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Management of Early Pregnancy Loss (EPL)

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Title: Management of Early Pregnancy Loss (EPL)


1
Management of Early Pregnancy Loss (EPL)
  • Sarah Prager, MD, MAS
  • Department of ob/gyn
  • University of Washington
  • September 29, 2008

2
Outline
  • Background information
  • Expectant management
  • Medical management
  • Methotrexate
  • Misoprostol (/- mifepristone)
  • Surgical management

3
Background
  • Spontaneous Abortion (SAb) is the most common
    complication of early pregnancy.
  • 8-20 clinically recognized pregnancies
  • 13-26 all pregnancies
  • 80 SAbs occur in the first trimester

4
Risk factors
  • Age
  • Prior SAb
  • Smoking
  • Alcohol
  • Caffeine (high intake)
  • Maternal weight
  • BMI lt 18.5 or gt 25
  • Celiac disease (untreated)
  • Alcohol
  • Cocaine
  • NSAIDs
  • High gravidity
  • Fever
  • Low folate levels

5
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

6
Clinical presentation
  • Bleeding
  • Pain/cramping
  • Falling or abnormally rising BhCG
  • Ultrasound findings
  • Absent fetal cardiac activity with CRL gt 5 mm
  • Absent fetal pole if mean sac diameter gt 25 mm
    (TA) or 18 mm (TV)
  • No/abnormal yolk sac (95 PPV)
  • No/abnormal fetal heart rate
  • Small sac size
  • Subchorionic hematoma

7
Management options
  • Expectant management
  • Medical management
  • Surgical management

Sotiriadis A, Obstet Gynecol 2005 Nanda K,
Cochrane Database Syst Rev 2006
8
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

9
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
10
What is success?
  • 15 mm endometrial thickness (ET)
  • 3 days to 6 weeks after diagnosis
  • No vaginal bleeding
  • Negative urine hCG

11
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 gt 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
12
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 (?)

13
Medical management
  • Misoprostol
  • Mifepristone plus Misoprostol
  • Methotrexate plus Misoprostol
  • There is no medical regimen for management of
    early pregnancy loss that is FDA approved.

14
Medical management
  • Requirements for therapy
  • Less than 13 weeks gestation
  • Stable vital signs
  • No evidence of infection
  • No allergies to medications used

15
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
16
Why misoprostol?
  • Do something while still avoiding surgery
  • Cost effective
  • Few side effects (especially with vaginal)
  • Stable at room temperature
  • Readily available

17
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
18
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
19
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
20
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 (?)

21
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
22
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
23
Surgical management
  • Suction dilation and curettage (DC)
  • Who should have surgical management?
  • Unstable
  • Significant medical morbidity
  • Infected
  • Very heavy bleeding
  • Anyone who wants immediate therapy

24
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)

25
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
26
Where to perform?
  • Canada
  • 92.5 women with SAb presenting to hospital have
    DC
  • 51 women with SAb presenting to family physician
    have DC
  • 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
27
Outcome comparison
  • Risk of incomplete abortion
  • Expectant gt surgical
  • Expectant medical
  • Resolution within 48 hours surgicalgtmedicalgtexpec
    tant 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
28
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
29
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
30
Future miscarriage risk
  • Increased risk of miscarriage in future pregnancy
  • 20 after 1 SAb
  • 28 after 2 SAbs
  • 43 after 3 SAbs

31
  • Thank You!
  • Questions?
  • pragers_at_u.washington.edu
  • O (206) 731-6292
  • P (206) 540-6077
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