (2015) included 121 participants with an average gestational age of 13 weeks, and found a significantly higher success rate in the group that took letrozole (10mg daily for three days prior to sublingual misoprostol)-77%-compared to placebo (43%, p<0.0001). Lee et al. (2011b) used a smaller dose of letrozole (7.5mg) and found no difference in complete abortion rates in a sample of 130 participants with an average gestational age of 15 weeks. In both of these studies, side effects were comparable between the two groups and no complications were reported. Two systematic reviews examining letrozole and misoprostol, compared to placebo and misoprostol-both of which included studies of second trimester abortion and one of which included a study using letrozole as a treatment for missed abortion-came to conflicting conclusions. Zhou et al. (2021), based on 4 heterogenous randomized controlled trials including a total of 497 patients, found that complete abortion was more likely with the addition of letrozole (relative risk [RR]: 1.38, 95% Confidence Interval [CI]: 1.07, 1.78). Nash et al. (2018), based on 3 randomized controlled trials including 503 patients, found no statistically significant difference in abortion success between letrozole and misoprostol (74%), or placebo and misoprostol (56%, RR: 1.24, 95% CI: 0.92, 1.66).

    Despite the limited evidence available to support its use, World Health Organization (WHO) has suggested that letrozole (10mg orally each day for three days), followed by misoprostol can be used for medical abortion before 12 weeks of gestation in settings where mifepristone is not available (WHO, 2022).

    Young people

    Safety and effectiveness of misoprostol-only abortion has been demonstrated in adolescents with pregnancies up to nine weeks gestation (Velazco et al., 2000) and between 9-12 weeks gestation (Carbonell et al., 2001). Success rates of misoprostol-only abortion in young women are similar to those seen in studies of older women.

    Who can provide medical abortion before 13 weeks gestation?

    The World Health Organization (WHO) makes service delivery recommendations for the provision of medical abortion before 13 weeks gestation, which includes assessment of medical abortion eligibility (determining pregnancy duration and assessing for contraindications to abortion medications), administration of abortion medications, management of the abortion process, and assessment of abortion success (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 abortion with mifepristone and misoprostol or misoprostol-only based on a variety of evidence, and the expected skills and knowledge for that type of health worker (WHO, 2022). WHO also recommends that the pregnant person can safely and effectively self-manage the medical abortion process, in whole or in part, when they have access to accurate information, quality assured medications including for pain management, the support of trained health care workers ,and access to a health facility, if needed (WHO, 2022). For more information about self-managed medical abortion, see 3.5.2: Recommendations for abortion before 13 weeks: Medical abortion self-management. 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)

    Misoprostol-only Gestational Dating Wheels

    Abortion Care Videos – Ipas: Medical Abortion in Early Pregnancy

    References

    Abubeker, F. A., Lavelanet, A., Rodriguez, M.I. &  Kim, C. (2020). Medical termination for pregnancy 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.

    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.

    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.

    Foster, A.M., Arnott, G., & Hobstetter, M. (2017). Community-based distribution of misoprostol for early abortion: Evaluation of a program along the Thailand-Burma border. Contraception, 96, 242-247.

    Foster, A.M., Messier, K., Aslam, M., & Shabir, N. (2022). Community-based distribution of misoprostol for early abortion: Outcomes from a program in Sindh, Pakistan. Contraception, 109, 49-51.

    Ganguly, R. P., Saha, S. P., Mukhopadhyay, S., Bhattacharjee, N., Bhattacharyya, S. K., & Patra, K. K. (2010). A comparative study on sublingual versus oral and vaginal administration of misoprostol for later first and early second trimester abortion. Journal of the Indian Medical Association, 108(5), 283-286.

    Grapsas, X., Liberis, V., Vassaras, G., Tsikouras, P., Vlachos, G., & Galazios, G. (2008). Misoprostol and first trimester pregnancy termination. Clinical and Experimental Obstetrics and Gynecology, 35(1), 32-34.

    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.

    Javanmanesh, F., Kashanian, M., Mirpangi, S. (2018). Comparison of using misoprostol with or without letrozole in abortion induction: A placebo-controlled clinical trial. Journal of Obstetrics, Gynecology and Cancer Research, 3(2), 49-52.

    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.

    Lee, V.C.Y., Ng, E.H.Y., Yeung, W.S.B., & Ho, P.C. (2011a). Misoprostol with or without letrozole pretreatment for termination of pregnancy: A randomized controlled trial. Obstetrics & Gynecology, 117(2Pt1), 317-323.Lee. V.C.Y., Tang, O.S, Ng, E.H.Y., Yeung, W.S.B., & Ho, P.C. (2011b). A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days. Contraception, 83(1), 62-67.

    Lee, V.C.Y., Tang, O.S., Ng, E.H.Y., Yeung, W.S.B., & Ho, P.C. (2011c). A prospective double-blinded, randomized, placebo-controlled trial on the use of letrozole pretreatment with misoprostol for second-trimester medical abortion. Contraception, 84, 628-633.

    Moseson, H., Herold, S., Filippa, S., Barr-Walker, J., Baum, S.E., & Gerdts, C. (2020a). Self-managed abortion: A systematic scoping review. Best Practice & Research Clinical Obstetrics and Gynaecology, 63, 87-110.

    Moseson, H., Jayaweera, R., Egwuatu, I., Grosso, B., Kristianingrum, I.A., Nmezi, S., Zurbriggen, R., Motana, R., Bercu, C., Carbone, S., & Gerdts, C. (2022). Effectiveness of self-managed medication abortion with accompaniment support in Argentina and Nigeria (SAFE): A prospective, observational cohort study and non-inferiority analysis with historical controls. Lancet Global Health, 10(1), e105-e113.

    Naghshineh, E., Allame, Z., & Farhat, F. (2015). The effectiveness of using misoprostol with and without letrozole for successful medical abortion: A randomized placebo-controlled clinical trial. Journal of Research in Medical Sciences, 20(6), 585-589.

    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.

    Sheldon, W. R., Durocher, J., Dzuba, I. G. , Sayette, H., Martin, R., Velasco, M. C., & Winikoff, B. (2019). Early abortion with buccal versus sublingual misoprostol alone: A multicenter, randomized trial. Contraception, 99(5), 272-277.

    Stillman, M., Owolabi, A., Fatusi, A.O., Akinyemi, A.I., Berry, A.L., Erinfolami, T.P., Olagunju, O.S., Vaisanen, H., & Bankole, A. (2020). Women’s self-reported experiences using misoprostol obtained from drug sellers: A prospective cohort study in Lagos state, Nigeria. BMJ Open, 10:e034670. Doi:10.1136/bmjopen-2019-034670.

    Tang O. S., Miao, B. Y., Lee, S. W. H., & Ho, P. C. (2002). Pilot study on the use of repeated doses of sublingual misoprostol in termination of pregnancy up to 12 weeks gestation: Efficacy and acceptability. Human Reproduction, 17(3), 654-658.

    Velazco A., Varela, L., Tanda, R., Sanchez, C., Barambio, S., Chami, S., … Carbonell, J. L. (2000). Misoprostol for abortion up to 9 weeks’ gestation in adolescents. European Journal of Contraception and Reproductive Health Care, 5(4), 227-233.

    Van Bogaert, L. J., & Misra, A. (2010). Anthropometric characteristics and success rates of oral or vaginal misoprostol for pregnancy termination in the first and second trimesters. International Journal of Gynecology & Obstetrics, 109(3), 213-215.

    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.

    von Hertzen, H., Piaggio, G., Wojdyla, D., Nguyen, T. M., Marions, L., Okoev, G., & Peregoudov, A. (2009). Comparison of vaginal and sublingual misoprostol for second trimester abortion: Randomized controlled equivalence trial. Human Reproduction, 24(1), 106-112.

    World Health Organization. (2022). Abortion care guideline. Geneva: World Health Organization.

    Yeung, T.W.Y., Lee, V.C.Y., Ng, E.H.Y., & Ho, P.C. (2012). A pilot study on the use of a 7-day course of letrozole followed by misoprostol for the termination of early pregnancy up to 63 days. Contraception, 86(6), 763-769.

    Zhang, J., Zhou, K., Shan, D., & Luo, X. (2022). Medical methods for first trimester abortion. Cochrane Database of Systematic Reviews, 5(5), CD002855.

    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

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