Medication Management of Early Pregnancy Loss

Talking Points
•This program is sponsored by the Association of Reproductive Health
Professionals (ARHP).
•This program is funded by unrestricted educational grants from Danco
Laboratories, LLC.
•This presentation may include information that is not on FDA-required
product labels.
•NOTE TO SPEAKER: Disclose any financial relationship(s) you have with
industry.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 1
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
2
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 3
Talking Points
• At the conclusion of this presentation, you should be able to:
• Identify three clinical indications for medical management of early
pregnancy loss
• Recognize four factors to consider when counseling women about
medical management of early pregnancy loss
• Screen patients for contraindications to medical management of early
pregnancy
• Implement at least one medication regimen used for medical
management of early pregnancy loss.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 4
Talking Points
• At the conclusion of this presentation, you should be able to:
• Identify three clinical indications for medical management of early
pregnancy loss
• Recognize four factors to consider when counseling women about
medical management of early pregnancy loss
• Screen patients for contraindications to medical management of early
pregnancy
• Implement at least one medication regimen used for medical
management of early pregnancy loss.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 5
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 6
[Insert Lecture Name Here]
Slide 7
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 8
Talking Points
In the United States, when clinically unrecognized miscarriages are included,
approximately 12%–24% of pregnancies end in spontaneous abortion before 20
weeks gestation.
This percentage represents about 600,000 to 800,000 pregnancies per year.
80% of early pregnancy loss occurs in first trimester
References
•Griebel CP, Halvorsen J, Golemon TB. Management of spontaneous abortion. Am
Fam Physician. 2005;72:1243–50.
•Everett C. Incidence and outcome of bleeding before the 20th week of
pregnancy: prospective study from general practice. BMJ. 1997;315:32–4.
•Smith NC. Epidemiology of spontaneous abortion. Contemp Rev Obstet Gynecol.
1988;1:43–9.
•Stirrat GM. Recurrent miscarriage I: definition and epidemiology. Lancet.
1990;336:673–5.
•Wilcox AJ, Weinberg CR, O'Connor JF, et al. Incidence of early loss of pregnancy.
N Eng J Med. 1988;319:189-194.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Slide 9
[Insert Lecture Name Here]
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 9
Talking Points
• Early pregnancy loss is defined as the loss of a pregnancy before the 20th
week of pregnancy without surgical or medical intervention to terminate
the pregnancy.
• Vaginal bleeding is an indicator of early pregnancy loss, and diagnosis
involves evaluating the bleeding with a full history, physical examination,
laboratory tests and ultrasonography.
• Early pregnancy loss is a broad term that includes:
• Inevitable abortion – in which the cervix has dilated but the pregnancy
has not been expelled
Complete abortion – in which the products of conception have passed
without the need for surgical or medical intervention
• Septic abortion involves early pregnancy loss that is complicated by
infection
• Recurrent spontaneous abortion involves three or more consecutive
pregnancy losses
•Incomplete abortion – in which some of the pregnancy has been passed
but some products remain
• Missed abortion – this is identified when ultr7asound detects a nonviable
Slide 10
[Insert Lecture Name Here]
pregnancy that has not been expelled. Missed abortion can also be further
categorized as:
• Anembryonic – in which the fetal sac is empty
• Embryonic – in which there is no evidence of fetal cardiac activity
• When discussing treatment options for medical management of EPL, this
talk will focus primarily on incomplete and missed abortion.
References
•Griebel CP, Halvorsen J, Golemon TB. Management of spontaneous abortion. Am
Fam Physician. 2005;72:1243–50.
•Godfrey EM, Leeman L, Lossy P. Early pregnancy loss needn’t require a trip to
the hospital. Journal of Family Practice. 2009;58;11:585-590.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 10
[Insert Lecture Name Here]
Talking Points
•Incomplete abortion occurs when a residual gestational sac is detected on
ultrasound, and vaginal bleeding and pelvic pain are present
References
•Griebel CP, Halvorsen J, Golemon TB. Management of spontaneous
abortion. Am Fam Physician. 2005;72:1243–50.
•Godfrey EM, Leeman L, Lossy P. Early pregnancy loss needn’t require a
trip to the hospital. Journal of Family Practice. 2009;58;11:585-590.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 11
[Insert Lecture Name Here]
Talking Points
Missed abortions occur when a nonviable pregnancy is detected on
ultrasound
There are two types of missed abortions:
• Anembryonic – Gestational sac develops without an associated embryo
or yolk sac. Formerly called “blighted ovum” a mean sac diameter > 10
mm and no yolk sac or a mean sac diameter of 20 mm and no embryo
on transvaginal ultrasound.
• Fetal demise – a crown rump length of ≥ 6 mm without cardiac activity
on transvaginal ultrasound
References
•Godfrey EM, Leeman L, Lossy P. Early pregnancy loss needn’t require a
trip to the hospital. Journal of Family Practice. 2009;58;11:585-590.
•Griebel CP, Halvorsen J, Golemon TB. Management of spontaneous
abortion. Am Fam Physician. 2005;72:1243–50.
•Royal College of Obstetricians and Gynaecologists. The Management of
Early Pregnancy Loss. Royal College of Obstetricians and Gynaecologists;
2006. Guideline 25.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
Slide 12
[Insert Lecture Name Here]
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 12
Talking Points
•Most medical facilities are still using the operating room to treat EPL.
•Study conducted by Dalton, VK et al. entailed a retrospective chart review
of more than 21,000 Medicaid visits and about 1,500 University Health
Plan Visits entailing EPL. They identified 35.3% of Medicaid and 18% of
university health plan enrolles as undergoing hosptial aspiration.
Misoprostol use was <1% in both groups. Conculsion: EPL is primarily
being treated with expectant management and surgical evacutaion in the
operating room.
Reference
Dalton VK, Harris LH, Clark SJ, et al. Treatment Patterns for Early
Pregnancy Failure in Michigan, J Womens Health, 2009
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Talking Points
•Most medical facilities are still using the operating room to treat EPL.
•Study conducted by Dalton, VK et al. entailed a retrospective chart review
of more than 21,000 Medicaid visits and about 1,500 University Health
Plan Visits entailing EPL. They identified 35.3% of Medicaid and 18% of
university health plan enrolles as undergoing hosptial aspiration.
Misoprostol use was <1% in both groups. Conculsion: EPL is primarily
being treated with expectant management and surgical evacutaion in the
operating room.
Reference
Dalton VK, Harris LH, Clark SJ, et al. Treatment Patterns for Early
Pregnancy Failure in Michigan, J Womens Health, 2009
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Talking Points
1. Simplify scheduling:
When women present to the emergency room with signs and symptoms of
a miscarriage, they may be put through many pelvic exams (first the
ER resident, then the ER attending, often followed by the gyn resident
and then gyn attending—none of whom are usually the woman’s own
physician). In a clinic setting, the woman usually undergoes one exam-by her own doctor, midwife, or nurse practitioner.
2. Patient centered care
Women undergoing miscarriages are usually not acutely ill. Both in the
emergency room as well as in the operating room, they usually receive
care only after sicker patients have already been treated. Patients who
received care in the hospital reported dissatisfaction with the fact that
“miscarriage was not perceived by medical staff as important or an
emergency.”(Lee 1996) Women do not like these long waits.
The operating room environment is extremely high-tech and mechanized.
Patients undergoing procedures in the OR must adhere to strict
protocols; this can be frustrating and intimidating for patients.
Recent study shows that women being treated in the outpatient setting
value being offered alternatives to expectant management.
3. Saves resources:
MIST trial – conducted in the UK. This trial compared the costeffectiveness of alternative management of first trimester miscarriage.
They found that expectant management was most cost effective.
However, they conclude that both expectant and medical management
of EPL poses significant advantages over traditional surgical
management.
Finland Study – Alternatively, RCT of 49 to medical and 49 to surgical for
EPL, cost estimate when including complications are similar.
[Insert Lecture Name Here]
Reference
Lee C, Slade P. Miscarriage as a traumatic event: a review of the literature and
new implications for intervention.” J. Psychosom Res 1996;40(3):235-44.
Petrou S, Trinder J, Brocklehurst P, Smith L. Economic evaluation of alternative
management methods of first trimester miscarriage based on results from
MIST trial. BJOG, 2006; 113 (80): 879-89.
Niinimaki M, Kariene P, Hartikainen AL, Pouta A. Treatment miscarriages: a
randomized study of cost effetiveness in medical or surgical choice. BJOG
2009; 116: 984-90.
Petrou S, McIntosh E. Womens preferences for attributes of first trimester
miscrriage management: a stated preference discrete-choic experiment. Value
Health 2009; 12 (4): 551-9.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 15
[Insert Lecture Name Here]
Talking Points
Graphic of the options are listed in order of effectiveness.
•Vacuum Aspiration
• Highly effective, success rates for use of uterine aspiration are near
100%.
• Is more cost effective than uterine evacuation in the OR. The cost of
uterine aspiration in the operating room is estimated at $1404 vs.
$827 when aspiration is done in the outpatient procedure.
• For more information on MVA, visit arhp.org/CORE to download
presentations on MVA and EPL.
•Medications
• Highly effective, rates of effectiveness for use of medication vary.
• Misoprostol for incomplete abortion has a success rate of 66-100%
within 1 to 2 weeks and a success rate of 60-93% within 1 to 2
weeks for missed abortions using the recommended doses .
• Mifepristone and misprostol has a success rate of 66.7% (10 days
follow-up) - 93% (one week) using the recommended doses.
• More cost effective than other methods of EPL management.
• We will go into more detail on this method in the this presentation.
•Expectant management
• Not as effective as the above methods, rates of effectivness range
between 40% (7 days) to 70%(14 days)
Slide 16
[Insert Lecture Name Here]
• Not going to cover EM in this presentation.
References
•Godfrey, EM, Leeman L, Panna, L. Early pregnancy loss needn’t require a trip to
the hospital. J Fam Pract. 2009 Nov;58(11):585-90.
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol sponsored by
Reproductive Health Technology Project and Gynuity Health Projects. June 9,
2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 16
Talking Points
•Mifepristone acts as an “antiprogestin” by binding to the progesterone receptor
without activating the receptor.
•Mifepristone is most effective in combination with a Prostaglandin analog.
•FDA approved for medical abortion in 2000
•Oral preparation
• 200 mg tablets
References
Creinin M, Danielsson KG. Chapter 9: Medical Abortion in Early Pregnancy. In
Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG, Creinin MD
(ed).Management of unintended and abnormal pregnancy comprehensive
abortion care. Oxford, UK: Wiley-Blackwell; 2009
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
MVA Education Partnership
Slide 17
[Insert Lecture Name Here]
Talking Points
•Mifepristone has several effects on the uterus and the cervix, including:
• Inducing uterine contractions
• Altering the endometrium and causing bleeding and a decrease in hCG
secretion into the maternal system
• Softens the cervix to allow for expulsion
•In addition, Mifepristone also causes nausea, vomiting and diarrhea.
References
Creinin M, Danielsson KG. Chapter 9: Medical Abortion in Early Pregnancy.
In Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG,
Creinin M (ed). Management of unintended and abnormal pregnancy
comprehensive abortion care. Oxford, UK: Wiley-Blackwell; 2009
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 18
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
Mifepristone should not be used for women with:
• A confirmed or suspected ectopic pregnancy
• An IUD in place
• Long-term corticosteroid use
• Hemorrhagic disorders or inherited porphyrias
• Concurrent anticoagulant use
• Chronic adrenal failure
• Allergy to mifepristone, misoprostol, or other prostaglandin
Reference
•Mifeprex [package insert]. New York, NY: Danco Laboratories, LLC. July,
2005.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 19
Talking Points
•Misoprostol belong to family of Eicosanoids, which are active metabolites of
arachidonic acied
•In the prostaglandins, the E-series (for example dinoprostone and sulprostone)
and F-series are the most important. E-series are more uteroselective and are
superior in cervical ripening.
•FDA approved for prevention and treatment of gastric and duodenal ulcers
•Misoprostol is heat stable, so it does not require refrigeration.
•It is inexpensive and widely available.
•Oral preparation
• 100 µg (non-scored) & 200 µg (scored) tablets
References
Creinin M, Danielsson KG. Chapter 9: Medical Abortion in Early Pregnancy. In
Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG, Creinin MD
(ed).Management of unintended and abnormal pregnancy comprehensive
abortion care. Oxford, UK: Wiley-Blackwell; 2009
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
MVA Education Partnership
Slide 20
[Insert Lecture Name Here]
Talking Points
•Acts on smooth muscle receptors
•In contrast to oxytocin, prostaglandins not only have an effect on
myometrial contractility, but they also accelerate the phsiological cervical
ripening.
•Prostaglandin receptors are always present in myometrial tissue, whereas
oxytocin receptors develop during the later part of pregnancy.
References
Creinin M, Danielsson KG. Chapter 9: Medical Abortion in Early Pregnancy.
In Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG,
Creinin M (ed). Management of unintended and abnormal pregnancy
comprehensive abortion care. Oxford, UK: Wiley-Blackwell; 2009
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 21
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
Misoprostol should not be used for women with:
• Known allergy to misoprostol
• Suspected ectopic pregnancy
• Unstable hemodynamics and shock
• Signs of pelvic infections and/or sepsis
•Caution should be taken when treating women with:
• An IUD in place. The IUD should be removed before administration of
the drug.
• A known bleeding disorder or currently taking anti-coagulants
Reference
•Gremzwll-Danielsson K, Ho P, Gomez Ponce de Leon RG, et al.
Misoprostol to treat missed abortion in the first trimester. Int J Gynecol
Obstet, Suppl. 2007;99:S182-S185.
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol
sponsored by Reproductive Health Technology Project and Gynuity Health
Projects. June 9, 2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
Slide 22
[Insert Lecture Name Here]
in the Outpatient Setting” in December 2009. Original funding received from
Danco Laboratories, LLC. through an educational grant. This slide is available at
www.arhp.org/core.
Slide 22
[Insert Lecture Name Here]
Talking Points
•Misoprotal can be administered via different routes, including:
• Oral
• Vaginal
• Buccal
• Sublingual
• Rectal
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 23
[Insert Lecture Name Here]
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 24
Talking Points
Standard dosage and dosing intervals have not been well established
Studies difficult to compare
• Various patient populations and dosing regimens
• Different routes of administration
• Varying definitions of success
References
•Chen BA, Creinin MD. Contemporary management of early pregnancy failure.
Clin Obstet Gynecol. 2007 Mar;50(1):67-88.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 25
Looked at studies that considered incomplete abortion in the first trimester.
[Insert Lecture Name Here]
Slide 27
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Slide 28
Looked at studies that considered incomplete abortion in the first trimester.
[Insert Lecture Name Here]
Slide 30
[Insert Lecture Name Here]
Talking Points
•Evidence has shown that Mifepristone in combination with Misoprotol has
excellent efficacy in induced abortions
•The FDA approved regimen of Mifepristone is 600 mg PO followed by
misoprostol 400 µg orally 48 hours later.
•The evidence-based regimens used are as effective and are more cost
effective.
References
•Winikoff B; Dzuba IG et al. Obstet Gynecol, 2008
•Creinin, Fox Obstet Gyn, 2004
•Creinin Schreiber Obstet Gyn 2007
Lohr PA, Reeves M, et al. Contraception 2007
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 31
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
• There is ample clinical evidence that a 200-mg dose of mifepristone is comparable in efficacy
to the 600-mg dose approved by the FDA.
• For instance, an open-label, randomized trial of 442 women (gestation up to 56 days after
LMP) found that 200 mg oral mifepristone followed by buccal administration of misoprostol (800
µg) was as effective as the same dose of mifepristone followed by vaginal (800 µg) misoprostol.
• Furthermore, vaginal administration of misoprostol (800 µg) has been studied extensively.
• Vaginal administration of misoprostol is associated with a lower rate of incomplete abortion
than oral misoprostol is (2.1% compared with 6.4%).
• However, this beneficial effect may result from the fact that studies using vaginal
misoprostol often involve two or more doses of the prostaglandin analogue.
• Other potential advantages of vaginal administration are:
• a lower incidence of gastrointestinal side effects
• more rapid expulsion of the conceptus
• and lower continuing pregnancy rates.
• In addition, studies using 200 mg of mifepristone and 800 µg of vaginal misoprostol have
demonstrated that:
•1) can be given simultaneously as mife (Creinin, 2004)
• 1) there is equal efficacy whether the misoprostol is used 24, 48, or 72 hours after
mifepristone and
• 2) initial follow-up can occur sooner than day 14 if ultrasound is used for evaluation of
expulsion.
•Buccal misoprosol can also be used up to 63 days. (Winnikoff, 2008)
•Has not shown to be effective when given simultaneously (Lohr, 2007)
•Sublingual has been studied with 200 mg mifepristone up to 63 days. Appears to be
superior to oral misoprostol.( (Raghavan S et al. 2009).
• Finally, home use of misoprostol is safe, effective and acceptable to patients. This is
considered standard of care.
Slide 32
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References
•Kahn JG, Becker BJ, MacIsaac L, et al. The efficacy of medical abortion: a metaanalysis. Contraception. 2000;61:29–40.
•El-Rafaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of
abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J
Med. 1995;332:983–7.
•Schaff E, Stadalius S, Eisinger SH, Franks P. Vaginal misoprostol administered at
home after mifepristone (RU 486) for abortion. J Fam Pract. 1997;44:353–9.
•Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ, Poppema S. Low-dose
mifepristone 200 mg and vaginal misoprostol for abortion. Contraception
1999;59:1-6.
•Schaff EA, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered 1, 2,
or 3 days after mifepristone for early medical abortion: a randomized trial. JAMA
2000;284:1948-1953.
•Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal
misoprostol at one day after mifepristone for early medical abortion.
Contraception 2001; 64: 81-85
•Schaff EA, Fielding SL, Eisinger SH, Stadalius LS, Fuller L. Low-dose mifepristone
followed by vaginal misoprostol at 48 hours for abortion up to 63 days.
•Winikoff B; Dzuba IG et al. Obstet Gynecol, 2008
•Creinin MD, Fox MC, Teal S, et al. A Randomized Comparison of Misoprostol 6 to
8 Hours Versus 24 Hours After Mifepristone for Abortion. Obstet Gynecol 2004;
103:851.
•Creinin Schreiber Obstet Gyn 2007
Lohr PA, Reeves M, et al. Contraception 2007
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 32
[Insert Lecture Name Here]
Talking Points
•Mifepristone and Misoprostol has been extensivly studied for induced
abortions. This combination is effective at terminating pregnancy up to 63
days.
•Has been studied in cases of early pregnancy loss. We will review some of
the studies that have been conducted on the use of mifepristone and
misoprostol in treatment of EPL in the next few slides.
•The regimen of mifepristone followed by vaginal misoprostol appears to
be an efficacious and acceptable treatment for EPL and may have
improved results over a single dose of misoprostol alone.
•Since progesterone levels are low in non-viable pregnancy, in contrast to
medical termination of pregnancy, mifepristone can be avoided and
prostaglandins only administered.
References
•Schaff EA, Fielding SL, Eisinger SH, Stadalius LS, Fuller L. Low-dose
mifepristone followed by vaginal misoprostol at 48 hours for abortion up to
63 days. Contraception 2000;61:41-46.
•Creinin M, Danielsson KG. Chapter 9: Medical Abortion in Early
Pregnancy. In Paul M, Lichtenberg ES, Borgatta L, Grimes DA,
Stubblefield PG, Creinin M (ed). Management of unintended and abnormal
pregnancy comprehensive abortion care. Oxford, UK: WileyBlackwell; 2009
Slide 33
[Insert Lecture Name Here]
•Schaff EA. Mifepristone: ten years later. Contraception. 2010;81(1)1-7.
•Schreiber CA, Creinin MD, Reeves MF, Harwood BJ. Mifepristone and misoprostol
for the treatment of early pregnancy failure: a pilot clinical trial. Contraception.
2006;74(6):458-62.
•Sagili H, Divers M. Modern management of miscarriage. The Obstetrician &
Gynaecologist 2007;9:2:102-108
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 33
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Slide 34
[Insert Lecture Name Here]
Talking Points
•Women with ultrasound diagnosis of a nonviable pregnancy up to 10
weeks gestation are candidates for medical management of missed
abortion with misoprostol.
•Non-viable pregnancy is diagnosed by ultrasound and/or subnormal rising
quantitative hCG levels. It is important to exclude ectopic pregnancy as
medical treatment for ectopic pregnancy differs from that of missed
abortion.
•Necessary labs: Rh screen, hemoglobin, quantitative serum hCG
•The evidence-based regimen dictates that 800 mcg of misoprostol is
placed in the vagina either by 1) the physician in the clinic or 2) by the
patient at home at a convenient time.
•The patient should be given a second dose of 800 mcg of misoprostol in
case passage of tissue does not occur with the first dose.
•The success rate for Misoprostol for missed abortions is between 60-93%
using the recommended doses .
•Highest success rates are achieved with extended follow-up (7 to 14
days) to allow completion of expulsion.
References
•Gremzwll-Danielsson K, Ho P, Gomez Ponce de Leon RG, et al.
Misoprostol to treat missed abortion in the first trimester. Int J Gynecol
Obstet, Suppl. 2007;99:S182-S185.
Slide 38
[Insert Lecture Name Here]
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol sponsored by
Reproductive Health Technology Project and Gynuity Health Projects. June 9,
2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 38
[Insert Lecture Name Here]
Talking Points
•Women with ultrasound diagnosis of a nonviable pregnancy up to 10
weeks gestation are candidates for medical management of missed
abortion with misoprostol.
•Non-viable pregnancy is diagnosed by ultrasound and/or subnormal rising
quantitative hCG levels. It is important to exclude ectopic pregnancy as
medical treatment for ectopic pregnancy differs from that of missed
abortion.
•Necessary labs: Rh screen, hemoglobin, quantitative serum hCG
•The evidence-based regimen dictates that 800 mcg of misoprostol is
placed in the vagina either by 1) the physician in the clinic or 2) by the
patient at home at a convenient time.
•The patient should be given a second dose of 800 mcg of misoprostol in
case passage of tissue does not occur with the first dose.
•The success rate for Misoprostol for missed abortions is between 60-93%
using the recommended doses .
•Highest success rates are achieved with extended follow-up (7 to 14
days) to allow completion of expulsion.
References
•Gremzwll-Danielsson K, Ho P, Gomez Ponce de Leon RG, et al.
Misoprostol to treat missed abortion in the first trimester. Int J Gynecol
Obstet, Suppl. 2007;99:S182-S185.
Slide 39
[Insert Lecture Name Here]
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol sponsored by
Reproductive Health Technology Project and Gynuity Health Projects. June 9,
2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 39
[Insert Lecture Name Here]
Talking Points
•Women with ultrasound diagnosis of a nonviable pregnancy up to 10
weeks gestation are candidates for medical management of missed
abortion with misoprostol.
•Non-viable pregnancy is diagnosed by ultrasound and/or subnormal rising
quantitative hCG levels. It is important to exclude ectopic pregnancy as
medical treatment for ectopic pregnancy differs from that of missed
abortion.
•Necessary labs: Rh screen, hemoglobin, quantitative serum hCG
•The evidence-based regimen dictates that 800 mcg of misoprostol is
placed in the vagina either by 1) the physician in the clinic or 2) by the
patient at home at a convenient time.
•The patient should be given a second dose of 800 mcg of misoprostol in
case passage of tissue does not occur with the first dose.
•The success rate for Misoprostol for missed abortions is between 60-93%
using the recommended doses .
•Highest success rates are achieved with extended follow-up (7 to 14
days) to allow completion of expulsion.
References
•Gremzwll-Danielsson K, Ho P, Gomez Ponce de Leon RG, et al.
Misoprostol to treat missed abortion in the first trimester. Int J Gynecol
Obstet, Suppl. 2007;99:S182-S185.
Slide 40
[Insert Lecture Name Here]
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol sponsored by
Reproductive Health Technology Project and Gynuity Health Projects. June 9,
2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 40
[Insert Lecture Name Here]
Talking Points
•Women with ultrasound diagnosis of a nonviable pregnancy up to 10
weeks gestation are candidates for medical management of missed
abortion with misoprostol.
•Non-viable pregnancy is diagnosed by ultrasound and/or subnormal rising
quantitative hCG levels. It is important to exclude ectopic pregnancy as
medical treatment for ectopic pregnancy differs from that of missed
abortion.
•Necessary labs: Rh screen, hemoglobin, quantitative serum hCG
•The evidence-based regimen dictates that 800 mcg of misoprostol is
placed in the vagina either by 1) the physician in the clinic or 2) by the
patient at home at a convenient time.
•The patient should be given a second dose of 800 mcg of misoprostol in
case passage of tissue does not occur with the first dose.
•The success rate for Misoprostol for missed abortions is between 60-93%
using the recommended doses .
•Highest success rates are achieved with extended follow-up (7 to 14
days) to allow completion of expulsion.
References
•Gremzwll-Danielsson K, Ho P, Gomez Ponce de Leon RG, et al.
Misoprostol to treat missed abortion in the first trimester. Int J Gynecol
Obstet, Suppl. 2007;99:S182-S185.
Slide 41
[Insert Lecture Name Here]
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol sponsored by
Reproductive Health Technology Project and Gynuity Health Projects. June 9,
2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 41
[Insert Lecture Name Here]
Talking Points
•Women with ultrasound diagnosis of a nonviable pregnancy up to 10
weeks gestation are candidates for medical management of missed
abortion with misoprostol.
•Non-viable pregnancy is diagnosed by ultrasound and/or subnormal rising
quantitative hCG levels. It is important to exclude ectopic pregnancy as
medical treatment for ectopic pregnancy differs from that of missed
abortion.
•Necessary labs: Rh screen, hemoglobin, quantitative serum hCG
•The evidence-based regimen dictates that 800 mcg of misoprostol is
placed in the vagina either by 1) the physician in the clinic or 2) by the
patient at home at a convenient time.
•The patient should be given a second dose of 800 mcg of misoprostol in
case passage of tissue does not occur with the first dose.
•The success rate for Misoprostol for missed abortions is between 60-93%
using the recommended doses .
•Highest success rates are achieved with extended follow-up (7 to 14
days) to allow completion of expulsion.
References
•Gremzwll-Danielsson K, Ho P, Gomez Ponce de Leon RG, et al.
Misoprostol to treat missed abortion in the first trimester. Int J Gynecol
Obstet, Suppl. 2007;99:S182-S185.
Slide 42
[Insert Lecture Name Here]
•Consensus Statement: Instructions for use of Misoprostol for treatment of
incomplete abortion and Miscarriage. Expert Meeting on Misoprostol sponsored by
Reproductive Health Technology Project and Gynuity Health Projects. June 9,
2004. New York, NY. (Updated June 2008)
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 42
[Insert Lecture Name Here]
Talking Points
•Necessary labs: Rh screen, hemoglobin, quantitative serum hCG
•The evidence-based regimen dictates that the recommendations for
medical abortion be followed (200mg mifepristone followed by 800 mcg of
misoprostol vaginally) or 800 mcg of misoprostol is placed in the vagina
either by 1) the physician in the clinic or 2) by the patient at home at a
convenient time.
•Other clinics use buccal misoprostol.
•The patient should be given a second dose of 800 mcg of misoprostol in
case passage of tissue does not occur with the first dose.
•Highest success rates are achieved with extended follow-up (7 to 14
days) to allow completion of expulsion.
•With continued research and given cost considerations for the patient,
some clinics are moving to using misoprostol only for treatment of missed
abortions.
References
•Schreiber CA, Creinin MD, Reeves MF, Harwood BJ. Mifepristone and
misoprostol for the treatment of early pregnancy failure: a pilot clinical
trial. Contraception. 2006;74(6):458-62.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
Slide 43
[Insert Lecture Name Here]
in the Outpatient Setting” in December 2009. Original funding received from
Danco Laboratories, LLC. through an educational grant. This slide is available at
www.arhp.org/core.
Slide 43
[Insert Lecture Name Here]
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 44
[Insert Lecture Name Here]
Slide 45
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
• Patient intake for medical management of early pregnancy loss is
relatively simple. Intake steps include:
• Confirm diagnosis of nonviable pregnancy via ultrasound
• Medical history: determine gestational age
• Lab work, including: Rh statusm hemaglobin and quantitative
serum human chorionic gonadotropin
• Explain the procedure to the patient
• In addition, clinicians should ensure that patients understand they
will need to attend for a follow-up visit, so that completion of
abortion can be confirmed.
• It’s helpful if the patient’s informed consent includes a statement
that the patient agrees to return for follow-up and clinician’s plan
for follow-up.
• This can help to reduce liability risk.
• If the patient is presenting for an induced abortion or if using
mifepristone for treatment of early pregnancy loss, then there are
additional steps that should be included.
• Review the patient agreement with the patient: this has been
developed by the manufacturer. The patient agrees that she has
read the medication guide, discussed it with her provider, has
contact information for her provider, and will return for follow-up.
• Review the medication guide: this has been developed by
manufacturer and provides information on side effects and
medications to avoid.
Slide 46
[Insert Lecture Name Here]
References
•WHO. Safe Abortion: Technical and Policy Guidance for Health Systems. Geneva,
Switzerland: World Health Organization, 2003.
•Mifeprex [package insert]. New York, NY: Danco Laboratories, LLC. July, 2005.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 46
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
• Following medical abortion, patients may take ibuprofen or acetaminophen
initially to manage pain.
• Most women are advised to take nonsteroidal anti-inflammatory drugs for 24–48
hours. If necessary, some physicians provide patients with a prescription for an
oral narcotic (for example, plain codeine) with instructions to take tablets if initial
pain medications are insufficient.
Reference
•Grimes DA, Creinin MD. Induced abortion: an overview for internists. Ann Intern
Med. 2004;140:620–6.
•Lichtenberg ES, Shott S. A randomized clinical trial of prophylaxis for vacuum
abortion: 3 versus 7 days of doxycycline. Obstet Gynecol. 2003;101:726–31.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 47
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
• As part of instructions for aftercare, women should be told when to
contact the clinician after an abortion procedure. Women should contact
their clinicians if they experience any of the following:
• Bleeding that becomes heavier and causes dizziness or
lightheadedness. Usually vaginal bleeding gets lighter over time.
• Heavy bleeding that soaks two or more maxi-pads per hour for
more than 2 hours.
• Pain that worsens, especially if it is not improved with ibuprofen.
• Flu-like symptoms.
• Fever or chills.
• Feeling faint
• Women should also be told that they can contact their clinician if they
have any questions.
Reference
•Food and Drug Administration. Questions and Answers on Mifeprex
(mifepristone). Available at:
http://www.fda.gov.cder.drug/infopage/mifepristone/mifepristoneqa20050719.htm. Accessed April 26, 2006.
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
Slide 48
[Insert Lecture Name Here]
in the Outpatient Setting” in December 2009. Original funding received from
Danco Laboratories, LLC. through an educational grant. This slide is available at
www.arhp.org/core.
Slide 48
Options for Early Pregnancy Loss:
MVA and Medication Management
Talking Points
Women who desire another pregnancy
• Women who have experienced early pregnancy loss may be concerned
about the effect of abortion on future desired pregnancies.
• Within a few days after the uterus no longer contains a source of
pregnancy hormone (hCG), a woman’s own normal hormone patterns
begin to return.
• Depending on how high her hCG level was, it will be cleared from the
bloodstream within a few days to a few weeks after medical abortion. Once
that occurs, the signals for ovarian hormone production are initiated, and
ovulation may occur as soon as 10–14 days after medication abortion, or
within the following 1–2 weeks.
• Women desiring a pregnancy should be encouraged to follow vitamin and
diet recommendations (as well as toxic-exposure avoidance guidelines).
• They should be encouraged to write down dates of menstrual cycles, to
avoid future doubt about the timing of a missed period.
References
•Creinin MD, Schwartz JL, Guido RS, Pymar HC. Early pregnancy failure—
current management concepts. Obstet Gynecol Surv. 2001;56(2):105–13.
•Goldberg AB, Dean G, Kang MS, Youssof S, Darney P. Manual versus
electric vacuum aspiration for early first-trimester abortion: a controlled
study of complication rates. Obstet Gynecol. 2004;103:101–7.
Slide 49
[Insert Lecture Name Here]
•Hemlin J, Moller B. Manual vacuum aspiration, a safe and effective alternative in
early pregnancy termination. Acta Obstet Gynecol Scand. 2001;80:563–7.
•Stewart FH, Ellertson C, Cates W, Jr. Abortion. In: Contraceptive Technology,
18th edition. New York, NY: Ardent Media, Inc; 2004.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 49
[Insert Lecture Name Here]
Talking Points
Women who want to avoid pregnancy
• Approximately 3 million unintended pregnancies occur each year in the
United States.
• In 2001, 44% of unintended pregnancies in the United States ended in
live birth; 42% ended in therapeutic abortion, and 14% ended in
miscarriage or fetal demise.
• Women who want to avoid further pregnancy should be given
contraceptive counseling and if possible, contraception should be initiated
at the time of medical abortion.
• Ovulation may occur within 7–10 days after abortion
• Dispense EC with instructions for use
• Hormonal contraceptives can be started at or before the follow-up visit
• Women can be provided with a prescription for oral contraception,
hormonal patch, or vaginal ring along with directions to start
contraception on an agreed-upon date after she has passed the POC
but before she returns for follow-up.
• Alternatively, woman can receive Depo Provera injection, IUC insertion,
or Implanon insertion at the follow-up visit.
References
•Creinin MD, Schwartz JL, Guido RS, Pymar HC. Early pregnancy failure—
Slide 50
[Insert Lecture Name Here]
current management concepts. Obstet Gynecol Surv. 2001;56(2):105–13.
•Goldberg AB, Dean G, Kang MS, Youssof S, Darney P. Manual versus electric
vacuum aspiration for early first-trimester abortion: a controlled study of
complication rates. Obstet Gynecol. 2004;103:101–7.
•Hemlin J, Moller B. Manual vacuum aspiration, a safe and effective alternative in
early pregnancy termination. Acta Obstet Gynecol Scand. 2001;80:563–7.
•Stewart FH, Ellertson C, Cates W, Jr. Abortion. In: Contraceptive Technology,
18th edition. New York, NY: Ardent Media, Inc; 2004.
--Original content for this slide submitted by ARHP’s Clinical Advisory Committee for
“Options for Early Pregnancy Loss: Medication Management in the Outpatient
Setting” in December 2009. Original funding received from Danco Laboratories,
LLC. through an educational grant. This slide is available at www.arhp.org/core.
Slide 50
Options for Therapeutic Abortion:
Aspiration Versus Medication
Talking Points
•Patients should be scheduled for follow-up in 1 to 2 weeks to ensure
completed abortion in one of two ways:
• Quantitative serum hCG = a drop of 50% between first and repeat hCG
• Transvaginal ultrasound showing absence of a gestational sac.
•If one of the two criteria are met, then no further follow-up of hCG serum
is needed.
•If the criteria is not met, patients may elect manual vacuum aspiration at
any time if gestational sac and/or embryo has not passed.
Reference
[Reference needed]
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 51
[Insert Lecture Name Here]
Talking Points
•Most payers pay for the entire visit for early pregnancy loss management.
•The codes for treatment of early pregnancy loss are:
• ICD-9 for spontaneous abortion = 637.9
• CPT code to treat missed abortion = 59820
• CPT code to treat incomplete abortion = 59812
• Misoprostal (S code = S0191 J code = J3490)
References
[Reference needed]
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 52
[Insert Lecture Name Here]
Talking Points
•Treatment for induced medication abortions is typically covered to the
same extent as surgical abortions by payers.
•You can find state-specific reimbursement information at
www.earlyoptionpill.com .
References
[Reference needed]
--Original content for this slide submitted by ARHP’s Clinical Advisory
Committee for “Options for Early Pregnancy Loss: Medication Management
in the Outpatient Setting” in December 2009. Original funding received
from Danco Laboratories, LLC. through an educational grant. This slide is
available at www.arhp.org/core.
Slide 53
[Insert Lecture Name Here]
Slide 54