Ultrasound prediction of miscarriage

Journal Club slides prepared by Dr Tommaso Bignardi(UOG Editor for Trainees)

UOG Journal Club: November 2011

Accuracy of first-trimester ultrasound in the diagnosis of early embryonic demise: a systematic reviewY. Jeve, R. Rana, A. Bhide, S. Thangaratinam

Limitations of current definitions of miscarriage using mean gestational sac diameter and crown–rump length measurements: a multicenter observational study

Y. Abdallah, A. Daemen, E. Kirk et al.Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study

Y. Abdallah, A. Daemen, S. Guha et al.Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurements of

gestational sac and crown–rump length at 6–9 weeks gestationPexsters, J. Luts, D. Van Schoubroeck et al.

Volume 38, Issue 5, Date: November 2011, pages 489–515 (all articles)

Diagnosis of miscarriage on TVSDiagnosis of miscarriage on TVS

Royal College of Obstetricians and Gynaecologists(RCOG) 2006

• CRL ≥ 6mm with no visible cardiac activity

• MSD ≥ 20mm without a visible embryo or yolk sac

American College of Radiologists (ACR) 2000

• CRL > 5mm with no visible cardiac activity

• MSD > 16mm without a visible embryo or yolk sac

Society of Obstetricians and Gynaecologists of Canada (SOGC) 2005• CRL > 5mm with no visible cardiac activity

• MSD > 8mm without a visible yolk sac

• MSD > 16mm without a visible embryo

CRL, crown–rump lengthMSD, mean sac diameter

Current guidelines are based on weak or moderate level of evidence (small studies or opinion)

The current criteria used to diagnose miscarriage at ultrasound show variation

The accurate diagnosis of miscarriage is fundamental, as any error may be associated with

inadvertent termination of a viable pregnancy

Search of:1. MEDLINE (1951 to 2011)2. Embase (1980 to 2011) 3. Cochrane Library

720 citations reviewed, 23 met search criteria

Eight articles involving a total of 872 women were included

Accuracy of first-trimester ultrasound in the diagnosis of early embryonic demise: a systematic review

Jeve Y et al., UOG 2011

Jeve Y et al., UOG 2011 Nov

Results

Best criteriahave 95% CIrange of0.96 to 1.00

Conclusions• First systematic review of ultrasound diagnosis of miscarriage

• Studies are 15–20 years old, small numbers of miscarriage, reference standards were poor (method of miscarriage confirmation)

• Various cut-off values used (4–6mm for CRL, 13–25mm for MSD), making pooling of data impossible

• Best (most specific) criteria appeared to be MSD > 25mm with a missing embryo or MSD > 20mm with a missing yolk sac

• These criteria had a 95% CI of 0.96–1.00, therefore up to 4 out of 100

diagnoses of early fetal demise may be wrong

Jeve Y et al., UOG 2011 Nov

Conclusions

Limitations of current definitions of miscarriage using mean gestational sac diameter and crown–rump length measurements: a multicenter observational study

Abdallah Y et al., UOG 2011 (a)

Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study.

Abdallah Y et al., UOG 2011 (b)

Inclusion criteria:- Intrauterine pregnancy of uncertain viability (IPUV) at sonography- IPUV defined as an MSD < 20mm with no obvious yolk sac/embryo orCRL < 6mm with no fetal heart activity

Exclusion criteria:- women clinically unstable - women who subsequently underwent uterine evacuation

2D-transvaginal scans (6–12 MHz) at 0 and 7–14 days later

Multicenter observational study of 1060 women in four London hospitals

Abdallah Y et al., UOG 2011 (a)

Results: 1st scan cut-off values

1060 IPUV473 (44.6%) viable at 11–13-week scan587 (55.4%) non-viable at follow-up scans

Yolk sac - NOYolk sac - NOEmbryo - NOEmbryo - NO

MSD > 16mm FPR 4.4%MSD > 20mm FPR 0.5%MSD ≥ 21mm FPR 0%

Yolk sac - YESYolk sac - YESEmbryo - NOEmbryo - NO

MSD > 16mm FPR 2.6%MSD > 20mm FPR 0.4%MSD ≥ 21mm FPR 0%

1st scan

Yolk sac - YESYolk sac - YESEmbryo - YESEmbryo - YES

CRL > 4mm FPR 8.3%CRL > 5mm FPR 8.3%CRL ≥ 5.3mm FPR 0%

*FPR, false-positive rate for miscarriage at subsequent scans Abdallah Y et al., UOG 2011 (a)

Results: 2nd scan growth rate

1060 IPUVSubset of 359 patients where a gestational sac was seen on the second scan 7–14 days later

Significant overlap of MSD and CRL growth between viable and non-viable pregnancies

2nd scan

Failure to visualize a yolk sac or embryo on the follow-up scan was always associated with miscarriage

Abdallah Y et al., UOG 2011 (b)

Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurement of gestational sac and crown–rump length at 6–9 weeks' gestation

Pexsters A et al., UOG 2011

Prospective cross-sectional study54 women at 6–9 weeks

• Observers blinded• CRL measured from the outer ends• Gestational sac measured in three planes• CRL and MSD measured twice by each observer

Pexsters A et al., UOG 2011

Results

• Based on 95% CI, for a given CRL of 6mm as measured by one observer, the second observer’s measurement may range from 5.4 to 6.7mm

• Similarly, given an MSD of 20mm as measured by one observer, the measurement for the second observer may range from 16.8 to 24.5mm

Summary• Data from these studies show that current definitions used to diagnose miscarriage are potentially unsafe

• Significant interobserver variability may be associated with a misdiagnosis of miscarriage

• Current national guidelines should be reviewed to avoid inadvertent termination of wanted pregnancy

• Large prospective studies with agreed reference standards are urgently required