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
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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 (?)

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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
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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

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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)

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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
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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
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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
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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
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Future miscarriage risk

• Increased risk of miscarriage in future pregnancy
• 20 after 1 SAb
• 28 after 2 SAbs
• 43 after 3 SAbs

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• Thank You!
• Questions?
• pragers_at_u.washington.edu
• O [phone]
• P [phone]