Update on Medical Abortion. P.C. Ho Department of O&G University of Hong Kong IWAC 2013 Bangkok

Transcription

1 Update on Medical Abortion P.C. Ho Department of O&G University of Hong Kong IWAC 2013 Bangkok

2 Mifepristone (RU486) Orally active progesterone antagonist at receptor level 97-98% bound to albumin and alpha-1 acid glycoprotein Doses > 100 mg do not produce dose-dependent in plasma conc Mifepristone alone complete abortion rate 60%

3 Regimen of medical abortion with mifepristone and PG analogue Mifepristone PG analogue Follow up 48h 2 weeks

4 Which prostaglanin? Misoprostol an orally active PGE1 analogue marketed for prevention of peptic ulcer (a) orally active (b) cheapest among the prostaglandins (c) stable at room temperature (d) effective - at least as effective as gemeprost

5 Which is the best route to administer misoprostol?

6 Medical abortion in first tirmester Initial results with oral misoprostol not very good especially with more advanced gestations Vaginal misoprostol is more effective (with lower incidence of side effects) than oral misoprostol (El-Rafael 1995) Most women prefer oral route (Ho et al)

7 Sublingual vs vaginal misoprostol in medical abortion (up to 9 wks) with mifepristone Sublingual Vaginal Complete Ab 98.2% 93.8% Nausea 54% 32%* Vomiting 37% 13%* Diarrhoea 40% 16%* Chills 30% 9%* Fever 39% 3%*

8 Dose of misoprostol After 200 mg mifepristone (24-48h), (a) 800 ug buccal vs 800 ug vaginal misoprostol (< 56 days) efficacy & S/E similar (Middleton et al 2005) (b) 800 ug buccal more effective than 800ug oral misoprostol but side effects similar (Winikoff et al 2008) (c)800 ug sublingual as effective as 800 ug buccal misoprostol (< 63 days) but more S/E (Chai et al 2012)

9 RCT comparing 400 mcg vs 800 ug buccal misoprostol in medical abortions (Chong et al 2012) 400 mcg 800 mcg n=555 n=560 < 42 days 98.5% 95.8% days 97.2% 96.2% days 94.3% 98.5%* p< days 95.4% 93% Total 96.4% 96.4% Significantly less vomiting & fever/chills in 400 mcg gp

10 Choice of route and dosage After mifepristone, vaginal, buccal and sublingual misoprostol is similar in efficacy 400 ug is adequate up to 49 days though 800 ug gives slightly better results beyond 49 days Sublingual is preferred if rapid action is needed but there may be more side effects Vaginal preferred if more persistent action needed

11 Dose of mifepristone The complete abortion rates with 200 mg, 400 mg and 600 mg mifepristone (when followed by 1 mg vaginal gemeprost) are similar: 93.8%, 94.1% & 94.3%. (WHO 1993) The complete abortion rates 100 mg and 200 mg of mifepristone are similar when followed by 800 mcg of vaginal misoprostol (von Hertzen et al 2008)

12 Medical abortion with 200 mg mifepristone systematic analysis (Raymond et al 2012) 87 trials of medical abortion (up to 63 days) using 200 mg mifepristone followed by misoprostol: 1. Failure rate: 4.8% (ongoing preg 1.1%) 2. Risk of failure higher among trial groups in which at least 25% > 8 weeks, mifepristonemisoprostol interval < 24h, total misoprostol dose 400 mcg or misoprostol given orally % hospitalized; 0.1% had blood transfusion (Raymond et al 2012)

13 Interval between mifepristone and misoprostol The complete abortion rates when 800 mcg vaginal misoprostol was given 1, 2 or 3 days after 200 mg mifepristone were similar (Schaff et al 2000). Complete abortion rates similar with 100 mg/200 mg mifepristone followed by 800 mcg vaginal misoprostol 24 or 48 hrs later (von Hertzen et al 09) Whether the interval can be shortened to 6-8 hrs is controversial (Crenin et al 2005; Guest et al 2007)

14 Some practical issues Use of NSAID for pain relief did not affect the complete abortion rates of medical abortion (Livshits et al 09). Preemptive use of ibuprofen at time of administration of misoprostol significantly reduced analgesic requirement without affecting success rates (Avraham et al 2012) Although endometrial thickness 1-2 weeks after medical abortion is thicker in those who subsequently needed surgical treatment, the positive predictive value of endometrial thickness was low and not useful clinically. (Reeves et al 2009)

15 Results & Complications of medical abortion Results from a series of 2000 cases of medical abortion with 200 mg mife followed h by 800 mcg miso (Ashok et al 98): Complete abortion rate 97.5% (significantly higher in those < 49 days % vs 96.7%) Haemostatic currettage 0.35% Transfusion 0.15% (all over 49 days) Use of antibiotics 4.6%

16 Infections with medical abortion 4 deaths associated with endometritis and toxic shock syndrome within 1 week of MA in USA (mifepristone + vag misoprostol) (Fischer et al 2005) Toxic shock syndrome also reported in medical abortion with mife + buccal misoprostol (C perfringes) (Cohen et al 2007). A death was also reported from Australia using mifepristone and buccal misoprostol (Goldstone et al 2012)

17 Infections in medical abortions Review of 65 studies on medical abortion infection rate is 0.92% (Shannon et al 2004) Changes in regimens (vaginal to buccal misoprostol; screening for infections; prophylactic antibiotics) led to significant reduction in serious infections from 0.93 to 0.06/1000 (Fjerstad et al, PPFA 2009 NEJM) Still uncertain whether prophylactic antibiotics are needed

18 Partially randomized comparison of medical abortion and VA at wks Medical 200 mg of mifepristone followed by 800 ug of vag misoprostol. Further 2 doses of oral or vag misoprostol 400 ug if abortion does not occur. Complete abortion rate higher in VA gp (97.9% vs 94.6%); side effects more common and bleeding more heavy and longer in MA gp; no significant difference in incidence of medical sequelae at 2-3 and 8 wks after procedure. Ashok et al 02

19 Outpatient medical abortion up to 70 days gestation (Winikoff et al 2012) days days Success rate 93.5% 92.8% Ongoing PR 3.1% 3% Acceptability 87.4% 88.3% Medical abortion with 200 mg mifepristone and 800 mcg buccal misoprostol

20 Can we use misoprostol alone for medical abortion? Repeated doses of sublingual or vaginal misoprostol - high incidence of side effects; overall complete abortion rates usually below 85% (Tang et al 2002; von Hertzen 07) but at gestational age < 49 days, may be 94% or more (Tang et al 2002; Prased et al 09) Most (97.7%) would choose medical abortion again even with misoprostol alone (Tang et al 2002)

21 Letrozole in medical abortion Letrozole a selective, reversible, nonsteroidal aromatase inhibitor; suppresses E biosynthesis 50% of pregnant baboons miscarried after given letrozole while baboons given letrozole and E2 maintained their pregnancies

22 RCT - letrozole (10mg D1-3)/placebo & vag misoprostol (800 mcg) for medical abortion up to 63 days Complete abortion Gestation Letrozole Gp Placebo Gp Up to 63 days 86.9% 72.6%* Up to 49 days 93.3% 78.7%* days 79.5% 64.9% *p<0.05 Significant reduction in incidence of vomiting (8.3% vs 19%; p<0.05)

23 7 day course of letrozole for medical abortion up to 63 day (Yeung et al 2012) Pilot study with 20 women requesting medical abortion up to 63 days of preg 10 mg letrozole daily for 7 days 800 mcg vaginal misoprostol on day 7 Complete abortion rate 95% with 1 incomplete abortion and no ongoing pregnancy; all 12 women with pregnancies up to 49 days had complete abortion

24 Contraception after medical abortion Barrier method RCT - starting the OC pills on the day of misoprostol does not affect the duration or amount of bleeding or the complete abortion rate (Tang et al 1999 and 2002) Progestogen depot injections or implants preferably after complete abortion 2 RCT - No significant difference in infection or expulsion rates between early (5-9 days) versus late insertion of IUD (4-6 weeks); increased uptake rate & less unprotected coitus with early insertion (Shimoni et al 2011; Saav et al 2012)

25 Risk of subsequent adverse pregnancy outcomes Study based on registry in Denmark - after adjustment for possible confounding variables, medical abortion (vs surgical abortion) was not associated with a significantly increased risk of ectopic pregnancy, spontaneous abortion, preterm birth or low birth weight in subsequent pregnancy (Virk et al NEJM 07) A Chinese study (Gan et al 2008) Incidence of miscarriage and PPH significantly lower in women with previous medical vs surgical abortion

26 Risk of subsequent adverse pregnancy outcomes (Bhattacharya et al BMJ 2012) Scottish Morbidity Records: , and women with a documented second pregnancy following an induced abortion, live birth & miscarriage, respectively, were identified. Surgical abortion increased the risk of spontaneous preterm birth compared with medical abortion (adj. RR 1.25, 95% CI 1.07 to 1.45). Medical termination was not associated with an increased risk of preterm delivery compared to primigravidae.

27 Review of acceptability of medical abortions (Ho 2006) In most studies, over 80% of women who chose medical abortion found it acceptable and would choose the same method in future or recommend the method to others. The acceptability of medical abortion decreases with increasing gestational age, failure of medical abortion, prolonged bleeding and high levels of discomfort or anxiety during the procedure. No significant difference in emotional response or incidences of psychiatric morbidity between medical or surgical abortions

28 Conclusion Medical abortion with 200 mg mifepristone followed by vaginal, buccal or sublingual misoprostol is safe & effective; misoprostol alone is less effective Mifepristone-misoprostol interval can be shortened to 24 ART in low income countries.pptx h without loss of efficacy Letrozole or moistening the misoprostol with normal saline/acetic acid may be useful when mifepristone not available but more research is needed Medical abortion is acceptable to most women who chose the method

29 Acknowledgement Hong Kong : QMH : OS Tang, Cora Ngai, BY Miao, Ivy Lee, C Chan, Winnie Lau, W Cheung, YM Chan, EHY Ng, J Chai, V Lee Sharon Lee, PC Ho FPA: Susan Fan, Grace Wong & their team KWH: KS Wong & colleagues Shanghai: Linan Cheng & her team Germany: H Schweer, Seyberth HW Sweden: K Gemzell-Danielsson & her team World Health Organization: H von Hertzen & research group