1. Early Medical Abortion: an overview
Patricia A. Lohr, FACOG FRCOG FFSRH (Hons)
Medical Director, British Pregnancy Advisory Service
Southern Taskgroup on Abortion and Reproductive Topics EMA Conference 6 October * Cork, Ireland

2. Diclosures
I am Medial Director of British Pregnancy Advisory Service, a non-profit provider of abortion services in the UK
I have no commercial disclosures

3. What is medical abortion?
Pregnancy termination without primary surgical intervention and resulting from the use of abortion-inducing medication
Recommended medications: mifepristone and misoprostol
“Early medical abortion”
≤70 days of gestation on day of mifepristone
Typically outpatient
Same medications may be used for termination throughout pregnancy; different regimes and location of care

4. Mifepristone: an antiprogestogen
Rhythmic
Uterine
Contractions
Progesterone Blockade
Decidual
Necrosis
Cervical
Softening
Detachment
Expulsion
Abortion
Binds to progesterone receptor
binding affinity > progesterone
does not activate the receptor
Effectiveness of mifepristone alone ≈ 60-80% at ≤49 days of gestation

5. Mifepristone also enhances uterine response to prostaglandins
Mifepristone sensitises the uterus to prostaglandin resulting in greater effectiveness of medical abortion regimen and faster expulsion than mife alone or prostaglandin alone
Bygdeman & Swahn Contraception 1985
Medical abortion - clinical aspects, C. Fiala

6. Misoprostol: prostaglandin analogue
Most commonly recommended for use with mifepristone
Cheap
Stable at room temperature
Multiple routes of administration: vaginal, buccal, sublingual, (oral)
Effective and efficient
Generally well-tolerated
In the very distant past, IM prostaglandins (E2 - associated with cardiovascular events) and temperature sensitive vaginal pessaries (E1 - gemeprost) used requiring hospitalisation

7. Early medical abortion: the past
Mifepristone: 600mg oral (office)
Interval: hours
Misoprostol: 400mcg oral (with observation period)
Gestation: ≤49 days of gestation
Follow-up: In-person ultrasound in 2 weeks
Higher dose mife, long interval between medications (based on timing to max effect of mife on uterus), lower dose of miso – often with in clinic observation period of variable lengths, limited gestation, if expulsion not observed return for scan

8. Early medical abortion: the present
Mifepristone: 200mg oral (home or office)
Interval: hours
Misoprostol: 800mcg vaginal, buccal or sublingual (home)
Gestation: ≤70 days of gestation
Follow-up: No need for routine (i.e., in person) check
Lower dose mife as effective and less expensive, data to support home or office administration, shorter interval – may reduce further or extend to 72 hours but sacrifice some effectiveness, higher dose miso by non oral routes allowed for extension of gestational age and more flexible intervals, regimen now seen as so effective that routine in person follow-up not needed and many alternatives for “remote” or self-assessment of outcome studied to reduce the burden on women and providers

9. Early medical abortion: efficacy
Showing outcomes with buccal regimen but all non-oral regimens very similar results
Highly effective through 63 and up to 70 days
Effectiveness does decline as gestation advances but it is gradual – this gradual decline continues in same way post 70 days
Chen & Creinin Obstet Gynecol 2015

10. Early medical abortion: efficiency
in % 20 15 10 5
Most women complete abortion in 4 hours and almost all by 24 hours 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Before miso
(hours after misoprostol)
unknown
uncertain
More than 24 h later
Time to expulsion of the sac in 1720 women with successful termination of pregnancy. The women took mifepristone on day 1 and misoprostol 48 hours later. Uncertain means expulsion at some point during 24 hours following misoprostol. Unknown means expulsion at some point later than 24 after misoprostol. Source: The New England Journal of Medicine, 1998; 338 (18): 1244
Medical abortion - clinical aspects, C. Fiala

11. Gestational age (days)
57-63 days vs days
Gestational age (days)
P-value
57-63
64-70
success
ongoing
Misoprostol regimen (number studies) N*
Success n (%)
Ongoing
n (%)
Success
800 mcg BUC (4)
781
730 (93.5)
18 (2.3)
480
444 (92.5)
15 (3.1)
0.25
0.19
400 mcg SL (1)
382
362 (94.8)
7 (1.8)
321
295 (91.9)
7 (2.2)
0.07
0.37
800 mcg PV (1) -
127
120 (94.5)
7 (5.5)
TOTAL
1163
1092 (93.9)
25 (2.1)
928
859 (92.6)
29 (3.1)
Comparing outcomes at days and days in prospective studies – no difference between and 64-70
*Number followed
Abbas D et. al Contraception 2015

12. Early medical abortion: side effects
Post mife side effects mainly spotting, some mild cramping. Post misoprostol side effects do occur but are transient and should resolve within if not before 24 hours after use.
Mifepristone package insert. Approved 2016
Mifepristone package insert. Approved 2016

13. Early medical abortion: safety
Retrospective review
200mg mifepristone + 800mcg buccal misoprostol ≤ 63 days
317 US sites over 2 years, N=233,805
Overall clinically significant adverse event: 1.6 per 1000
A&E treatment 1 per 1000
IV antibiotics 2 per 10,000
Transfused 5 per 10,000
Hospitalised 6 per 10,000
Undiagnosed ectopic 7 per 100,000
Mortality: 0.4/100,000
One of the most studied methods of abortion, there is now a very large body of evidence demonstrating the safety and effectiveness of early medical abortion up to 9 weeks gestation
Cleland K et al Obstet Gynecol 2013

14. 57-63 days vs days
Fewer expulsions within 3h; no difference by 24h
More vomiting, diarrhoea, fever, weakness
No difference adverse events, e.g., hospital admissions, transfusions (0.7% vs. 0.5%, p=0.31)
Work on-going to 77 days
p=0.001 at 3 h
p=0.43 at 24 h
Winikoff B et al Obstet Gynecol 2012
Time to expulsion shorter in day group, more frequent side effects but importantly no difference in adverse events
Abbas D, et al. Contraception 2015

15. Ectopic pregnancy: a very rare occurrence with early abortion
Ectopic pregnancy in the general population: ≈1 in 100
Ectopic pregnancy in women seeking abortion
US trial of surgical abortions <6 weeks’ gestation: 5.9 per 1,000
Largest single study of medical abortion (n=16,369): 1.3 per 1,000
Review of 57 prospective medical abortion trials (n=44,789) found a rate of 2 in 10,000 diagnosed after treatment
Edwards J and Carson A AJOG 1997; Ulmann A et al Acta Obstet Gynecol Scand ; Shannon C et al Obstet Gynecol 2004

16. Early medical abortion care pathway
Decision-making
Eligibility
Contraception/STI
Assessment
Tablets or prescription
Anti-D if needed
Expulsion at home
Treatment
Remote or in person
Review as needed
Aftercare

17. Pre-abortion assessment
Understand woman’s decision about the pregnancy
Determine gestational age ≤10 weeks
Assess eligibility for method and location of care
Decide if anti-D prophylaxis is indicated
An invitation to discuss contraception and screening for STIs also form part of pre-abortion care

18. Do women need counselling?
Most women seeking abortion
Are sure of their decision before contacting a clinician
Have already discussed the decision with friends/relatives (9% with a counselling service)
Do not want further counselling
In one study, 18% (33 of 185) wanted decision-making support from their doctor or nurse
Of these, 6 chose not to have the abortion
None booked with local counselling service
Allen 1985; Barrett et al 2004; Lakha & Glasier 2006; Cameron & Glasier 2013, Baron et al 2015

19. What women want: decision-making support
Qualitative interviews with women seeking abortion advise that most women need/want
Non-judgmental interaction with a provider
An explanation of treatment options and risks
Prompt treatment
Decision-support tools available to assist the generalist or referral to existing counselling/crisis pregnancy centres
Baron C et al J Fam Plann Reprod Health Care ; Kumar U et al J Fam Plann Reprod Health Care. 2004

20. Determining gestational age
Goal: determine eligibility for early medical abortion
No need to be as accurate as when dating for antenatal care
Regimen effectiveness decreases gradually with gestation
Absence of evidence that routine ultrasound improves the safety of medical abortion
Some evidence that most women seeking medical abortion know their LMP and that LMP (± bimanual) can accurately determine eligibility for most women
Kulier and Kapp Contraception. 2011: Kaneshiro et al Contraception. 2011; Schonberg et al 2014; Raymond & Bracken 2015

21. Indications for ultrasound
Unknown LMP
Adnexal mass or pain
Significant size/dates discrepancy
Provider uncertainty with exam
History of previous ectopic pregnancy
Became pregnant with IUD in place

22. Contraindications and cautions
Chronic adrenal failure (long term systemic steroid use)
Severe asthma uncontrolled by therapy
Inherited porphyria
Suspected extra-uterine pregnancy
Haemorrhagic disorders or concurrent anticoagulant therapy
Allergy to mifepristone or misoprostol
If IUD in situ, remove before treatment
In the absence of specific studies, mifepristone not recommended those with malnutrition, hepatic or renal failure

23. Treatment Tailoring to women’s needs
Medications (office or home use) and how to use them
Advice on pain and symptom management
Normal process vs. worrying signs and symptoms
How to get help/advice
Mel Chin "RU 486 Quilt" (1996)

24. Misoprostol at home: safe, effective, preferred by women
Systematic review: 9 prospective cohort studies
Home vs. in-clinic use (n = 4,522)
Odds complete abortion: 0.8 (95% CI: 0.5–1.5)
Serious complications rare and not different between groups
More choosing home use would choose medical again
Ngo TD et al Bull WHO 2011

25. Mifepristone at home also preferable, acceptable, feasible and safe
Armenia, the Republic of Georgia, Azerbaijan, and Uruguay) explicitly allow this option in their clinical guidelines.
Australia allows for pharmacy distribution of mifepristone
Telemedicine medical abortion services such as Women on Web and the Willow Women's Clinic in Vancouver have demonstrated the feasibility of outside-office use of mifepristone or methotrexate in regular clinical services as they send the medical abortion drugs to women through the mail after consultation
Success and complication rates not different between home and clinic users
Gold M and Chong E Contraception 2015

26. Routine (in person) follow-up no longer recommended after medical abortion
Treatment highly effective; very few need intervention
With guidance, those needing intervention will present
Out-of-hours helpline helpful
Multiple visits neither feasible nor desirable for women or providers
Routine post-scan may increase unnecessary interventions
Options
Pre/post serum hCG
Urine hCG with phone call or self assessment checklist
Ultrasound only as needed or if preferred
“I still feel pregnant” both sensitive and specific
WHO Safe abortion: technical and policy guidance for health systems Grossman D et al Obstet Gynecol

27. hCG decline after misoprostol
Can assess for percentage decline from baseline using serum hCG as soon as 4 days post-abortion or use a low sensitivity pregnancy tests 2 weeks post or high sensitivity urine pregnancy test 3-4 weeks post – long tail to value less than high sensitivity pregnancy test so be mindful of false positives but don’t delay assessment for ongoing pregnancy.
Poicus KD et al Contraception 2017

28. In case of…
Ongoing pregnancy: surgical evacuation, repeat regimen (no data but common), repeat misoprostol only ≈ 35% effective
Incomplete abortion or retained non-viable pregnancy: repeat misoprostol, surgical evacuation, or watch and wait
Urgent or emergent intervention very uncommon
Reeves MF et al Contraception 2008

29. Early medical abortion care pathway
Decision-making
Eligibility
Contraception/STI
Assessment
Tablets or prescription
Anti-D if needed
Expulsion at home
Treatment
Remote or in person
Review as needed
Aftercare

30. Thank you for your attention.