First Trimester Bleeding: Evaluation and Management


Am Fam Physician. 2019 Feb 1;99(3):166-174.

  Patient information: See related handout on bleeding in early pregnancy, written by the authors of this article.

  Related letter: Progestin Therapy Not Likely to Be Harmful in Women with First Trimester Bleeding

Author disclosure: No relevant financial affiliations.

Approximately one-fourth of pregnant women will experience bleeding in the first trimester. The differential diagnosis includes threatened abortion, early pregnancy loss, and ectopic pregnancy. Pain and heavy bleeding are associated with an increased risk of early pregnancy loss. Treatment of threatened abortion is expectant management. Bed rest does not improve outcomes, and there is insufficient evidence supporting the use of progestins. Trends in quantitative β subunit of human chorionic gonadotropin (β-hCG) levels provide useful information when distinguishing normal from abnormal early pregnancy. The discriminatory level (1,500 to 3,000 mIU per mL) is the β-hCG level above which an intrauterine pregnancy should be visible on transvaginal ultrasonography. Failure to detect an intrauterine pregnancy, combined with β-hCG levels higher than the discriminatory level, should raise concern for early pregnancy loss or ectopic pregnancy. Ultrasound findings diagnostic of early pregnancy loss include a mean gestational sac diameter of 25 mm or greater with no embryo and no fetal cardiac activity when the crown-rump length is 7 mm or more. Treatment options for early pregnancy loss include expectant management, medical management with mifepristone and misoprostol, or uterine aspiration. The incidence of ectopic pregnancy is 1% to 2% in the United States and accounts for 6% of all maternal deaths. Established criteria should be used to determine treatment options for ectopic pregnancy, including expectant management, medical management with methotrexate, or surgical intervention.

Approximately 25% of pregnant women experience bleeding before 12 weeks' gestation.1,2  The differential diagnosis includes nonobstetric causes, bleeding in a viable intrauterine pregnancy, early pregnancy loss, and ectopic pregnancy. Physical examination findings, laboratory testing, and ultrasonography can be used to diagnose the cause of first trimester bleeding and provide appropriate management. A glossary of terms used in this article is available in Table 1.36


A meta-analysis evaluating the accuracy of a single progesterone test to predict pregnancy outcomes for women with first trimester bleeding showed that a progesterone level less than 6 ng per mL (19.1 nmol per L) reliably excluded viable pregnancy, with a negative predictive value of 99%.

Guidelines for ultrasound diagnosis of early pregnancy loss have been established to decrease the likelihood of false diagnosis and of intervening in a desired viable pregnancy.

Oral mifepristone (Mifeprex), 200 mg, followed 24 hours later by misoprostol, 800 mcg vaginally, is the most effective regimen for medical management of early pregnancy loss and, when available, should be recommended over misoprostol alone.

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Clinical recommendationEvidence ratingReferences

The initial β-hCG level should be considered when following the rate of β-hCG increase in early pregnancy. In viable intrauterine pregnancies with initial β-hCG levels of less than 1,500 mIU per mL, 1,500 to 3,000 mIU per mL, or greater than 3,000 mIU per mL, there is a 99% chance that the β-hCG level will increase by at least 49%, 40%, and 33%, respectively, over 48 hours.



Rho (D) immune globulin (Rhogam) should be administered to Rh-negative women with early pregnancy loss, especially when it occurs later in the first trimester.



Early pregnancy loss can be definitively diagnosed in women with ultrasound findings of a mean gestational sac diameter of 25 mm or greater and no embryo or embryonic cardiac activity when the crown-rump length is at least 7 mm.


4, 5

Clinicians should expect to see a gestational sac on transvaginal ultrasonography when β-hCG levels reach 1,500 to 3,000 mIU per mL.


10, 15

Bed rest or progestins should not be recommended to prevent early pregnancy loss in patients with first trimester bleeding because these interventions have not been proven effective.


3, 18, 19

Expectant management, medical management, and uterine aspiration are safe methods for treating anembryonic gestations and fetal demise. Patient preference should guide treatment decisions.


2023, 28

Oral mifepristone (Mifeprex), 200 mg, followed 24 hours later by misoprostol, 800 mcg vaginally, is the most effective regimen for medical management of early pregnancy loss and, when available, should be recommended over misoprostol alone.



Treatment for incomplete abortion should rely on shared decision making. Patients should be informed that expectant management is more than 90% effective.


22, 24

β-hCG = β subunit of human chorionic gonadotropin.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series.

The Authors

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ERIN HENDRIKS, MD, is a clinical assistant professor in the Department of Family Medicine at the University of Michigan Medical School, Ann Arbor....

HONOR MACNAUGHTON, MD, is an associate professor in the Department of Family Medicine at Tufts University School of Medicine, Boston, Mass.

MARICELA CASTILLO MACKENZIE, MD, is a clinical assistant professor in the Department of Family Medicine at the University of Michigan Medical School.

Address correspondence to Erin Hendriks, MD, at Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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