Time for Action: Managing Early Pregnancy Loss and ... · - Also called an induced abortion, pregnancy termination, or abortion ACOG 2018 Zuckerberg San Francisco General Reproductive

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Zuckerberg San Francisco General

Time for Action:Managing Early Pregnancy Loss and Medication Abortion in Primary CareCME Medical Care of Vulnerable and Underserved Populations

Jessica Beaman, MD MPHAssistant Professor of MedicineDivision of General Internal Medicine at ZSFG


Disclosures

I have no financial disclosures

I present off-label indications for mifepristone and misoprostol



“We acknowledge our awareness of the sensitive and

emotional nature of the abortion controversy; of the

vigorous opposing views, even among physicians.”

-- From Justice Harry A. Blackmun’s majority opinion in Roe v. Wade (January 22, 1973)


Learning Objectives1. Describe early pregnancy loss and abortion trends in the

United States

2. Analyze current evidence for medical management of early pregnancy loss and medication abortion

3. Effectively counsel your patients about medical management of early pregnancy loss and medication abortion

4. List key clinical and legal considerations for integration of mifepristone in to practice




United States





Overview



Terminology

Distinct clinical conditions

Early pregnancy loss (EPL) = nonviable, intrauterine pregnancy before 13 weeks gestation- Commonly referred to as miscarriage

Elective abortion = when a medication is taken or a procedure is performed to end a pregnancy- Also called an induced abortion, pregnancy termination, or abortion

ACOG 2018


Reproductive age women in primary care

61 million US women of reproductive age (15-44)- 10% become pregnant annually

Half of all US women will seek primary care in an internal medicine or family medicine clinic each year

CDC NCHS 2010 Pregnancy Rates Amongst U.S. Women (most recent data available) Daniels et al. Natl Health Stat Report 2015Petterson et al. JWH 2014



Prenatal Care


““On average, U.S. women want to have two children. To accomplish that goal, a woman will spend close to three years pregnant, postpartum, or attempting to become pregnant, and about three decades… trying to avoid an unintended pregnancy.”

Sonfield et al.From in “Moving Forward: Family Planning in the Era of Health Reform” (2014)



Lifetime Prevalence of Common Medical Conditions47

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Guttmacher InstituteNational Cancer Institute Surveillance, Epidemiology, and End Results ProgramNational Center for Health Statistics

Percent

Breast CancerCervical CancerDepressionDiabetesHypertension

Breast CancerCervical CancerDepressionDiabetesHypertension


Unintended Pregnancy is Common47

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Guttmacher InstituteNational Cancer Institute Surveillance, Epidemiology, and End Results ProgramNational Center for Health Statistics



Unintended Pregnancy

45% of all pregnancies are unintended

Mistimed = wants to become pregnant in the future but not at the time she became pregnant

Unwanted = did not want to become pregnant then or at any time in the future

Intended55%Unintended -

mistimed27%

Uninteded -unwanted

18%

Pregnancy Intentions

Finer and Zolna, NEJM 2016


Outcomes of Pregnancy

Early Pregnancy Loss (EPL) Abortion

Estimated that 10-20% of all pregnancies end in EPL- 80% of all pregnancy loss

is EPL

Half of all unintended pregnancies end in abortion- 1 in 4 women will have an

abortion by age 45 (20% by age 30)

ACOG 2018Guttmacher Institute 2018

Over 1/3 of all pregnancies result in EPL or elective abortion



Trends in Early Pregnancy Loss

Self-reported early pregnancy loss rate is increasing in US- 22,000 births

- Risk of EPL increased by 2% annually

- Exception = women 20-24 years old

Rossen et al Paediatr Perinatal Epidemiol 2018 (data from National Survey of Family Growth)


Early Pregnancy Loss

50% of all cases of early pregnancy loss are due to fetal chromosomal abnormalities

Risk Factors- Advanced maternal age 9-17% from 20-30 years

80% at 45 years

- Prior early pregnancy loss

- Substances (alcohol, caffeine, cigarette (> 10/day), cocaine)

- Comorbidities (e.g., APLS, DM, thyroid disease)Stephenson et al. Hum Reprod 2002American Society for Reproductive Medicine Fertil Steril 2012



Trends in Abortion

Guttmacher Institute 2018








Access to Care90% of women live in US county without an abortion clinic

Guttmacher Institute 2018



Impact on Patients

42 clinics 19 clinics


Impact on Patients

Grossman et al. JAMA 2017

- Dark blue = no facility, > 100 miles traveled

- Mean distance Δ = 51 miles- Decrease in abortions



Turnaway Study (UCSF, 2018 and ongoing)ANSIRH (Advancing New Standards in Reproductive Health)

Large, longitudinal study (N=1000)

- 8000 interviews

Women turned away based on GA

Lasting impacts

- Unemployment/living below FPL

- In relationship w/ abusive partner

- Less likely to have aspirational plans

No increased likelihood for:

- Depression

- Anxiety

- Suicidal ideationFoster et al. ANSIRH 2018


Incorporating Abortion into Primary Care

• 2012 by Page et al• 90 Patients in academic PCC• 67% felt PCC should offer medical abortions• 87% would want PCP to perform

• 2005 by Schwarz and Luetkemeyer• 212 Residents, 11 residencies• 42% IM residents willing to prescribe

medication abortion

• 2010 by Godfrey et al• 299 Patients in NYC and Chicago• 58% would choose primary care clinic (PCC)

for abortion



2018Support Policies for Comprehensive Reproductive

Health


Well-suited to provide high-quality women’s health care

Should receive appropriate training

Essential for women to have access to comprehensive, nondiscriminatory health coverage

Oppose legislations or regulations that limit access, including abortion

2018Support Policies for Comprehensive Reproductive

Health



OverviewSummary PCPs care for reproductive-age women who have a high

likelihood of experiencing:- Early pregnancy loss

- Unintended pregnancy

- Abortion

Rates of early pregnancy loss are increasing

Health disparities exist in who experiences abortion and has access to care

Patients and providers have shown interest in integrating abortion care into primary care



United States






Evidence


Early Pregnancy Loss Management

EPL management has traditionally been one of the following:- Expectant management (days to weeks)

Day 7 – 50% Day 46 = 90%

- Medications

- D&C procedure

Medication protocols- Misoprostol alone

- Mifepristone and misoprostol

Nanda et al. Cochrane Database Syst Rev 2012



Early Pregnancy Loss Management

EPL management has traditionally been one of the following:- Expectant management (days to weeks)

Day 7 – 50% Day 46 = 90%

- Medications = patient preference

- D&C procedure

Medication protocols- Misoprostol alone

- Mifepristone and misoprostolZhang et al. N Engl J Med 2005Kollitz et al. Am J Obstet Gynecol 2011Schreiber et al. Obstet Gynecol 2016


Medications for EPL

Mifepristone: A progesterone receptor blocker- Leads to detachment of pregnancy from endometrium

- Also softens/ripens cervix and primes myometrium for misoprostol

Misoprostol: A prostaglandin analogue- Stimulates uterine contractions



Update in Medical Management for EPLJune 7, 2018


Study Details Women experiencing an EPL between 5-12 weeks gestation

N = 300

Randomized to:- Misoprostol-alone (800 µg of vaginal misoprostol)

- Mifepristone-pretreatment group (200mg oral mifepristone followed by 800 µg of vaginal misoprostol 24 hours later)*

Primary outcomes:- Gestational sac expulsion by first follow-up visit (24-72 hours)

- No additional intervention (e.g., additional misoprostol, D+C) within 30 days of treatment



Study Details Women experiencing an EPL between 5-12 weeks gestation

N = 300

Randomized to:- Misoprostol-alone (800 µg of vaginal misoprostol)

- Mifepristone-pretreatment group (200mg oral mifepristone followed by 800 µg of vaginal misoprostol)

Primary outcomes:- Gestational sac expulsion by first follow-up visit

- No additional intervention (e.g., additional misoprostol, D+C) within 30 days of treatment


Clinical Outcomes among Women Who Received Medical Treatment for Early Pregnancy Loss.

Schreiber et al. NEJM 2018



Clinical Outcomes among Women Who Received Medical Treatment for Early Pregnancy Loss.



Adverse Events among Women Who Received Medical Treatment for Early Pregnancy Loss.




ACOG Practice Bulletin on EPL: Revision


Mifepristone + Misoprostol for EPL is the

BEST PRACTICE



Medication Regimen for EPL = Medication Abortion


First Trimester Abortion Management

~ 90% of abortions occur in first trimester

Medication abortion can take place up to 70 days gestation or 10 weeks

Women are increasingly choosing medication for early abortions

Of US abortion providers, 17% offer only medication abortion- Improves access



Overview of Abortion


First Trimester Abortion

523

9577

2001 2014

Medication Abortion Surgical Abortion

CDC 2018Jones and Jerman Perspect Sex Reprod Health 2014



First Trimester AbortionMedication Procedure

- Non-invasive- No anesthesia- Efficacy = 95-97%- Can occur at home- May need f/u medications or procedures

- Minimally invasive- Usually anesthesia or local block- Available later in pregnancy- Efficacy = 98-99%- Procedure < 10 minutes


Safety of Mifepristone and Abortion (2018)

48

• All forms of abortion are safe and effective

• Abortion can be safely performed in an office-

based setting

• No procedural skill needed for medication

• Does not increase risk of:

• Secondary infertility

• Breast cancer

• Depression/anxiety/PTSD

• Serious complications are < 1%



FDA-Labeling for Mifepristone

REMS (Risk Evaluation and Mitigation Strategies)- 79 FDA-approved medications with

“serious safety concerns”

- Registration of clinicians in central database

- Must be dispensed in-person

No pharmacy

No mail


FDA-Labeling for Mifepristone

REMS

Label updates



FDA Labeling Update2000 2016

Original FDA approved regimen

(2000)

Updated FDA approved regimen

(2016)

Gestational age limits 49 days gestation 70 days gestation

Mifepristone dose 600 mg on day 1 in clinic 200 mg on day 1 in clinic

Misoprostol dose and administration

400 mcg orally in clinic on day 3 800 mcg buccally at home 24-48 hours after mifepristone

Follow-up assessment 7-14 days post-mifepristone in clinic

14 days post-mifepristone*


FDA-Labeling

REMS

Label updates

Black Box warning- Rare infection

Clostridium sordellii

Clostridium perfringens



Current EvidenceSummary

EPL may be managed in one of three ways: expectant, medication, or procedure

The most effective medication regimen for EPL management is mifepristone followed by misoprostol

Mifepristone is safe and efficacious for use in both EPL and abortion

One must be aware of the REMS for mifepristone to comply with federal regulations for dispensing of medication



United States






Counseling


Counseling PatientsGeneral Principles

Preference-sensitive counseling

Use language and tone that demonstrate respect

Patient-centered communication (e.g., open-ended questions, nonjudgmental listening)

Options counseling- EPL: patient treatment priorities for miscarriage

- Unintended pregnancy: abortion, adoption, parenting

Address specific patient concerns/preferences and provide anticipatory guidance




Pregnancy Options Counseling FrameworkTEACH Early Abortion Training Workbook



What about contraceptive counseling? Timing

- 61% of patients reported they did not want to discuss contraception (N=1959)

History of reproductive injustices

- Involuntary sterilization

CA: 150 inmates from 2006 to 2010 undergoing sterilization --> Gov. Jerry Brown signs SB 1135 (Prison Anti-Sterilization Bill, 2014)

- Probation

TN: 2009 case of 21-year-old undergoing court ordered tubal ligation

Provider bias

Cansino Contraception 2015


Contraceptive Counseling

Dehlendorf et al., Am J Obstet Gynecol 2010



Contraceptive Counseling

Dehlendorf et al., Am J Obstet Gynecol 2010

• N=524 (OB/FM)• Low SES Black and Latina

patients were most likely to have IUD recommended

• Low SES > High SES


Counseling re: Mifepristone and Misoprostol Review how to take medications (two-step process)

- Misoprostol can be taken 0-72 hours after mifepristone

Timing depends on route

Anticipatory guidance- Symptoms – what is normal, what is not

- Return precautions and who to call/where to go for care

Impact on patients- EPL associated with grief, depression, and anxiety

- Abortion with no increased risk of depression, anxiety, SI though certainly can be associated with grief, sadness, guilt, or shame



Patient CounselingSummary

Preference-sensitive counseling is key

Tools and frameworks are available online to support patients in decisions related to EPL and abortion

Consider patient preference and provider bias in discussions of contraceptive counseling, especially in regards to EPL and abortion

Counseling for EPL and abortion should include a review of the medications, anticipatory guidance, and patient support



United States






Clinical Considerations


Mifepristone in Primary CareFor EPL and Medication Abortion

Power to destigmatize

Know and engage key stakeholders

Changes to culture/practice

Patient satisfaction:- Achieving rapid appointment access

- Staff courtesy

- Ready information to questions

Taylor Am J Med Qual 2013



Who can provide mifepristone?

42 states require clinics who perform medication abortions to be physicians

Know your state laws- Guttmacher Institute

“An Overview of Abortion Laws” (Updated Feb, 1 2019)


State-Based Abortion Restrictions



Clinic Protocol: 5 Key Items

1. Consent and eligibility

2. Labs

3. Storing/administering pills + Rhogam prn

4. Patient calls

5. Referrals



1. Consent and eligibility

2. Labs


4. Patient calls

5. Referrals



1. Consent

Available from Dancowebsite

(manufactures, markets, distributes

mifepristone as Mifeprex)


1. Eligibility Clinical dating

- LMP equivalent to U/S

- Alternative: serial beta hCG

Rule out contraindications:- IUD in place

- Allergy to prostaglandins or mifepristone

- Chronic adrenal failure or long-term systemic corticosteroid therapy

- Known or suspected ectopic pregnancy

- Hemorrhagic disorders or concurrent anticoagulant therapy

- Inherited porphyria




1. Consent

2. Labs – CBC, Rh, +/- beta hCG Consider safety if Hb < 10


4. Patient calls

5. Referrals



1. Consent

2. Labs – CBC, Rh, +/- beta hCG

3. Storing/administering pills + Rhogam prn Rhogam 50mcg IM within 72 hours of

mifepristone

4. Patient calls

5. Referrals



3. Administering PillsProtocol (from RHAP)

FDA Regimen 2016Buccal Misoprostol

Alternative: Vaginal Misoprostol

Mifepristone dose/location

200mg orallyDispensed in office

Same

Misoprostol dose/route 800 mcg buccally 800 mcg vaginally

Misoprostol timing 24-48 hours after mifepristone

6-72 hours after mifepristone

Misoprostol location Home Same

Follow-up/location 7-14 days after mifepristoneLocation not specified

7-14 days after mifepristoneOffice or alternative

75



1. Consent

2. Labs – CBC, Rh, +/- beta-hCG


4. Patient calls

5. Referrals



4. Patient Calls

Common side effects of misoprostol:- GI: Nausea/vomiting/diarrhea

- Low grade fevers/chills/myalgias are common

Usually resolve within 6 hours of use

Pain management

Changes in menses- Heavy first menses is common following mifepristone and

misoprostol


Pain Management

Mean pain score = 5.5 +/- 2.2

Ibuprofen vs opiates vs pregabalin

Most women use two 800mg tablets

Quick recovery- 12 hrs after miso 46-82% with no

pain

Raymond et al. Obstet Gynecol 2013Friedlander et al. Obstet Gynecol 2018

Rx: Ibuprofen 600-800mg q6-8h




1. Consent

2. Labs – CBC, Rh, +/- beta-hCG


4. Patient calls

5. Referrals Ultrasound, transfusion, vacuum aspiration


What You Don’t Need

No need to perform a pap smear or test for STIs



Anticipatory Guidance/Return Precautions No bleeding 24 hours after misoprostol

Soaked > 2 maxi-pads for > 2 consecutive hours

Unmanageable pain

Sustained fever > 100.4 or onset of fever > 24 hours after misoprostol

Abdominal pain, weakness, “feeling sick”, nausea, vomiting, or diarrhea > 24 hours after misoprostol

Must provide emergency contact service on 24 hour basis


Follow-upUp to day 14

In-person or not

Ultrasound = absence of gestational sac or embryo- Endometrial thickening is normal unless accompanied by symptoms

Serial hCG- Decrease from baseline hCG of 60% in 6-10 days of treatment

Self-assessment is non-inferior to routine follow-up

Chen et al. Contraception 2016NAF 2018Oppegard et al. Lancet 2015



Legal Considerations


• Affirm right to abortion in state constitution (9 states)

• Medicaid coverage for abortion (15 states)• Allow non-physicians to provide abortion (8

states)• Mandate private health insurance plans cover

abortion (3 states)


Zuckerberg San Francisco General85


Types of RegulationsPhysician/Clinic Patient

Physician-only (42)

Two physicians (19)

Hospital-based (19)

Public funding (33)

Private insurance (11)

Gestational limits (43)

State-mandated counseling (18)

Waiting periods (27)

Parental involvement (37)



State-Based Abortion Restrictions


What to do if you are a CHCRHAP FAQ on Integrating Medication Abortion Care into CHC



HHS Revision to Title X FundingFebruary 22, 2019 Proposed revision on June 1, 2018

- Received 500,000 comments

Final ruling:- Clear financial AND physical separation

between Title X funded projects/programs in facilities where abortion is offered

- Prohibit use of Title X funds to perform, promote, refer for, or support abortion for family planning

- Permits, but no longer requires, nondirective pregnancy counseling (including on abortion)

Takes effect in 60 days

- Physical separation (1 year)


What to do if you are a CHCRHAP FAQ on Integrating Medication Abortion Care into CHC

Separation of funds (Title X versus 330 funds)

Malpractice insurance- If CHC is FQHC and purchases FQHC insurance from federal

gov’t then policy excludes abortion services

Miscarriage management (medications, MVA) are covered

Safety concerns

Stakeholders

Expense (Mifepristone = $90 each)



Legal ResourcesFor integrating mifepristone in to your clinic

ACLU Reproductive Freedom Project

The Guttmacher Institute

Physicians for Reproductive Health

National Abortion Federation

Reproductive Health Access Project- Regional clusters and national IM cluster

(Danco)


Highlight: Future StudyUCSF + Multiple Community Sites

Expanding primary-care provision of medication abortion via mail-order mifepristone

Recruiting for primary care sites to start later this year

Sites will receive training, materials, ongoing support, reimbursement for services

After evaluation by clinician, patients will obtain medications from mail-order pharmacy and will be asked to complete 2 surveys

If interested, email [email protected] or [email protected]



Conclusion


Summary Mifepristone is safe and effective in the management of both

EPL and abortion

The medication regimen for mifepristone is identical in EPL and abortion

Mifepristone can be provided safely by clinicians working in a wide range of clinical settings

Expanding the number of clinicians who have integrated mifepristone in to their clinical practice is a simple way to provide high-quality comprehensive women’s health care for our patients



Eligibility and Exclusion Criteria: Mife + Miso

Eligibility criteria: < 70 days desiring medication abortion Exclusion criteria:

- IUD in place (must be removed prior to administration of the medications)

- Allergy to prostaglandins (misoprostol) or mifepristone

- Chronic adrenal failure or long-term systemic corticosteroid therapy

- Known or suspected ectopic pregnancy

- Hemorrhagic disorders or concurrent anticoagulant therapy

- Inherited porphyria



Efficacy of Mifepristone and Misoprostol for Abortion

Most studies = ~95%

Society of Family Planning Guidelines (2014)- 92% up to 49 days

- 85% from 49-70 days

TEACH Workbook (Chen and Creinin 2015)- 95-99% up to 63 days

- 91-94% from 64-70 days

Danco Label- 96-97% effective through 70 days

Documents

Time for Action: Managing Early Pregnancy Loss and ... · - Also called an induced abortion, pregnancy termination, or abortion ACOG 2018 Zuckerberg San Francisco General Reproductive