S. Bobdiwala

Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two‐step triage protocol

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two‐step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2).

Factors to consider in pregnancy of unknown location

The management of women with a pregnancy of unknown location (PUL) can vary significantly and often lacks a clear evidence base. Intensive follow-up is usually required for women with a final outcome of an ectopic pregnancy. This, however, only accounts for a small proportion of women with a pregnancy of unknown PUL location. There remains a clear clinical need to rationalize the follow-up of PUL so women at high risk of having a final outcome of an ectopic pregnancy are followed up more intensively and those PUL at low risk of having an ectopic pregnancy have their follow-up streamlined. This review covers the main management strategies published in the current literature and aims to give clinicians an overview of the most up-to-date evidence that they can take away into their everyday clinical practice when caring for women with a PUL.

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.

Validation and updating of risk models based on multinomial logistic regression

BackgroundRisk models often perform poorly at external validation in terms of discrimination or calibration. Updating methods are needed to improve performance of multinomial logistic regression models for risk prediction.MethodsWe consider simple and more refined updating approaches to extend previously proposed methods for dichotomous outcomes. These include model recalibration (adjustment of intercept and/or slope), revision (re-estimation of individual model coefficients), and extension (revision with additional markers). We suggest a closed testing procedure to assist in deciding on the updating complexity. These methods are demonstrated on a case study of women with pregnancies of unknown location (PUL). A previously developed risk model predicts the probability that a PUL is a failed, intra-uterine, or ectopic pregnancy. We validated and updated this model on more recent patients from the development setting (temporal updating; n = 1422) and on patients from a different hospital (geographical updating; n = 873). Internal validation of updated models was performed through bootstrap resampling.ResultsContrary to dichotomous models, we noted that recalibration can also affect discrimination for multinomial risk models. If the number of outcome categories is higher than the number of variables, logistic recalibration is obsolete because straightforward model refitting does not require the estimation of more parameters. Although recalibration strongly improved performance in the case study, the closed testing procedure selected model revision. Further, revision of functional form of continuous predictors had a positive effect on discrimination, whereas penalized estimation of changes in model coefficients was beneficial for calibration.ConclusionsMethods for updating of multinomial risk models are now available to improve predictions in new settings. A closed testing procedure is helpful to decide whether revision is preferred over recalibration. Because multicategory outcomes increase the number of parameters to be estimated, we recommend full model revision only when the sample size for each outcome category is large.

OC19.02: Is the presence or absence of intracavity fluid associated with a final diagnosis of ectopic pregnancy in women with a pregnancy of unknown location?

evaluated with QF-PCR or SNP array. However, in these cases, cfDNA testing was able to give the result. Conclusions: Considering nonviable pregnancies, fetal cfDNA is present in the maternal plasma with fetal fraction more than 4% in 72 % of cases between 5 an 12 weeks and thus can be used in aneuploidy detection, especially in cases, where decidual samples cannot be assessed using QF-PCR or SNP array because of maternal contamination which occurs in 26% of cases.

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

Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis.

There is no international consensus on how to manage women with a pregnancy of unknown location (PUL).

The potential value of activin B and fibronectin for the triage of pregnancies of unknown location and prediction of first trimester viability

We have assessed the potential predictive ability of the biomarkers activin B and fibronectin (FN1) alone and when added to established markers for triaging patients as being at low or high risk of ectopic pregnancy (EP). We also assessed their use as predictors of viability at 12 weeks gestation.

OP11.08: The management of recurrent ectopic pregnancy: a multicentre observational study

S. Bobdiwala1, S. Saso1, J.Y. Verbakel2,3, M. Al-Memar1, D. Timmerman2,4, T. Bourne1,2 1Tommys’ National Centre for Miscarriage Research, London, United Kingdom; 2Department of Development and Regeneration, KU Leuven, Leuven, Belgium; 3Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom; 4Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium

OC08.06: *Association of vaginal microbiota composition and outcomes in women found to have a pregnancy of unknown location (PUL) on an initial early pregnancy ultrasound scan

Objectives: To understand the reproductive health of a population, it is important to account for all conceptions and spontaneous pregnancy loss. Reported rates with spontaneous conceptions are conflicting. We conducted a prospective pre-conception study of women planning a pregnancy, to examine per-cycle conception and miscarriage, including early pregnancy loss (EPL) rates. Methods: Healthy women who were planning to conceive naturally were recruited into a pre-conception study. With an ovulation and pregnancy testing monitor, subjects commenced ovulation testing from cycle day 6 till LH surge was detected. Pregnancy testing commenced 7 days post-ovulation till a positive pregnancy result, or next menses. Monitor digital data was downloaded, providing semi-quantitative levels of LH and HCG. The interval between ovulation and a first rise in HCG baseline taken to represent implantation (O-I), and trend of rise in hCG, were related to pregnancy outcome (viable or miscarriage). Results: Of 387 women recruited, 293 pregnancies were conceived, with per-cycle conception rate of 34.2% and interval to conception of 3.1 months. 87 pregnancies ended in 1st trimester miscarriages. 41% of miscarriages were ‘biochemical’ losses which would otherwise be clinically unrecognised. There were significant differences in O-I interval mean distance to median (p <0.001), and in hCG signal form as early as 1 day of rise in baseline (p <0.0001), between pregnancies that miscarried, and viable pregnancies. Conclusions: Spontaneous pregnancy per-cycle conception rate is 34.2% with pregnancy loss rate of 30%, higher than that previously reported in the literature, as EPL were also accounted for. A vast number of pregnancies are lost prior to the window of ultrasound-diagnostic miscarriage criteria. Both short and long O-I interval, and different b-hCG rise from very early stages is associated with miscarriage.