1. Updates in Medication Abortion
Cynthia Calixte, MD
Martha Simmons, MD

2. Disclosures Dr. Calixte has no disclosures
Dr. Simmons receives financial support from the ARHP for presentations
Outline:
Safety of First Trimester Abortions
Epidemiology
Regimen
FDA changes
Contraception
Cases

3. First Trimester Abortion is Very Safe
SAFETY OF ABORTION: Website:
• A first-trimester abortion is one of the safest medical procedures, with minimal risk—less than 0.05%—of major complications that might need hospital care.[9]
• Abortions performed in the first trimester pose virtually no long-term risk of such problems as infertility, ectopic pregnancy, spontaneous abortion (miscarriage) or birth defect, and little or no risk of preterm or low-birth-weight deliveries.[10]
• Exhaustive reviews by panels convened by the U.S. and British governments have concluded that there is no association between abortion and breast cancer. There is also no indication that abortion is a risk factor for other cancers.[10]
• Leading experts have concluded that, among women who have an unplanned pregnancy, the risk of mental health problems is no greater if they have a single first-trimester abortion than if they carry the pregnancy to term.[11]
• The risk of death associated with abortion increases with the length of pregnancy, from one death for every one million abortions at or before eight weeks to one per 29,000 at 16–20 weeks—and one per 11,000 at 21 weeks or later.[12]
• Fifty-eight percent of abortion patients say they would have liked to have had their abortion earlier. Nearly 60% of women who experienced a delay in obtaining an abortion cite the time it took to make arrangements and raise money.[13]
• Teens are more likely than older women to delay having an abortion until after 15 weeks of pregnancy, when the medical risks associated with abortion are significantly higher.[13]

4. Contraceptive Method/Activity Chance of Death in 1 Year (per 100,000)
Oral contraceptives
Nonsmoker aged 35-44
Smoker aged 35-44
3.0
19.2
Medication Abortion
1.0
Tubal sterilization
1.5
Pregnancy (beyond 20 weeks)
14.5
Spontaneous abortion
0.70
Legal induced abortion at 13–15 weeks
1.7
Automobile driving 20
Trussell J. Contraceptive Technology: Twentieth Revised Edition. 2011
Add medication abortion to table

5. Epidemiology

6. Case
Sara is a 29 year old G2P2 who is 8 week post-partum. She tells you that she has been feeling nauseous for the past couple of weeks. You decide to do a urine pregnancy test. It comes back positive.

7. What other questions would you ask?

8. Office Visit for a Med AB
Estimate GA
Full options counseling
R/o CI’s to MAB
Counsel specifically re: MAB process
Labs: drawn the day before/day of MAB
Order:
CBC
Rh status
Hcg quantitative
Sonogram?

9. Old FDA Protocol vs. Current Protocol
Currently FDA Protocol
OLD PROTOCOL
Gestational age limit
70 days
49 days
Mifepristone dose
200 mg oral
600 mg oral
Mifepristone
side effects
Little – none
Potential for spotting
Bleeding, cramping, N/V
Misoprostol dose, route, and timing
800 mcg. vag/buccal
home administration
6-72 hr later (vaginal)
24-48 hr later (buccal)
400 mcg. oral
Office administration
48 hours later
Office follow-up visit
4-14 days after mifepristone
10-15 days after mifepristone
Minimum office visits
1-2 (or none?) 3
Cost of medications
$90 for mifepristone
$4.00 for misoprostol
$270 for mifepristone
$2.00 for misoprostol
Using evidence-based medicine provides another dosing option, reduces side effects & visits, and decreases overall cost. More effective.
Mife, miso combo is the most commonly used regimen in the US and Western Europe.
References for extended gestational limit
•Bracken, H., N.T.N. Ngoc, E. Schaff, K. Coyaji, S. Ambardekar, E. Westheimer, B. Winikoff. Mifepristone Followed in 24 Hours to 48 Hours by Misoprostol for Late First-Trimester Abortion. Obstetrics and Gynecology (Apr 2007), 109 pp
•Schaff EA, Fielding SL, Eisinger SH, Stadalius LS, Fuller L. Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception. Jan 2000;61(1):41-46.
•Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy. Contraception. Oct 2002;66(4):
References for lower mifepristone dose
•Weeks AD and Stewart P. The use of low dose mifepristone and vaginal misoprostol for first trimester termination of pregnancy. Br J Fam Planning 1995;21:85-86.
•World Health Organization Task Force on Post-Ovulatory Methods of Fertility Regulation. Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomized trial. BJOG (4):
•Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ, Poppema S. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception. Jan 1999;59(1):1-6.
References for higher misoprostol dose
•Coyaji,K., U. Krishna, S. Ambardekar, H. Bracken, V. Raote, A. Mandlekar, B. Winikoff. Are two doses of misoprostol after mifepristone for early abortion better than one? British Journal of Obstetrics and Gynaecology, (Mar 2007), 114 (3), pp. 271–278.
References for non-oral misoprostol route: Schaff EA, et al. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. J Fam Pract 1997;44: Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Contraception. Aug 2001;64(2): Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy. Contraception. Oct 2002;66(4): Winikoff B. Oral vs buccal administration of misoprostol after mifepristone for medication abortion up to 63 days. Obstetrics and Gynecology 2008, accepted for publication.
References for misoprostol timing: Guest J, Chien P, Thomson M, Kosseim ML. Randomised controlled trial comparing efficacy of same day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36- to 48-hour protocol. Bjog. Oct 2005;112(10): Schaff EA, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial. Jama. Oct ;284(15): Shannon C., E. Wiebe, F. Jacot, E. Guilbert, S. Dunn, W.R. Sheldon, B. Winikoff. Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial. British Journal of Obstetrics and Gynaecology (Jun 2006), 113(6), pp Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA: MOD Study Trial Group: A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet. Gynecol (5 Pt. 1):

10. Mechanism of Action Mechanism of Mifepristone-induced Abortion:
Mifepristone, an anti-progestin, interferes with early pregnancy by competing with progesterone, causing:
•decidual necrosis - edema, dissociation of capillary walls and cytoplasmic lysis of decidual cells; and
•cervical ripening - softening and dilation of the cervix.
Detachment è detachment of pregnancy
These effects usually occur within a few hours after mifepristone administration (4 hours).
References:
Baird D. Mode of action of medical methods of abortion. JAMWA. 2000; 35(3): S
Herrmann WL et al. Effects of the antiprogesterone RU 486 in early pregnancy and during the menstrual cycle. Future aspects in contraception Ch. 22:
Swahn ML, Cekan S, Wang G, Lujndstrom V, Bygdeman M. Pharmacokinetic and clinical studies of RU 486 for fertility regulation. In: Beaulieu EE, Siegel S, eds. The Antiprogestin Steroid RU 486 and Human Fertility Control. New York, NY: Plenum; 1985:

11. Initiating Contraception
Implant (Raymond et al, Contraception 2015)
At time of Mifepristone, day 1
Pills, ring, patch
Day 2-3
Depo Provera (Raymond et al, Contraception 2015)
At follow-up visit
IUD
After ensuring passage of gestational sac
No antibiotics
Medical abortion outcomes following quickstart of contraceptive implants
Raymond et al 2015 abstract: co-administration of etonogestrel implants and mifepristone on medical abortion outcome and 6-month pregnancy rate.
RCT 476 women showed that it did not decrease medication abortion success and should be offered.
Data on depoprovera not published, but prelim data had failure rate of 3.9% depo vs 0.9% afterstart, so not recommended
-236 to the quickstart group and 240 to the afterstart group. In the quickstart and afterstart groups, respectively, 9 (3.8%) and 9 (3.8%) had surgery to complete the abortion, a difference of 0.06% (90%CI −3.1%, 3.2%), which excluded our pre-specified non-inferiority margin of 5 percentage points. In the quickstart and afterstart groups, respectively, 12 (5.1%) and 17 (7.1%) received extra abortifacient medication; 211 (89.4%) and 209 (87.1%) required no additional treatment; and 4 (1.7%) and 5 (2.1%) were lost to follow-up. We found no evidence of a difference between groups in unscheduled clinical visits, mean abortion-related pain, days of bleeding or serious adverse events. Women in the quickstart group were more satisfied with their group assignment. Data on subsequent pregnancies are not yet available. Conclusion: Concurrent administration of etonogestrel implants with mifepristone did not decrease medical abortion success or cause other adverse clinical consequences and was preferred by women. This option should be routinely offered to patients.

12. Algorithm For Phone Triage Of Bleeding With Medication Abortion
Algorithm For Phone Triage Of Bleeding With Medication Abortion. Reproductive Health Access Project (2014)

13. Common Questions
Patient calls you and says that she vomited the mifepristone.
Patient calls and says that she has a fever.
Patient calls and says that she has not bled after taking her misoprostol.

14. Questions?

15. Resources http://www.reproductiveaccess.org/