COMPARISON OF MEDICATION ABORTION REGIMENS
Mifepristone with Misoprostol Regimens
- Mifepristone, in a regimen with misoprostol, was approved by the US Food and Drug Administration (FDA) for abortion in 2000. The FDA updated mifepristone’s labeling in 2016 to reflect newer evidence for improved efficacy, safety, and side effects (FDA label 2016), then updated again in 2021 to remove the in-person dispensing requirement (ACOG 2023).
- Motivated to maintain access during the COVID pandemic and after the Dobbs decision, many organizations implemented telehealth MAB, which is safe and effective (Grossman 2024, Upadhyay 2022). Sample protocols can be adapted to office or telehealth provision.
- No-Test Medication Abortion: Sample protocol during a pandemic and beyond
- RHAP Telehealth for Medication Abortion Protocol
- RHEDI Checklist for Minimal Contact Medication Abortion
- WHO Abortion Care Guideline (WHO 2022)
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Evidence-Based Mifepristone Regimens Partially adapted from NAF Clinical Practice Guidelines 2024 |
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| Gestational Age | Mifepristone Dose (Day 1) | Misoprostol Dose & Route | Efficacy | Core References |
| <6 wks¹ |
Mifepristone 200mg PO
|
Misoprostol 800 mcg vaginal 0-48 hours later OR Misoprostol 800 mcg buccal, or sublingual 24-48 hours later |
87-95% |
Brandell 2024, Burton 2025, Dethier 2024, Tai 2023, Upadhyay 2024 |
| 6-9 wks | Misoprostol 800 mcg vaginal 0-48 hours later OR Misoprostol 800 mcg buccal or sublingual 24-48 hours later |
95-99% |
ACOG 2020, Ashok 1998, Chai 2013, Creinin 2004, Gatter 2015, Middleton 2005, Schaff 1999, 2000, 2002, Tang 2003, Schmidt-Hansen 2020a, Zhang 2022 |
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| 9 – 11 wks2 | Misoprostol 800 mcg buccal, vaginal, or sublingual 24-48 hours later followed by 2nd dose of misoprostol 800 mcg 4 hours after 1st dose |
1 dose: 92-95% 2 doses: 99.6% |
Boersma 2011, Bracken 2014, Chen 2015, Dzuba 2020a, 2020b, Hsia 2019, Sanhueza Smith 2015, Winikoff 2012 | |
| 12 – 24 wks3 | Misoprostol 400 mcg buccal, vaginal, or sublingual 24-48 hours later. Repeat every 3 hours until fetus and placenta expelled |
92-99% |
Abbas 2016, Ashok 2004, Dabash 2015, Ipas 2023, Louie 2017, WHO 2022 | |
- Very Early Medication Abortion (before pregnancy can be visualized on US, ~42 days) has been shown to be non-inferior to waiting until confirmation of an IUP (Brandell 2024, Dethier 2024, Tai 2023)
- Medication abortion at 10-11 weeks gestation is evidence-based, and success rates in the late first trimester are higher with repeat misoprostol doses (Dzuba 2020b, Kapp 2019, WHO 2022).
- Established to be safe, effective, and used globally from both 12-14 weeks (Kapp 2019, Whitehouse 2020), and 14-24 weeks (see Table above). (See Ch 12: MAB > 14 weeks for more information. Recommended misoprostol dosing differs >24 wks (See FIGO 2023).
Misoprostol-Only Regimens
- Misoprostol-only is another safe regimen (Moseson 2022, Stillman 2020) that is more widely available and less expensive than regimens with mifepristone. This regimen takes more time to complete, is potentially more painful, and some studies show higher rates of ongoing pregnancy and incomplete abortion (Blum 2012, Kulier 2011, Moseson 2022, Raymond 2023).
- Misoprostol is available over the counter in many countries, and by prescription in the U.S., where it is approved to prevent gastric ulcers.
- A misoprostol-only protocol can be useful when mifepristone is contraindicated or unavailable.
| Gestational Duration | Misoprostol Dose & Route | Efficacy | Core References |
| <11 weeks | Misoprostol 800 mcg vaginal, sublingual1, or buccal every 3 hours x 3 doses. Additional doses may be used if bleeding is insufficient. | 81-1002% | Gynuity 2013, Ipas 2023, Moreno-Ruiz 2007, Moseson 2024, Sheldon 2019, Von Hertzen 2007, WHO 2022 |
| 12 – 24 weeks | Misoprostol 400 mcg vaginal, sublingual or buccal every 3 hours until expulsion. | 75-81% | Bhattacharjee 2008, Ipas 2023, Von Hertzen 2009, Whitehouse 2020, Wildschut 2011, WHO 2022, |
- Increased efficacy demonstrated with sublingual compared to buccal misoprostol in misoprostol-only regimens through 10 weeks gestation, though with increased incidence of side effects (Sheldon 2019).
- High success rates were shown with multiple doses of misoprostol and 3-4 weeks follow up for outcome measures in two global observation studies (Foster 2022, Jayaweera 2023).
Methotrexate-Misoprostol Regimen
Methotrexate (50 mg/m2) IM or PO when combined with misoprostol can be used for termination of intrauterine pregnancy or pregnancy of unknown location (PUL). It is also an effective treatment for early unruptured ectopic pregnancy, but compared with mifepristone/misoprostol, is less effective and requires a longer time to complete abortion (Tarafdari 2024). Success is determined by serial hCG testing and clinical improvement (Barnhart 2021, Seeber 2006). For simple clinical pathways for outpatient methotrexate treatment of ectopic pregnancy (in unrestricted and restricted settings), see Access Bridge protocols.
Letrozole-Misoprostol Regimen
Another MAB protocol for <12 weeks gestation includes letrozole 10 mg orally daily for a variable number of days followed by misoprostol. Compared with mifepristone/misoprostol, letrozole regimens are less effective and require a longer time to complete abortion (Tarafdari 2024, Shochet 2023, WHO 2022). More research is needed on this regimen.
Ulipristal-Misoprostol Regimen
A small study of 60 mg of oral ulipristal, followed by 800 mcg of buccal misoprostol through 63 days of pregnancy showed an effectiveness rate of 97% (Winikoff 2025). This study had no comparison group, therefore it is not sufficient to make a recommendation for or against this regimen, but warrants further study (Grossman 2025). Ulipristal alone at lower dose (30 mg) is used for emergency contraception and is not an abortifacient, in the absence of misoprostol.