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Management of Early Pregnancy Loss (EPL). Sarah Prager, MD, MAS Department of ob/gyn University of Washington. Outline. Background information Expectant management Medical management Methotrexate Misoprostol (+/- mifepristone) Surgical management. Background.
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Management of Early Pregnancy Loss (EPL) Sarah Prager, MD, MAS Department of ob/gyn University of Washington
Outline • Background information • Expectant management • Medical management • Methotrexate • Misoprostol (+/- mifepristone) • Surgical management
Background • Miscarriage is the most common complication of early pregnancy. • 8-20% clinically recognized pregnancies • 13-26% all pregnancies • 80% of miscarriages occur in the first trimester
Age Prior SAb Smoking Alcohol Caffeine (high intake) Maternal weight BMI < 18.5 or > 25 Celiac disease (untreated) Alcohol Cocaine NSAIDs High gravidity Fever Low folate levels Risk factors
Etiology • 33% anembryonic • 50% due to chromosomal abnormalities • Autosomal trisomies 52% • Monosomy X 19% • Polyploidies 22% • Other 7% • Host factors • Structural abnormalities • Maternal infection/endocrinopathy/coagulopathy • Unexplained
Clinical presentation • Bleeding • Pain/cramping • Falling or abnormally rising BhCG • Ultrasound findings: • Absent fetal cardiac activity with CRL > 5 mm • Absent fetal pole if mean sac diameter > 25 mm (TA) or 18 mm (TV) • No/abnormal yolk sac (95% PPV) • No/abnormal fetal heart rate • Small sac size • Subchorionic hematoma
Management options • Expectant management • Medical management • Surgical management Sotiriadis A, Obstet Gynecol 2005; Nanda K, Cochrane Database Syst Rev 2006
Expectant management • Requirements for therapy: • Less than 13 weeks gestation • Stable vital signs • No evidence of infection • What to expect: • Most expulsions occur in the first 2 weeks after diagnosis • Prolonged follow-up may be needed • Acceptable and safe to wait up to 4 weeks post-diagnosis
Outcomes • Overall success rate of 81% • Success rates vary by type of miscarriage • 91% for incomplete/inevitable abortion • 76% with missed abortion • 66% with anembryonic pregnancies Luise C, Ultrasound Obstet Gynecol 2002
What is success? • ≤15 mm endometrial thickness (ET) • 3 days to 6 weeks after diagnosis • No vaginal bleeding • Negative urine hCG
Problems with ET measurements • No clear rationale for this cut off • In a study of 80 women with successful medical abortion: • Mean ET at 24 hours 17.5 mm (7.6 – 29 mm) • At one week: 15% with ET > 16 mm • Study of medical management after miscarriage: • 86% success rate if use absence of gestational sac • 51% success rate if use ET ≤15 mm Harwood B, Contraception 2001; Reynolds A, Eur. J Obstet Gynecol Reproduct. Biol 2005
When to intervene • Vaginal bleeding and pos. UPT can continue for 2-4 weeks, so not good measures of success • Continued gestational sac • Clinical symptoms • Patient preference • Time (?)
Medical management • Misoprostol • Mifepristone plus Misoprostol • Methotrexate plus Misoprostol • There is no medical regimen for management of early pregnancy loss that is FDA approved.
Medical management • Requirements for therapy: • Less than 13 weeks gestation • Stable vital signs • No evidence of infection • *No allergies to medications used
Misoprostol • Prostoglandin E1 analogue • FDA approved for prevention of gastric ulcers • Used off-label for many ob/gyn indications • Labor induction • Cervical ripening • Medical abortion (with mifepristone) • Prevention/treatment of post-partum hemorrhage • Can be administered by oral, buccal, sublingual, vaginal and rectal routes Chen B, Clin Obstet Gynecol 2007
Why misoprostol? • Do something while still avoiding surgery • Cost effective • Few side effects (especially with vaginal) • Stable at room temperature • Readily available
Dosing Regimens • Creinin: 400 mcg po vs 800 pv 25% vs. 88% • Ngoc: 800 mcg po vs 800 pv: 89% vs. 93% (NS) • Tang: 600 mcg SL vs 600 pv q 3 hrs x 3 doses: 87.5% • SL had more side effects (diarrhea 70% vs 27.5%) • Phupong: 600 mcg po x 1 vs. q 4 hrs x 2 doses: 82% vs 92% (NS) • Repeat dosing increased diarrhea (40% vs 18%) • Gilles: 800 mcg pv saline-moistened vs. dry: 83% vs 87% (NS) Creinin MD, Obstet Gynecol 1997; Ngoc NTN, Int.J Gynaecol Obstet 2004; Tang OS, Hum Reproduct 2003; Phupong V, Contraception 2005; Gilles JM, Am J Obstet Gynecol 2004
Outcomes • Single dose 400 – 800 mcg misoprostol • 25 – 88% success rate • Repeat dose x 1 if incomplete at 24 hours • 80 – 88% success rate • Placebo success rates: • 16 – 60% • Success rate depends on type of miscarriage: • 100% with incomplete abortion • 87% for all others Wood SL, Obstet Gynecol 2002; Bagratee JS, Hum Reproduct 2004; Blohm F, BJOG: Int J Obstet Gynecol 2005
Side effects and complications • Misoprostol vs. placebo: • Nausea, vomiting and diarrhea: no difference • Pain: more pain and analgesics in one study • Hemoglobin concentration: no difference • Infection: 0 for placebo vs. 2 - 4.7% for misoprostol • No benefit with repeat dosing within 3-4 hrs. • Improved outcome with one repeat dose at 24 hrs. if incomplete • 90% found medical management acceptable and would elect same treatment again Wood SL, Obstet Gynecol 2002; Bagratee JS, Hum Reproduct 2004; Blohm F, BJOG: Int J Obstet Gynecol 2005
Misoprostol bottom line • 800 mcg. per vagina (or buccal) • Repeat x 1 at 12-24 hours if incomplete • Measure success as with expectant management • Intervene with surgical management if: • Continued gestational sac • Clinical symptoms • Patient preference • Time (?)
Mifepristone and misoprostol • Mifepristone: progestin antagonist that binds to progestin receptor • Used with elective medical abortion to “destabilize” the implantation site • Current evidence-based regimen: 200 mg Mifepristone and 800 mcg misoprostol • Success rates for mifepristone and misoprostol in EPL: • 52 – 84% (observational trials using non-standard dosing) • 90 – 93% ( with standard dosing) • No direct comparison b/w misoprostol alone and mifepristone/misoprostol with standard dosing • Mifepristone may help, data still pending Gronlund A, Acta Obstet Gynaecol 1998; Nielsen S, Br J Obstet Gynaecol 1997; Niinimaki M, Fertility Sterility 2006; Schreiber CA, Contraception 2006
Methotrexate and misoprostol • Methotrexate: folic acid antagonist • Cytotoxic to the trophoblast • Used in medical management for ectopic pregnancy • Introduced in 1993 in combination with misoprostol to treat elective abortion medically. • Success rates up to 98% (misoprostol administered 7 days after methotrexate) • No data for use in early pregnancy loss Creinin MD, Contraception 1993
Surgical management • Suction dilation and curettage (D&C) • Who should have surgical management? • Unstable • Significant medical morbidity • Infected • Very heavy bleeding • Anyone who wants immediate therapy
Surgical Management • Benefits: • Convenient timing • Observed therapy • High success rates: (93 – 100%) • Risks: • Infection (1/200) • Perforation (1/2000) • Cervical trauma • Uterine synechiae (very rare)
Infection prophylaxis • Periabortal antibiotics reduce infection risk 42% • No strong evidence on what to use • Doxycycline • 2 -14 doses • Metronidazole • Bacterial vaginosis • Trichomoniasis • Suspicious discharge Sawaya GF, Obstet Gynecol 1996; Prieto JA, Obstet Gynecol 1995
Where to perform? • Canada: • 92.5% women with SAb presenting to hospital have D&C • 51% women with SAb presenting to family physician have D&C • Manual vacuum aspiration (MVA) in outpatient setting can decrease hospital costs by 41% Weibe E, Fam Med 1998; Finer LB, Perspect Sexu Reproduct Health 2003; Blumenthal PD, Int J Gynaecol Obstet 1994
Outcome comparison • Risk of incomplete abortion: • Expectant > surgical • Expectant ≥ medical • Resolution within 48 hours: surgical>medical>expectant management • Risk of Infection: 2-3% • Expectant = Medical = Surgical Nanda K, Cochrane Database Syst Rev 2006; Nielsen S, Br J Obstet Gynaecol 1999; Shelly JM, Aust. NZ J Obstet Gynaecol 2005; Sotiriadis A, Obstet Gynecol 2005; Tinder J, (MIST) BMJ, 2006
Cost analysis • Medical management most cost effective • 2 studies • Misoprostol vs. expectant vs. surgical: • 1000 vs. 1172 vs. 2007 dollars • Expectant management most cost effective • MIST trial • Expectant vs. medical vs. surgical: • 1086 vs. 1410 vs. 1585 pounds Doyle NM, Obstet. Gynecol 2004; You JH, Hum Reprod 2005; Petrou S, BJOG 2006
Postmiscarriage care • Rhogam at time of diagnosis or surgery • Pelvic rest for 2 weeks • No evidence for delaying conception • Initiate contraception upon completion of procedure (even IUDs!) • Expect light-moderate bleeding for 2 weeks • Menses return after 6 weeks • Negative BhCG values after 2-4 weeks • Appropriate grief counseling Goldstein R, Am J Obstet. Gynecol 2002; Wyss P, J Perinat Med 1994; Grimes D, Cochrane Database Syst Rev 2000
Future miscarriage risk • Increased risk of miscarriage in future pregnancy • 20% after 1 miscarriage. • 28% after 2 miscarriages • 43% after 3+ miscarriages
Thank You! • Questions? • pragers@u.washington.edu • O: (206) 731-6292 • P: (206) 540-6077