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.
Note: Research (RCT) demonstrates the administration of 200 mg mifepristone followed by 800 micrograms misoprostol improves outcomes
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.
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”
ACOG Practice Bulletin 200: Early Pregnancy Loss
Manual vacuum aspiration: an outpatient alternative for surgical management of miscarriages.
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
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.
ACOG Practice Bulletin 200: Early Pregnancy Loss
AIUM Practice Parameter for the Performance of Limited Obstetric Ultrasound Examinations by Advanced Clinical Providers
Diagnostic criteria for nonviable pregnancy early in the first trimester. Society of Radiologists in Ultrasound Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy.
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
Vulvovaginal candidiasis occurs frequently during pregnancy. Only topical azole therapies, applied for 7 days, are recommended for use among pregnant women
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ACOG Practice Bulletin 215: Vaginitis in Nonpregnant Patients
Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth
Use of oral fluconazole during pregnancy and the risk of birth defects
Exposure to fluconazole and risk of congenital malformations in the offspring: A systematic review and meta-analysis
Fluconazole use and birth defects in the National Birth Defects Prevention Study
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.
Use of antibiotics during pregnancy and risk of spontaneous abortion
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.
Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes
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:
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.
Trying to conceive after an early pregnancy loss: an assessment on how long couples should wait
Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial
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