Early Pregnancy Loss (EPL) describes a nonviable intrauterine pregnancy identified prior to 13 weeks gestation, often a consequence of significant fetal chromosome abnormalities incompatible with life. Frequency of EPL increases with maternal age.
Limit expectant management to the first trimester
Spontaneous complete expulsion will occur in 80% of women with EPL ≤8 weeks gestation
Educate patient on moderate-to-heavy bleeding and cramping
Provide support and pain medications as needed
Ultrasound expulsion criteria
Absence of gestational sac and endometrial thickness <30 mm (common criteria)
No evidence of increased morbidity with thicker endometrium
Prior to medical management, ensure patient does not have
Misoprostol 800 micrograms vaginally
Repeat once, as needed, no earlier than 3 hours and within 7 days if no response
Consider mifepristone (if available) 200 mg orally 24 hours before misoprostol (see ‘Note’ and ‘Related ObG Topics’ below)
Mifepristone is limited by FDA restrictions
ACOG supports “improving access to mifepristone for reproductive health indications”
Counsel patient about bleeding and cramping
If soaking >2 maxipads/hour for > 2 hours, surgical intervention may be indicated
Use ultrasound to document expulsion or serial quantitative HCGs if ultrasound is unavailable
In case of failure, patient can still consider expectant management (see above) or surgical intervention
Note: Research (RCT) demonstrates the administration of 200 mg mifepristone followed by 800 micrograms misoprostol improves outcomes
83.8% of women in the mifepristone-pretreatment group vs 67.1% in the misoprostol-alone group experienced complete expulsion (see summary in ‘Related ObG Topics’, below)
Suction curettage in office or ambulatory surgery setting with local anesthesia/sedation
May be preferred treatment by women who want a faster and more controlled treatment path
ACOG recommends a single preoperative dose of doxycycline to prevent infection following surgical management
200-mg dose of doxycycline 1 hour prior to surgery (consensus and expert opinion)
Surgical intervention is management of choice in the following scenarios
Expectant, medical or surgical management to treat miscarriage are considered equivalent. Unless there is a change in clinical status (e.g. hemorrhage or infection), patient preference can guide decision making.
Risk of serious complications after treatment of EPL are rare, and comparable for all three treatment types
Medical management compared to expectant management
Increases time to complete expulsion
Does not increase need for surgical intervention
Medical management with misoprostol appears to be the most cost-effective treatment of EPL
Women should avoid intercourse for 1-2 weeks after passage of pregnancy tissue is complete
Risk and dosage for women undergoing EPL
Risk is low
‘Consider’ for women undergoing EPL, especially later in first trimester
If given, administer ‘at least’ 50 micrograms Rh(D)-immune globulin within 72 hours
Note: In the case of medical management, the ACOG Guideline states that “Women who are Rh(D) negative and unsensitized should receive Rh(D)-immune globulin within 72 hours of the first misoprostol administration”
Higher risk of alloimmunization
Patients ‘should receive’ at least 50 micrograms Rh(D)-immune globulin
Early Pregnancy Loss: How to Make the Ultrasound Diagnosis
Early Pregnancy Loss (EPL) is defined as a nonviable intrauterine pregnancy identified before 13 weeks gestation. ACOG states that ultrasound is the “preferred modality to verify the presence of a viable intrauterine gestation.” The AIUM Practice Parameter (see ‘Learn More – Primary Sources’ below) states
With transvaginal imaging, cardiac motion is usually observed when the embryo is 2 mm or greater in length. If an embryo less than 7 mm in length is seen without cardiac activity, a subsequent scan in 1 week is recommended to determine viability
Ultrasound Guidelines: The following criteria are derived from the 2012 Society of Radiologists in Ultrasound Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy
Diagnostic Criteria (Transvaginal)
CRL of ≥7 mm and no heartbeat
Mean sac diameter of ≥25 mm and no embryo
Absence of embryo with heartbeat ≥2 weeks after a scan showing a gestational sac without a yolk sac
Absence of embryo with heartbeat ≥11 days after a scan showing a gestational sac with a yolk sac
Suggestive, But Not Diagnostic (Transvaginal) – Follow up at 7-10 days
CRL <7 mm and no heartbeat
Mean sac diameter of 16 to 24 mm and no embryo
Absence of embryo with heartbeat 7 to 13 days after an ultrasound showing a gestational sac without a yolk sac
Absence of embryo with heartbeat 7 to 10 days after an ultrasound scan showing a gestational sac with a yolk sac
Absence of embryo for ≥6 weeks 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 CRL
Early pregnancy loss may present with clinical symptoms such as cramping and bleeding. However, these findings can be present in normal, ectopic or molar pregnancies. Ultrasound, if available, is a critical diagnostic modality but must be used in combination with clinical and laboratory findings, particularly serum β-hCG. For more information on recommended management when pregnancy location cannot be confirmed, see ‘Related ObG Topics’ below.
Document presence or absence of cardiac activity with M‐mode imaging or a 2D video clip
Pulsed Doppler ultrasound should not be used in the first trimester to “hear” the heartbeat
ACOG highlights the limitations of the above guidelines including
Cut-offs may be overly conservative based on available evidence
When taking care of patients with potential miscarriage
Consider a patient’s desire to have certainty of the loss prior to intervention
Discuss benefits of alternatives to surgical intervention as well as associated risks including
Spontaneous, unplanned passage of POCs
Additional ACOG ‘suggestive’ criteria (not diagnostic) that also require follow up at 7 to 10 days
Following a Danish study in 2016 by Nielsen et al. (JAMA, 2016), which concluded that fluconazole was associated with miscarriage, the FDA undertook a review to determine the safety of fluconazole in pregnancy. The FDA concluded (October 2019) that
Based on our reviews of several studies, FDA has determined that the available data do not provide conclusive evidence of an increased risk of miscarriage or stillbirth with a single 150 mg dose of oral fluconazole (Diflucan)
We reviewed the 2016 study cited in this DSC and four additional epidemiological studies
We approved updated prescribing information in 2018 to include all available information on the use of fluconazole in women who are pregnant or breastfeeding
It adequately addresses the potential risk of harm to unborn babies
Does Antibiotic Use Increase Risk of Spontaneous Abortion?
This study by Muanda et al. (CMAJ, 2017) aimed to determine if antibiotic use during pregnancy is associated with spontaneous abortion.
Nested Case-Control Study
Each case of spontaneous abortion (<20 weeks’ gestation) was matched for gestational age and year against 10 randomly selected controls. Antibiotic use was compared to non-exposure and exposure to penicillins or cephalosporins. After adjusting for potential confounders, multiple types of antibiotic use were associated with an increased risk of spontaneous abortion: azithromycin (adjusted odds ratio 1.65, 95% CI 1.34-2.02) clarithromycin (adjusted odds ratio 2.35, 95% CI 1.90-2.91), metronidazole (adjusted odds ratio 1.70, 95% CI 1.27-2.26), sulfonamides (odds ratio 2.01, 95% CI 1.36-2.97), tetracyclines (adjusted odds ratio 2.59, 95% CI 1.97-3.41) and quinolones (adjusted odds 2.72, 95% CI 2.27-3.27). These findings held whether comparing against non-exposure or exposure to penicillins or cephalosporins. The authors note that one potential confounder, that of severity of infection, could not be assessed in this study. Nevertheless, they do suggest that macrolides (excluding erythromycin) quinolones, tetracyclines, sulfonamides and metronidazole may be associated with miscarriage prior to 20 weeks and policies may need to update guidelines to reflect these findings.
This study by Scheller et al. (NEJM, 2017) aimed to determine if exposure to the quadrivalent HPV vaccine during pregnancy leads to adverse outcomes.
Matched case control study
Data from pregnant women in Denmark between 2006-2013 were extracted from national registries. Women who had been vaccinated during pregnancy were matched against women who had not been vaccinated in a 1:4 ratio. No increased risk was found for birth defects, spontaneous abortion, preterm birth, low birth weight, small size for gestational age or stillbirth. The authors conclude that exposure of quadrivalent HPV vaccine in pregnancy is safe and not associated with higher risk for adverse outcomes.
Conceiving After Pregnancy Loss – Is Waiting Beneficial?
A common question for providers following an early pregnancy loss is how long to wait before trying to conceive again. The authors performed a secondary analysis of a previous randomized controlled trial (RCT) to determine if there is any benefit to waiting after miscarriage by comparing time to pregnancy and live birth among couples based upon the time interval from fetal loss to attempting to conceive.
The authors found that in women who tried to conceive within a 3 month interval rather than waiting:
There was a statistically significant higher pregnancy rate – 68.9% compared to 51.1% (P< 0.01)
There was a statistically significant higher live birth rate – 53.2% compared to 36.1% (P<0.001)
After adjusting for age, race, BMI, education and subfertility, the 0-3 month group had a shorter time to achieve a pregnancy and shorter time to a pregnancy that resulted in a live birth
Waiting longer than 12 months may increase time to achieve pregnancy
There were no increased pregnancy complications in the 0 to 3 month group
The authors of this study (Obstet Gynecol, 2016) analyzed data from a well designed RCT that looked at the effects of preconception-initiated aspirin in women with prior losses (Lancet, 2014). In this present study the authors were able to compare 765 couples who attempted conception within 3 months to 233 couples who waited longer. The authors did adjust for aspirin therapy, although results did not show any significant effect.
This results of this paper do not support delaying pregnancy after a loss
The decision to conceive after loss may involve issues beyond physiological factors, which should be included in the informed decision making process between provider and patient
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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