Abortion research developments Dan Grossman, MD Ibis Reproductive Health June 26, 2008

Early medical abortion

Number of abortions by gestational age, England and Wales, Abortion Statistics, England and Wales: 2007

What are the barriers to uptake of medical abortion? Too many visits—3 (or more) in some settings Evidence supports safety and acceptability of home use of misoprostol 1 Excessive reliance on ultrasound To determine gestational age eligibility To confirm completion Restrictions on the type of clinician who can provide medical abortion 1. Clark, Gold, Grossman, Winikoff. Contraception 2007

Have we grown too enamored of our ultrasound machines?

Do we need ultrasound to determine gestational age? Women seeking abortion in India and US were accurate in their self-assessment of gestational age 1 Approximately 10% underestimated their gestational age and most of those only by 1 week Clinicians in South Africa were accurate at assessing gestational age 2 74% of provider assessments within 2 weeks of ultrasound measurement Only 12% clinically assessed to be 63 days Women were less accurate 1.Ellertson, et al., Lancet Blanchard, et al., BJOG 2007

Do we need ultrasound to determine completion? Ultrasound may lead to excessive intervention at follow-up, especially when service initiated 1,2 Primary aim of follow-up is to identify ongoing pregnancies, since incomplete abortion is symptomatic Ongoing pregnancy is rare (<1%) with the mifepristone regimen 3 Alternative strategies to identify ongoing pregnancy may be as effective as ultrasound and more feasible 1.Borgatta, et al. JAMWA Suhonen, et al. Contraception Hausknecht. Contraception 2003

Women’s ability to self-assess completion Study of mifepristone regimen in China, Cuba and India (n=222) 1 All women with incomplete abortion (n=17) thought that to be the case 110 women incorrectly thought their abortion was not complete Studies of mifepristone regimen in US Among women >49 days GA who thought abortion was complete, 4% had ongoing pregnancy (n=2,121) 2 In another study, of 16 ongoing pregnancies, clinical history only detected 8 3 Study of methotrexate regimen in US (n=50) 3 28 thought they had aborted by day 9, and 13 of those (46%) had in fact not passed the pregnancy 1.Ellertson, Elul, Winikoff. Reprod Health Matters Harper, Ellertson, Winikoff. Contraception Rossi, et al. Contraception Creinin, et al. Contraception 1996

Decline of β-hCG with medical abortion With mifepristone regimen, β-hCG falls to ~200 IU/L by Day 14 1 With methotrexate regimen, β-hCG falls to <26 IU/L by mean of 32 days 2 Honkanen et al, Hum. Reprod (9): Walker, et al. Contraception Creinin, et al. Contraception 1994

Using hCG measurements with medical abortion hCG measurement should fall to at least 20% of pre-abortion level by follow-up visit if abortion complete 1-3 Protocol using serial hCG measurements demonstrated effective and feasible in series from US clinic (n=151) 4 63% had pre-treatment ultrasound All who did not receive post-abortion ultrasound aborted successfully Only 4 of 91 had >20% decline in hCG at Day 7 1.Fiala, et al. Eur J Gyn Rep Biol Schaff, et al. Arch Fam Med Creinin. AJOG Clark et al. Contraception 2007

Urine pregnancy testing after medical abortion One study using a urine test sensitive to 2000 IU/L found it to have a high false-positive rate (PPV 1%) 1 Recently completed study suggests that a clinic- based low-sensitivity urine test can be used as a screening test for ongoing pregnancy 2 A low-sensitivity pregnancy test was recently validated that could be used at home 3 More research needed 1.Godfrey et al. Contraception Bracken et al. NAF presentation Grossman et al. Contraception 2007

Advanced practice clinicians and medical abortion Because medical abortion is not invasive procedure, it can be performed by a practitioner with minimal training as long as clinical back-up or referral is available In about 15 US states, APCs are allowed to provide medical abortion Innovative provision models involving technologies such as telemedicine may improve access and extend reach of physicians in settings where legislation limits APC provision

Mifepristone approval

Misoprostol approval

Estimated reduction in global abortion-related mortality with misoprostol -17% Harper, Blanchard, Grossman, Henderson & Darney, IJGO 2007 Current20%80%60%40% Percent of unsafe abortions initiated with misoprostol -34%-51%-68%

Improving access to medical abortion: next steps Implement proven strategies Home use of misoprostol Ultrasound as needed to assess gestational age Serial serum hCG tests with ultrasound as needed Non-physician provision where feasible More research needed Women’s self-assessment of completion Low sensitive urine pregnancy test (or serial urine tests) to screen for ongoing pregnancy in clinic or home

Second trimester abortion

Second trimester abortion procedures Approximately 10-15% 1,2 of abortions occur in second trimester, although as high as 25% in some countries 3 D&E most commonly performed procedure in US (98%) 1 and UK (76%) 2 Medical induction used almost exclusively in Finland, Sweden 4 and most of South Africa 3 Little research has directly compared methods 3.Rep. of South Africa Dept of Health Statistics, Stakes, CDC, Government Statistical Service, 2008

Comparing complications between medical and surgical abortion Autry, et al., AJOG 2002

RCT comparing D&E to medical induction with mifepristone- misoprostol USA: after 1 year, only 18 women recruited Women randomized to medical induction Reported significantly more pain (p=0.03) Experienced more complications (RR 6.0, 95% CI 0.9−40.3) Retained tissue requiring instrumental removal, fever, delivering fetus showing signs of life Reported more symptoms such as nausea, vomiting, dizziness and headache (p>0.05) Grimes, et al., BJOG 2004

Comparison of complications Retained POC Hemor- rhage Trans- fusion Perf/ uterine rupture Infec- tion Cerv lac D&E Mifepristone− misoprostol Country United States Viet NamCanada United States Scotland Year of study 1972− − − − − −2001 Weeks of pregnancy Number of cases 11,7471, ,2181,002 Uterine perforation 0.4%00.5%0.2% 0 Uterine rupture % Haemorrhage requiring transfusion 0.2%0.6%0.2% 0.09%0.7% Incomplete abortion 0.3%1%00.4%0.05%8% Cervical laceration with repair 1%00.2%00.1%0 Mild infection 0.8% 4.1% c 02%0.09%2.6% Severe infection 0.06%00.4%0.05%0 Grossman, Blanchard, Blumenthal. Reproductive Health Matters (in press)

Acceptability of 2 nd trimester abortion methods Little research has focused on women’s perspectives Slow recruitment in US RCT because minority of eligible women agreed to be randomised, and 93% of those who declined stated preference for D&E 1 Ongoing study in South Africa suggests women undergoing medical induction are less satisfied than those undergoing D&E 1. Grimes, et al., BJOG 2004

D&EMedical induction OutpatientInpatient (requires more hospital beds) More physician trainingMore dependent on nursing care Need case volume to maintain skills Less dependent on volume May be more emotionally difficult for provider May be more emotionally difficult for woman Need back-up for rare complications Need back-up for approximately 10-20% requiring D&C Comparing D&E and medical induction

Outstanding questions Research suggests that complications are less frequent with D&E, and where trained providers are available, is the preferred method Data also suggest that many women prefer D&E A larger RCT is needed that directly compares the two methods More information is needed on women’s and providers’ preferences for 2 nd trimester abortion methods

Conclusions Although we can expect small advances in abortion techniques, new research can lead to improvements in service delivery by making abortion More accessible More acceptable Research that takes into account women’s and providers’ perspectives is particularly useful when looking to put new findings into practice

Thank you!