D. Gould

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

There is significant variation in cut‐off values for mean gestational sac diameter (MSD) and embryo crown–rump length (CRL) used to define miscarriage, values suggested in the literature ranging from 13 to 25 mm for MSD and from 3 to 8 mm for CRL. We aimed to define the false‐positive rate (FPR) for the diagnosis of miscarriage associated with different CRL and MSD measurements with or without a yolk sac in a large study population of patients attending early pregnancy clinics. We also aimed to define cut‐off values for CRL and MSD that, on the basis of a single measurement, can definitively diagnose a miscarriage and so exclude possible inadvertent termination of pregnancy.

Defining safe criteria to diagnose miscarriage: prospective observational multicentre study

Objectives To validate recent guidance changes by establishing the performance of cut-off values for embryo crown-rump length and mean gestational sac diameter to diagnose miscarriage with high levels of certainty. Secondary aims were to examine the influence of gestational age on interpretation of mean gestational sac diameter and crown-rump length values, determine the optimal intervals between scans and findings on repeat scans that definitively diagnose pregnancy failure.) Design Prospective multicentre observational trial. Setting Seven hospital based early pregnancy assessment units in the United Kingdom. Participants 2845 women with intrauterine pregnancies of unknown viability included if transvaginal ultrasonography showed an intrauterine pregnancy of uncertain viability. In three hospitals this was initially defined as an empty gestational sac <20 mm mean diameter with or without a visible yolk sac but no embryo, or an embryo with crown-rump length <6 mm with no heartbeat. Following amended guidance in December 2011 this definition changed to a gestational sac size <25 mm or embryo crown-rump length <7 mm. At one unit the definition was extended throughout to include a mean gestational sac diameter <30 mm or embryo crown-rump length <8 mm. Main outcome measures Mean gestational sac diameter, crown-rump length, and presence or absence of embryo heart activity at initial and repeat transvaginal ultrasonography around 7-14 days later. The final outcome was pregnancy viability at 11-14 weeks’ gestation. Results The following indicated a miscarriage at initial scan: mean gestational sac diameter ≥25 mm with an empty sac (364/364 specificity: 100%, 95% confidence interval 99.0% to 100%), embryo with crown-rump length ≥7 mm without visible embryo heart activity (110/110 specificity: 100%, 96.7% to 100%), mean gestational sac diameter ≥18 mm for gestational sacs without an embryo presenting after 70 days’ gestation (907/907 specificity: 100%, 99.6% to 100%), embryo with crown-rump length ≥3 mm without visible heart activity presenting after 70 days’ gestation (87/87 specificity: 100%, 95.8% to 100%). The following were indicative of miscarriage at a repeat scan: initial scan and repeat scan after seven days or more showing an embryo without visible heart activity (103/103 specificity: 100%, 96.5% to 100%), pregnancies without an embryo and mean gestational sac diameter <12 mm where the mean diameter has not doubled after 14 days or more (478/478 specificity: 100%, 99.2% to 100%), pregnancies without an embryo and mean gestational sac diameter ≥12 mm showing no embryo heartbeat after seven days or more (150/150 specificity: 100%, 97.6% to 100%). Conclusions Recently changed cut-off values of gestational sac and embryo size defining miscarriage are appropriate and not too conservative but do not take into account gestational age. Guidance on timing between scans and expected findings on repeat scans are still too liberal. Protocols for miscarriage diagnosis should be reviewed to account for this evidence to avoid misdiagnosis and the risk of terminating viable pregnancies.

NICE guidance on ectopic pregnancy and miscarriage restricts access and choice and may be clinically unsafe

We welcome National Institute for Health and Clinical Excellence (NICE) guidance on wider use of pregnancy tests in primary care and its focus on considering ectopic pregnancy (EP), but we are worried about recommendations that restrict access, limit choice, and may be clinically unsafe.1

Can risk factors, clinical history and symptoms be used to predict risk of ectopic pregnancy in women attending an early pregnancy assessment unit?

To examine whether risk factors and symptoms may be used to predict the likelihood of ectopic pregnancy (EP) in women attending early pregnancy assessment units in the UK.

OP11.02: Endometrial thickness and its value in triaging women with a pregnancy of unknown location

Objectives: In normal fetuses the CPR falls after 34 weeks’ gestation. However, the cerebroplacental ratio (CPR) is lower in fetuses suffering from fetal growth restriction, and therefore at risk of stillbirth. It is possible that the magnitude or rate of fall could be useful in identifying those fetuses at risk. The aim of this study was to investigate the longitudinal change in small for gestational age (SGA) fetuses that had stillbirth or perinatal death. Methods: A longitudinal study of singleton pregnancies undergoing ultrasound monitoring of fetal biometry and Dopplers. Major structural abnormalities, aneuploidy, genetic syndromes or missing outcomes were excluded. Analysis of repeated measures with multilevel mixed-effects linear model (fixed effects and random effects) was performed. Regression analysis was used to investigate and adjust for potential confounding variables. ROC curve analysis was used to investigate the predictive accuracy. Results: 6906 observations were recorded in 2481 pregnancies: 1546 AGA fetuses, 31 SGA fetuses that had perinatal death, and 903 SGA fetuses that survived. There was a quadratic increase of CPR with GA in the AGA fetuses (p<0.01). CPR values were significantly lower in the SGA compared to the AGA fetuses (p<0.01). Women whose pregnancies were complicated by perinatal death were more likely to be smokers, non-Caucasian, nulliparous and delivered at an earlier GA (p<0.001 for all), compared to those who survived. CPR was significantly associated with the risk of stillbirth and perinatal death (p<0.001 for both). CPR recorded at the initial assessment had AUC 0.77 (95%CI 0.74-0.79; sensitivity 80.7%, specificity 76.6%, PPV 10.5%, NPV 99.1%), while CPR at the last assessment had AUC 0.82 (95%CI 0.79-0.84; sensitivity 80.7%, specificity 81.8%, PPV 13.2%, NPV 99.2%). Conclusions: CPR is a predictor of stillbirth and perinatal death in SGA fetuses, both at the initial and last assessments.

OC05.01: Reducing the follow-up required in women with a failing pregnancy of unknown location

Methods: A prospective cohort of 278 women of Caucasian origin with a singleton pregnancy was recruited before 15 weeks gestation and followed up until delivery. They were categorized into 4 prepregnancy BMI classes based on the WHO criteria. Cross-sectional analysis was performed for CRL at 12 weeks according to prepregnancy BMI, maternal weight increase up to 12 weeks, maternal age and smoking. Results: The population consisted of 20 (7.2%) women of class 1 (BMI < 18.5), 61 (21.9%) women of class 2 (BMI = 18.5–25), 79 (28.4%) women of class 3 (BMI = 25–35) and 118 (42.5%) women of class 4 (BMI > 35). A patient with a BMI of 28.7 before pregnancy, maternal age of 29 years, a gestational age of 85.91 days and an increase in weight of 1.38 kg from 0 to 12 weeks has a CRL of 59.95 mm around 12 weeks. Significant findings were derived from subsequent analysis. Pre-pregnancy BMI significantly affects the CRL at 12 weeks with one BMI unit increasing the CRL by 0.08 mm. A one-year increment of maternal age increases the CRL by of 0.14 mm at 12 weeks. An increment of one kilogram in maternal weight in the time period before 12 weeks increases the CRL by 0.28 mm. Conclusions: Pre-pregnancy BMI and maternal age have a small but discernible effect on the first trimester fetal size. Increased maternal weight gain in the first trimester, however, seems to have an increasing influence on the CRL at 12 weeks. These observations have implications on first trimester dating and trisomy screening, and indicate an influence of maternal weight and nutrition on the embryo at an early stage.

OC19.05: Evaluating cut-off values for progesterone, single hCG and hCG ratio to define pregnancy viability and location in women with a pregnancy of unknown location (PUL)

S. Bobdiwala1, E. Christodoulou2, C. Kyriacou1, J. Farren3, N. Mitchell-Jones4, F. Ayim5, B. Chohan6, O. Abughazza7, B. Guruwadahyarhalli8, M. Al-Memar1, S. Guha8, V. Vathanan6, C. Bottomley4, D. Gould3, C. Stalder1, D. Timmerman2,9, B. Van Calster2,10, T. Bourne1,2 1Tommy’s National Centre for Miscarriage Research, Queen Charlotte’s and Chelsea Hospital, Imperial College, London, United Kingdom; 2Department of Development and Regeneration, KU Leuven, Leuven, Belgium; 3St Mary’s Hospital, London, United Kingdom; 4Chelsea and Westminster NHS Trust, London, United Kingdom; 5Hillingdon Hospital, London, United Kingdom; 6Wexham Park Hospital, London, United Kingdom; 7Royal Surrey County Hospital, Guildford, United Kingdom; 8West Middlesex University Hospital, London, United Kingdom; 9University Hospital Leuven, Leuven, Belgium; 10Leiden University Medical Centre, Leiden, Netherlands