Issues in Early Medical Abortion Mitchell Creinin MD
Issues in Early Medical Abortion Mitchell Creinin, MD Professor Director of Gynecologic Specialties Director of Family Planning University of Pittsburgh, PA USA
Objectives Very early surgical abortion • Home use of misoprostol • Shortening the interval between mifepristone and misoprostol • Follow-up intervals shorter than two weeks •
Medical Abortion Early pregnancy termination (usually before 9 weeks gestation) performed without primary surgical intervention and resulting from the use of abortion-inducing medications
Early surgical abortion MVA • • • Manual vacuum aspirator with locking valve Portable and reusable Generates vacuum equivalent to electric pump Efficacy same as electric vacuum (98– 99%) Semi-flexible plastic cannula
Early Abortion with Vacuum Aspiration Date N Paul et al. 2002 1, 132 (MVA+EVA) <6 98% Creinin & Edwards 1997 2, 399 MVA <6 99% Hemlin & Möller 2001 91 MVA <8 98% Laufe 1977 12, 888 “About 6” 98% Author Gestational Efficacy Age Paul ME, et al. Am J Obstet Gynecol 2002; 187: 407 -11. Creinin MD, Edwards J. Curr Prob Obstet Gynecol Fertil 1997; 20: 6 -32. Hemlin J, Möller B. Acta Obstet Gynecol Scand 2001; 80: 563 -7. Laufe LE. Stud Fam Plann 1977; 8: 253 -6.
Early Abortion with MVA Methods • 2, 399 MVA procedures • <6 weeks LMP, high sens UCG , vaginal sono • Meticulous inspection of products of conception immediately after MVA Results • 99. 2% effective in terminating pregnancy • 6 repeat aspirations (0. 25%) • 14 ectopic pregnancies (0. 6%) diagnosed & treated Creinin MD, Edwards J. Curr Prob Obstet Gynecol Fertil 1997; 20: 6 -32.
Mifepristone abortion Can we provide this regimen in an easier fashion and with less cost? Variations: • mifepristone dose • non-oral misoprostol go together • gestational age limits • timing of misoprostol - dependent on route • easier follow-up
Objectives Very early surgical abortion • Home use of misoprostol • Shortening the interval between mifepristone and misoprostol • Follow-up intervals shorter than two weeks •
Home use of misoprostol • Majority of trials in North America High acceptability • High efficacy • • Allowed in the regulatory labeling for mifepristone in the U. S. • Standard of care in North America
Home use of misoprostol • Early studies of mifepristone and vaginal misoprostol in U. S. • • • Women allowed choice of returning Only 3 (1. 9%) of 158 women asked the clinician to place the misoprostol. Initial follow-up studies in the U. S. • • >4300 women with home use of vaginal misoprostol 90% home use acceptable; no difference by • • • prior abortion experience gestational age time between MIF and MIS (1, 2 or 3 days) Schaff et al. Contraception 1999; 59: 1 -6. Schaff et al. Contraception 2000; 61: 41 -6. Schaff et al. JAMA 2000; 284: 1948 -53.
Home use of misoprostol Adverse events in the hours after MIS • 4/4365 women (0. 1%) had emergencies: • • Two emergent aspiration for heavy bleeding • • One vasovagal reaction to cramping • • neither required a blood transfusion. treated with intravenous fluids. One syncopal episode while bleeding • fell and broke her nose. Schaff et al. Contraception 1999; 59: 1 -6. Schaff et al. Contraception 2000; 61: 41 -6. Schaff et al. JAMA 2000; 284: 1948 -53.
Home use in Europe • U. K. • • • 49 women up to 56 days Lived within 12 miles of facility Sublingual MIS at home Contacted at 4 hour intervals by RN 98% -- no trouble with the regimen woman came to hospital after MIS) 93% -- would use it at home again (1 Hamoda et al. J Fam Plann Reprod Health Care 2005; 31: 189 -92.
Home use in Europe • Sweden and France 130 women up to 49 days • oral MIS at home • 98% -- no trouble with the regimen • 98% -- would use it at home again • • In 2004, Sweden changed its regulatory guidelines to allow medical abortion at home up to 63 days gestation. Fiala et al. Contraception 2004; 70: 387 -92. Clark et al. Eur J Contracept Reprod Health Care 2005; 10: 184 -91.
Objectives Very early surgical abortion • Home use of misoprostol • Shortening the interval between mifepristone and misoprostol • Follow-up intervals shorter than two weeks •
Mifepristone Actions Progesterone Blockade Decidual Necrosis Rhythmic Uterine Contractions Detachment Cervical Softening Expulsion Abortion >18 hours for mifepristone effects
Shortened interval overview • Oral misoprostol 24 -36 hours effective with 800 mcg dose • 6 -8 hours doesn’t work • • Vaginal misoprostol 24 hours • 6 -8 hours • <15 minutes • • Buccal misoprostol • 24 hours
Timing of Misoprostol Dosing • • 2, 255 women <56 days gestation Mifepristone 200 mg PO, misoprostol 800 mcg PV Interval randomized 24, 48 or 72 hours Complete medical abortion • • 98% (95% CI 97, 99%) in the 24 hour group; 98% (95% CI 97, 99%) in the 48 hour group; 96% (95% CI 95, 97%) in the 72 hour group. Time waiting for expulsion acceptable • • • 86% in the 24 hour group; 79% in the 48 hour group; 76% in the 72 hour group (p=0. 0001). Schaff EA et al. JAMA 2000; 284: 1948 -53.
Medical abortion in One Day 1, 080 women enrolled at 4 centers (4/02 - 6/03) • Women received mifepristone 200 mg followed • 6 to 8 hours later OR • 23 to 25 hours later • by misoprostol 800 mcg vaginally • Follow-up 7 (+ 1) days and 14 (+ 2) days after mifepristone • Repeat misoprostol dose at first follow-up if no expulsion • Follow-up phone call 5 weeks after mifepristone Creinin MD, et al. Obstet Gynecol 2004; 103: 851 -9.
Abortion outcome (%) 23 -25 hours (n=531) 6 -8 hours (n=525) Complete abortion TOTAL with 1 dose misoprostol 98 (97, 99) 97 (95, 98) 96 (94, 97) 95 (93, 97) <49 days gestation 50 -56 days gestation 57 -63 days gestation 98 (96, 100) 98 (94, 99) 98 (94, 100) 97 (94, 99) 94 (89, 98) 95 (90, 98) Creinin MD, et al. Obstet Gynecol 2004; 103: 851 -9.
Medical Abortion at the Same Time 1, 128 women enrolled at 4 centers (4/04 – 5/06) • Women received mifepristone 200 mg followed • within 15 minutes OR • 23 to 25 hours later • by misoprostol 800 mcg vaginally • Follow-up 7 (+ 1) days and 14 (+ 2) days after mifepristone • Repeat misoprostol dose at first follow-up if no expulsion • Follow-up phone call 5 weeks after mifepristone Creinin MD, et al. Obstet Gynecol 2007; 109: 885 -94.
Abortion outcome (%) 23 -25 hours (n=546) witihin 15 min (n=554) Complete abortion TOTAL with 1 dose misoprostol 97 (95, 98) 94 (92, 96) 95 (93, 97) 91 (88, 93) <49 days gestation 50 -56 days gestation 57 -63 days gestation 98 (96, 99) 95 (91, 98) 97 (92, 99) 96 (92, 98) 94 (90, 97) 95 (90, 98) Creinin MD, et al. Obstet Gynecol 2007; 109: 885 -94.
Questioning results UK study • Randomized trial • 450 women up to 63 days gestation • 6 hour interval (n=225) stayed in clinic • 36 -48 hours (n=225) went home and returned for misoprostol • • Complete abortion rates 89% in 6 hour group • 96% in 36 -48 hour group • Guest J et al. BJOG 2007; 114: 207 -15.
Why a difference? Smaller study (450 vs. 1056) • Ultrasound use • • U. S. study Sonography at 7 days • Assess if sac present • If present, repeat dose of misoprostol and return in one week. • • U. K. study Sonography at 2 -7 days • Assess for a gestational sac and also for evidence of “nonviable products of conception. ” • If present, could have a suction aspiration or more misoprostol; however, women who wanted another dose of misoprostol were required to remain under observation for 4 -6 hours with a follow-up in one week. • Creinin MD et al. Obstet Gynecol 2004; 103: 851 -9. Guest J et al. BJOG 2007; 114: 207 -15.
Why a difference? • Protocol biases results • success rate with a single dose of MIS in 6 -8 h group • • • Incomplete abortion rates • • • U. S. study = 2% U. K. study = 4% Aspiration for persistent sac • • • U. S. study = 95% U. K. study = 79% U. S. study = 0. 6% U. K. study = 4% Increased interventions in U. K. women b/o management schema Creinin MD et al. Obstet Gynecol 2004; 103: 851 -9. Guest J et al. BJOG 2007; 114: 207 -15.
Differences in continuing (viable) pregnancy rate Schaff et al (2000) < 49 d 50 -56 d 57 -63 d Creinin et al (2004) < 49 d 50 -56 d 57 -63 d Creinin et al (2007) < 49 d 50 -56 d 57 -63 d interval rate 48 h 0. 2% 0. 4% 1. 0% 6 -8 h 0 0 0. 8% 24 h 0 0. 6% 0 <15 min 0. 4% 1. 3% 0. 8% 24 h 0. 4% 0 0 Schaff EA, et al. Contraception 2000, 61: 41 -6. Creinin MD, et al. Obstet Gynecol 2004; 103: 851 -9 Creinin MD, et al. Obstet Gynecol 2007; 109: 885 -94.
Mifepristone Actions Progesterone Blockade Decidual Necrosis Rhythmic Uterine Contractions Detachment Cervical Softening Expulsion Abortion WHAT REALLY IS IMPORTANT?
Objectives Very early surgical abortion • Home use of misoprostol • Shortening the interval between mifepristone and misoprostol • Follow-up intervals shorter than two weeks •
Shorter Follow-up Intervals Most studies include follow-up at 1 -7 days following treatment • Earlier follow-up with transvaginal ultrasound • compare to standard regimen
Follow-up No studies validate this practice • Does earlier evaluation result in high rates of later intervention? • What is the best way to use ultrasound?
Follow-up 2 U. S. trials followed subjects who had not had a suction aspiration for 5 weeks after treatment Study Women for 5 week follow-up (no known aspiration) #1 1, 060 #2 1, 103 Women contacted 829 (88%) 974 (78%) Aspiration since last visit (includes aspiration at 5 week follow-up) 14 (1. 7%) 13 (1. 3%) Creinin MD, et al. Obstet Gynecol 2004; 103: 851 -9. Creinin MD, et al. Obstet Gynecol 2007; 109: 885 -94.
Post-abortion uterus transverse longitudinal
Is follow-up exam necessary? Is the ultrasound examination necessary to evaluate for expulsion? • Is a clinical examination necessary to evaluate for expulsion? • • Clinician and patient both feel pregnancy is expelled: Happens in 95% of treatments • They are right 99% of time • Rossi et al. Contraception 2004; 70: 313 -7.
Mifepristone regimens • • • Acceptable alternatives to the Standard Regimen Mifepristone 200 mg mifepristone Home administration of misoprostol Misoprostol 800 mcg vaginally through 63 days gestation 0 -72 hours after the mifepristone Misoprostol 800 mcg buccally through 63 days gestation 24 -48 hours after the mifepristone Follow-up within 1 week using ultrasound
Etienne-Emile Baulieu "Choice is freedom, science cannot and must not dictate our beliefs. But science can provide choices. ” 1991
Mifepristone and Buccal Misoprostol Mifepristone 200 mg • Misoprostol 800 mcg buccally or orally 1 -2 days later • Follow-up 7 -14 days after misoprostol • • • If no expulsion, aspiration or additional misoprostol 966 women up to 63 days gestation Dzuba et al (submitted for publication)
Mifepristone and buccal misoprostol Complete abortion TOTAL* oral (n=546) buccal (n=554) 91 (88, 94) 96 (94, 98) <42 days gestation 98 (92 , 100) 99 (93, 100) 42 -49 days gestation 95 (89, 98) 97 (92, 99) 50 -56 days gestation* 89 (81, 94) 96 (89, 99) 57 -63 days gestation* 85 (77, 91) 95 (89, 98) *p<. 05 Dzuba et al (submitted for publication)
Mifepristone and buccal misoprostol 16 Percentage 12 Buccal Failure Oral Failure Buccal Ongoing Oral Ongoing 8 4 0 ? 42 43 -49 50 -56 57 -63 Gestational age (days) Dzuba et al (submitted for publication)
Buccal misoprostol at same time Mifepristone 200 mg and misoprostol 800 mcg buccally gestational age (days) N expulsion at 24 hours after misoprostol* abortion rate at 2 weeks <49 40 50 -56 40 57 -63 40 29 73% (56, 85%) 27/39 69% (52, 83%) 29 73% (56, 85%) 39 98% (87, 100%) 37/37 100% (91, 100%) 37/39 95% (83, 99%) *1, 1, and 2 subjects, respectively, had an aspiration for incomplete abortion. Lohr PA, et al. Contraception 2007; 76: 215 -20.
Buccal misoprostol at same time 115 subjects (96%) completed the post-treatment questionnaire. Would choose medical abortion again Recommend medical abortion to a friend Disliked some part of the buccal misoprostol taste objectionable buccal retention uncomfortable oral irritation, numbness, or oral ulcers did not work 91% 97% 72% 43% 30% 10% 6% Lohr PA, et al. Contraception 2007; 76: 215 -20.
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