Miscarriage is the most common complication of pregnancy, and affects 25% of women who have been pregnant by the age of 39 years. It is essential that ultrasound diagnosis is made with 100% specificity, so that there is no danger of inadvertent termination of a viable pregnancy.

Abstract:

Miscarriage is the most common complication of pregnancy, and affects 25% of women who have been pregnant by the age of 39 years. It is essential that ultrasound diagnosis is made with 100% specificity, so that there is no danger of inadvertent termination of a viable pregnancy. Over the past few years, cut off values of sizes beyond which gestation sac contents, or embryo heart activity, should be seen, have been defined and tested. Evidence based recommendations for minimum time intervals between scans, to allow time for a healthy pregnancy to clearly develop, have also become available. In the interim, prior to definitive diagnosis of either viability or non-viability, it is referred to as a pregnancy of uncertain viability (PUV). Once miscarriage is diagnosed, management options are expectant, medical or surgical. 

Keywords: miscarriage, pregnancy of uncertain viability, PUV, gestation sac, yolk sac, crown rump length, ultrasonography.

Authors: Jessica Farren1, 2, Shabnam Bobdiwala1, Tom Bourne1

  1. Tommy’s National Centre for Miscarriage Research, Imperial College, Queen Charlottes and Chelsea Hospital, London, UK
  2. Department of Gynaecology, St Mary’s Hospital, London, UK

Reviewer: Christoph Brezinka

Definition

Miscarriage is defined by the World Health Organisation as the spontaneous loss of a pregnancy before 23 weeks gestation and weighing up to 500g (i.e. before reaching potential viability.)1 Recurrent miscarriage describes the loss of three or more consecutive pregnancies. 
Pregnancy of uncertain viability (PUV) describes the situation in which transvaginal ultrasonography shows an intrauterine gestation sac, but neither an embryonic heartbeat, nor definite findings of pregnancy failure.
 

Epidemiology

Miscarriage affects approximately 25% of women who have been pregnant by the age of 39 years, and up to 20% of pregnancies overall.2. 1% of women experience recurrent miscarriage.3
The vast majority of miscarriages occur in the first trimester. The most common cause of miscarriage is chromosomal abnormalities of the fetus, for which maternal age at conception is the most significant risk factor.4 Other risk factors include smoking, excess alcohol intake, illicit drug use, uterine surgery or abnormalities, and certain systemic diseases (including SLE, uncontrolled diabetes, antiphospholipid syndrome.)
 

Ultrasound characteristics

A miscarriage can be considered in terms of deviation from the normal trajectory of growth seen in early pregnancy. In a normal early pregnancy, a gestation sac would first become visible as a hypoechoic round or oval structure placed asymmetrically within the decidua at or near the fundus. This is usually visible by 32 days after the last menstrual period.5 Thereafter, it can be expected to grow at a rate of 1mm per day. The mean sac diameter (MSD) is the standard measurement of gestation sac size, and consists of measurements in three orthogonal planes. The yolk sac, a spherical hyperechoic ring, can usually be seen at 35 days, and the embryo first appears as a thickening of this ring (which takes on a ‘signet ring’ appearance) from approximately 37 days.6. The crown-rump length is used to determine the gestation of a normal first trimester pregnancy. Fetal heart activity can usually be seen as soon as the fetal pole becomes visible. The amnion is a thin hyperechoic ring that surrounds the embryo from approximately 49 days. 
The most important principle in the diagnosis of miscarriage is that it should be made with absolute certainty. A false positive diagnosis may potentially lead to inadvertent termination. 
A considerable amount of work has been done in the past few years to define and test appropriate cut-offs for the diagnosis of miscarriage.7, 8 In a single scan, an empty gestation sac with a mean sac diameter of more than or equal to 25mm, or an embryo with crown rump length of more than or equal to 7mm with no fetal heart activity, is sufficient to diagnose miscarriage.9 New evidence suggests that, where a woman is certain of the date of her last menstrual period, and gestation is more than 70 days, these cut-offs can be brought down; to 18mm MSD for an empty sac, and 3mm CRL for an fetus without heart activity.10
If findings are inconclusive, a repeat scan is required at a time interval. The exact time interval which can be considered conclusive for diagnosis has not yet been adopted by national guidance11, but a consensus paper suggested at least 14 days if an empty gestation sac had been seen on first scan, or 11 days if a gestation sac with a yolk sac had been seen12. According to recent evidence, seven days is sufficient if the MSD was more than 12mm, or there was a visible embryo, at the initial scan.10 At subsequent scan, an embryo with heart activity should be seen. If the initial MSD is less than or equal to 12mm, a minimum interval of 14 days should be left, after which point failure for the gestation sac to double in size is diagnostic for miscarriage. 
There are other features that are suggestive of, but not diagnostic for, miscarriage. These include findings close to the aforementioned diagnostic boundaries. Also suspicious are findings of discordant growth, such as the appearance of the amnion without an embryo within (so called the ‘empty amnion sign’), or less than 5mm difference between the CRL and the MSD.12 Other concerning features include an irregular sac, which may be surrounded by blood (a subchorionic hematoma), or may sit low in the cavity. If a sac is seen low in the cavity, care must be taken to exclude a cervical or Caesarean section scar ectopic.   
 

Clinical symptoms

Features of miscarriage, or threatened miscarriage, commonly include pelvic pain and vaginal bleeding, or passage of identifiable pregnancy tissue. 
Miscarriage can also be asymptomatic, and picked up incidentally on routine scanning, or have more subtle features such as a reduction in pregnancy symptoms (nausea and breast tenderness.)
 

Management

Following definitive diagnosis of a miscarriage, management options can be discussed. Expectant management can be expected to be successful in 70% of women after 2 weeks.13 This is cost-effective, but women may find difficult the uncertainty associated with not knowing when bleeding or pain may occur.

Medical management with misoprostol administered vaginally (NICE recommends 800 or 600 mcg11), usually performed on an outpatient basis, is successful in 84% women after 8 days.14 Women may experience gastrointestinal side effects. As a result of heavier bleeding and increased risk of emergency admission at larger sizes and later gestations, many units will have cut-offs beyond which they will recommend inpatient medical management or surgical management. 
Surgical management with suction evacuation (which may increasingly be performed without general anaesthetic – termed ‘manual vacuum aspiration’) is the most predictable, with the highest success rates, and the shortest duration of bleeding and pain, and the lowest risk of unplanned admission or intervention. However, there are potential surgical complications, including uterine perforation, which are higher at more advanced gestations.
Overall, patients should be reassured that regardless of their choice of management, there is no evidence of any difference in infection or future fertility.15

References

1. Definitions and indicators in family planning, maternal and child health and reproductive health. WHO Regional Strategy on Sexual and Reproductive Health. . World Health Organization 
2. Blohm F, Friden B, Milsom I. A prospective longitudinal population-based study of clinical miscarriage in an urban Swedish population. BJOG 2008;115(2):176-82; discussion 83.
3. Stirrat GM. Recurrent miscarriage. Lancet (London, England) 1990;336(8716):673-5.
4. Nybo Andersen AM, Wohlfahrt J, Christens P, et al. Maternal age and fetal loss: population based register linkage study. Bmj 2000;320(7251):1708-12.
5. Timor-Tritsch IE, Farine D, Rosen MG. A close look at early embryonic development with the high-frequency transvaginal transducer. Am J Obstet Gynecol 1988;159(3):676-81.
6. Bottomley C, Bourne T. Dating and growth in the first trimester. Best Pract Res Clin Obstet Gynaecol 2009;23(4):439-52.
7. Jeve Y, Rana R, Bhide A, et al. Accuracy of first-trimester ultrasound in the diagnosis of early embryonic demise: a systematic review. Ultrasound Obstet Gynecol 2011;38(5):489-96.
8. Pexsters A, Luts J, Van Schoubroeck D, et al. Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurement of gestational sac and crown-rump length at 6-9 weeks' gestation. Ultrasound Obstet Gynecol 2011;38(5):510-5.
9. Abdallah Y, Daemen A, Kirk E, et al. Limitations of current definitions of miscarriage using mean gestational sac diameter and crown-rump length measurements: a multicenter observational study. Ultrasound Obstet Gynecol 2011;38(5):497-502.
10. Preisler J, Kopeika J, Ismail L, et al. Defining safe criteria to diagnose miscarriage: prospective observational multicentre study. Bmj 2015;351:h4579.
11. NICE. Ectopic pregnancy and miscarriage: diagnosis and initial management, 2012.
12. Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369(15):1443-51.
13. Luise C, Jermy K, May C, et al. Outcome of expectant management of spontaneous first trimester miscarriage: observational study. Bmj 2002;324(7342):873-5.
14. Zhang  J, Gilles  JM, Barnhart  K, et al. A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Failure. New England Journal of Medicine 2005;353(8):761-69.
15. Trinder J, Brocklehurst P, Porter R, et al. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ 2006;332(7552):1235-40.

This article should be cited as: Farren J., Bobdiwala S., Bourne T.: Miscarriage and Pregnancy of Uncertain Viability, Visual Encyclopedia of Ultrasound in Obstetrics and Gynaecology, www.isuog.org, May 2016 


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