Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

DEGUM Recommendations on Diagnostic Puncture in Prenatal Medicine. / Empfehlungen der DEGUM zu diagnostischen Punktionen in der Pränatalmedizin.

Diagnostic puncture (amniocentesis, chorionic villus sampling, and fetal blood sampling) is an essential part of prenatal diagnostics and the only established and sufficiently scientifically evaluated possibility of diagnosing genetic diseases from pregnancy-specific cells. The number of diagnostic punctures in Germany, as in other countries, has fallen significantly. This is largely due to the introduction of first-trimester screening with further detailed ultrasound examination of the fetus and the analysis of cf-DNA (cell-free DNA) from maternal blood (noninvasive prenatal test - NIPT). On the other hand, knowledge about the incidence and appearance of genetic diseases has increased. The development of modern molecular genetic techniques (microarray and exome analysis) makes a differentiated investigation of these diseases increasingly possible. The requirements for education and counseling regarding these complex correlations have thus increased. The studies performed in recent years make it clear that diagnostic puncture performed in expert centers is associated with a low risk of complications. In particular, the procedure-related miscarriage risk hardly differs from the background risk for spontaneous abortion. In 2013, the Section of Gynecology and Obstetrics of the German Society for Ultrasound in Medicine (DEGUM) published recommendations on diagnostic puncture in prenatal medicine 1. The developments described above and new findings in recent years make it necessary to revise and reformulate these recommendations. The aim of this review is to compile important and current facts regarding prenatal medical puncture (including technique, complications, genetic examinations). It is intended to provide basic, comprehensive, and up-to-date information on diagnostic puncture in prenatal medicine. It replaces the publication from 2013 1.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Foetal loss after chorionic villus sampling and amniocentesis in twin pregnancies: A multicentre retrospective cohort study.

OBJECTIVE: We aimed to determine foetal losses for DCDA and MCDA twins following transabdominal CVS or amniocentesis performed <22+0  weeks. METHODS: Retrospective cohort study conducted in the UK and Belgium 01/01/00-01/06/20. Cases with unknown chorionicity, monochorionic complications or complex procedures were excluded. Uncomplicated DCDA and MCDA twins without invasive procedures were identified as controls. We reported foetal losses <24+0  weeks and losses of genetically and structurally normal foetuses. RESULTS: Outcomes were compared for DCDA foetuses; 258 after CVS with 3406 controls, 406 after amniocentesis with 3390 controls plus MCDA foetuses, 98 after CVS with 1124 controls, and 160 after amniocentesis with 1122 controls. There were more losses <24+0  weeks with both procedures in DCDA (CVS RR 5.54 95% CI 3.38-9.08, amniocentesis RR 2.36 95% CI 1.22-4.56) and MCDA twins (CVS RR 5.14 95% CI 2.51-10.54, amniocentesis RR 7.01 95% CI 3.86-12.74). Losses of normal foetuses were comparable to controls (DCDA CVS RR 0.39 95% CI 0.05-2.83, DCDA amniocentesis RR 1.16 95% CI 0.42-3.22, MCDA CVS RR 2.3 95% CI 0.71-7.56, and MCDA amniocentesis RR 1.93 95% CI 0.59-6.38). CONCLUSIONS: This study indicates increased foetal losses for DCDA and MCDA twins following CVS and amniocentesis with uncertain risk to normal foetuses.

Outcome of antenatal invasive diagnostic tests in a fetal medicine unit with low case load in North Wales, United Kingdom.

The aim of this retrospective cohort study was to review rate of miscarriage following antenatal invasive diagnostic procedures from a unit where relatively low annual numbers of procedures are undertaken. Data were analysed for 201 chorionic villous samplings (CVSs) performed between January 2007 and June 2019 and 511 amniocenteses performed between January 2008 and June 2019, in singleton pregnancies. The miscarriage rates after CVS was 0% at 48 hours, 0.6% at 2 weeks and 2.5% up to 24 weeks of gestation. All four miscarriages following CVS had significant inherent high-risk features, therefore, it would be inappropriate to attribute these losses solely to the procedure itself. None of the women who had an amniocentesis had a miscarriage during the study period. We did not find a causal association between number of invasive procedures performed by an operator and miscarriage rate in our setting even with low annual numbers of invasive procedures.Impact StatementWhat is already known on this subject? Royal College of Obstetricians and Gynaecologists (RCOG) of UK recommends a minimum of at least 30 CVSs or amniocenteses procedures per year for a practitioner in order to maintain skills. A centre performing more fetal invasive procedures has lower miscarriage rates due to more experience of practitioners.What the results of this study add? This study is the first long-term audit data from a smaller fetal medicine unit with relatively low annual case load, suggesting that miscarriage risk may actually be lower than the current understanding. No additional risk of miscarriage or pregnancy loss following fetal invasive procedures even with relatively low annual numbers than that recommended by the RCOG.What the implications are of these findings for clinical practice and/or further research? The findings of this study are important in the era of non-invasive prenatal testing which will see the overall number of fetal invasive procedures decline with time. Competence in safely undertaking antenatal invasive procedure can possibly be maintained with lower annual procedure numbers. Units undertaking low number of antenatal invasive procedure must continuously audit their practice to ensure satisfactory standards and outcomes. More research is needed from smaller units to corroborate or refute the findings of this study.

Fetal loss after chorionic villus sampling in twin pregnancy.

OBJECTIVE: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG). METHODS: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free ß-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. RESULTS: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. CONCLUSION: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Consensus on Training and Assessment of Competence in Performing Chorionic Villus Sampling and Amniocentesis: An International Delphi Survey.

INTRODUCTION: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. METHODS: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. RESULTS: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. CONCLUSION: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

Risk of fetal loss following amniocentesis or chorionic villus sampling in twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure-related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure-related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head-to-head meta-analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta-analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls. RESULTS: Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head-to-head meta-analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4-3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9-4.6%) in those not undergoing amniocentesis. Head-to-head meta-analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0-6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3-4.2%) in those not undergoing CVS. CONCLUSION: The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Riesgo de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas en un embarazo de gemelos: revisión sistemática y metaanálisis OBJETIVO: Evaluar la tasa de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas (BVC) en un embarazo de gemelos. MÉTODOS: Se hizo una búsqueda en las bases de datos MEDLINE, EMBASE y Cochrane de estudios que habían reportado complicaciones relacionadas con el procedimiento después de una amniocentesis o una BVC en un embarazo de gemelos. El resultado primario fue la tasa de pérdida del feto relacionada con el procedimiento. Los resultados secundarios fueron la pérdida del feto producida antes de las 24 semanas de gestación y la pérdida del feto producida dentro de las 4 semanas posteriores al procedimiento. Se utilizaron metaanálisis cara a cara para comparar cada resultado directamente, entre las mujeres que se sometieron a una amniocentesis y las que no se sometieron a ella, y entre las mujeres que se sometieron a una BVC y las que no se sometieron a ella, así como para calcular las diferencias de riesgo (DR) combinadas entre las mujeres expuestas y las no expuestas a cada procedimiento agresivo. Además, se utilizaron los metaanálisis de proporciones para estimar las tasas combinadas de cada uno de los tres resultados en las mujeres que se sometieron a amniocentesis o a BVC y en los controles. RESULTADOS: Se incluyeron 16 estudios (3.419 embarazos de gemelos sometidos a un procedimiento agresivo y 2.517 no sometidos). Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos sometidos y no sometidos a amniocentesis mostraron un mayor riesgo de pérdida general del feto en total en los sometidos a amniocentesis (Razón de Momios (RM), 1,46 (P=0,04); DR, 0,013 (P=0,04)), mientras que no hubo diferencias en el riesgo de pérdida del feto antes de las 24 semanas de gestación (RM, 1,59 (P=0,06); DR, 0,010 (P=0,11)) ni en el de las 4 semanas posteriores al procedimiento (RM, 1,38 (P=0,3); DR, 0,003 (P=0,8)). En general, la tasa conjunta de pérdida del feto fue del 2,4% (IC 95%, 1,4-3,6%) en los embarazos de gemelos sometidos a amniocentesis, en comparación con el 2,4% (IC 95%, 0,9-4,6%) en los que no se sometieron a amniocentesis. Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos que se sometieron y que no se sometieron a una BVC no mostraron diferencias significativas ni en la pérdida del feto en total (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)) ni en la pérdida del feto antes de las 24 semanas de gestación (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)). En general, la tasa combinada de pérdida del feto fue del 2,0% (IC 95%, 0,0-6,5%) de los embarazos de gemelos sometidos a BVC, comparada con el 1,8% (IC 95%, 0,3-4,2%) de los que no se sometieron a BVC. CONCLUSIÓN: El riesgo de pérdida del feto tras la amniocentesis y la BVC en gemelos es menor que lo reportado en el pasado y la tasa de pérdida del feto antes de las 24 semanas de gestación, o dentro de las 4 semanas posteriores al procedimiento, no difiere de la del riesgo de contexto en los embarazos de gemelos que no se someten a pruebas prenatales agresivas. Estos datos pueden servir de guía para el asesoramiento prenatal de los embarazos de gemelos que se someten a procedimientos agresivos.

New approach for estimating risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher). CONCLUSIONS: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Nuevo enfoque para estimar el riesgo de aborto después de una biopsia de vellosidades coriónicas OBJETIVO: Estimar el riesgo de aborto asociado con la biopsia de vellosidades coriónicas (BVC). MÉTODOS: Se trata de un estudio retrospectivo de cohorte de mujeres que acudieron a un examen ecográfico de rutina entre las 11+0 y las 13+6 semanas de gestación a una de entre un total de ocho centros de medicina fetal en España, Bélgica y Bulgaria, entre julio de 2007 y junio de 2018. En el estudio se incluyeron dos poblaciones: 1) todos los embarazos con feto único sometidos a evaluación del primer trimestre en el Hospital Clínico Universitario Virgen de la Arrixaca de Murcia (España), a las que no se les hizo una BVC (grupo no BVC); y 2) todos los embarazos con feto único sometidos a BVC tras la evaluación del primer trimestre en uno de los ocho centros participantes (grupo BVC). Se excluyeron los embarazos diagnosticados con anomalías genéticas o defectos fetales importantes antes o después del nacimiento, los que resultaron en una interrupción y los que más tarde se sometieron a amniocentesis durante el embarazo. Para estimar la relación entre la BVC y el aborto espontáneo se utilizó el pareamiento por puntaje de propensión (PPP). Se comparó el riesgo de aborto de los grupos BVC y no BVC después del pareamiento PPP (razón 1:1). Este procedimiento creó dos grupos comparables en los que las características de la madre y el embarazo que se asocian con la BVC estaban equilibradas, de manera similar a cómo funciona la aleatorización en un ensayo clínico aleatorizado. RESULTADOS: La población de estudio consistió en 22.250 embarazos en el grupo no BVC y 3.613 en el grupo BVC. La incidencia de abortos en el grupo BVC (2,1%; 77/3.613) fue significativamente mayor que en el grupo no BVC (0,9% (207/22.250); P<0,0001). El algoritmo del PPP emparejó 2.122 BVC con 2.122 casos no BVC, de los cuales 40 (1,9%) y 55 (2,6%) embarazos en los grupos BVC y no BVC, respectivamente, resultaron en un aborto espontáneo (razón de momios (RM), 0,72 (IC 95%, 0,48-1,10); P=0,146). Se encontró una interacción significativa entre el riesgo de aborto espontáneo después de una BVC y el riesgo de aneuploidía, lo que sugiere que el efecto de la BVC en el riesgo de aborto espontáneo difiere según las características del contexto. Concretamente, cuando el riesgo de aneuploidía es bajo, el riesgo de aborto después de una BVC aumenta (RM, 2,87 (IC 95%, 1,13-7,30)) y cuando el riesgo de aneuploidía es alto, paradójicamente el riesgo de aborto después de una BVC se reduce (RM, 0,47 (IC 95%, 0,28-0,76)), presumiblemente debido al diagnóstico prenatal y a la interrupción de embarazos con aneuploidías importantes que, de otro modo, hubieran provocado un aborto espontáneo. Por ejemplo, en una paciente para quien el riesgo de aneuploidía es de 1 entre 1000 (0,1%), el riesgo de aborto después de la BVC aumenta al 0,3% (0,2 puntos porcentuales más alto). CONCLUSIONES: El riesgo de aborto espontáneo en las mujeres que se someten a una BVC es aproximadamente un 1% mayor que el de las mujeres a las que no se les hace, aunque este exceso de riesgo no se atribuye únicamente al procedimiento agresivo sino, en cierta medida, a las características demográficas y del embarazo de cada paciente. Después de tener en cuenta estos factores de riesgo y limitar el análisis a los embarazos de bajo riesgo, la BVC parece triplicar aproximadamente el riesgo de aborto en comparación con el riesgo de fondo de la paciente. Aunque se trata de un aumento sustancial en términos relativos, en los embarazos sin factores de riesgo de aborto, después de una BVC el riesgo de aborto sigue siendo bajo y similar, o ligeramente superior, al de la población en general. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Do chorionic villus samplings (CVS) or amniocenteses (AC) induce RhD immunisation? An evaluation of a large Danish cohort with no routine administration of anti-D after invasive prenatal testing.

OBJECTIVE: To evaluate the risk of inducing RhD immunisation in pregnancies of RhD-negative mothers with an RhD-positive fetus undergoing chorionic villus samplings (CVS) or amniocenteses (AC). DESIGN, SETTING AND POPULATION: Registry-based study in a Danish cohort which has not been given rhesus prophylaxis. METHODS: Data were retrieved from the Department of Clinical Immunology at Rigshospitalet. All RhD-negative women carrying an RhD-positive fetus with screen test results from weeks 8-12 and weeks 25-29 were linked to data from the Danish Fetal Medicine Database. Data were divided into cases where no invasive prenatal diagnostic procedure was performed, cases that had AC performed, and cases that had CVS performed. MAIN OUTCOME MEASURES: A comparison of the proportion of women who developed RhD immunisation between the two screen tests. RESULTS: The cohort consisted of 10 085 women: 9353 had no invasive procedures performed, 189 had AC and 543 had CVS performed. No women were immunised spontaneously or due to the procedure between the first and second screen test in the group with no procedure performed, or in the AC group. One woman was immunised in the CVS group. When comparing the proportion of women who was immunised in the CVS group with the no invasive test group a non-significant difference was found (P = 0.055). CONCLUSION: The RhD immunisation rate before gestational weeks 25-29 in RhD-negative women carrying an RhD-positive fetus is very low, even in women undergoing prenatal invasive testing without rhesus prophylaxis. TWEETABLE ABSTRACT: The RhD immunisation rate during pregnancy is very low even in women undergoing prenatal invasive testing.

Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis.

OBJECTIVE: To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis. METHODS: A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random-effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive-testing and control groups. Heterogeneity was assessed using the I2 statistic. Egger's bias was estimated to assess reporting bias in published studies. RESULTS: The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73-1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47-0.70%). The weighted procedure-related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11-0.49%; I2 = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76-2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86-1.59%). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95% CI, -0.13 to 0.52%; I2 = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure-related risk for amniocentesis was 0.12% (95% CI, -0.05 to 0.30%; I2 = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I2 = 0%). CONCLUSIONS: The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Riesgo de aborto después de una amniocentesis o una biopsia de vellosidades coriónicas: revisión sistemática de bibliografía y metaanálisis actualizado OBJETIVO: Estimar el riesgo de aborto relacionado con el procedimiento de la amniocentesis o la biopsia de vellosidades coriónicas (BVC) mediante una revisión sistemática de bibliografía y un metaanálisis actualizado. MÉTODOS: Se realizó una búsqueda en MEDLINE, EMBASE y The Cochrane Library para identificar estudios que reportaron sobre complicaciones después de una BVC o amniocentesis. Se consideraron elegibles para su inclusión los estudios controlados de gran tamaño que reportaron datos sobre la pérdida del embarazo antes de las 24 semanas de gestación. Se estableció contacto con los autores de los estudios cuando fue necesario para identificar datos adicionales necesarios. Se introdujeron en tablas de contingencia los datos de los casos que se sometieron a un procedimiento invasivo y controles y se estimó el riesgo de aborto para cada estudio. Las estadísticas resumen basadas en un modelo de efectos aleatorios se calcularon después de tener en cuenta la ponderación para cada estudio incluido en la revisión sistemática. El riesgo de aborto relacionado con cada procedimiento se estimó como una diferencia de riesgo ponderada de las estadísticas resumen para los casos y controles. Los análisis de subgrupos se realizaron de acuerdo con la similitud en los niveles de riesgo de anomalías cromosómicas entre los grupos de prueba invasiva y de control. La heterogeneidad se evaluó mediante el test estadístico I2 . Se estimó el sesgo de Egger para evaluar el sesgo de información reportada en los estudios publicados. RESULTADOS: La búsqueda electrónica arrojó 2943 citas potenciales, de las cuales se seleccionaron para su inclusión en la revisión sistemática 12 estudios controlados para la amniocentesis y siete para la BVC. Después de los 63723 procedimientos de amniocentesis sucedieron un total de 580 abortos, lo que resultó en un riesgo ponderado de pérdida de embarazo del 0,91% (IC 95%, 0,73-1,09%). En el grupo de control hubo 1726 abortos en 330469 embarazos, con una tasa de pérdida del 0,58% (IC 95%, 0,47-0,70%). El riesgo ponderado de aborto relacionado con el procedimiento de amniocentesis fue del 0,30% (IC 95%, 0,11-0,49%; I2  = 70,1%). Después de 13011 procedimientos de BVC se produjeron un total de 163 abortos, lo que resultó en un riesgo de pérdida de embarazo del 1,39% (IC 95%, 0,76-2,02%). En el grupo de control hubo 1946 abortos en 232680 embarazos, lo que supuso una tasa de pérdida del 1,23% (IC 95%, 0,86-1,59%). El riesgo ponderado de aborto relacionado con el procedimiento de BVC fue de 0,20% (IC 95%, -0,13-0,52%; I2  = 52,7%). Sin embargo, cuando se consideraron los estudios que incluyeron sólo mujeres con perfiles de riesgo similares para la anomalía cromosómica en los grupos de intervención y control, el riesgo relacionado con el procedimiento de la amniocentesis fue de 0,12% (IC 95%, -0,05-0,30%; I2  = 44.1%) y para el MVC fue de -0,11% (IC 95%, -0,29-0,08%; I2  = 0%). CONCLUSIONES: Los riesgos de aborto relacionados con el procedimiento de la amniocentesis y la BVC son menores que los actualmente mencionados a las mujeres. El riesgo parece ser insignificante cuando estas intervenciones se compararon con grupos de control del mismo perfil de riesgo.

Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis.

OBJECTIVES: To estimate the procedure-related risks of miscarriage following chorionic villus sampling (CVS) and amniocentesis in a large unselected screened population, and to determine whether these risks are consistent with those reported in systematic reviews and meta-analyses. METHODS: This was a retrospective cohort study carried out on data obtained from a large fetal medicine unit in the UK between January 2009 and May 2018. We included all women with singleton pregnancy who booked for pregnancy care at our unit before 20 weeks' gestation, after excluding those with multiple pregnancy, major fetal defect, pregnancy termination and loss to follow-up. We estimated the risk of miscarriage in women who underwent a CVS or amniocentesis as well as in those who did not have an invasive procedure. The procedure-related risk of miscarriage was estimated as risk difference (95% CI) between the two groups. Univariate and multivariate regression analyses were used to derive odds ratios (95% CI) and determine which maternal and pregnancy characteristics provided a significant contribution in the prediction of miscarriage and whether CVS or amniocentesis provided a significant independent contribution. RESULTS: During the study period, 45 120 singleton pregnancies were booked for pregnancy care at our hospital, of which 1546 had an invasive procedure. We excluded 1429 (3.2%) pregnancies due to fetal defects, termination of pregnancy or missing outcomes. Of the 43 691 pregnancies included in the study population, 861 underwent CVS and 375 amniocentesis. In pregnancies that underwent CVS, the risk of miscarriage was 1.5% (13/861), compared with 1.2% (476/39 152) in pregnancies that had first-trimester combined screening and did not have an invasive procedure (P = 0.437). In pregnancies that underwent an amniocentesis, the risk of miscarriage was 0.8% (3/375), compared with 1.2% (491/42 463) in those that did not undergo an invasive procedure (P = 0.520). Univariate and multivariate regression analysis demonstrated that there was no significant contribution in the prediction of the risk of miscarriage from CVS (P = 0.399 and P = 0.592, respectively) or amniocentesis (P = 0.543 and P = 0.550, respectively). The risk of procedure-related loss attributed to CVS was 0.29% (95% CI, -0.53 to 1.12%) and that following amniocentesis was -0.36% (95% CI, -1.26 to 0.55%), which was not significantly different from the risk in women who did not have any procedure. CONCLUSIONS: The procedure-related risks of miscarriage following CVS and amniocentesis in our study are considerably lower than those currently quoted and are consistent with the estimates of such risks reported by systematic reviews and meta-analyses. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Procedural and obstetric outcomes after embryo reduction vs fetal reduction in multifetal pregnancy.

OBJECTIVE: To compare the obstetric outcome and incidence of procedure-related adverse events after embryo reduction (ER) vs fetal reduction (FR), in multifetal pregnancies undergoing reduction to twins or singletons. METHODS: We analyzed retrospectively data from multifetal pregnancies that underwent transvaginal ER (n = 181) at a mean gestational age of 7.6 weeks or transabdominal FR (n = 115) at a mean gestational age of 12.9 weeks between December 2006 and January 2017. FR was performed after a detailed fetal anomaly scan. The two groups were compared with respect to obstetric outcomes, such as incidence of miscarriage, early or late preterm delivery, maternal complications and fetal loss, and procedure-related adverse events, including incidence of subchorionic hematoma and procedure-related fetal loss. RESULTS: Compared with pregnancies that underwent ER, the incidence of procedure-related fetal loss was lower in the FR group (7.2% vs 0.9%; P = 0.039; odds ratio (OR), 0.12; 95% CI, 0.02-0.89). Mean gestational age at delivery for twins was 34.2 weeks in the ER group and 35.7 weeks in the FR group (P = 0.014). Compared with the ER group, the FR group had lower miscarriage (8.8% vs 2.6%; P = 0.045; OR, 0.28; 95% CI, 0.08-0.97) and overall fetal loss (13.3% vs 5.2%; P = 0.031; OR, 0.36; 95% CI, 0.14-0.91) rates. CONCLUSIONS: The FR procedure is, overall, a better and safer approach to reducing morbidity and mortality in multifetal pregnancies. Spontaneous demise of one fetus may occur after ER, and FR has the advantage that chorionic villus sampling and ultrasound screening for increased nuchal translucency and anatomical defects can be conducted before the procedure. The ER approach is still reasonable when a patient's religious or other ethical concerns are of primary importance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Managing pain and anxiety during transabdominal chorionic villus sampling. A noninferiority randomized trial of nitrous oxide vs local anesthesia.

INTRODUCTION: Transabdominal chorionic villus sampling (CVS) is an invasive procedure for prenatal diagnosis reported to be associated with anxiety and pain. In this context, the need for analgesia during CVS has been considered useful. Even though several authors have been interested in pain management during amniocentesis, no study has been published on pain reduction during CVS. Our objective was to evaluate pain and anxiety management during transabdominal CVS using nitrous oxide (N2 O) and local anesthesia. MATERIAL AND METHODS: In a randomized controlled noninferiority trial, self-administered nitrous oxide (N2 O) inhalation (equimolar premix of oxygen and nitrous oxide) was compared with local anesthesia (1% lidocaine) before CVS. Primary outcome was pain and secondary outcome was anxiety, both measured on a visual analog scale 30-60 minutes before, immediately after (5-10 minutes) and 30-60 minutes after CVS. With a statistical power of 90%, type I error of 5% and two-sided test and potential exclusions, a sample size of 96 patients per group was enrolled and randomized. No patient was enrolled before the trial registration date. RESULTS: From 13 March 2013 through 10 February 2015, 192 patients (96 per group) were screened and randomized. Most characteristics were similar across groups. Pain in the N2 O group was 2.65 ± 0.22 vs 3.32 ± 0.26 in local anesthesia group [mean ± standard error of mean  (SEM)]. Mean anxiety in the N2 O group was 3.17 ± 0.27 vs 5.19 ± 0.30 in the local anesthesia group. CONCLUSION: N2 O was as efficient and even superior to local anesthesia for both pain and anxiety reduction during CVS, as the 95% confidence intervals were both below the prespecified noninferiority margin of 0.8 and below zero.

Procedure related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study.

Background The aim of this study was to compare transabdominal and transcervical chorionic villus sampling (CVS) as well as amniocentesis (AC) with respect to their rates of premature delivery and fetal growth restriction. Methods We retrospectively evaluated the mentioned procedures of invasive prenatal testing performed in a single center between 2001 and 2016. Seven hundred and ninety-nine cases of AC and 719 cases of CVS were included, of which 400 were performed transvaginally. Only singleton pregnancies with a normal karyotype and delivery after 24 + 0 weeks of gestation were included. Fetal growth restriction was defined as birth weight below the 10th percentile. Premature delivery was defined as delivery before 37 + 0 weeks of gestation. Data were compared to a control group without an invasive procedure. Results The frequency of premature delivery was 8.5% after transabdominal CVS, 6.3% after transcervical CVS and 10.5% after AC as compared to 10.8% in the control group. The frequency of fetal growth restriction was 8.2% after transabdominal CVS 6.8% after transcervical CVS and 8.4% after AC as compared to 9.7% in the control group. Conclusion Our study supports that the three different methods of invasive prenatal testing do not lead to a higher risk of either premature delivery or fetal growth restriction when compared to controls. We found no difference in risk profile among the three techniques.

Obstetrical Outcomes of Amniocentesis or Chorionic Villus Sampling in Dichorionic Twin Pregnancies.

BACKGROUND: Under certain situations, women with twin pregnancies may be counseled to undergo invasive prenatal diagnostic testing. Chorionic villus sampling and amniocentesis are the two generally performed invasive prenatal diagnostic tests. Studies comparing procedure-related fetal loss between first-trimester chorionic villus sampling and second-trimester amniocentesis in twin pregnancies are limited. This study aimed to evaluate the procedure-related fetal loss and the obstetrical outcomes of these two procedures, chorionic villus sampling and amniocentesis in twin pregnancies. METHODS: The data from dichorionic-diamniotic twin pregnancies on which first-trimester chorionic villus sampling (n = 54) or second-trimester amniocentesis (n = 170) was performed between December 2006 and January 2017 in a single center were retrospectively analyzed. The procedure-related fetal loss was classified as loss of one or all fetuses within 4 weeks of procedure, and overall fetal loss was classified as loss of one or all fetuses during the gestation. The groups were compared with respect to the procedure-related and obstetrical outcomes. RESULTS: The difference in proportion of procedure-related fetal loss rate (1.9% for chorionic villus sampling vs. 1.8% for amniocentesis; P = 1.000) and the overall fetal loss rate (7.4% for chorionic villus sampling vs. 4.7% for amniocentesis; P = 0.489) between the two groups was not significant. The mean gestational ages at delivery were not statistically significant. CONCLUSION: Both the overall fetal loss rate and the procedure-related fetal loss rate of chorionic villus sampling and amniocentesis in dichorionic twin pregnancies had no statistical significance. Both procedures can be safely used individually.

Obstetrical outcomes after first-trimester chorionic villus sampling in twin pregnancies: A retrospective case-control study.

AIM: Prenatal diagnostic testing by chorionic villus sampling (CVS) is sometimes recommended for women with twin pregnancies. However, few studies have compared the outcomes between twins with CVS and control twins without intervention. This study aimed to compare the obstetrical outcomes of CVS in twin pregnancies and those in non-intervention twin pregnancies. METHODS: First-trimester transabdominal CVS was performed on dichorionic-diamniotic twins (n = 54; Group 1) between December 2006 and January 2017 at the Department of Obstetrics and Gynecology at our hospital, and the data were retrospectively analyzed. CVS risks were evaluated by comparing obstetrical outcomes with those of a control population of 155 dichorionic-diamniotic twins without intervention (Group 2). RESULTS: The difference in the overall fetal loss rate (Group 1, 7.4% vs Group 2, 3.9%; P = 0.287) between the two groups was not statistically significant. The miscarriage rate, defined as delivery at <24 gestational weeks, and early preterm delivery, defined as delivery at <34 gestational weeks, were not significant between the groups (miscarriage: Group 1, 5.6% vs Group 2, 3.2%; P = 0.428; early preterm delivery: Group 1, 11.1% vs Group 2, 9.0%; P = 0.788). The mean gestational age at delivery, birth weights and neonatal intensive care unit admission rate were not statistically significant between the groups. Thus, the overall fetal loss rate and obstetrical outcomes of Group 1 were comparable with those of Group 2. CONCLUSION: In conclusion, the overall obstetrical outcomes were not significantly different between twins with CVS and control twins with the advantage of enabling early decision-making about selective feticide in twins with CVS.

Complication rates after chorionic villus sampling and midtrimester amniocentesis: A 7-year national registry study.

PURPOSE: To assess the complication rates following chorionic villus sampling (CVS) and midtrimester amniocentesis in Taiwan. METHODS: This is a national registry-based cohort study from Taiwan. We included all women with singleton pregnancies who received either CVS (n = 1409) or midtrimester amniocentesis (n = 250,566) during 2006-2012. We assessed preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD), infection and spontaneous abortion (SA) that occurred within fourteen days after the procedures. We also assessed the risks of preterm delivery and miscarriage before 24 gestational weeks after amniocentesis. These complications were collected from the Genetic Disease Database of the Ministry of Health and Welfare, Taiwan National Birth Certificate Registry, and the Taiwan National Health Insurance Database. Pearson χ2 tests were used to compare the distributions between groups. RESULTS: For patients who underwent midtrimester amniocentesis, the rates of PPROM, IUFD, infection and SA within fourteen days were 0.24%, 0.11%, 0.05%, and 0.05%, respectively. Women with a normal fetal karyotype had a preterm birth rate (<37 gestational weeks) of 9.38%. The miscarriage rate (<24 gestational weeks) was 0.68%, which was 0.22% higher than those who did not receive the invasive procedures (p < 0.0001). After CVS, the IUFD rate was 1.68%, and the SA rate within fourteen days was 0.77%. CONCLUSION: The use of our large cohort demonstrated that the procedure-related complication rates were comparable to recent review or meta-analysis. This dataset might facilitate counselling in women who consider invasive genetic diagnostic procedures.

Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial.

Importance: Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancies at a high risk of trisomy 21 to decrease the number of required invasive fetal karyotyping procedures and their associated miscarriages. The effect of this strategy has not been evaluated. Objective: To compare the rates of miscarriage following invasive procedures only in the case of positive cfDNA test results vs immediate invasive testing procedures (amniocentesis or chorionic villus sampling) in women with pregnancies at high risk of trisomy 21 as identified by first-trimester combined screening. Design, Setting, and Participants: Randomized clinical trial conducted from April 8, 2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first-trimester screening. Interventions: Patients were randomized to receive either cfDNA testing followed by invasive testing procedures only when cfDNA tests results were positive (n = 1034) or to receive immediate invasive testing procedures (n = 1017). The cfDNA testing was performed using an in-house validated method based on next-generation sequencing. Main Outcomes and Measures: The primary outcome was number of miscarriages before 24 weeks' gestation. Secondary outcomes included cfDNA testing detection rate for trisomy 21. The primary outcome underwent 1-sided testing; secondary outcomes underwent 2-sided testing. Results: Among 2051 women who were randomized and analyzed (mean age, 36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial. The miscarriage rate was not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk difference of -0.03% (1-sided 95% CI, -0.68% to ∞; P = .47). The cfDNA detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%). Conclusions and Relevance: Among women with pregnancies at high risk of trisomy 21, offering cfDNA screening, followed by invasive testing if cfDNA test results were positive, compared with invasive testing procedures alone, did not result in a significant reduction in miscarriage before 24 weeks. The study may have been underpowered to detect clinically important differences in miscarriage rates. Trial Registration: ClinicalTrials.gov Identifier: NCT02127515.