Miscarriage Management Training Initiative

1
Miscarriage Management Training Initiative
Management of Early Pregnancy Loss

• Sarah Prager, MD
• Department of Obstetrics and GynecologyUniversity
  of Washington

2
MM-TI Goals

• Move miscarriage management from the operating
  room to the outpatient setting
• Train primary care clinicians and support staff
  in miscarriage management

3
Purpose

• Expand patient access to prompt, appropriate care
• Improve patient safety
• Improve patient satisfaction
• Decrease costs

4
Challenges and Solutions

• Difficult to influence physician practice
  patterns
• Target training during residency
• Use a systems approach (include faculty,
  residents, key administrative personnel and
  support staff)

5
Clarification

• We are not talking about elective abortion
• We are teaching and promoting miscarriage
  management

6
MVA Safety and Efficacy Summary

• MVA is simple
• Easily incorporated into office setting
• Expanded pain management options
• Ultrasound as needed
• Patient-provider interaction

7
Management of Early Pregnancy Loss

• Objectives
• Review etiologies of EPL
• Review the three methods of EPL management
  Expectant Medical Surgical
• Discuss benefits of outpatient EPL management

8
NomenclatureManagement of Early Pregnancy Loss

• Early Pregnancy Loss (EPL)
• Spontaneous Abortion (SAb)
• Miscarriage

These all mean exactly the same thing!
9
BackgroundManagement of Early Pregnancy Loss

• Spontaneous Abortion (SAb) most common
  complication of early pregnancy 820
  clinically recognized pregnancies 1326 all
  pregnancies
• 800,000 SABs each year in the US
• 80 of SAbs occur in 1st trimester

10
Samantha

• 26 yo G2P1 presents to your office for a new ob
  visit. An ultrasound sows a CRL of 7mm but no
  cardiac activity.
• She wants to know why this happened.

11
Risk FactorsManagement of Early Pregnancy Loss

• Age
• Prior SAb
• Smoking
• Alcohol
• Caffeine (controversial)
• Maternal BMI lt18.5 or gt25
• Celiac disease (untreated)
• Cocaine
• NSAIDs
• High gravidity
• Fever
• Low folate levels

12
EtiologyManagement of Early Pregnancy Loss

• 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

13
Normal Implantation DevelopmentManagement of
Early Pregnancy Loss

• Implantation 5-7 days after fertilization
  Takes 72 hours Invasion of trophoblast into
  decidua
• Embryonic disc 1 wk post-implantation If
  no embryonic disc, trophoblast still grows, but
  no embryo (anembryonic pregnancy)
• Embryonic disc embryonic/fetal pole

14
U/S Dating in Normal PregnancyManagement of
Early Pregnancy Loss
Mean Sac Diameter(mm) 30 OR Crown-Rump
Length(mm) 42

• Gestational Age (days)

15
Clinical Presentation of EPLManagement of Early
Pregnancy Loss

• Bleeding
• Pain/cramping
• Falling or abnormally rising ßhCG
• Decreased symptoms of pregnancy
• No symptoms at all!

16
Ultrasound Findings of EPLManagement of Early
Pregnancy Loss

• Anembryonic Pregnancy No fetal pole with mean
  sac diam gt25 mm (transabdominal) OR gt18 mm
  (transvaginal) lt4 mm growth in 7 days (No
  yolk sac, with mean sac diameter gt10 mm)
• Embryonic Demise No cardiac activity with CRL
  5 mm

Mishell DR, Comprehensive Gynecology 2007
17
Samantha

• Samantha and her partner request information on
  all the treatment options. You confirm the rest
  of her history.
• PMH wisdom teeth removed
• Ob Hx term SVD without complication
• All NKDA

18
Management OptionsEarly Pregnancy Loss

• Do Nothing Expectant management
• Do Something Medical management
• Do Surgery Surgical management

Sotiriadis A, Obstet Gynecol 2005Nanda K,
Cochrane Database Syst Rev 2006
19
Do NothingExpectant Management

• Requirements for therapy lt13 weeks gestation
  Stable vital signs No evidence infection
• What to expect Most expel within 1st 2 wks
  after diagnosis Prolonged follow-up may be
  needed Acceptable and safe to wait up to 4 wks
  post-diagnosis

20
OutcomesDo Nothing Expectant Management

• Overall success rate 81
• Success rates vary by type of miscarriage(helpful
  to tailor counseling) Incomplete/inevitable
  abortion 91 Embryonic demise 76 Anembryonic
  pregnancies 66

Luise C, Ultrasound Obstet Gynecol 2002
21
What is Success?Definitions Used in Studies

• 15 mm endometrial thickness (ET)3 days to 6
  weeks after diagnosis
• No vaginal bleeding
• Negative urine hCG

22
Problems with ET Cut-off

• No clear rationale for this cut-off
• Study of 80 women with successful medical
  abortion Mean ET at 24 hours 17.5 mm (7.629
  mm) At one week 15 with ET gt16 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 2001Reynolds A, Eur. J
Obstet Gynecol Reproduct. Biol 2005
23
When to intervenefor Expectant Management?

• Continued gestational sac
• Clinical symptoms
• Patient preference
• Time (?)
• Vaginal bleeding and positive UPT are possible
  for 24 weeks Poor measures of success

24
Samantha

• Samantha appears anxious about waiting and shares
  with you that she really needs to do something.

25
Do SomethingMedical Management

• Misoprostol
• Misoprostol Mifepristone
• Misoprostol Methotrexate

No medical regimen for managementof EPL is FDA
approved
26
Medical ManagementRequirement for Therapy

• lt13 weeks gestation
• Stable vital signs
• No evidence of infection
• No allergies to medications used
• Adequate counseling and patient acceptance
  of side effects

27
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/treatmen
  t of postpartum hemorrhage
• Can be administered by oral, buccal, sublingual,
  vaginal and rectal routes

Chen B, Clin Obstet Gynecol 2007
28
Why Misoprostol?

• Do something while still avoiding surgery
• Cost effective
• Stable at room temperature
• Readily available

29
Misoprostol Dosing RegimensEmbryonic Demise
Anembryonic Pregnancy

• Study Dose Efficacy
• 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 87.5 q 3 hrs x 3
  doses (SL had more side effects diarrhea, 70
  vs 27.5)
• Phupong 600 mcg po x 1 vs. 82 vs 92 (NS) q 4
  hrs x 2 doses (Repeat dosing increased
  diarrhea, 40 vs 18)
• Gilles 800 mcg pv saline- 83 vs 87
  (NS) moistened vs. dry

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
30
Misoprostol DosingIncomplete Abortion

• Study N Dose vs. Results
• Weeks et al, 05 317 600 oral d1,2 MVA 96.3 in
  12 wks
• Moodliar et al, 05 94 600 vag DC 91.5
  in 1 wk
• Zhang et al, 05 652 800 vag d1,3 DC 84 in 8
  days
• Coughlin et al, 04 131 400 oral x 2 78 1
  dose/ 92.4 ultimately
• Ngai et al, 01 30 400 vag d1,3,5 observe 83 by
  day 15
• Pang et al, 01 103 800 oral 65 in 24
  hrs 95 800 vaginal 61 in 24 hrs
• Demetroulis, 01 40 800 vaginal DC 93 in
  8-10 hrs
• Chung et al, 99 321 400 oral q4h DC 50
• Chung et al, 97 225 400 oral tid DC 50
• Chung et al, 95 141 400 oral q4h 50
  

also included missed abortions
31
Pooled OutcomesMedical Management

• Success Rates
• Placebo 1660
• Single dose misoprostol 2588 400800 mcg
• Repeat dose x 1 if incomplete 8088 at 24
  hours

• 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
32
Serum Level ComparisonMisoprostol by Route of
Administration
33
Uterine Tone Over 5 HoursMisoprostol by Route of
Administration
Rectal p .006
Meckstroth, not yet published
34
Uterine Activity Over 5 HoursMisoprostol by
Route of Administration
Meckstroth, not yet published
35
Side Effects and ComplicationsMisoprostol vs.
Placebo

• N/V, Diarrhea No difference
• Pain More pain and analgesics in one study
• Hemoglobin Conc No difference
• Infection 0 for placebo vs. .24.7 for
  misoprostol
• No benefit with repeat dosing within 34 hours
• Improved outcome with 1 repeat dose at 24
  hours, 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
36
Misoprostol Bottom LineMedical Management

• 800 mcg pv (or buccal)
• Repeat x 1 at 1224 hours, if incomplete
  Occasionally repeat more than once
• Measure success as with expectant management
• Intervene with surgical management if Continued
  gestational sac Clinical symptoms Patient
  preference Time (?)

37
Mifepristone and Misoprostol Medical Management

• Mifepristone Progestin antagonist that binds
  to progestin receptor Used with elective
  medical abortion to destabilize implantation
  site Current evidence-based regimen 200 mg
  mifepristone 800 mcg misoprostol
• Success rates for mifepristone misoprostol in
  EPL 5284 (observational trials,
  non-standard dose) 9093 (standard dose)
• No direct comparison between 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
38
Methotrexate and Misoprostol Medical Management

• Methotrexate Folic acid antagonist
  Cytotoxic to 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
39
Samantha

• Samantha opts to try misoprostol and returns to
  the office 7 days later for follow up. How do you
  assess whether or not her treatment is complete?

40
Samantha

• At her follow-up appointment, Samantha says that
  she had a period of heavy bleeding and is now
  spotting. Her cramping has resolved. She has
  noted a marked decrease in breast tenderness and
  nausea.
• Her ultrasound shows a uniform endometrial stripe
  measuring 30mm in its greatest width.
• Is she complete?

41
Samantha
42
Rebecca

• 32 yo G3P2 at 8 weeks by LMP was diagnosed with a
  fetal demise on her ultrasound and presents to
  your office after 2 weeks of expectant management
  stating that she wants to be done. She declines
  medical management and requests a DC.

43
Rebecca

• What questions would you ask to see if she was a
  good candidate?

44
Surgical ManagementEarly Pregnancy Loss

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

45
Surgical ManagementEarly Pregnancy Loss
BENEFITS
RISKS

• Convenient timing
• Observed therapy
• High success rates (almost 100)

• Infection (1/200)
• Perforation (1/2000)
• Cervical trauma
• Uterine synechiae(very rare)

46
Infection ProphylaxisSurgical Management

• Periabortal antibiotics ? infection risk 42
• No strong evidence on what to use
• Doxycycline (214 doses)
• Metronidazole Bacterial vaginosis
  Trichomoniasis Suspicious discharge

Sawaya GF, Obstet Gynecol 1996 Prieto JA, Obstet
Gynecol 1995
47
Comparison of Outcome by MethodManagement of
Early Pregnancy Loss

• Factor Comparison of Methods
• Success rate Surgical gt Medical Medical
  Expectant
• Resolution Surgical gt Medical gt Expectant
  within 48 hrs
• Infection risk Expectant Medical
  Surgical.23

Number differed by highly variable success rates
reported for expectant management
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
48
Patient SatisfactionManagement of Early
Pregnancy Loss

• Meta-analysis shows studies report high
  satisfaction with medical management
• Caution Few studies looked at satisfaction
• Satisfaction depended on choice If women
  randomized 55-74 satisfied If women chose
  84-88 satisfied Both were independent of
  method
• Unsuccessful expectant resulting in surgical
  showed most profound anxiety and depression

Sotiriadis 2005
49
Zhang, NEJM 2005
50
Cost AnalysisManagement of Early Pregnancy Loss

• Medical management most cost effective 2
  studies Misoprostol vs. expectant vs. surgical
  1000 vs. 1172 vs. 2007
• Expectant management most cost effective MIST
  trial Expectant vs. medical vs. surgical
  1086 vs. 1410 vs. 1585

Doyle NM, Obstet. Gynecol 2004 You JH, Hum
Reprod 2005 Petrou S, BJOG 2006
51
Rebecca

• Refer to OR?
• Manage with MVA?
• The clinic schedule is packeddoes this have to
  be done today?

52
Where to perform?Surgical Management

• Women with SAb in Canada 92.5 presenting to
  hospital have DC 51 presenting to family
  physician have DC
• Manual vacuum aspiration (MVA) in outpatient
  setting can ? hospital costs by 41

Weibe E, Fam Med 1998 Finer LB, Perspect Sexu
Reproduct Health 2003 Blumenthal PD, Int J
Gynaecol Obstet 1994
53
AdvantagesMoving Rx from OR to Outpatient Setting

• Avoid repeated exams that often occur in
  hospital
• Simplify scheduling and reduce wait time
  Average OR waiting time in UK-based study 14
  hours, with 42 of women not satisfied
• Save resources
• Avoid cumbersome OR protocols Prolonged NPO
  requirements and discharge criteria

Demetroulis 2001 Lee and Slade 1996
54
AdvantagesMoving Rx from OR to Outpatient Setting

• Office affords more treatment options Vacuum
  aspiration or misoprostol Pain management
  choices
• Improved patient autonomy and privacy
• Convenience
• Personalized care

Lee and Slade 1996
55
Moving Incomplete Abortion to Outpatient
SettingJohns Hopkins Study

• Methods
• N 35, incomplete 1st-trimester abortion
• Treatment comparison

Manual Conventional vacuum care aspiration
(suction (MVA) curretage) LD OR
Procedure Setting
vs.
Blumenthal and Remsburg 1994
56
Moving Incomplete Abortion to Outpatient
SettingJohns Hopkins Study

• Results
• ? Anesthesia requirements
• ? Overall hospital stay, from 19 6 hours
• ? Patient waiting time by 52
• ? Procedure time, from 33 19 minutes
• ? Costs per case 1,404 in OR 827 in
  LD 200 or less in ER

Blumenthal 1994
57
Use Outpatient Management Cautiously in Women
with

• Uterine anomalies
• Coagulation problems
• Active pelvic infection
• Extreme anxiety
• Any condition causing patient to be medically
  unstable

58
What Is a Manual Vacuum Aspirator?

• Locking valve
• Portable and reusable
• Equivalent to electric pump
• Efficacy same as electric vacuum (9899)
• Semi-flexible plastic cannula

Creinin MD, et al. Obstet Gynecol Surv. 2001.
Goldberg AB, et al. Obstet Gynecol. 2004. Hemlin
J, et al. Acta Obstet Gynecol Scand. 2001.
59
ComparisonEVA to MVA
EVA MVA
Vacuum Electric pump Manual aspirator
Noise Variable Quiet
Portable Not easily Yes
Cannula 416 mm 412 mm
Capacity 3501,200 cc 60 cc
Suction Constant Decreases to 80 (50 mL) as aspirator fills
Dean G, et al. Contraception. 2003.
60
Clinical Indications for MVA

• Uterine evacuation in the first trimester
• Induced abortion
• Spontaneous abortion
• Incomplete medication abortion
• Uterine sampling
• Post-abortal hematometra
• Hemorrhage

Creinin MD, et al. Obstet Gynecol Surv. 2001.
Edwards J, Creinin MD. Curr Probl Obstet Gynecol
Fertil.1997. Castleman LD et al. Contraception.
2006 MVA Label. Ipas. 2007.
61
MVA Instruments
62
Steps for Performing MVA
A step-by-step poster is available from the
manufacturer to guide clinicians through the
procedure is in your packet - Performing
Manual Vacuum Aspiration (MVA). . .
63
Complications with MVA

• Very rare
• Same as EVA
• May include Incomplete evacuation Uterine
  or cervical injury Infection Hemorrhage
  Vagal reaction

MVA Label. Ipas. 2004.
64
MVA vs. EVA Complication Rates

• Methods
• Vacuum aspiration for abortion up to 10 wks LMP
• Retrospective cohort analysis
• Choice of method (MVA vs. EVA) up to physician
• n 1,002 for MVA n 724 for EVA
• Charts reviewed for complications

more
Goldberg AB, et al. Obstet Gynecol. 2004.
65
MVA vs. EVA Complication Rates (continued)
more
Elective not spontaneous studies
Goldberg AB, et al. Obstet Gynecol. 2004.
66
MVA vs. EVA Complication Rates (continued)
Goldberg AB, et al. Obstet Gynecol. 2004.
67
MVA and POC Study

• In group overall
• n 1,726, up to 10 weeks LMP
• Complication rates between MVA and EVA
• 37 patients at lt 6 weeks gestation
• In 35 of 37, provider chose MVA
• No re-aspirations needed in patients lt 6 weeks

more
Goldberg AB, et al. Obstet Gynecol. 2004.
68
MVA and POC Study (continued)
Significantly more re-aspirations for inability
to accurately identify the pregnancy occurred in
electric group.
Goldberg AB et al. Obstet Gynecol, 2004
Goldberg AB, et al. Obstet Gynecol. 2004.
69
Early Abortion with MVA Study

• Methods
• 2,399 MVA procedures, lt 6 weeks LMP
• Meticulous inspection of POC immediately after
  MVA
• Results
• 99.2 effective in terminating pregnancy
• 6 repeat aspirations (0.25)
• 14 ectopic pregnancies (0.6) diagnosed and
  treated

Edwards J, Creinin MD. Curr Probl OIbstet Gynecol
Fertil. 1997.
70
Products of Conception (POC)

• Procedure is complete when POC are identified

Edwards J, et al. Am J Obstet Gynecol.
1997. MacIsaac L, et al. Am J Obstet Gynecol.
2000.
71
Patient Satisfaction

• Both EVA and MVA groups were highly satisfied
• No differences in
• Pain
• Anxiety
• Bleeding
• Acceptability
• Satisfaction
• More EVA patients were bothered by noise

Bird ST, et al. Contraception. 2003. Dean G, et
al. Contraception. 2003. Edelman A, et al. Am J
Obstet Gynecol. 2001.
72
MVA Safety and Efficacy Summary

• MVA is simple
• Easily incorporated into office setting
• Training/Practice Issues
• Expanding pain management options
• Ultrasound as needed
• No sharp curettage
• Patient-provider interaction
• Instrument processing for multiple use (new
  guidelines)

73
Rebecca

• Rebecca is wanting to have an office procedure,
  but she is concerned about the pain.
• What can you tell her about pain management in
  the office?

74
MVA and Pain

• Pain is made worse by
• Fearfulness
• Anxiety
• Depression

Belanger E, et al. Pain. 1989. Smith GM, et al.
Am J Obstet Gynecol. 1979. Hansen GR, Streltzer
J. Emerg Med Clin N Am. 2005.
75
Effective Pain Management

• Respectful, informed, and supportive staff
• Warm, friendly environment
• Gentle operative technique
• Womens involvement
• Effective pain medications

76
Pain Management Techniques

• With addition of
• Focused breathing 76
• Visualization 31
• Localized massage 14

General or nitrous
Local IV
Local
Lichtengerg ES, et al. Contraception. 2001. Good
M, et al. Pain Manag Nurs. 2002.
77
Efficacy of Ancillary Anesthesia

• Importance of psychological preparation and
  support
• Music as analgesia for abortion patients
  receiving paracervical block
• 85 who wore headphones rated pain as 0,
  compared with 52 of controls
• Verbicaine (Vocal Local)/Distraction Therapy

Shapiro AG, Cohen H. Contraception. 1975.
Stubblefield PG.Suppl Int J Gynecol Obstet. 1989.
78
Paracervical Block
Deep Injection
Regular Injection
Castleman L, Mann C. 2002. Maltzer DS, et al.
1999.
79
Sharp Curettage and Pain

• Often requires increased dilatation
• Often painful
• More difficult to reduce anesthesia

Forna F, Gulmezoglu AM. Cochrane Library. 2002.
80
Sharp Curettage and MVA

• Generally not indicated
• Not routinely recommended after MVA

more
WHO. 2003
81
Ultrasound and MVA

• Not required for MVA
• Used by some providers routinely
• Use contingent on provider preference and
  experience

Word Health Organization. 2003.
82
Counseling for MVA

• Effective counseling occurs before, during, and
  after the procedure
• Prepare women for procedure-related effects
• Address womens concerns about future desired
  pregnancies

more
Breitbart V, Repass DC. J Am Med Womens Assoc.
2000. Hogue CJ, et al. Epidemiol Rev. 1982
Steward FH, et al. 2004. Hyman AG, Castleman L.
2005
83
Rebecca

• Rebecca is scheduled for a uterine aspiration
  with MVA procedure during the next procedure
  clinic.
• The procedure is uncomplicated and her questions
  include
• Can I get pregnant right away?
• Am I at risk for another miscarriage?

84
Future Miscarriage Risk
43
28
20
85
Counseling for MVA (continued)
Patient satisfaction with care
Quality of counseling
Picker Institute. 1999.
86
Postmiscarriage CareManagement of Early
Pregnancy Loss

• 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 ßhCG values after 24 weeks
• Appropriate grief counseling

Goldstein R, Am J Obstet. Gynecol 2002 Wyss P, J
Perinat Med 1994 Grimes D, Cochrane Database
Syst Rev 2000
87
When Women Should Contact Clinician

• Heavy bleeding with dizziness, lightheadedness
• Worsening pain not relieved with medication
• Flu-like symptoms lasting gt24 hours
• Fever or chills
• Syncope
• Any questions

88
For more information on EPL

• Association of Reproductive Health Professionals
  (ARHP) archived webinar Options for Early
  Pregnancy Loss MVA and Medication Management
• www.arhp.org/healthcareproviders/cme/webcme/index
  .cfm
• Ipas WomanCare Kit for Miscarriage Management
• www.ipaswomancare.com

89
Thanks!

• Questions
• Papaya Demonstration to Follow
• pragers_at_u.washington.edu

?