Why Am I Bleeding?

Why am I Bleeding?
Management of 1st Trimester Bleeding
Alison Jacoby, MD
Dept. of Obstetrics, Gynecology & Reproductive Sciences
University of California, San Francisco
Disclosures
• I have no relevant financial disclosures.
• I will discuss off-label use of misoprostol.
Acknowledgements
• Robin Wallace, Carolyn Sufrin, Jody
Steinauer and Meg Autry
Julie is a 23 year-old G1P0 at 6+5 by LMP
with spotting x 1 day, no pain, β-HCG = 2672.
MSD = 25mm, no fetal pole
Objectives
1. Review early pregnancy loss
2. Review clinical, serum, and
ultrasonographic diagnostic features
3. Compare management options
– Discuss role of patient preferences
– Expectant, medical, surgical (office vs. OR)
Early Pregnancy Loss (EPL)
Clinical diagnosis:
Ultrasound diagnosis:
Spontaneous abortion
Anembryonic gestation
Vaginal bleeding + IUP, <20 wks
threatened, inevitable, incomplete,
complete
Trophoblast development without
development of an embryo
Embryonic demise
>7 mm embryo
with no cardiac activity
• 15-20% of clinically-recognized pregnancies
• 1 in 4 women experience EPL
Stages of SAB:
VB, + IUP, <20 wks
STAGE:
Threatened
Inevitable
Incomplete
Os:
Closed
Open
Tissue & U/S:
No tissue passed
IUP on U/S
No tissue passed
IUP on U/S
Open
Tissue passed
+/- IUP on U/S
Tissue passed
Complete
Closed
No IUP on U/S
Normal Implantation
Implantation:
•5-7 days after fertilization
•Takes ~72 hours
•Invasion of trophoblast into
decidua production of
HCG
Embryonic disk:
1 wk after implantation
Diagnosis of EPL
1. Clinical presentation
2. β-HCG
3. Ultrasound
Bleeding, pain, LMP,
examination
Isolated value, trend
Sac, pole, pseudosac
Beta Curves, Redefined
Letting go of the “double in 48 hours” rule
• Rate of increase depends on gestational age1
• 49 normal intrauterine pregnancies
• Doubling time varies by gestational age
<5 wks: 1.5 d
5-6 wks: 2 d
>7 wks: 3d
1. Pittaway 1985 Fertil Steril & Am J Ob Gyn
Beta Curves, Redefined
Letting go of the “double in 48 hours” rule
• Early studies used 85% CI as lower limit1
– Retrospective study of 20 women
– Mean doubling time 2 days
– 66% increase in 48 hrs
• Poor sensitivity and specificity in cohort:
– Of 12 ectopics – 17% normal rise
– Of 16 normal pregnancies - 18% abnormal rise
• Newer data - different median and mean 2
1. Kadar 1981 Obstet Gynecol
2. Barnhart 2004 Obstet Gynecol
Beta Curves, Redefined
Letting go of the “double in 48 hours” rule
• 287 women with pain or bleeding and +UPT
– No IUP on U/S but eventually had normal IUP
– Initial β-HCG < 5000
• Ave GA by LMP = 38 days (range, 0-107)
• At least 2 β-HCG’s within 7 days
Barnhart 2004 Obstet Gynecol
β HCG Trends in Normal IUP
99%
of nlrise:
IUPs
Median
1 day
rise 50%
≥ 24%
1 day=
22
day
rise
≥ 53%
day
=124%
Slowest expected increase for normal pregnancy = 53%
Barnhart 2004 Obstet Gynecol
Ultrasound & Early Pregnancy:
Key Findings
Gestational
sac
Double decidual sign
Grows ~ 1mm/day
Yolk Sac
Early circulatory system
Embryonic
Pole
Grows ~ 1mm/day
Cardiac
Activity
100bpm140 bpm
Ultrasound Milestones
Gestational Sac
When should
you see it?
Abnormality
Discriminatory Level
Ectopic v. abnl IUP
Multiple gestation
Complete SAB
(wait for fetal pole)
β = 1500-2000
Yolk sac
Fetal pole
Cardiac activity
MSD>13-16mm
MSD >20mm
Anembryonic
gestation
Fetal pole ≥ 5.3mm
Embryonic demise
5mm cut off = 8.3% false +
5.3mm cut off = 0 false +
(Abdallah et al 2011 [Oct] Ultrasound Obstet Gynecol)
Ultrasound Diagnosis of EPL:
Anembryonic Gestation
Mean sac diameter >=21mm
(20 mm = 0.5% false positive)
AND no fetal pole
Growth?
Cut off 0.6mm/day 90% spec
Cut off 0.2mm/day 99% spec
1.4mm/week
Abdallah et al 2011 (Aug) Ultrasound Obstet Gynecol
ACR Appropriateness Criteria
for First Trimester Bleeding
Failed pregnancy can be
diagnosed by:
Mean sac diameter
>= 25mm AND no embryo
Absence of cardiac activity in
an embryo > 7mm in CRL
Barton et al 2013 (Jun) Ultrasound Quarterly
Ultrasound: Poor Prognostic Signs
• Yolk sac > 7 mm
• Abnl Sac size / Embryo size
– Sac too small (MSD-CRL < 6mm)
– Sac too big
•
•
•
•
•
Slow embryonic heart rate (<80)
Subchorionic hematoma
Thin decidual reaction (<3 mm)
Irregular sac contour
Low position in uterus
Not diagnostic, but may help with counseling
Summary: Diagnosis of EPL
• Be cautious of only one point of information
(Lab and ultrasound errors occur)
• Clinical history varies
• HCG rise in 48 hours: Minimum 53%
Average 124%
• Ultrasound:
– No growth of small sac (IUP not confirmed)
– No cardiac motion of embryo > 7 mm CRL
– Anembryonic MSD > 25 mm
Julie is a 23 year-old G1P0 at 6+5 by
LMP with spotting x 1 day, no pain.
β-HCG = 2672
Anembryonic Gestation
MSD = 25mm, no fetal pole
EPL Management
Expectant
Medical
Surgical
Depends on:
1. Hemodynamic stability
2. Patient preference and follow-up
3. Stage in miscarriage process
4. Local resources
Women’s Preferences
There is no “one best way.”
Expectant management is preferred
over aspiration by 70% of women.
When uterine aspiration is indicated
or preferred, the majority of women
will choose an office-based procedure
over one in the OR.
Smith 2006; Wieringa-de Waard 2002; Dalton 2006
Women’s Preferences
• Patients report higher quality-of-life and
satisfaction when treated according to preference
• Surgery
– Quick resolution
– Want and value support from hospital staff1
• Expectant
–
–
–
–
Desire a natural solution1
Fear of operation1
More preferred with higher level information & support2
71% with success would opt for same in future3
• Misoprostol
– Faster resolution
– More natural solution without surgery
1. Ogden & Marker Brit J ObGyn 2004; 2. Molnar J Am Board of Fam Pract;
3. Wieringa-DeWaard et al. J of Clin Epi, 2004
Women’s Preferences
• Up to 89% express a preference
– Challenges in recruitment for RCTs
– Expectant mgt. increasingly preferred (38% in 1997 to
70% in 2002), increased if good counseling and support
– Increasing interest in medical
• Physician recommendation is influential
1. Molnar et al. Am Brd of Fam Pract 2000; O’Connor Health Aff 2007; Dalton ObGyn 2006;
Petrou Value Health 2008; Smith BJGP 2006; Wieringa-de Waard Hum Reprod 2002
Patient Priorities
Pain
Time
Complications
Safety
Bleeding
Privacy
Anesthesia
Past
experience
Finality
Adapted from Wallace et al 2010 Patient Educ Couns
©Robin Wallace, 2011
Personal Priorities
Physical Priorities
o
Treatment by your own provider
o
Least amount of pain possible
o
Recommendation of treatment from friend
o
Fewest days of bleeding after treatment
or family member
o
Lowest risk of complications
o
Provider recommendation of treatment
o
Lowest risk of need for other steps
o
Experience symptoms of bleeding and
o
Avoid invasive procedure
cramping in private
o
Avoid medications with side effects
Family responsibilities/needs
o
Avoid seeing blood
o
Avoid going to sleep in case of a surgical
o
procedure
o
Emotional Priorities
o
Most natural process
o
Avoid seeing the pregnancy tissue
Want to be asleep in case of a surgical
procedure
Time and Cost Priorities
o
Shortest time before miscarriage is complete
Previous Miscarriage or Abortion
o
Shortest time in the clinic or hospital
(if applicable)
o
Fastest return to fertility or normalcy
o
Different treatment from previous
o
Fewest number of clinic visits
o
Similar treatment to previous
o
Lowest cost of treatment to you
Adapted from Wallace et al 2010 Patient Educ Couns
©Robin Wallace, 2011
EPL Management Practices in the U.S.
Percent of EPF providers
50
45
40
35
30
Ob/Gyn
CNM
FP
25
20
15
10
5
0
Expectant
Misoprostol
Office aspiration
OR
n=976 ob-gyn, family medicine, CNMs
Adapted from Dalton AJOG 2010
Provider Issues
Training
Safety
Concerns
Efficacy
System
Resources
Time
Assumptions
of patients
Overall success rates
Expectant
(14 days)
Misoprostol
(7 days)
Aspiration
Overall
Anembryonic
Embryonic Demise
Incomplete
60%-70%
50%
35%-60%
75% - 85%
800 mcg PV
Anembryonic
Embryonic Demise
Incomplete
70% - 96%
81%
88%
93%
97% - 100%
Expectant Management:
Completion Rates
Day 7
(%)
Day 14
(%)
Day 46
(%)
Incomplete Ab (n=221)
53
71*-84
91
Anembryonic gestation
(n=92)
25
53*/52
66
Embryonic demise (n=138)
30
35*-59
76
Total (n=451)
40
61*-70
81
* n=203 - Casikar
Luise 2002 BMJ
*Casikar 2010 Ultrasound Obstet Gynecol
Expectant Management:
MIST Trial
• MIST – RCT of 1200 women
– Expectant, medical, surgical
• Infection:
– No difference - expectant, medical, surgical
(3%, 2%, 3%, p=NS)
• Unscheduled D&C
– 44% (expectant)
– Higher efficacy with incomplete
• Transfusion:
– Expectant > surgical (2% vs. 0% of embryonic
demise)
Trinder 2006 BMJ
Expectant Management:
Contraindications
•
•
•
•
•
Uncertain diagnosis
Severe hemorrhage or pain
Infection
Suspected gestational trophoplastic disease
Indicated karyotyping
Same contraindications for medical management
Expectant Limitations
• Size: Studies generally include gestations
up to 9 weeks
• Time: Safety established up to 6 weeks of
observation
• Maternal conditions: inappropriate for
bleeding at home
• Social: inability to obtain prompt
emergency care, understand precautions
Medical Management of EPL
Advantages:
Disadvantages
• Avoidance of
anesthesia and surgery
• Faster completion of
miscarriage compared
to expectant
• Reduced emergency
visits and D&C’S
• Pain and increased
analgesic requirements
• Increased duration of
bleeding vs. surgical
• Gastrointestinal and
systemic side effects
• Surgical management
may still be necessary
Misoprostol
• PGE1 analogue
• Tabs 100 mcg unscored, 200 mcg scored
• Inexpensive
• Rapidly absorbed PO, PV, PR, SL, buccal
• Common obstetrical uses: labor induction,
medical abortion, PPH, cervical ripening
Misoprostol: Off-label Use
• FDA approved for prevention/tx
of gastric ulcers
• Once licensed, FDA does
not regulate how used1
• Commonly practiced, often
standard of care1
• Not experimental if based on
sound scientific evidence2
1. Friedman, FDA Deputy Commissioner speech to U.S. House of Representatives 1996
2. Rayburn, Obstet Gynecol 1993
Physiologic Effects of Misoprostol
Uterine: • Stimulates contractions
Cervical:
Gastrointestinal:
• Softens and primes cervix
• Prevents/treats ulcers
• Nausea & vomiting
• Diarrhea
Systemic:
• Fever, chills
Medical Management:
Misoprostol for EPL
• Small studies with wide range of doses, followup and definition of success
– 800 mcg vaginally, repeated in 24h PRN1,2
– ↑ Side effects with PO, buccal, SL
– 400-600 mcg buccal or sublingual3
• Success (avoid surgical intervention) 70-96%4
– Incomplete: higher success
• More acceptable than surgical5,6
• 90% would choose again
1. .Zhang et al, NEJM, 2005
2. Weeks et al, Obstet Gynecol 2005
3. Gemzell-Danielsson, Int J Obstet Gynecol 2007
4.
5.
6.
Sur et al. Best Pract ObG 2009
Wood et al, Ob Gyn 2002
Demetroulis et al, Hum Reprod 2001
Misoprostol vs. Surgical:
MEPF Study
• 652 ♀ w/ EPL or incomplete Ab Miso or D&C
• D1: Miso 800 mcg PV
– D3: Repeat miso if not complete
– D8: Uterine aspiration if still not complete
– D15: follow-up (all)
• Success (no need for additional D&C) by D 8
– Miso: 84% (CI, 81-87) vs. D&C: 97% (CI, 94-100)
– Lowest for embryonic demise (81%)
– 70% success after 1 dose; 60% after 2nd dose
• Complications: No difference
• Satisfaction: No difference (78% vs. 83%)
Zhang et al 2005 NEJM
Example of Misoprostol Algorithm
Miso 800 mcg PV
Cramping w/ clot/tissue
in 24-48 hrs
(Rhogam for Rh- women)
7 Days
Clinical f/u
U/S if indicated
Clinical signs
of passage
DONE!
No clinical passage
in 24-48 hrs
2nd Dose Miso on D3
No Sac &
(endometrium<=30mm)
DONE!
Follow up precautions
Bleeding should stop in 2-3 wks
Menses should resume in 6-8 weeks
Sac present or
(Endometrium >30 mm)
If still sac (or endo>30mm) after 2 doses:
Recommend suction
If wants expectant mgmt, f/u 2-4 wks
Suction if signs of infection or HD instability
Adapted from Goldberg 2009 in Mgmt of unintended & abnl pregnancy
Medical Management:
Mifepristone and Misoprostol
• Does not appear to increase efficacy
– Mife 600 + Miso 400 PV vs. Miso alone1
• 74% vs. 71% success at 1 week
– Mife 200 + Miso 800 PV
• 84%2-90%3 success at 3 days or 1 week2,3
1. Gronlund 2002 Acta Obstet Gynecol Scand
2. Wagaarachchi 2001 Human Reproduction
3. Schreiber 2006 Contraception
Surgical Management:
Suction Curettage
• Safe, high efficacy (>95%)
• No need to do in Operating Room
– Outpatient or ED setting – cost-effective
– Manual Uterine Aspiration / Manual Vacuum Aspiration
Used with 5-12 mm cannulae
Capacity 60 cc
Surgical Management:
MUA/MVA
• Manual v. electric: no difference - complication
(2.5% vs. 2.1%)1, pain, provider or pt. satisfaction2,3
• MUA in ER compared to EVA in OR:4
EVA in OR
MUA in ER
7.14 hrs
3.45 hrs
Procedure time
33 min
19 min
Total cost (↓ 41%)
$1404
$827
Wait time (↓52%)
2012 study supports cost-effectiveness of outpatient MUA to OR-based UA5
1.Goldberg 2004 Ob Gyn; 2.Dean, Contraception 2003; 3.
Edelman A. Ob Gyn 2001;184:1564; 4. Blumenthal 1992
IJOG; 5. Raush Fertil Steril 2012.
Moving MUA out of OR
90% uterine aspirations are done in OR
• Process described by U Michigan
– Medical evidence review
– Review of hospital policy for office procedures
– Trained physicians, nurses, and MAs
• Hands-on workshops
– Institution of privileging program
– Review experience of patients
– Review cost – gyn reimbursement same,
lower institutional cost - $1965 v. $968
Harris, AJOG, 2007.
Overall Success Rates
Expectant up to 70-85% in 2 wks
Misoprostol (800 mcg pv) up to
81-96% success in 1 week
D&C: 97%-100%
Follow-up for Miscarriage
Confirm pregnancy passed:
• Surgical: done at time of aspiration
• Expectant & Medical
– Symptoms, ultrasound or pregnancy test
– Phone call is an option
Other benefits of an office visit:
– Emotional support
– Preconception counseling or contraception
– Recurrence risk – 2% after first SAB
The Patient – provider Interaction
•Affects patient choice and satisfaction
•One half of women would change their
decision based on our recommendation
Support women in identifying their
values in and priorities for management.
Be prepared to offer all options, including
misoprostol and office-based uterine aspiration.
Molnar 2000
The Patient – provider Interaction
• Threatened Abortion
– Keep the patient informed
• Provide reassurance, but avoid guarantees that
“everything will be all right”
• Provide support through process
• What does the bleeding mean?
– 50% ongoing pregnancy with closed os
– 85% ongoing pregnancy with viable IUP on u/s
– Up to 30% of normal pregnancies have VB
The Patient – provider Interaction
•
•
•
•
•
•
•
•
•
Remain silent after initial results or information
Follow-up with open-ended questions & active listening
Use neutral responses
Determine how the woman feels about the pregnancy
Normalize emotions
Validate feelings rather than trying to change them
Avoid opinions about what patient ‘‘should’’ do
Encourage seeking emotional support from others
Assure that you will be available to her through the
process, and answer questions as they arise
Wallace, Patient Educ Couns, 2010.
Key Points: Management
• Offer all 3 management options if stable
– Know success rates when counseling patients
– Patient preference plays a major role
– Minimal difference in risk
• Need for surgical intervention should be
based on clinical judgment
• Outpatient MUA is acceptable to women
and cost-effective