Imperial College London

Professor Tom Bourne

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Chair in Gynaecology
 
 
 
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Contact

 

+44 (0)20 3313 5131t.bourne Website

 
 
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Location

 

Early pregnancy and acute gynaecologyInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

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Bobdiwala S, Kyriacou C, Christodoulou E, Farren J, Mitchell-Jones N, Al-Memar M, Ayim F, Chohan B, Kirk E, Abughazza O, Guruwadahyarhalli B, Guha S, Vathanan V, Gould D, Stalder C, Timmerman D, Van Calster B, Bourne Tet al., 2021, Evaluating cut-off levels for progesterone, β human chorionic gonadotropin and β human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study., Acta Obstet Gynecol Scand

INTRODUCTION: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and β human chorionic gonadotropin (βhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, βhCG, and βhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. MATERIAL AND METHODS: This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial βhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, βhCG, and βhCG ratio. RESULTS: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for βhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had βhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single βhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the βhCG ratio. Although the median βhCG ratio associated with viabilit

Journal article

Jordans IPM, Verberkt C, de Leeuw RA, Bilardo CM, van den Bosch T, Bourne T, Brölmann HAM, Dueholm M, Hehenkamp WJK, Jastrow N, Jurkovic D, Kaelin Agten A, Mashiach R, Naji O, Pajkrt E, Timmerman D, Vikhareva O, van der Voet LF, Huirne JAFet al., 2021, Definition and sonographic reporting system for Cesarean scar pregnancy in early pregnancy: modified Delphi method., Ultrasound Obstet Gynecol

OBJECTIVE: To develop a standardized sonographic evaluation and reporting system for a cesarean scar pregnancy (CSP) in the first trimester for both general gynecology and expert clinic. METHODS: A modified Delphi procedure. Twenty-eight experts in obstetrics and gynecology ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate cesarean section scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement on at least 70% per item, and minimum of three Delphi rounds were planned (two online questionnaires and one group meeting). RESULTS: Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total 58 items were identified to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurement for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. First cesarean scar evaluation to determine the location of the pregnancy is recommended to be performed at 6-7 weeks of pregnancy using transvaginal ultrasound. MRI is not needed. It was agreed that a CSP is defined as pregnancies with implantation in or in close contact with the niche. Relevant items to register include gestational size, vascularity, localization in relation to uterine vascularity, thickness of the residual myometrium and its localization in relation to the uterine cavity and serosa. According to its localization a CSP can be reported as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedde

Journal article

Vaulet T, Al-Memar M, Fourie H, Bobdiwala S, Saso S, Pipi M, Stalder C, Bennett P, Timmerman D, Bourne T, De Moor Bet al., 2021, Gradient boosted trees with individual explanations: An alternative to logistic regression for viability prediction in the first trimester of pregnancy., Comput Methods Programs Biomed, Vol: 213

BACKGROUND: Clinical models to predict first trimester viability are traditionally based on multivariable logistic regression (LR) which is not directly interpretable for non-statistical experts like physicians. Furthermore, LR requires complete datasets and pre-established variables specifications. In this study, we leveraged the internal non-linearity, feature selection and missing values handling mechanisms of machine learning algorithms, along with a post-hoc interpretability strategy, as potential advantages over LR for clinical modeling. METHODS: The dataset included 1154 patients with 2377 individual scans and was obtained from a prospective observational cohort study conducted at a hospital in London, UK, from March 2014 to May 2019. The data were split into a training (70%) and a test set (30%). Parsimonious and complete multivariable models were developed from two algorithms to predict first trimester viability at 11-14 weeks gestational age (GA): LR and light gradient boosted machine (LGBM). Missing values were handled by multiple imputation where appropriate. The SHapley Additive exPlanations (SHAP) framework was applied to derive individual explanations of the models. RESULTS: The parsimonious LGBM model had similar discriminative and calibration performance as the parsimonious LR (AUC 0.885 vs 0.860; calibration slope: 1.19 vs 1.18). The complete models did not outperform the parsimonious models. LGBM was robust to the presence of missing values and did not require multiple imputation unlike LR. Decision path plots and feature importance analysis revealed different algorithm behaviors despite similar predictive performance. The main driving variable from the LR model was the pre-specified interaction between fetal heart presence and mean sac diameter. The crown-rump length variable and a proxy variable reflecting the difference in GA between expected and observed GA were the two most important variables of LGBM. Finally, while variable intera

Journal article

Van Calster B, Bourne T, Froyman W, Timmerman D, Valentin Let al., 2021, Re: "Diagnostic Accuracies of the Ultrasound and Magnetic Resonance Imaging ADNEX Scoring Systems for Ovarian Adnexal Mass: Systematic Review and Meta-Analysis"., Acad Radiol, Vol: 28, Pages: 1643-1644

Journal article

Kyriacou C, Cooper N, Robinson E, Parker N, Barcroft J, Kundu S, Letchworth P, Sur S, Gould D, Stalder C, Bourne Tet al., 2021, Ultrasound characteristics, serum biochemistry and outcomes for ectopic pregnancies presenting during the SARS-CoV-2 pandemic: retrospective analysis, Ultrasound in Obstetrics and Gynecology, ISSN: 0960-7692

OBJECTIVES: To describe and then compare the characteristics of ectopic pregnancies (EP) in the year prior to and then during the SARS-CoV-2 pandemic. METHODS: This was a retrospective analysis from 1st January 2019 to 31st December 2020 of women diagnosed with an EP (n=275) at a London dual center early pregnancy assessment service. Women were identified via the AstraiaTM ultrasound reporting system using coded and non-coded outcomes of 'EP' or 'pregnancy outside the uterine cavity'. Data relating to predefined outcomes were collected using AstraiaTM and CernerTM electronic reporting systems. Main outcome measures included clinical, ultrasound and biochemical features of EP, in addition to reported complications and management. Statistical analysis was carried out using GraphPad Prism v8.2.1. RESULTS: Similar numbers and proportions of EP were seen in 2019 (n=141, 1%) and 2020 (n=134, 1%). Both cohorts were comparable in age, ethnicity, weight and method of conception. Gestational age at first ultrasound and at diagnosis was similar, with no difference in EP location, size or morphology. Human chorionic gonadotrophin (hCG) levels at time of EP diagnosis were higher in 2020 than 2019 (1005 IU/L vs 665 IU/L, p=0.03). The type of final EP management was similar, but more failed first line management during the pandemic (16% vs 6%, p=0.01). Rates of blood visualized on ultrasound within the pelvis (hemoperitoneum) (23% vs 27%, p=0.58) and of rupture confirmed surgically (9% vs 3%, p=0.07) were both similar. CONCLUSIONS: No difference was observed in the location, size, morphology and gestational age of ectopic pregnancies. Complication rates and management were also unchanged. HCG levels were higher, and a greater proportion of conservative management measures failed during the pandemic. Our findings suggest women continued to access appropriate care for EP during the SARS-CoV-2 pandemic, with no evidence of diagnostic delay or increase in adverse outcomes in our popul

Journal article

Timmerman D, Cibula D, Planchamp F, Bourne T, Landolfo C, Testa AC, du Bois A, Chiva L, Concin N, Fisherova D, Froyman W, Lemley B, Loft A, Mereu L, Morice P, Querleu D, Vergote I, Vandecaveye V, Scambia G, Fotopoulou Cet al., 2021, Response to: Correspondence on "ESGO/ISUOG/IOTA/ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors" by Thomassin-Nagarra et al, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 1396-1397, ISSN: 1048-891X

Journal article

Harmsen MJ, Van den Bosch T, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, Hehenkamp W, Groenman F, De Bruyn C, Rasmussen C, Lazzeri L, Jokubkiene L, Jurkovic D, Naftalin J, Tellum T, Bourne T, Timmerman D, Huirne JAFet al., 2021, Consensus on revised definitions of morphological uterus sonographic assessment (MUSA) features of adenomyosis: results of a modified Delphi procedure., Ultrasound Obstet Gynecol

OBJECTIVE: To update the Morphological Uterus Sonographic Assessment (MUSA) definitions of adenomyosis if deemed necessary, and to reach consensus on the updated definitions METHODS: A modified Delphi procedure among European gynecologists with expertise in ultrasound diagnosis of adenomyosis was performed. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings including also three-dimensional (3D) still images) of transvaginal ultrasound (TVUS) examinations of the uterus were presented in an online survey in the first Delphi round. Experts were asked to confirm or refute the presence of each of nine MUSA features of adenomyosis in each of the 15 videoclips and to give comments. In the second round, the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVUS examinations and to provide feedback on the proposed revisions. A third round, an on-line face-to-face meeting, was used to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. RESULTS: Sixteen of eighteen invited experts agreed to participate. Eleven experts completed and four experts partly finished the first assessment round. The experts identified a need for more detailed definitions of some MUSA features. They recommended to use 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts joined the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the on-line meeting, discussed, and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct feature

Journal article

Phylactou M, Abbara A, Al-Memar M, Kyriacou C, Pei Chia E, Nadir R, Izzie-Engbeaya C, Clarke S, Mills E, Daniels E, Huo L, Pacuszka E, Yang L, Patel B, Tan T, Bech P, Comninos A, Fourie H, Kelsey T, Bourne T, Dhillo W, Abbara Aet al., 2021, Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestation during the first trimester, Fertility and Sterility, Vol: 116, Pages: 809-819, ISSN: 0015-0282

ObjectiveTo compare the performance of kisspeptin and beta human chorionic gonadotropin (βhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester.DesignProspective, nested case-control study.SettingTertiary Centre, Queen Charlotte Hospital, London, United Kingdom.Patient(s)Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples).Intervention(s)The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and βhCG levels during the first trimester.Main Outcome Measure(s)The ability of plasma kisspeptin and βhCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage.Result(s)Gestation-adjusted levels of circulating kisspeptin and βhCG were lower in samples from women with miscarriages than in women with healthy pregnancies by 79% and 70%, respectively. The area under the receiver-operating characteristic curve for identifying miscarriage during the first trimester was 0.874 (95% confidence interval [CI] 0.844–0.904) for kisspeptin, 0.859 (95% CI 0.820–0.899) for βhCG, and 0.916 (95% CI 0.886–0.946) for the sum of the two markers. The performance of kisspeptin in identifying miscarriage improved with increasing length of gestation, whereas that of βhCG worsened. A decision matrix incorporating kisspeptin, βhCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage.Conclusion(s)Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to βhCG alone, especially during later gestational weeks of the first trimester.

Journal article

Phylactou M, Abbara A, Al-Memar M, Daniels E, Patel B, Eng PC, Nadir R, Izzi-Engbeaya C, Clarke S, Mills E, Hunjan T, Pacuszka E, Yang L, Bech P, Tan T, Comninos A, Kelsey T, Kyriacou C, Fourie H, Bourne T, Dhillo Wet al., 2021, Changes in circulating kisspeptin levels during each trimester in women with antenatal complications, Journal of Clinical Endocrinology and Metabolism, ISSN: 0021-972X

ContextAntenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all three trimesters in women with antenatal complications.ObjectiveTo assess whether kisspeptin levels are altered in women with antenatal complications.DesignWomen with antenatal complications (n=105) and those with uncomplicated pregnancies (n=265) underwent serial ultrasound scans and blood-sampling at least once during each trimester (March 2014 to March 2017).SettingEarly Pregnancy Assessment Unit at Hammersmith Hospital, UK.ParticipantsWomen with antenatal complications: HDP (n=32), FGR (n=17), GDM (n=35) and PTB (n=11), and 10 women with multiple complications, provided 373 blood samples, and a further 265 controls provided 930 samples.Main outcomeDifferences in circulating kisspeptin levels.ResultsThird trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking and parity were increased by 30% (95%CI 16-47%; p<0.0001), and of FGR were reduced by 28% (95%CI 4-46%; p=0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (p=0.014), and lower in those affected by GDM (p=0.020), but not significantly on multivariable analysis.ConclusionWe delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.

Journal article

Grewal K, Lee Y, Smith A, Brosens J, Al-Memar M, Bourne T, Kundu S, MacInytre D, Bennett Pet al., 2021, Lactobacillus deplete vaginal microbial composition is associated with chromosomally normal miscarriage and local inflammation, Publisher: OXFORD UNIV PRESS, Pages: 56-56, ISSN: 0268-1161

Conference paper

Grewal K, Lee YS, Smith A, Brosens JJ, Bourne T, Al-Memar M, Kundu S, MacIntyre DA, Bennett Pet al., 2021, Euploid Miscarriage Is Associated with Lactobacillus spp. Deplete Vaginal Microbial Composition and Local Inflammation., Publisher: SPRINGER HEIDELBERG, Pages: 77A-77A, ISSN: 1933-7191

Conference paper

Timmerman D, Planchamp F, Bourne T, Landolfo C, du Bois A, Chiva L, Cibula D, Concin N, Fischerova D, Froyman W, Madueno GG, Lemley B, Loft A, Mereu L, Morice P, Querleu D, Testa AC, Vergote I, Vandecaveye V, Scambia G, Fotopoulou Cet al., 2021, ESGO/ISUOG/IOTA/ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors, International Journal of Gynecological Cancer, Vol: 31, Pages: 961-982, ISSN: 1048-891X

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

Journal article

Fourie H, Al-Memar M, Smith A, Ng S, Lee Y, Timmerman D, Bourne T, MacIntyre D, Bennett Pet al., 2021, The relationship between systemic oestradiol and vaginal microbiota composition in miscarriage and normal pregnancy, Publisher: OXFORD UNIV PRESS, Pages: 311-312, ISSN: 0268-1161

Conference paper

Timmerman D, Planchamp F, Bourne T, Landolfo C, du Bois A, Chiva L, Cibula D, Concin N, Fischerova D, Froyman W, Gallardo G, Lemley B, Loft A, Mereu L, Morice P, Querleu D, Testa AC, Vergote I, Vandecaveye V, Scambia G, Fotopoulou Cet al., 2021, ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumors, ULTRASOUND IN OBSTETRICS & GYNECOLOGY, Vol: 58, Pages: 148-168, ISSN: 0960-7692

Journal article

Timmerman D, Planchamp F, Bourne T, Landolfo C, du Bois A, Chiva L, Cibula D, Concin N, Fischerova D, Froyman W, Gallardo G, Lemley B, Loft A, Mereu L, Morice P, Querleu D, Testa C, Vergote I, Vandecaveye V, Scambia G, Fotopoulou Cet al., 2021, ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumours., Facts Views Vis Obgyn, Vol: 13, ISSN: 2032-0418

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumours, including imaging techniques, biomarkers and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumours and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumours and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

Journal article

Kyriacou C, Bobdiwala S, Doulgeraki T, Fourie H, Farren J, Mitchell-Jones N, Ayim F, Chohan B, Guha S, Kirk E, Abughazza O, Al-Memar M, Vathanan V, Gould D, Stalder C, Timmerman D, Bourne Tet al., 2021, Assessing progesterone cut-off levels in pregnancy of unknown location risk prediction, Publisher: WILEY, Pages: 38-38, ISSN: 1470-0328

Conference paper

Kyriacou C, Abbara A, Bobdiwala S, Fourie H, Al-Memar M, Phylactou M, Eng CP, Izzi-Engbeaya C, Mills E, Bech P, Comninos A, Huo L, Dhillo W, Bourne Tet al., 2021, Circulating kisspeptin levels in ectopic pregnancy and pregnancy of unknown location, Publisher: WILEY, Pages: 38-39, ISSN: 1470-0328

Conference paper

Kyriacou C, Kapur S, Jeyapala S, Bobdiwala S, Fourie H, Parker N, Barcroft J, Grewal K, Shah H, Landolfo C, Sur S, Stalder C, Syed S, Bourne Tet al., 2021, Point of care hCG performance and efficiency in pregnancy of unknown location, Publisher: WILEY, Pages: 37-37, ISSN: 1470-0328

Conference paper

Coomarasamy A, Gallos ID, Papadopoulou A, Dhillon-Smith RK, Al-Memar M, Brewin J, Christiansen OB, Stephenson MD, Oladapo OT, Wijeyaratne CN, Small R, Bennett PR, Regan L, Goddijn M, Devall AJ, Bourne T, Brosens JJ, Quenby Set al., 2021, Sporadic miscarriage: evidence to provide effective care, The Lancet, Vol: 397, Pages: 1668-1674, ISSN: 0140-6736

The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units.

Journal article

Coomarasamy A, Dhillon-Smith RK, Papadopoulou A, Al-Memar M, Brewin J, Abrahams VM, Maheshwari A, Christiansen OB, Stephenson MD, Goddijn M, Oladapo OT, Wijeyaratne CN, Bick D, Shehata H, Small R, Bennett PR, Regan L, Rai R, Bourne T, Kaur R, Pickering O, Brosens JJ, Devall AJ, Gallos ID, Quenby Set al., 2021, Recurrent miscarriage: evidence to accelerate action, The Lancet, Vol: 397, Pages: 1675-1682, ISSN: 0140-6736

Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.

Journal article

Quenby S, Gallos I, Dhillon-Smith R, Podesek M, Stephenson M, Fisher J, Brosens J, Brewin J, Ramhorst R, Lucas E, McCoy R, Anderson R, Daher S, Regan L, Al-Memar M, Bourne T, MacIntyre D, Rai R, Christiansen O, Sugiura-Ogasawara M, Odendaal J, Devall A, Bennett P, Petrou S, Coomarasamy Aet al., 2021, Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss, The Lancet, Vol: 397, Pages: 1658-1667, ISSN: 0140-6736

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5–18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3–11·4%), two miscarriages is 1·9% (1·8–2·1%), and three or more miscarriages is 0·7% (0·5–0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need

Journal article

Mullins E, Hudak ML, Banerjee J, Getzlaff T, Townson J, Barnette K, Playle R, Bourne T, Lees C, PAN-COVID investigators and the National Perinatal COVID-19 Registry Study Groupet al., 2021, Pregnancy and neonatal outcomes of COVID-19: co-reporting of common outcomes from PAN-COVID and AAP SONPM registries, Ultrasound in Obstetrics and Gynecology, Vol: 57, Pages: 5733-581, ISSN: 0960-7692

OBJECTIVE: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with SARS-CoV-2 infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the US American Academy of Pediatrics Section on Neonatal Perinatal Medicine (AAP SONPM) National Perinatal COVID-19 Registry. METHODS: This was an analysis of data from the PAN-COVID registry (January 1st to July 25th 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP SONPM National Perinatal COVID-19 registry (April 4th to August 8th 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented both overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection. RESULTS: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP SONPM). For obstetric outcomes, in PAN-COVID overall, those with confirmed infection in PAN-COVID and AAP SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was pre-term (<37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.2% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP SONPM. Extremely preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP SONPM. Neonatal SARS-CoV-2 infection was reported in 0.8% of all deliver

Journal article

Al-karawi D, Al-Assam H, Du H, Sayasneh A, Landolfo C, Timmerman D, Bourne T, Jassim Set al., 2021, An Evaluation of the Effectiveness of Image-based Texture Features Extracted from Static B-mode Ultrasound Images in Distinguishing between Benign and Malignant Ovarian Masses, ULTRASONIC IMAGING, Vol: 43, Pages: 124-138, ISSN: 0161-7346

Journal article

Dall'Asta A, Forlani F, Shah H, Paramasivam G, Yazbek J, Bourne T, Cali G, Lees Cet al., 2021, Evaluation of the Tramline Sign in the Prediction of Placenta Accreta Spectrum and Perioperative Outcomes in Anterior Placenta Previa, ULTRASCHALL IN DER MEDIZIN, ISSN: 0172-4614

Journal article

Christodoulou E, Bobdiwala S, Kyriacou C, Farren J, Mitchell-Jones N, Ayim F, Chohan B, Abughazza O, Guruwadahyarhalli B, Al-Memar M, Guha S, Vathanan V, Gould D, Stalder C, Wynants L, Timmerman D, Bourne T, Van Calster Bet al., 2021, External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study., BJOG: an International Journal of Obstetrics and Gynaecology, Vol: 128, Pages: 552-562, ISSN: 1470-0328

OBJECTIVE: To externally validate five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). DESIGN: Secondary analysis of a prospective cohort study. SETTING: Eight UK early pregnancy assessment units. POPULATION: Women presenting with a PUL and BhCG >25 IU/L. METHODS: Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone ≤2 nmol/L; the remaining cases returned two days later for triage based on M6P. EP risk ≥5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta-analysed centre-specific results. MAIN OUTCOME MEASURES: Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. RESULTS: Of 2899 eligible women, the primary analysis excluded 297 (1 0%) women who were lost to follow-up. The area under the ROC curve for EP was 0.89 (95% confidence interval 0.86-0.91) for M6P, 0.88 (0.86-0.90) for 2ST, 0.86 (0.83-0.88) for M6NP, and 0.82 (0.78-0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4), and 58% (BhCG-RC); false positive rates were 35%, 33%, 39%, 24%, and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres. CONCLUSIONS: 2ST and M6P performed best to predict and triage PUL.

Journal article

Banerjee J, Mullins E, Townson J, Playle R, Shaw C, Kirby N, Munnery K, Bourne T, Teoh TG, Dhanjal M, Poon L, Wright A, Lees Cet al., 2021, Pregnancy and Neonatal Outcomes in COVID-19: Study protocol for a global registry of women with suspected or confirmed SARS-CoV-2 infection in pregnancy and their neonates, understanding natural history to guide treatment and prevention, BMJ Open, Vol: 11, Pages: 1-6, ISSN: 2044-6055

Introduction: Previous novel coronavirus pandemics, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), observed an association of infection in pregnancy with pre-term delivery, stillbirth and increased maternal mortality. Coronavirus disease2019(COVID-19), caused by SARS-CoV-2 infection, is the largest pandemic in living memory. Rapid accrual of robust case data on women in pregnancy and their babies affected by suspectedCOVID-19or confirmed SARS-CoV-2 infection will inform clinical management and preventative strategies in the current pandemic and future outbreaks. Methods and analysis: The Pregnancy And Neonatal outcomes in COVID-19 (PAN-COVID) registry is an observational study collecting focussed data on outcomes of pregnant mothers who have had suspected COVID-19 in pregnancy or confirmed SARS-CoV-2 infection and their neonatesvia a web-portal. Amongst the women recruited to the PAN-COVID registry, the study will evaluate the incidence of:1. Miscarriage and pregnancy loss2. FGR and stillbirth 3. Pre-term delivery 4. Vertical transmission(suspected or confirmed) and early-onset neonatal SARS-CoV-2 infection Data will be centre based and collected on individual women and their babies. Verbal consent will be obtained, to reduce face-to-face contact in the pandemic whilst allowing identifiable data collection for linkage. Statistical analysis of the data will be carried out on a pseudonymised dataset by the study statistician. Regular reports will be distributed to collaborators on the study research questions. Ethics and dissemination: This study has received research ethics approval in the UK. For international centres, evidence of appropriate local approval will be required to participate, prior to entry of data to the database. The reports will be published regularly. The outputs of the study will be regularly disseminated to 4participants and collaborators on the study

Journal article

Farren J, Jalmbrant M, Falconieri N, Mitchell-Jones N, Bobdiwala S, Al-Memar M, Tapp S, Van Calster B, Wynants L, Timmerman D, Bourne Tet al., 2021, Differences in post-traumatic stress, anxiety and depression following miscarriage and ectopic pregnancy between women and their partners: a multicenter prospective cohort study, Ultrasound in Obstetrics and Gynecology, Vol: 57, Pages: 141-148, ISSN: 0960-7692

OBJECTIVES: To investigate and compare post-traumatic stress, depression and anxiety in women and their partners over a 9-month period following miscarriage or ectopic pregnancy. METHODS: This was a prospective cohort study. Consecutive women and partners were approached in the early pregnancy units of three hospitals in central London. One, three and nine months after early pregnancy loss, recruits were emailed links to surveys containing the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Diagnostic Scale (PDS). The proportion of participants meeting screening criteria for moderate/severe anxiety or depression and post-traumatic stress (PTS) was assessed. Mixed-effects logistic regression was used to analyse differences between women and their partners and the evolution over time. RESULTS: 386 partners were approached after the woman in whom the loss had been diagnosed consented to participate. 192 couples were recruited. All partners were male. Response rates were 57%, 45% and 38% for partners, and 76%, 68% and 57% for women, at month 1, 3 and 9 respectively. For partners, 7% met the criteria for PTS at month 1, 8% at month 3 and 4% at month 9, compared to 34%, 26% and 21%, respectively, of women. Partners also experienced lower rates of moderate/severe anxiety (6% vs 30% at month 1, 9% vs 25% at month 3, 6% vs 22% at month 9) and depression (2% vs 10% at month 1, 5% vs 8% at month 3, 1% vs 7% at month 9). The odds ratios for morbidity in partners vs women after 1 month was 0.02 (95% CI, 0.004-0.12) for post-traumatic stress, 0.05 (95% CI, 0.01-0.19) for moderate/severe anxiety and 0.15 (95% CI, 0.02-0.96) for moderate/severe depression. Morbidity for each outcome decreased modestly over time, without strong evidence of a different evolution for women and their partners. CONCLUSIONS: Partners experience far lower levels of post-traumatic stress, anxiety and depression than women after early pregnancy loss. This article is protected by copyright. A

Journal article

Moro F, Esposito R, Landolfo C, Froyman W, Timmerman D, Bourne T, Scambia G, Valentin L, Testa ACet al., 2021, Ultrasound evaluation of ovarian masses and assessment of the extension of ovarian malignancy, BRITISH JOURNAL OF RADIOLOGY, Vol: 94, ISSN: 0007-1285

Journal article

Moro F, Verdecchia V, Romeo P, Ciccarone F, Zannoni GF, Valentin L, Timmerman D, Bourne T, Froyman W, Scambia G, Testa ACet al., 2021, Ultrasound, macroscopic and histological features of malignant ovarian tumors, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 150-151, ISSN: 1048-891X

Journal article

Van den Bosch T, Verbakel JY, Valentin L, Wynants L, De Cock B, Pascual MA, Leone FPG, Sladkevicius P, Alcazar JL, Votino A, Fruscio R, Lanzani C, Van Holsbeke C, Rossi A, Jokubkiene L, Kudla M, Jakab A, Domali E, Epstein E, Van Pachterbeke C, Bourne T, Van Calster B, Timmerman Det al., 2021, Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding, ULTRASOUND IN OBSTETRICS & GYNECOLOGY, Vol: 57, Pages: 164-172, ISSN: 0960-7692

Journal article

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