CRL 6MM Is transvaginal ultrasound a reliable test in the diagnosis of early embryonic demise? Outcomes of embryos of less than 6mm in crown-rump length without cardiac activity. R Hassan, L Sandu Aana, Rich K, Lal S Early Pregnancy Assessment Unit University Hospital of Wales Cardiff 24 April 2009 EPAU, UHW, Cardiff

Aims To assess the outcomes of embryos with crown-rump length (CRL) of ≤6mm without embryonic cardiac activity (CA). This is to establish whether the absence of CA at CRL <6 mm has a high predictive value of determining early embryonic demise. EPAU, UHW, Cardiff

Background With TVS it is possible to identify embryos with CRL of 1mm. Embryonic CA begins by 22 days embryonic age at which point the CRL is ~ 1.5-3.0mm. Investigators have evaluated multiple US findings and their role in the assessment of a non-viable pregnancy. CRL 2.2 CRL 3.7 EPAU, UHW, Cardiff

Background What’s in the literature ___________________________________________________________________ Authors n Ultrasound Positive test Sensitivity Specificity criteria % % ___________________________________________________________________________ Brown et al (1988) 217 CRL >4mm Absent CA NA 100 Levi et al (1990) 71 CRL >3mm Absent CA 65 88 Goldstein (1992) 96 CRL >3mm Absent CA 54 100 Schouwink (1999) 372 CRL ≥ 5mm Absent CA 68 100 Abaid et al (2007) 179 CRL ≥ 3.5mm Absent CA 75 100 EPAU, UHW, Cardiff

Method Prospectively collected computerised database from January 2006 to December 2008. Inclusion criteria: All patients with single embryos with CRL ≤ 6mm were included regardless of clinical presentation and other sonographic findings. Embryonic viability was determined by a repeat US after one week and further outcomes at dating scan. Setting: Early pregnancy assessment unit, UHW, Cardiff. Sub-analysis on the effects of presenting symptoms on the outcome of embryonic viability was carried out. EPAU, UHW, Cardiff

*did not meet inclusion criteria or no record of follow up Results A Total of 1388 patients had embryos with CRL ≤6mm. 1388 CA located 1295 CA not located 93 92 1082 213 excluded* 1 no f/u 80 non-viable (87%) 12 viable (13%) 135 non-viable (12%) 947 viable (88%) *did not meet inclusion criteria or no record of follow up EPAU, UHW, Cardiff

Results Risk of embryonic demise _______________________________________________________ CRL mm CA present (n=1082) CA absent (n=92) n (%) n (%) 1.0-1.9 3/12 (25) 1/3 (33) 2.0-2.9 26/183 (14) 12/15 (80) 3.0-3.9 37/193 (19) 20/22 (91) 4.0-4.9 13/234 (6) 18/21 (86) 5.0-5.9 26/224 (12) 19/21 (90) 6.0 30/236 (13) 10/10 (100) 135/1082 (12) 80/92 (87) EPAU, UHW, Cardiff

Results Absence of CA at predicting embryonic demise _________________________________________________________________________ CRL mm Sensitivity Specificity PPV NPV n (%) n (%) n (%) n (%) _________________________________________________________________ 1.0-1.9 1/4 (25) 9/11 (81) 1/3 (33) 9/12 (75) 2.0-2.9 12/38 (32) 157/160 (98) 12/15 (80) 157/183 (86) 3.0-3.9 20/57 (35) 156/158 (99) 20/22 (91) 156/193 (81) 4.0-4.9 18/31 (58) 221/224 (99) 18/21 (86) 221/234 (94) 5.0-5.9 19/45 (42) 198/200 (99) 19/21 (90) 198/224 (88) 6.0 10/40 (25) 206/206 (100) 10/10 (100) 206/236 (87) PPV= total non-viable without CA/total embryos without CA NPV= total viable embryos with CA/total embryos with CA Sensitivity= total non-viable without CA/total non-viable embryos Specificity=total viable embryos with CA/total viable embryos EPAU, UHW, Cardiff

Results Symptoms in patients with absent CA (n=92) ________________________________________________________ Symptom Viable (n=12) Non-viable (n=80) (n) n (%) n (%) ______________________________________________________________ Pain (14) 7/14 (50) 7/12 (50) Bleeding (45) 2/45 (4) 43/45 (96) Pain + Bleed (16) 0/16 (0) 16/16 (100) Anxiety (9) 2/9 (22) 7/9 (78) Unknown (8) 1/7 (14) 6/7 (86) EPAU, UHW, Cardiff

Conclusion Our data suggests that a single TVS is a reliable test to diagnose non-viable pregnancy if CRL ≥6 mm. Based on our findings US should be repeated when the CRL is <6 mm in order to establish viability. The presence of vaginal bleeding and pain increases the likelihood of embryonic demise, whereas pain alone is of little significance. EPAU, UHW, Cardiff

Limitations Data collected retrospectively does not allow for inter observer variability. The results may vary with different types of US machines and transducers (we used Toshiba Xario 6mHz) Other biometric measures may increase predictive value (e.g. heart rate, morphology of yolk sac, GSD) EPAU, UHW, Cardiff

References Abaid et al 2007 Relationship between crown-rump length and early detection of cardiac activity. The Journal of Reproductive Medicine 52:375-378 Levi et al 1990 Endovaginal US: demonstration of cardiac activity in embryos of less than 5.0mm in crown rump length. Genitourinary Radiology. 176:71-74. Aziz et al 2008 Five-millimeter and smaller embryos without embryonic cardiac activity. Journal of Ultrasound Medicine 27:1559-61. Shouwink et al 2000 Ultrasonographic Criteria For Non-Viability Of First Trimester Intra-Uterine Pregnancy. Early Pregnancy 4:203-213. RCOG Green Top Guideline: Management of early pregnancy Loss. EPAU, UHW, Cardiff

Thank You EPAU, UHW, Cardiff