INTRODUCTION — Pregnancy loss, also referred to as miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks of gestation. Early pregnancy loss, which occurs in the first trimester (ie, up to 12+6 weeks gestation), is the most common type. The diagnosis of pregnancy loss is generally confirmed with transvaginal ultrasound evaluation.

This topic will review the clinical criteria and when they may be applied for making an ultrasound diagnosis of pregnancy loss. Related content on risk factors and etiology, clinical presentation, treatment options, and management protocols is presented separately.

●(See "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology".)

●(See "Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation".)

●(See "Pregnancy loss (miscarriage): Comparison of treatment options and discussion of related care".)

●(See "Pregnancy loss (miscarriage): Management techniques".)

Content specific to individuals with recurrent pregnancy loss is discussed elsewhere.

●(See "Recurrent pregnancy loss: Definition and etiology".)

●(See "Recurrent pregnancy loss: Evaluation".)

●(See "Recurrent pregnancy loss: Management".)

In this topic, we will use the term "patient" to describe genetic females and use “woman/en” as used in the included studies. However, we recognize that not all people capable of pregnancy identify as women and we encourage the reader to consider the specific counseling needs of transgender and gender nonbinary individuals.

ROLE OF ULTRASOUND — When available, ultrasound, particularly transvaginal ultrasound, is generally performed in all pregnant individuals with signs or symptoms suggestive of pregnancy loss to confirm an intrauterine gestation, assess for cardiac activity, and exclude ectopic pregnancy.

●(See "Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation".)

●(See "Ectopic pregnancy: Clinical manifestations and diagnosis".)

Choice of imaging route — Transvaginal ultrasound is typically utilized for early pregnancy. Transabdominal ultrasound may be used in instances where the gestational sac is high above the cervix (for example, in fibroid uterus), and transperineal ultrasound may also be utilized, albeit infrequently [1]. The choice of transducer route and frequency is based on the clinical scenario, patient habitus, likely gestational age of pregnancy (if known), and availability of equipment. (See "Ultrasonography of pregnancy of unknown location", section on 'Transabdominal versus transvaginal'.)

If transabdominal ultrasound is inconclusive, then transvaginal or transperineal ultrasound may be performed to increased image clarity (image 1A-B) [1]. Patients whose transvaginal ultrasound confirms an intrauterine pregnancy without fetal cardiac activity often undergo repeat ultrasound at a future date, although care based on a single ultrasound may be appropriate. (See 'Single ultrasound diagnostic criteria' below.)

Ultrasound findings in first trimester — When using transvaginal ultrasound, gestational landmarks include identification of a gestational sac (4.5 to 5 weeks) (image 1A), yolk sac (5 weeks) (image 1B-C), cardiac activity (5.5 to 6 weeks) (movie 1), and crown-rump length (CRL; 6 weeks) (image 2 and table 1). Measurement of the CRL provides the most accurate assessment of gestational age, but mean sac diameter can also be used (table 1 and table 2) [2]. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'First-trimester gestational age assessment'.)

●An international standard for ultrasound dating of pregnancy based on CRL measurement was developed by the International Fetal and Newborn Growth Consortium for the 21^st Century and is available online at INTERGROWTH-21 [2]. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'First-trimester gestational age assessment'.)

●The specific components of late first- versus second- and third-trimester examinations are described in detail in the American Institute of Ultrasound in Medicine-American College of Radiology-American College of Obstetricians and Gynecologists-Society for Maternal-Fetal Medicine-Society of Radiologists in Ultrasound (AIUM-ACR-ACOG-SMFM-SRU) Practice Parameter for the Performance of Standard Diagnostic Obstetric Ultrasound Examinations, which is beyond the scope of this topic [3]. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Second- and third-trimester gestational age assessment'.)

Timing of ultrasound from last menstrual period — The timing of initial ultrasound in asymptomatic pregnant individuals varies. We advise that a pelvic ultrasound be deferred until seven weeks of gestation from the last menstrual period to avoid unnecessary evaluations for pregnancy of unknown location or embryos with slow or absent cardiac activity. An initial ultrasound for a patient at seven to eight weeks of gestation is more likely to identify the presence of embryonic cardiac activity and thus avoid the need for a follow-up ultrasound. Individuals with risk factors for pregnancy loss may undergo ultrasound at the initial prenatal visit, while for others the first ultrasound may occur at the time of first-trimester aneuploidy screening or at the time of second-trimester fetal anatomy assessment. (See "Ultrasonography of pregnancy of unknown location".)

ULTRASOUND DIAGNOSIS OF PREGNANCY LOSS — Pregnancy loss can be diagnosed with both serial and single ultrasound studies; the selection depends on the clinical findings and the patient's preferences, including tolerance for a false-positive diagnosis.

Serial ultrasound studies — Once an intrauterine pregnancy is identified on ultrasound, pregnancy loss is diagnosed if any subsequent ultrasound (performed routinely or for symptoms) shows no intrauterine pregnancy or loss of previously seen cardiac activity [4]. Ultrasound is further used to confirm intrauterine location of pregnancy, presence of cardiac activity, and approximate gestational age at which development stopped. The gestational age of the pregnancy by ultrasound criteria may differ from the gestational age by last menstrual period. (See 'Additional diagnostic challenges' below.)

Single ultrasound diagnostic criteria

Our approach — The choice of diagnostic criteria is driven by the preferences of the patient:

●Highest diagnostic certainty – For patients who desire more time to confirm the diagnosis and/or desire the highest diagnostic certainty, we apply the Society of Radiologists in Ultrasound (SRU) criteria that include a mean gestational sac diameter ≥25 mm (without a yolk sac or embryo (image 3A-B)) or an embryo with crown-rump length (CRL) ≥7 mm (without cardiac activity (image 4)) as visualized with transvaginal ultrasound [4,5]. This approach is endorsed by the SRU as well as several academic societies and government agencies globally [4-9]. (See 'Available diagnostic criteria' below.)

With this approach, the specificity and positive predictive values are essentially 100 percent [5], which is important as many clinicians of variable ultrasound training and skill perform these examinations. These criteria may be particularly helpful for individuals who wish to wait longer to confirm pregnancy loss and/or wish the lowest risk of false diagnosis, but this may result in treatment delay for some individuals if applied universally.

●Reasonable diagnostic certainty – For patients who desire expedited treatment for pregnancy loss, it is reasonable to apply the criteria that include a mean gestational sac diameter ≥21 mm or a CRL of ≥6 mm without cardiac activity, demonstrated with transvaginal ultrasound, to confirm pregnancy loss [10]. (See 'Available diagnostic criteria' below.)

This approach allows the patient to efficiently proceed with treatment in the setting of high-quality ultrasound with high diagnostic certainty (0 percent false-positive rate in some studies). As imaging studies can be limited both by the quality of the machine used and the technician's interpretation, these variables should be taken into account when managing patients whose pregnancies are at the threshold of the measurement cut points and placed into the context of the patient's needs. Patients should understand that there may be a slight risk of interrupting normal progress.

●Rationale – The concern with using the criteria set forth by the SRU is that interobserver reliability was already accounted for in the prior studies, which resulted in less conservative criteria (see 'Available diagnostic criteria' below). However, much of the research in diagnosis of pregnancy loss relies on data from expert sonographers and radiologists. Variations in ultrasound equipment and skill or training of the provider will affect measurements. Furthermore, many patient factors, such as obesity, uterine fibroids, and uterine position, can make visualization of the pregnancy more difficult. Some experts advocate for more conservative diagnostic criteria to account for these factors.

While the clinicians would never want to falsely diagnose a live pregnancy as a miscarriage, we similarly would never want a patient to have delayed management of a pregnancy loss due to not meeting overly conservative ultrasonographic criteria. Additionally, ultrasound imaging is only one element of diagnosing a miscarriage, and the overall clinical picture includes other data that might suggest a benefit from applying less conservative ultrasonographic criteria (eg, plateau or fall in human chorionic gonadotropin levels). (See "Clinical manifestations and diagnosis of early pregnancy", section on 'Diagnosis'.)

Based on the observational data, mean gestational sac diameter ≥21 mm or CRL ≥6 mm could be reasonably used as cutoffs for diagnosing pregnancy loss with a single ultrasound and without the need for a follow-up study or evaluation (table 3). The rationale for rounding up from 5.3 to 6 mm is the limited submillimeter precision of ultrasound measurements in this setting, coupled with the known false-positive rate at 5 mm with absent cardiac activity [11]. While the authors of the study advise a mean gestational sac diameter cutoff of ≥25 mm and a CRL cutoff of ≥7 to conservatively allow for interobserver variability and minimize the risk of a false-positive diagnosis of miscarriage, we believe these cutoffs are overly cautious given the false-positive rates of 0 and use mean gestational sac diameter ≥21 mm and CRL ≥6 mm in our practices.

Points of debate — Criteria for diagnosing pregnancy loss with a single ultrasound examination are a matter of debate and interpretation of available data because the criteria are influenced by the dataset used, clinical context, expertise of the sonographer, quality of the ultrasound machine, and the patient's need for diagnostic certainty.

●Concern for false-positive test result – One concern is that a false-positive test result (ie, a live pregnancy is incorrectly diagnosed as a pregnancy loss) could inadvertently result in termination of a desired, healthy pregnancy.

●Clinical context and patient-centered care – The entire clinical context must be taken into consideration when implementing the available guidelines. Clinical issues for consideration include the individual's "desire to continue the pregnancy, willingness to postpone intervention to achieve 100 percent certainty of pregnancy loss, and the potential consequences of waiting for intervention, including unwanted spontaneous passage of pregnancy tissue, the need for an unscheduled visit or procedure, and patient anxiety" [4]. Depending on a patient's desires and preferences, it is appropriate to diagnose and manage early pregnancy loss when the clinical context is highly suggestive of loss but does not meet the strictest diagnostic criteria.

●Impact of sonographer, anatomic approach, and equipment – When using single ultrasound criteria to evaluate for pregnancy loss, baseline considerations include use of transvaginal or transabdominal approach, skill of sonographer, and quality of equipment. Additionally, M-mode is advised for evaluation of fetal cardiac activity rather than pulsed or color Doppler to minimize the power used over the embryo.

In cases where the sac or embryonic pole measurement is at the diagnostic boundary, the experience and skill of the sonographer become extremely important because interobserver variability has been described [11]. In settings of diagnostic uncertainty, repeat imaging may be warranted if the patient desires additional confirmatory data.

Available diagnostic criteria — The suggested ultrasound criteria below for diagnosing nonviable pregnancy are based on studies performed starting in the early 1990s through the early 2000s (table 3). As these studies were performed, ultrasound technology and experience continued to evolve, which may account, in part, for their differences.

●Observational study data – A 2011 observational cross-sectional study attempted to define the false-positive rates (FPRs) for different CRLs and mean gestational sac diameters by ultrasound assessment [10]. Data were collected prospectively for 1060 patients with a diagnosis of intrauterine pregnancy of uncertain viability. For the 585 individuals with nonviable pregnancies, the authors reported the following:

•In the setting of an embryo with absent heartbeat, the FPR was 8.3 percent with CRLs of 4 and 5 mm, but 0 for a CRL ≥5.3 mm.

•For mean gestational sac diameter, in the absence of both embryo and yolk sac, the FPRs for correctly diagnosing nonviable pregnancy were 4.4, 0.5, and 0 percent for cutoffs of 16, 20, and ≥21 mm, respectively.

•For mean gestational sac diameter with a visible yolk sack but absent embryo, FPRs of 2.6, 0.4, and 0 percent were reported for mean gestational sac diameter cutoffs of 16, 20, and ≥21 mm, respectively.

●SRU criteria – In 2013, the SRU reviewed the available data and proposed even more stringent criteria than that which resulted in a 0 percent FPR in the prior studies (table 3) [5,10]. Their stated goal was to achieve 100 percent specificity and positive predictive value (ie, no chance of incorrectly diagnosing a live pregnancy as nonviable), citing concerns about the potential for intra- and interobserver variability and/or differing levels of provider skill or ultrasound precision and their potential to lead to a false-positive diagnosis of pregnancy loss in the setting of a pregnancy that was actually alive [4,5].

The 2012 SRU Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy guidelines proposed the following ultrasound criteria to diagnose pregnancy loss [5]:

•A gestational sac ≥25 mm in mean diameter that does not contain a yolk sac or embryo (image 3A-B).

•An embryo with a CRL ≥7 mm that does not have cardiac activity.

•Absence of an embryo with a heartbeat in ≥2 weeks from a prior ultrasound demonstrating a gestational sac without a yolk sac.

•After a pelvic ultrasound showed a gestational sac with a yolk sac, absence of an embryo with a heartbeat in ≥11 days.

●Historical data – Initial studies published in the early 1990s attempted to determine the embryonic size at which cardiac activity was always present in normal pregnancy. After evaluating 398 transvaginal ultrasound studies performed in early pregnancy, the authors concluded that absence of cardiac activity in a visualized embryo usually signified embryonic demise [12]. However, in the absence of cardiac activity, definitive diagnosis of pregnancy demise was to be avoided if the CRL was less than 5 mm because two embryos (2 and 4 mm) initially had absent cardiac activity but progressed to normal outcome. The second study prospectively evaluated 309 consecutive early pregnancies, of which 175 were normal, with vaginal and abdominal ultrasound [13]. Using vaginal ultrasound, one-third of embryos with CRL <5 mm did not have visualized cardiac activity compared with 100 percent of embryos ≥5 mm. Additionally, an empty gestational sac of <12 mm average diameter was not able to predict nonviable pregnancy.

Based on these studies, initial criteria for nonviable early pregnancy included (table 3):

•CRL of 5 mm without cardiac activity.

•Empty gestational sac measuring 16 mm in mean gestational sac diameter.

Additional diagnostic challenges — Scenarios that can make the assessment of early pregnancy more challenging include discrepancy in the gestational age based on last menstrual period or date of conception versus ultrasound, presence of multiple gestations, and inability to identify an intrauterine pregnancy with the resultant diagnosis of pregnancy of unknown location.

●Gestational age discrepancy – In patients for whom the gestational age of the pregnancy measured on ultrasound is substantially smaller than the expected gestational age based on last menstrual period or conception date, providers must discuss the possibility that ovulation occurred later than expected and discuss the diagnostic criteria needed to confirm pregnancy loss. The gestational age can be determined using mean sac diameter (table 2). (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

●Multiple gestation – Occasionally, ultrasound will visualize a multiple gestation with one gestational sac showing reduced growth or lack of yolk sac or embryonic pole. In these cases, pregnancy loss is not diagnosed unless both gestational sacs meet the above criteria. (See "Twin pregnancy: Overview".)

●Pregnancy of unknown location – Individuals with a positive pregnancy test but no intrauterine pregnancy seen on ultrasound are assessed as having a pregnancy of unknown location and followed carefully with repeat imaging and possibly serial serum human chorionic gonadotropin levels until the location can be determined. Alternatively, diagnostic uterine aspiration can be performed to expedite the location diagnosis when preserving a possible intrauterine pregnancy is not the priority [14]. Differential diagnosis includes an early intrauterine pregnancy, an ectopic pregnancy, a miscarriage, or a molar pregnancy. (See "Ultrasonography of pregnancy of unknown location".)

Other ultrasound findings in early pregnancy — Separate from the criteria above, additional ultrasound findings may be suggestive of nonviable or live pregnancy.

●Suggestive of non-viable pregnancy

•Expanded or empty amnion – The presence of an expanded amnion greater than expected for the size of the embryo or an empty amnion can confirm pregnancy loss (image 5 and image 6). With appropriate ultrasound training and experience, these signs are very helpful since they allow for earlier diagnosis of a nonviable pregnancy [15,16]. The amnion is not typically seen as a separate structure, and is larger than the embryo until about eight to nine weeks; an amnion without an embryo or a small embryo with an amnion greater than anticipated size by gestational age is consistent with pregnancy loss.

●Findings consistent with live pregnancy

•Gestational sac with yolk sac only – A gestational sac with a yolk sac does not have an embryonic pole early in development (image 7). In the presence of symptoms (vaginal bleeding, pain), a repeat ultrasound may be warranted in 7 to 10 days to confirm viability.

•Normal pregnancy with amnion – In early pregnancy with normal development, the amnion expands well beyond the limits of the embryo itself after approximately eight weeks (image 8).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pregnancy loss (spontaneous abortion)".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Miscarriage (The Basics)" and "Patient education: Bleeding in early pregnancy (The Basics)")

●Beyond the Basics topics (see "Patient education: Miscarriage (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Role of ultrasound – When available, transvaginal ultrasound is generally performed in all pregnant individuals with signs or symptoms suggestive of pregnancy loss to confirm an intrauterine gestation, assess for cardiac activity, and exclude ectopic pregnancy. (See 'Role of ultrasound' above.)

•Imaging approach – Transabdominal, transvaginal, and transperineal ultrasound may all be used to assess pregnancy; the approach is determined by patient factors and available equipment. (See 'Choice of imaging route' above.)

•Pregnancy landmarks by gestational age – When using transvaginal ultrasound, gestational landmarks include identification of a gestational sac (4.5 to 5 weeks) (image 1A), yolk sac (5 weeks) (image 1B-C), cardiac activity (5.5 to 6 weeks) (movie 1), and crown-rump length (6 weeks) (image 2 and table 1). Measurement of the crown-rump length (CRL) provides the most accurate assessment of gestational age, but mean sac diameter can also be used (table 1 and table 2) [2]. (See 'Ultrasound findings in first trimester' above.)

●Serial ultrasound criteria – Once an intrauterine pregnancy is identified on ultrasound, pregnancy loss is diagnosed if any subsequent ultrasound (performed routinely or for symptoms) shows no intrauterine pregnancy or loss of previously seen cardiac activity. (See 'Serial ultrasound studies' above.)

●Single ultrasound criteria – Criteria for diagnosing pregnancy loss with a single ultrasound examination are a matter of debate and interpretation of available data because the criteria are influenced by the dataset used, clinical context, and the patient's need for diagnostic certainty. (See 'Points of debate' above and 'Available diagnostic criteria' above.)

•Highest diagnostic certainty – For patients who desire more time to confirm the diagnosis and/or desire the highest diagnostic certainty, we apply the Society of Radiologists in Ultrasound (SRU) criteria that include a mean gestational sac diameter ≥25 mm (without a yolk sac or embryo) or an embryo with CRL ≥7 mm (without cardiac activity) as visualized with transvaginal ultrasound. (See 'Our approach' above.)

•Expedited diagnosis – For patients who desire expedited treatment for pregnancy loss, it is reasonable to apply the criteria that include a mean gestational sac diameter ≥21 mm or a CRL ≥6 mm without cardiac activity, demonstrated with transvaginal ultrasound, to confirm pregnancy loss. Imaging studies can be limited both by the quality of the machine used and the technician's interpretation. These variables should be taken into account when managing patients whose pregnancies are at the threshold of the measurement cut points and placed into the context of the patient's needs. Patients should understand that there may be a slight risk of interrupting a normal pregnancy. (See 'Our approach' above.)

●Additional challenges – Scenarios that can make the diagnosis of pregnancy loss more challenging include discrepancy in the gestational age based on last menstrual period or date of conception versus ultrasound, presence of multiple gestations, and pregnancy of unknown location. (See 'Additional diagnostic challenges' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Togas Tulandi, MD, MHCM, and Haya M Al-Fozan, MD, who contributed to an earlier version of this topic review.