SELF MANAGED ABORTION - A REALITY ? LONG WAY TO GO.
S.CHHABRA*, S. KARAPATE**, S.CHOPRA***
Women of all walks of life use safe / unsafe means of abortions to eliminate unwanted pregnancies. In India around 80% of pregnancies are unplanned and 30% unwanted, so the need for abortions is always there and the resultant clandestine abortions continue to be one of the major causes of maternal deaths. Some 70,000 women die of unsafe abortions annually, making it one of the leading causes of maternal mortality (13%)1. Further five million women suffer temporary or permanent disability, even when abortion is performed at safe places. This is so because surgical abortion could result in cardiac arrest, hemorrhage, uterine perforation and infection. Studies show increased psychological problems with surgical abortion including post-traumatic stress disorder. Embolism and infection have decreased over the years but complications related to anesthesia continue. So, there has been a constant endeavor to have safe, simple, effective and cheap
methods.
Since years various drugs have been tried, some continue to be used, some not so, because of side effects.
1 PROSTAGLANDINS
During the 1970s natural prostaglandins, PGE1 and PGF2 were used to induce early abortion effectively with transcervical or vaginal administration 2. By 1980 more stable analogues, including Gemeprost and the injectable analogue sulprostone were introduced, but have been abandoned because of side effects.
Misoprostol, an orally-active synthetic analogue, derivative of prostaglandin E1 FDA approved for the prevention of gastric ulcers caused by non-steroidal anti-inflammatory drugs, has been tried to induce abortion. Now there is enough evidence of its safety and effectiveness when used alone or in combination with mifepristone, with complete abortion rates of 95% to 97%3,4. It can be given sublingually, orally, vaginally or rectally; can be stored at room temperature and is cheap.
R
RE
EV
VI
IE
EW
W
A
AR
RT
TI
IC
CL
LE
E
*Director & Prof.,**Ex Postgraduate, ***Postgraduate, Dept. of Obstetrics and Gynecology, MGIMS, Sevagram
There are reports that intravaginal route is more effective than oral because of three times higher bioavailability. In a study it was observed that complete expulsion rate was 95% with vaginal route and 87% with oral.3 However the efficacy of vaginal misoprostol in the first trimester varies widely from 47 to 97%4 because it is absorbed at different rates, is cumbersome with possibility of local changes and hemorrhage.
2 OTHERS
Mifepristone(RU 486) is an antiprogestin analogue of norethindrone, with strong affinity for the progesterone receptors and acts as an antagonist, blocking the effects of natural progesterone in cases of amenorrhora of less than 50 days . This synthetic steroid has been marketed in France as an abortifacient since 1988.5 In Europe and China, millions of women have received mifepristone in doses of 1400 to 1600mg administered over 1-10 days for gestation upto 49 days, with complete abortion rates of 64% to 85%.With the lower doses, the number of ongoing pregnancies was much higher (26% with the dose of 200 mg).4 Review done by Henderson6 has reported that the safety of mifepristone is high and few serious medical complications occur in routine clinical use.
Methotrexate in low dose used for extrauterine pregnancy, gestational trophoblastic neoplasia and was believed to be a potential agent for successful abortion because of its direct cytotoxic hydrofolate reductase inhibitor action on the trophoblastic tissue which decreases the production of human chorionic gonadotrophin. Iamakov et al7 have reported that methotrexate and misoprostol both are effective and can be offered, however with methotrexate bleeding does not begin until many days after treatment and it is a potentially toxic drug.
Tamoxifen, a selective estrogen
receptor modulator has been tried to induce abortion. It interferes with continuation of pregnancy by modulation of estrogen receptors, however used alone, it has shown poor success.
3 COMBINATIONS
The efficacy of prostaglandins to complement the antiprogesterone effect of mifeprostone for termination of early pregnancy is well established. All three prostaglandin analogues have been used in combination with mifepristone for early abortion. A study carried out in France revealed the safety and efficacy of Mifepristone and Misoprostol combination with a success rate of 92.4%.8
The recommended regimen for abortion of less than 7 weeks (49 days) gestation is oral mifepristone 200 mg followed by vaginal misoprostol 800 mcg after 36-48 hours 9 however it has been reported that the interval between mifepristone and misoprostol can be decreased to 6-8 hours without loss of efficacy10. Home administration of misoprostol is safe and feasible. In trials of less than 9 weeks gestation it was revealed that a lower dose of mifepristone, 200 mg is as effective as the 600 mg when combined with a prostaglandin analogues11, but efficacy declines from 97% to 89% if the gestation is 64 days or more12. Ngai13 has found that addition of water increases the abortion rate from 65% to 85%. Reports vary in efficacy. In one study with mifepristone (400 mg) and misoprostol (800 mcg), administered vaginally, the complete abortion rate was only 61%11. Liao et al14 have reported that 75 mg mifepristone in capsule form combined with 600 mcg misoprostol is as effective as 150 mg mifepristone in tablet form up to 49 days of pregnancy. Buccal administration of misoprostol after low dose mifepristone is highly effective and acceptable alternative compared with vaginal administration in pregnancies of 56 days15. While success of surgical abortion is 98-99%, combination of methotrexate with misoprostol gives 90-100% and mifepristone and misoprostol 94-99% success. In a study by Banerjee et al16, women
with pregnancy duration of 56 days or less received 200mg mifepristone followed by in-clinic adminis tration of 400mcg misoprostol, orally in Delhi and sublingually in Kolkata, successful medical abortion occurred in 92.5% and 99.3% of women respectively.
Crenin17 evaluated oral methotrexate 25 mg and 50 mg with vaginal misoprostol of 800 mcg, repeated 1-2 days later if the pregnancy had not been expelled, although not statistically significant, the pregnancy passed within 24 hrs of the first or second dose of misoprostol, more often with 50 mg than with 25 mg. Mitchell9 reported 3% failures (need of surgical abortion for continuing viable pregnancy) for 49 days gestation or less and 12% for 50-56 days.
Tamoxifen has been reported to be effective at a dose of 20mg orally once a day for 4 days followed by 800mcg of misoprostol intravaginal, at gestation less than 56 days with complete abortion in 92%.18
MEDICALLY ADDED SURGICAL PROCEDURE
Earlier the most commonly used methods of cervical dilation like intracervical tents, Isapgol husk, laminaria tent; are not used nowadays.
Mifepristone, Gemeprost and misoprostol have all shown to be effective for pre-operative cervical dilatation. Misoprostol 400 mcg 2-4 hour before vaccum aspiration given either vaginally or orally gives satisfactory results.
Higher doses of misoprostol (600 and 800 mcg) achieve the desired successful cervical dilation of 8 mm or more with a shorter evacuation interval of 2 hours compared with 400 mcg but have more side effects including abdominal pain and fever.19
ADVANTAGES OF MEDICAL ABORTION
Medical abortion is more private, thus more acceptable in situations where social stigma is attached to induced abortion, also it is feasible and safe in situations where trained manpower and surgical facilities are insufficient overcoming the serious complications associated with surgical methods and there is no effect on future fertility like infertility, ectopic gestation, recurrent spontaneous abortion, preterm labour, and reduced birth weight. However surgical backup is essential.
CONTRAINDICATIONS TO MEDICAL ABORTION
Women with confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass, chronic adrenal failure, history of allergy
to medications, haemorrhagic disorders or concurrent anticoagulant therapy, inherited porphyrias, should not be subjected to medical abortion and also it should not be done if there is no access to medical facilities equipped to provide emergency treatment of incomplete abortion, blood transfusion and emergency resuscitation.
COMPLICATIONS
With medical means of abortion side effects like nausea, vomiting and / or diarrhea are usually self limiting. Some women will require surgical procedure for control of bleeding, resolution of incomplete expulsion or termination of continuing pregnancy. In the study by Creinin20, the incidence of vomiting, bleeding spotting in women who received misoprostol on the same day as mifepristone were significantly less compared with women who received misoprostol 24 hours after the mifepristone. Gastrointestinal side effects are less severe with the analogues than with natural prostaglandins. Some report that the side effects are significantly less with vaginal route. Compared with surgical termination, medical abortion is associated with a lower risk of pelvic inflammatory disease. The frequency
of failure after medical abortion, followed by subsequent surgical intervention, is
2 to 6% in cases of mifepristone with vaginal prostaglandin analogue.21 Winikoff et al22 have
reported that in general, failure rates reported with medical and surgical abortion were 8.6% and 0.4% respectively in China and 16.0% and 4.0% in Cuba and 5.2% and 0% in India These researchers have concluded that although the failure rates for medical abortion were much more (5-16%) than those of surgical abortion (0- 4.0%).Women were satisfied with either method but preferred medical abortion. More than 40% of the women whose medical abortion failed stated that they would have a surgical procedure for a subsequent abortion compared with <3% of the women who had a successful termination. Extra visits, blood tests and lack of emotional support at home may be deterrent. In most acceptability surveys the best feature has been avoidance of a surgical procedure and worst features were uncertainty and fear of side effects. Early
ectopic pregnancy was difficult to detect and possible occurrence makes a follow up visit 8-15 days mandatory.
If pregnancy continues congenital anomalies are a concern. There is no teratogenic effect of mifepristone. Methotrexate causes fetal anomalies in higher doses and reports after low dose are sparse. Misoprostol causes mild uterine contractions resulting in decreased blood flow leading to possibilities of congenital malformations in case the pregnancy continues.
Educational initiatives are needed to help clinicians to overcome any barriers and to actualize potential medical abortion in women's health care with clear knowledge of advantages and disadvantages.
REFERENCES :
1. www.ippf.org
2. Mocsary P Csapo AJ. Menstrual induction with PGF2a and PGE2 Prostagladins, 1975; 10: 545-47.
3. Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day
after mifepristone for early medical abortion. Contraception. 2001; 64(2):81-5.
4. 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. 2002; 66(4): 247-50.
5. Silvestre L, Dubois C, Renault M, Rezvane Y. Baulieu EE, Ulmann A : Voluntary intervention of
pregnancy with mifepristone (RU 486) and a Prostaglandin analogue 'A' large scale French experience. N. Eng J Med 1990;8,322(10): 645-648.
6. Henderson J, Hwang A., Cynthia C. Safety of mifepristone abortions in clinical use. Contraception
2005; 72: 175-178.
7 Lamakov K, Pekhivanov B., Amallev I., Medical abortion using methotrexate And misoprostol. Efficacy and tolerability. Akush Ginekol (Sofiia) 2005; 44 (3):16-18
8 Largeaud M, EI Guindi W, Perotti F, Montoya Y, Caries G, Seve B. Medical termination of pregnancy at 9-14 weeks gestation Prospective study of 105 cases in Saint-Laurent-du-Maronl (French Guyana). J Gynecol Obstet Biol Reprod ( Paris) 2004;33(2):119-24
9 Mitchell D, Creimin, Jill L, Schwartz, Helen CP, Wendy F. Efficacy of mifepristone followed on the
same day by misoprostol for early termination of pregnancy report of a randomised trial. Br J Obstet Gynaecol 2001; 108: 469-473.
10 Schaff E. Evidence for shortening the time interval of prostaglandin after mifepristone for medical
abortion. Contraception 2006 ;74:42-44
11 Sharma S, EI-Refaev H, Mitchel H, Ozturk O, Rodeck C. Mifepristone vaginally in an early medical
abortion regimen : a pilot study. Contraception 2006, 73(3): 261-263
12 Bracken H, Ngoc NT, Schaff E, Coyaji K, Ambardekar S, Westheimer E, Winikoff B. Mifepristone
followed in 24 hours to 48 hours by misoprostol for Late first trimester abortion. Obstet Gynecol. 2007; 109(4):895-901.
13 Ngai SW vaginal misoprostol alone for medical abortion up to 9 wks of gestation: efficacy and
acceptability. Hum reprod - 2000; 15: 1159 - 1162
14 Liao All, Han XJ, Wu SY, Xiao DZh, Xtong CL, Wu XR. Randomized, double-blind controlled trail of
mifepristone in capsule versus tablet form followed by misoprostol for early medical abortion. Eur J. Obstet Gynecol Reprod Biol 2001; 116 (2):211-6.
15 Schaff E, Middleton T., Randomized trial of mifepristone and buccal or Vaginal misoprostol for
abortion through 56 days of last menstrual period. Contaception 2005 ;72: 328-33
16 Banerjee A, Anand A, Elul B, Kalyanwala S. Mifepristone-misoprostol abortion in free standing
reproductive health clinics in India. J Obstet Gynaecol India 2009; 59(5) : 432-439
17 Crenin MD, Vithinghoff E, Keder L. Methotrexate and Misoprostol for early Abortion: a multicentric
trial, safety and efficacy. Contraception 1996; 53:321
18 Mishell DR Jr. Jain JK, Byrne JD, Lacarra MD. A medical method of early pregnancy termination
using tamoxifen and misoprostol. Contraception 1998; 58 (1):1-6.
19 Singh K, Fong YF, Prasad RN, Dong E, Evacuation interval after vaginal misoprostol for preabortional
cervical priming a randomized trial, Obstet Gynecol 1999. ; 94(3):431-4.
20 Creinin MD, Shreiber CA, Bednarek P, Lintu H, Wagner MS, Mevn LA. Medical Abortion at the
same time ( MAST) study trial group. Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion : randomized controlled trial. Obstet Gynecol 2007; 109(4):885-94.
21 Schaff EA, Fielding SL, Westhoff C ,Charlotte E, Steven H., Lisa S .Vaginal misoprostol administered
1,2, or 3 days after mifepristone for early medical abortion: a randomized trial. J Am Med Assoc 2000; 284, 1948-1953.
22 Winikoff B. Sivin I, Coyaji KJ, Cabezas E, Xiao B, Gu S, Du MK, Krishna O R, Eschen A, Ellerton C. Safety
efficacy accessibility of medical abortion In China mifepristone misoprostol versus surgical abortion. Am. J. Obst Gynaecol 1997 ;176(2): 431 - 7.
