Download Treatment Options for First Trimester Loss

Management of Early
Pregnancy Loss (EPL)
Sarah Prager, MD, MAS
Department of ob/gyn
University of Washington
Outline
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Background information
Expectant management
Medical management
Methotrexate
 Misoprostol (+/- mifepristone)
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Surgical management
Background
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Miscarriage is the most common complication
of early pregnancy.
8-20% clinically recognized pregnancies
 13-26% all pregnancies
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80% of miscarriages occur in the first trimester
Risk factors
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Age
Prior SAb
Smoking
Alcohol
Caffeine (high intake)
Maternal weight
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BMI < 18.5 or > 25
Celiac disease (untreated)
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Alcohol
Cocaine
NSAIDs
High gravidity
Fever
Low folate levels
Etiology
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33% anembryonic
50% due to chromosomal abnormalities
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Host factors
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Autosomal trisomies 52%
Monosomy X 19%
Polyploidies 22%
Other 7%
Structural abnormalities
Maternal infection/endocrinopathy/coagulopathy
Unexplained
Clinical presentation
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Bleeding
Pain/cramping
Falling or abnormally rising BhCG
Ultrasound findings:
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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
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Expectant management
Medical management
Surgical management
Sotiriadis A, Obstet Gynecol 2005; Nanda K, Cochrane Database Syst Rev 2006
Expectant management
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Requirements for therapy:
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Less than 13 weeks gestation
Stable vital signs
No evidence of infection
What to expect:
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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
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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
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Luise C, Ultrasound Obstet Gynecol 2002
What is success?
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≤15 mm endometrial thickness (ET)
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3 days to 6 weeks after diagnosis
No vaginal bleeding
Negative urine hCG
Problems with ET measurements
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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
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Study of medical management after miscarriage:
86% success rate if use absence of gestational sac
 51% success rate if use ET ≤15 mm
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Harwood B, Contraception 2001; Reynolds A, Eur. J Obstet Gynecol Reproduct. Biol 2005
When to intervene
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Vaginal bleeding and pos. UPT can continue for
2-4 weeks, so not good measures of success
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Continued gestational sac
Clinical symptoms
Patient preference
Time (?)
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Medical management
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Misoprostol
Mifepristone plus Misoprostol
Methotrexate plus Misoprostol
There is no medical regimen for management of
early pregnancy loss that is FDA approved.
Medical management
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Requirements for therapy:
Less than 13 weeks gestation
 Stable vital signs
 No evidence of infection
 *No allergies to medications used
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Misoprostol
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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
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Can be administered by oral, buccal, sublingual,
vaginal and rectal routes
Chen B, Clin Obstet Gynecol 2007
Why misoprostol?
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Do something while still avoiding surgery
Cost effective
Few side effects (especially with vaginal)
Stable at room temperature
Readily available
Dosing Regimens
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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%
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Phupong: 600 mcg po x 1 vs. q 4 hrs x 2 doses: 82% vs
92% (NS)
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SL had more side effects (diarrhea 70% vs 27.5%)
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
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Single dose 400 – 800 mcg misoprostol
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Repeat dose x 1 if incomplete at 24 hours
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80 – 88% success rate
Placebo success rates:
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25 – 88% success rate
16 – 60%
Success rate depends on type of miscarriage:
100% with incomplete abortion
 87% for all others
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Wood SL, Obstet Gynecol 2002; Bagratee JS, Hum Reproduct 2004; Blohm F, BJOG: Int J Obstet Gynecol 2005
Side effects and complications
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Misoprostol vs. placebo:
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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
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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 (?)
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Mifepristone and misoprostol
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Mifepristone: progestin antagonist that binds to
progestin receptor
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Success rates for mifepristone and misoprostol in EPL:
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Used with elective medical abortion to “destabilize” the
implantation site
Current evidence-based regimen: 200 mg Mifepristone and
800 mcg misoprostol
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
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Methotrexate: folic acid antagonist
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Used in medical management for ectopic
pregnancy
Introduced in 1993 in combination with
misoprostol to treat elective abortion medically.
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Cytotoxic to the trophoblast
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
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Suction dilation and curettage (D&C)
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Who should have surgical management?
Unstable
 Significant medical morbidity
 Infected
 Very heavy bleeding
 Anyone who wants immediate therapy
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Surgical Management
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Benefits:
Convenient timing
 Observed therapy
 High success rates: (93 – 100%)
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Risks:
Infection (1/200)
 Perforation (1/2000)
 Cervical trauma
 Uterine synechiae (very rare)
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Infection prophylaxis
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Periabortal antibiotics reduce infection risk 42%
No strong evidence on what to use
Doxycycline
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2 -14 doses
Metronidazole
Bacterial vaginosis
 Trichomoniasis
 Suspicious discharge
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Sawaya GF, Obstet Gynecol 1996; Prieto JA, Obstet Gynecol 1995
Where to perform?
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Canada:
92.5% women with SAb presenting to hospital have
D&C
 51% women with SAb presenting to family physician
have D&C
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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
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Risk of incomplete abortion:
Expectant > surgical
 Expectant ≥ medical
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Resolution within 48 hours:
surgical>medical>expectant management
Risk of Infection: 2-3%
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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
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Medical management most cost effective
2 studies
 Misoprostol vs. expectant vs. surgical:
 1000 vs. 1172 vs. 2007 dollars
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Expectant management most cost effective
MIST trial
 Expectant vs. medical vs. surgical:
 1086 vs. 1410 vs. 1585 pounds
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Doyle NM, Obstet. Gynecol 2004; You JH, Hum Reprod 2005; Petrou S, BJOG 2006
Postmiscarriage care
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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
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Increased risk of miscarriage in future pregnancy
20% after 1 miscarriage.
 28% after 2 miscarriages
 43% after 3+ miscarriages
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Thank You!
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Questions?
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[email protected]
O: (206) 731-6292
P: (206) 540-6077
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