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A. Epidemiology [2] navigator

  1. About 3 million unwanted pregnancies per year in USA
  2. About 1.4 million abortions per year in USA
  3. Most abortions are surgical, mainly dilitation and curretage (D and C)
    1. Estimated 314 induced abortions per 1000 live births
    2. 20% of patients having induced abortions in 1996 were <20 years old
    3. 80% were unmarried and 59% were white
    4. Mortality is <0.6 per 100,000 abortions when performed by professionals
  4. Multiple methods for inducing abortion using medications have been developed
    1. Most abortions are done by suction curettage under local anesthesia in clinics
    2. Increasing number and options for medical (drug induced) abortions
  5. Post-Coital or Emergency Contraception [3]
    1. Previously called "morning after" pill
    2. Utilizes high dose of birth control pill (OCP)
    3. Progestin only regimen also effective
    4. Antiprogestin mifepristone also effective
  6. Medical abortion methods may become first line in underdeveloped countries
  7. When surgical abortions are performed incorrectly, morbidity and mortality are very high
  8. Septic abortion can occur following incorrect surgical abortion
  9. No increase breast cancer in risk in women whose pregnancies end in spontaneous or induced abortion [4]
  10. Up to 100,000 women die annually each year of complications of illegal/unsafe abortions
  11. Overall cost ~ $372 at 10 weeks
  12. Contraception and emergency contraception reduce need for abortion

B. Post-Coital (Emergency) Contraception [3,5] navigator

  1. Average risk of conception following intercourse is 8-20%
  2. Most methods prevent ovulation and/or implantation
  3. Efficacy
    1. Estrogen-progestin ~80%, or ~2% pregnancy risk
    2. Progestin only >90%, or ~1% pregnancy risk
    3. Nearly 100% for mefepristone
  4. Methods of Post-Coital Contraception
    1. Estrogen (100µg ethinyl estradiol) + levonorgestrel (0.5mg) given twice 12 hours apart
    2. Preven® is now FDA approved: 2 tablets given twice, 12 hours apart
    3. First dose should be given within 72 hours of intercourse
    4. Progestin only is more effective than estrogen/levonorgestrel
    5. Levonorgestrel 1.5mg once or 0.75mg twice 12 hours apart (Plan B®)
    6. Single dose 600mg or 10mg mifepristone is effective
    7. Copper intrauterine device may be inserted within 5 days of intercourse (ParaGard T®)
  5. For patients on oral contraceptives who miss a pill:
    1. If pill missed <12 hours prior to intercourse, take missed pill and continue normally
    2. If pill missed >12 hours prior to intercourse, take most recent pill, discard any earlier missed pills, use extra precautions (such as a condom) for next week
    3. For case (b), if 7 or more pills left in packet, maintain usual break before next packet
    4. For case (b), if fewer than 7 pills left, skip the break and start next packet next day
  6. Estimated that these methods could prevent up to 2 million unwanted conceptions
  7. Emergency contraception with as low as 10mg mifepristone associated with ~1.1% pregnancies (similar to 600mg dose, but safer)
  8. Mifepristone is currently only available in USA as 200mg tablets, however

C. Pharmacologic Abortion [5]navigator

  1. Pathophysiology
    1. Implantation and myometrial stabilization require progesterones
    2. Blockade or inhibition of progestin function can lead to termination
    3. Induction of myometrial contractions with prostaglandins
    4. Inhibition of trophoblast development with methotrexate (blocks proliferation)
    5. Combinations of agents are most effective
  2. Medications
    1. Misoprostol - prostaglandin E2 analog given intravaginally or sublingually
    2. Mifepristone (RU486) - very high rate of sucess, used with misoprotol (see below)
    3. Methotrexate - usually combined with misoprostol
    4. Multiple dose oral contraceptives on morning after unprotected intercourse may be effective at preventing conception (see above)
  3. Misoprostol for Abortion [17]
    1. Combined with methotrexate or mifepristone for inducing abortion
    2. Dosed intravaginally (slightly more effective) or sublingually
    3. Three doses of 0.8mg are given, at least 3 hours apart
    4. Intravaginal misoprostol can be given 3-12 hours apart with good efficacy
    5. Sublingual misprostol should be given 3 hours apart to maintain efficacy
    6. Efficacy with mifepristone is ~85% for pregnancy termination
  4. Misoprostol (Intravaginal) for Early Pregnancy Failure [15]
    1. Used alone for EPF, which occurs in ~15% of clinically recognized prengnacies
    2. EPF includes spontaneous abortion, anembryonic gestation, embryonic/fetal death
    3. Dilatation and curettage (DandC) was most commonly used for EPF to remove all remnants
    4. One to 2 intravaginal 800µg doses of misoprostal are as safe and effective as D&C
    5. Misoprostal gave 71% complete expulsion by day 3, 84% by day 8
    6. Treatment failure in 16% of misoprostal group versus 3% in surgical group gi. ~80% of women prefered misoprostal for EPF treatment
  5. Common Complications
    1. Hemorrhage
    2. Acute hematometria
    3. Retained tissue
    4. Infection - endometritis
    5. Very low risk for endometritis with toxic shock due to Clostrium sordellii following mifepristone and vaginal misoprostol [16]
  6. No link between abortion and breast cancer [1,4]

D. Mifepristone (RU 486, Mifeprex®) [6,7,8]navigator

  1. Progesterone receptor antagonist recently approved in USA
    1. Approved for termination of intrauterine pregnancies of 49 days or less
    2. Used in combination with misoprostol
    3. Mifepristone used alone for abortion induction is very weak
  2. Pharmacologic Properties
    1. Has 5-fold higher affinity for progestin receptor compared to progesterone
    2. RU486 complex with progestin receptor inhibits transcription
    3. Decidual necrosis and detachment of embryo occurs
    4. RU586 also promotes uterine contractions through induction of prostaglandins
  3. Potent Abortion Induction Agent
    1. Most potent in combination with misoprostol (Cytotec®), a PGE1 analog
    2. Misoprostol (400-800µg) given intravaginally is more effective than orally
    3. Mifepristone is given as single dose 600mg (FDA approved dose)
    4. Mifepristone single dose 200mg dose is as effective as 600mg [2,7]
    5. Misoprostol given 1-3 days later 800µg intravaginal [8] or 400µg orally 2 days later [7]
    6. Women are usually observed for 4 hours after the misoprostol
    7. Simplified regimen: mifepristone 200mg x 1 in clinic, misoprostal 400µg oral 2 days later at home or in clinic (>90% efficacy) [9]
  4. Efficacy for Abortion Induction [7]
    1. Mifepristone + intravaginal misoprostol was 85-95% effective for early termination [10,17]
    2. For terminations <49 days, efficacy was 92-99%
    3. FDA approved dose is 600mg
  5. Post-Coital Emergency Contraception [3,11]
    1. Very effective for post-coital contraception when used within 72-120 hours
    2. Dose as low as 10mg x 1 was as effective as single 600mg dose
    3. Low dose (10mg) associated with more rapid return of normal menses
  6. Investigational for induction of labor
  7. Side Effects
    1. Bleeding persists for 9-15 days after combination of mifepristone and misoprostal
    2. Up to 8% of patients bleed for 30 days or more; 1% require curettage to control bleeding
    3. Headache, diarrhea, nausea and some vomiting, mainly related to oral misoprostal
    4. Crampy abdominal pain is common and expected after abortion
    5. Surgical termination of pregnancy is strongly recommended in event of drug failure
  8. Recently approved in the USA
    1. Approved in Sweden, United Kingdom, and France
    2. Very commonly used in China

E. Methotrexate + Misoprostol [10,12]navigator

  1. Combination is >90% effective for terminating pregnancies
    1. Methotrexate is toxic to proliferating trophoblastic tissue
    2. Misoprostol stimulates uterine contraction and expulsion of conceptus
  2. Vaginal misoprostol is more effective and safer than oral [13]
  3. Combination of agents is more effective than misoprostol alone [14]
    1. 86% had complete abortion within 24 hours after misoprostol
    2. Those who do not abort within 24 hours are given a second dose (10% more abort)
    3. <5% of women may require suction curettage to terminate the pregnancy
  4. Doses
    1. Methotrexate is given as single intramuscular injection (50mg/m2)
    2. Misoprostol is given as intravaginal dose 800µg, 5-7 days after the methotrexate
  5. Regimens are well tolerated, with no serious complications to date

References navigator

  1. Grimes DA and Creinin MD. 2004. Ann Intern Med. 140(8):620 abstract
  2. Grimes DA. 1999. JAMA. 282(12):1169 (Case Discussion) abstract
  3. Westhoff C. 2003. NEJM. 349(19):1830 abstract
  4. Collaborative Group on Hormonal Factors in Breast Cancer. 2004. Lancet. 363(9414):1007 abstract
  5. Glasier A. 1997. NEJM. 337(15):1058 abstract
  6. Spitz IM, Bardin CW, Benton L, Robbins A. 1998. NEJM. 338(18):1241 abstract
  7. Mifepristone (RU 486). 2000. Med Let. 42(1091):101 abstract
  8. Christin-Maitre S, Bouchard P, Spitz IM. 2000. NEJM. 342(13):946 abstract
  9. Elul B, hajri S, Ngoc NTN, et al. 2001. Lancet. 357(9265):1402
  10. Methotrexate and Misoprostal for Abortion. 1996. Med Let. 38(973):39 abstract
  11. Task force on Postovulatory Methods of Fertility Regulation. 1999. Lancet. 353(9154):697 abstract
  12. Hausknecht RU. 1995. NEJM. 333(9):537 abstract
  13. El-Refaey H, Rajasekar D, Abdalla M, et al. 1995. NEJM. 332(15):983 abstract
  14. Crenin MD and Vittinghoff E. 1994. JAMA. 272:1190 abstract
  15. Zhang J, Gilles JM, Barnhart K, et al. 2005. NEJM. 353(8):761 abstract
  16. Fischer M, Bhatnagar J, Guarner J, et al. 2005. NEJM. 353(22):2353
  17. Von Hertzen H, Piaggio G, Huong NT, et al. 2007. Lancet. 369(9577):1938 abstract