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EARLY PREGNANCY LOSS

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OFFICE EVALUATION AND MANAGEMENT

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CE PRE-TEST.

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Please complete this pre-test on your phone or computer in order to receive CE credit for participation in this workshop. You can access the pre-test at:

https://www.surveymonkey.com/r/eplpre

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DISCLOSURES

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Participants must attend 100% of this workshop.

Participants must complete the evaluation survey at the beginning and end of the workshop

No relevant financial relationships to disclose with ineligible companies.

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LEARNING OBJECTIVES.

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Conduct a history and physical exam for first trimester bleeding to help distinguish normal from abnormal pregnancies.
Interpret ultrasound and labs results to diagnose early pregnancy loss (EPL)
Describe the three options for management of EPL

- Expectant management

- Medical management

- Aspiration procedure management

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TERMINOLOGY

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MISCARRIAGE

EARLY PREGNANCY LOSS (EPL)

SPONTANEOUS ABORTION

Interchangeable for a nonviable pregnancy in the first trimester (<13 weeks of gestation); preferred terminology is early pregnancy loss (EPL)

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Additional Terminology

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Threatened Abortion
Incomplete Abortion
Missed Abortion
Anembryonic Pregnancy
Embryonic or Fetal Demise
Ectopic Pregnancy
Pregnancy of Unknown Location (PUL)

Ask audience to define

Definitions:

Threatened Abortion: Bleeding before 20 weeks of pregnancy with a closed cervix. Pregnancy is viable at time of diagnosis.

Incomplete Abortion: Some, but not all products of conception have passed.

Missed Abortion: Early pregnancy loss is diagnosed on ultrasound but patient is asymptomatic.

Anembryonic Pregnancy: Pregnancy in which a gestational sac develops without any embryonic structures (no yolk sac or fetal pole). Previously referred to as “empty sac” or blighted ovum

Embryonic or Fetal Demise: Subcategory of early pregnancy loss in which an embryonic or fetal tissue is present but is not viable

Ectopic Pregnancy: Any pregnancy outside of the endometrium. Most commonly in the fallopian tube, but can also be in the cervix, ovary, or abdomen

Pregnancy of Unknown Location: When a patient presents with a positive pregnancy test, but no pregnancy is seen on ultrasound. Differential includes early intrauterine pregnancy, early pregnancy loss, and ectopic pregnancy.

Reference: Prine, Linda W., and Honor MacNaughton. "Office management of early pregnancy loss." American family physician 84.1 (2011).

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EPIDEMIOLOGY

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1 in 4 women* will experience EPL

10% of clinically diagnosed pregnancies

50% caused by chromosomal abnormalities

The most common risk factors are advanced maternal age and a previous pregnancy loss

One in four women will experience early pregnancy loss in her lifetime*

Note to facilitator: At RHAP we recommend mentioning that many times if we’re showing data or quoting studies they may describe their patient population as “women” – what they are referring to is cisgender women. We know that people of all genders can experience early pregnancy loss, use contraception, birth children, and have abortions. That is why we talk about our patients and we do not use the word WOMEN to describe the people who come to our clinics/offices, because that leaves out a significant portion of our patient population.

10% of diagnosed pregnancies result in a pregnancy loss - increasing in frequency with age, up to 80% at age 45

Some may only form a gestational sac, also sometimes called an anembryonic pregnancy, or the demise may occur after the embryo forms.

Most miscarriages happen at 6 weeks, with another smaller peak at 10 weeks gestational age.

The cause of approximately 50% of EPL is chromosomal abnormalities. Advanced maternal age and a previous pregnancy loss are the most commonly associated risk factors. However, given the prevalence, further testing is not recommended until patients experience 2 or more episodes of EPL.

Reference: American College of Obstetricians and Gynecologists. "Early Pregnancy Loss. ACOG Practice Bulletin No. 200." Obstet Gynecol vol. 132, no. 5 (2018): e197-207.

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SIGNS AND SYMPTOMS OF EPL

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Vaginal bleeding
Pelvic pain or cramping
Absent fetal heart tones on Doppler when pregnancy should be > 10 weeks
Size-dates discrepancy on bimanual exam
POCs seen by clinician at cervical os or in vaginal vault on speculum exam

Especially in desired pregnancies, it is important to distinguish between viable and nonviable pregnancies with a high degree of certainty before proceeding with treatment. The history and physical exam can be combined with Beta HCG levels and ultrasound results to make this diagnosis.

Clinical findings that are suspicious for EPL include:

Vaginal bleeding (common, occurring in up to 25% of pregnancies- can be normal but generally requires further evaluation)

- Pelvic pain or cramping (with or without bleeding) and a positive pregnancy test

- No fetal heart tones on doppler exam after 10 weeks

Bimanual exam with a size-dates discrepancy
Speculum exam with an open cervical os or POCs seen in the vaginal vault or at the cervix

Reference: Prine, Linda W., and Honor MacNaughton. "Office management of early pregnancy loss." American family physician 84.1 (2011).

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1^ST TRIMESTER BLEEDING ALGORITHM

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ALGORITHM FOR DIAGNOSIS OF PREGNANCY OF UNKNOWN LOCATION (PUL)

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DIAGNOSIS – ULTRASOUND FINDINGS

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Table 2. Guidelines for Transvaginal Ultrasonographic Diagnosis of Pregnancy Failure in a Woman with an Intrauterine Pregnancy of Uncertain Viability
Findings Diagnostic of Pregnancy Failure	Findings Suspicious for, but not Diagnostic of, Pregnancy Failure
Crown-rump length of ≥ 7 mm and no heartbeat Mean sac diameter of ≥ 25 mm and no embryo Absence of embryo with heartbeat ≥ 2 wk after a scan that showed a gestational sac without a yolk sac Absence of embryo with heartbeat ≥ 11 days after a scan that showed a gestational sac with a yolk sac	Crown-rump length of < 7 mm and no heartbeat Mean sac diameter of 16-24 mm and no embryo Absence of embryo with heartbeat 7-13 days after a scan that showed a gestational sac without a yolk sac Absence of embryo with heartbeat 7-10 days after a scan that showed a gestational sac with a yolk sac Absence of embryo ≥ 6 wk after last menstrual period Empty amnion (amnion seen adjacent to yolk sac, with no visible embryo) Enlarged yolk sac (> 7 mm) Small gestational sac in relation to the size of the embryo (< 5 mm difference between mean sac diameter and crown-rump length)

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DIAGNOSIS – ULTRASOUND FINDINGS

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CLASSIFICATION	VAGINAL BLEEDING	ENDOMETRIAL THICKNESS	PRODUCTS OF CONCEPTION SEEN ON ULTRASOUND
COMPLETE EARLY PREGNANCY LOSS	Little or none	Any, though typically < 30 mm	None
INCOMPLETE EARLY PREGNANCY LOSS	Little or none	Any	Heterogenous tissues (with or without a gestational sac) distorting the endometrial midline
EMBRYONIC OR FETAL DEMISE	Yes or no	Any	Gestational sac with fetal tissue (i.e., fetal pole or yolk sac) present, meeting ultrasound criteria for SAB (i.e. >7 mm with no FH)
ANEMBRYONIC PREGNANCY	Yes or no	Any	Gestational sac without fetal tissue (i.e. no fetal pole or yolk sac) present, meeting ultrasound criteria for SAB (i.e. MSD > 25 mm without yolk sac)

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OUTPATIENT MANAGEMENT

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EXPECTANT

Watchful waiting

MEDICATION

PROCEDURE

Mifepristone*

+

Misoprostol

Uterine Aspiration

* Mifepristone is not always available. With mifepristone, the success rate is 84% overall. With only misoprostol, the success rate is 67% overall.

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PATIENT CASE: JENNIFER

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She/Her pronouns
22 years old
LMP was 7 weeks ago
Positive urine pregnancy
She is having some vaginal bleeding

ADDITIONAL HISTORY? AND ON PHYSICAL?

Ask participants about next steps.

History and Physical:

-Was her last period normal (is LMP accurate?)

-If pelvic pain - midline or lateral?

-Prior PID? Miscarriages? Surgeries?

-Uterine size

-Tissue or just blood from os? And how much bleeding is she having?

Clinical Signs of First Trimester Pregnancy Loss:

-Patient presents with pelvic pain with or without bleeding and a positive pregnancy test

-Vaginal bleeding

-No fetal heart tones on doppler exam after 10 weeks

-Report from radiology - Non-viable pregnancy on ultrasound

Clinicians can make this diagnosis and offer treatment to your patient. No need to send every patient with a positive pregnancy test and vaginal bleeding to the ER!

Image Source: https://unsplash.com/photos/U4JDjYmjn1g

Photo Credit: https://www.flickr.com/photos/wocintechchat/25900759582/

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1^ST TRIMESTER BLEEDING ALGORITHM

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JENNIFER’S ULTRASOUND.

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ANEMBRYONIC GESTATION

Mean sac diameter >25 mm with no embryo

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DIAGNOSIS – ULTRASOUND FINDINGS

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Table 2. Guidelines for Transvaginal Ultrasonographic Diagnosis of Pregnancy Failure in a Woman with an Intrauterine Pregnancy of Uncertain Viability
Findings Diagnostic of Pregnancy Failure	Findings Suspicious for, but not Diagnostic of, Pregnancy Failure
Crown-rump length of ≥ 7 mm and no heartbeat Mean sac diameter of ≥ 25 mm and no embryo Absence of embryo with heartbeat ≥ 2 wk after a scan that showed a gestational sac without a yolk sac Absence of embryo with heartbeat ≥ 11 days after a scan that showed a gestational sac with a yolk sac	Crown-rump length of < 7 mm and no heartbeat Mean sac diameter of 16-24 mm and no embryo Absence of embryo with heartbeat 7-13 days after a scan that showed a gestational sac without a yolk sac Absence of embryo with heartbeat 7-10 days after a scan that showed a gestational sac with a yolk sac Absence of embryo ≥ 6 wk after last menstrual period Empty amnion (amnion seen adjacent to yolk sac, with no visible embryo) Enlarged yolk sac (> 7 mm) Small gestational sac in relation to the size of the embryo (< 5 mm difference between mean sac diameter and crown-rump length)

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PATIENT CASE: JENNIFER

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This is not her fault
She can decide on the management option

What does she need to know?

Remember – half of all pregnancies are unintended, not everyone is sad to lose a pregnancy.

Very important to give info to the partner that pregnancy loss is no one’s fault.

Risk factors: Age, prior miscarriages, smoking, cocaine use, fever/infection

Miscarriage myths:

Air travel

Blunt abdominal trauma

Contraceptive use

Exercise

HPV vaccine

Previous abortions

Sexual activity

Important in counseling: patient can decide on their management option. Better mental health outcomes when the patient is involved in the decision making.

Cochrane review found all options have pros and cons and that all should be offered.

Reference: Ghosh J, Papadopoulou A, Devall AJ, Jeffery HC, Beeson LE, Do V, Price MJ, Tobias A, Tunçalp Ö, Lavelanet A, Gülmezoglu AM, Coomarasamy A, Gallos ID. Methods for managing miscarriage: a network meta-analysis. Cochrane Database of Systematic Reviews 2021, Issue 6. Art. No.: CD012602. DOI: 10.1002/14651858.CD012602.pub2.

Photo Credit: https://www.flickr.com/photos/wocintechchat/25392468193/

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EXPECTANT MANAGEMENT

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SUCCESS OF EXPECTANT MANAGEMENT

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Group	N	Complete Day 7	Complete Day 14	Success Day 49
Incomplete	221	117 (53%)	185 (84%)	201 (91%)
Fetal demise	138	41 (30%)	81 (59%)	105 (76%)
Anembryonic	92	23 (25%)	48 (52%)	61 (66%)
TOTAL	451	181 (40%)	314 (70%)	367 (81%)

When counseling patients about the likelihood of expectant management being successful, it is important to have a sense of how successful each option is. One can remember them by thinking that, of course, an incomplete will finish on it’s own most easily. Note though, that anembryonic pregnancies have the lowest success rate without intervention (they have the highest failure rate for medical management also). Not sure why this is, but that empty sac just hangs in there…while a demise is more likely to be rejected, and come out with less intervention…

The other important point to note is that these statistics came from a study, where there were established end points, as noted. In real clinical time, we might wait longer than 49 days, or try combinations of medication and expectant management.

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RISKS

Timing not predictable
Less effective
Infection (rare)
Need for emergent uterine aspiration (rare)
Hemorrhage/transfusion (very rare)

EXPECTANT MANAGEMENT

BENEFITS

Noninvasive
More Private
More “natural”
Inexpensive
No medication side effects
Availability

Butler et al J Fam Pract 2005 54:889-90

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PATIENT INSTRUCTIONS: EXPECTANT MANAGEMENT

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Expect cramping and heavy bleeding

Pain control: ibuprofen, +/- low dose narcotic, heating pad

Call for “heavy bleeding”: soaking through ≥ 2 pads per hour for two hours in a row

Give contact information for reaching clinician

Patient does NOT need to bring products of conception back to the clinician

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MEDICAL MANAGEMENT: MIFEPRISTONE AND MISOPROSTOL

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Jennifer does not want to wait anymore

Ask if anyone has done this?

Patients often choose medication management because it feels more natural and yet happens more predictably

Standard dosing of 800mcg of miso administered vaginally required a second dose of miso in 15-40% of patients (schrieber). Now, with the addition of Mifepristone, we have improved success rates if a patient does decide to treat their early pregnancy loss with medication.

Administration of miso vaginally vs buccal does not have difference in success (cochrane 2017 review) but buccally can give more GI side-effects

References:

Kim C, Barnard S, Neilson JP, Hickey M, Vazquez JC, Dou L. Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev 2017;1:CD007223-CD007223

Photo Credit: https://www.flickr.com/photos/wocintechchat/25900759582/

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RISKS

Side effects from medications
Infection (rare)
Need for aspiration (rare)
Hemorrhage or transfusion (rare)
Mifepristone not available widely

MEDICAL MANAGEMENT

BENEFITS

Timing of bleeding more predictable than expectant management
Noninvasive
Private
Inexpensive
Flexible timing

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SUCCESS RATES WITH MISOPROSTOL ALONE VS MIFEPRISTONE AND MISOPROSTOL

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SUCCESS RATE (EXPULSION OF GESTATIONAL SAC) BY DAY 2	MISOPROSTOL ALONE	MIFEPRISTONE AND MISOPROSTOL
ALL SUBCATEGORIES OF EPL	67%	84%
EMBRYONIC DEMISE	68%	85%
ANEMBRYONIC	65%	80%

Medical management can be done with misoprostol alone or with the combination of mifepristone followed by misoprostol 24 hours later.

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GUIDELINES FOR MEDICAL MANAGEMENT

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1. Candidates

Those with diagnosis of nonviable intrauterine pregnancy less than 12 weeks by ultrasound

2. Labs

Rh screen if > 8 weeks (if status is not available)
Hematocrit
Quantitative serum hCG (quant not always needed if ultrasound diagnosis is definitive)
Consider gonorrhea/chlamydia if patient is at risk

3. Consent forms

Danco or GenBioPro mifepristone agreement; consider additional evidence-based consent form

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GUIDELINES FOR MEDICAL MANAGEMENT

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1. Mifepristone 200mg (one tab) orally

Dispensed in the office
Patient instructed to take when convenient

2. Misoprostol 800mcg (four tabs) vaginally

If prescribed with mifepristone, use 24 hours following mifepristone
If prescribed alone, use when convenient
Repeat misoprostol dose if no bleeding or only light bleeding

3. Pain management

Ibuprofen 600-800 mg Q6 hours
A few tablets of narcotics available if needed

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SIDE EFFECTS OF MISOPROSTOL

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Bleeding
Cramping
Low grade fevers and/or chills
Nausea and vomiting
Diarrhea

All side effects should resolve within 24 hours

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PATIENT INSTRUCTIONS

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Lie down for 30 minutes after using misoprostol; okay if medication falls out after 30 minutes

Warning signs same as for expectant management:

Call for “heavy bleeding,” fever, purulent vaginal discharge, or uncontrolled pain not improved with medication
Patient does NOT need to bring products of conception back to the clinician
Contact information for reaching clinician

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WHAT DO YOU NEED TO START USING MEDICATION FOR EPL IN YOUR PRACTICE?

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Office aspiration or referral

A PLAN FOR WHEN MEDICATION DOESN’T WORK

DANCO CONSENT FORM

PATIENT HANDOUTS

ORDER MIFEPRISTONE TO STOCK IN OFFICE

CLINICAL GUIDELINES

ON-CALL GROUP ALL FAMILIAR WITH MEDICAL MANAGEMENT

RESOURCE FOR HANDOUTS: WWW.REPRODUCTIVEACCESS.ORG

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DIAGNOSING COMPLETION AFTER MEDICAL MANAGEMNT OF EPL

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Quant bHCG drop of more than 50% 48 hours or 80% by 7 days

Vaginal ultrasound with no sac or pregnancy after prior ultrasound documenting intrauterine pregnancy�

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OFFICE PROCEDURE OPTION: UTERINE ASPIRATION

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Manual Vacuum Aspiration (MVA)

Sharp curettage (D&C) no longer an acceptable option due to higher complication rates

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MVA INSTRUMENTS & SUPPLIES

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Advantages to Office MVA

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Avoid repeated exams that occur in hospital
Cost
Avoid cumbersome OR protocols (NPO requirements, discharge criteria)
Reduced wait time, OR scheduling difficulties
Personalized care
Convenience, privacy, patient autonomy

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KEY�LEARNING POINTS.

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There are three office options to be offered for miscarriage management:

- Expectant

- Medical (mifepristone and misoprostol, and misoprostol alone)

- Procedure: MVA

Mental health outcomes for patients are best when they are involved in the decision-making around their care

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RESOURCES.

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REFERENCES.

Allison JL, Sherwood RS, Schust DJ. “Management of first trimester pregnancy loss can be safely moved into the office.” Rev Obstet Gynecol; 2011;4(1):5-14

American College of Obstetricians and Gynecologists. "Early Pregnancy Loss. ACOG Practice Bulletin No. 200." Obstet Gynecol vol. 132, no. 5 (2018): e197-207.

Butler, Charles et al. “Clinical Inquiries. How Long Is Expectant Management Safe in First-Trimester Miscarriage?” The Journal of family practice 54.10 (2005): 889–890.

Chen B, Creinin M, “Contemporary Management of Early Pregnancy Failure.” Clin Obstet and Gynecol Volume 50, Number 1, (2007) 67–88.

Creinin, Mitchell D. et al. “Factors Related to Successful Misoprostol Treatment for Early Pregnancy Failure.” Obstetrics and gynecology 107.4 (2006): 901–907.

Doubilet, Peter M. et al. “Diagnostic Criteria for Nonviable Pregnancy Early in the First Trimester.” Ultrasound quarterly 30.1 (2014): 3–9.

Emily M. Godfrey, Lawrence Leeman, and Panna Lossy. “Early Pregnancy Loss Needn’t Require a Trip to the Hospital.” Journal of Family Practice 58.11 (2009): 585–590.

Ghosh J, Papadopoulou A, Devall AJ, Jeffery HC, Beeson LE, Do V, Price MJ, Tobias A, Tunçalp Ö, Lavelanet A, Gülmezoglu AM, Coomarasamy A, Gallos ID. Methods for managing miscarriage: a network meta-analysis. Cochrane Database of Systematic Reviews 2021, Issue 6. Art. No.: CD012602. DOI: 10.1002/14651858.CD012602.pub2.

Luise, Ciro et al. “Outcome of Expectant Management of Spontaneous First Trimester Miscarriage: Observational Study.” BMJ 324.7342 (2002): 873–875.

Milingos, D. S. et al. “Manual Vacuum Aspiration: A Safe Alternative for the Surgical Management of Early Pregnancy Loss.” BJOG: an international journal of obstetrics and gynaecology 116.9 (2009): 1268–1271.

Prine LW, Macnaughton, H. “Office Management of Early Pregnancy Loss.” AAFP 84.1 (2011): 75–82.

Tunçalp, Ozge, A. Metin Gülmezoglu, and João Paulo Souza. “Surgical Procedures for Evacuating Incomplete Miscarriage.” Cochrane database of systematic reviews 9 (2010): CD001993.

Wallace, Robin, Angela DiLaura, and Christine Dehlendorf. “‘Every Person’s Just Different’: Women’s Experiences with Counseling for Early Pregnancy Loss Management.” Women’s health issues: official publication of the Jacobs Institute of Women's Health 27.4 (2017): 456–462.

Wallace, Robin R. et al. “Counseling Women with Early Pregnancy Failure: Utilizing Evidence, Preserving Preference.” Patient education and counseling 81.3 (2010): 454–461.

Zhang, Jun et al. “A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Failure.” The New England journal of medicine 353.8 (2005): 761–769.

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CE �POST-TEST.

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Please complete this post-test on your phone or computer in order to receive CE credit for participation in this workshop. You can access the pre-test at:

https://www.surveymonkey.com/r/EPLPost

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THANK YOU.

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