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Three-dimensional (3D) ultrasound is an invaluable tool in the detection and evaluation of many uterine anomalies and improves upon the traditional approach of two-dimensional (2D) ultrasonography. We aim to describe an easy way of assessing the uterine coronal plane using the basic three-dimensional ultrasound in everyday gynecological practice.

To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses.We recruited 51 fetuses with two or more defects, non-immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in-house standard operating procedures.Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty-three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%-57.8%) pregnancies.In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases.

A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal abnormalities, and genetic diseases. We aim to illustrate the basic and detailed second trimester scan, according to current international and national guidelines, as well as to our own every-day practice in the Department for Prenatal Diagnosis at the University of Tübingen, Germany.

Screening for chromosomal disorders, especially for trisomy 21, has undergone a number of changes in the last 50 years. Today, cell-free DNA analysis (cfDNA) is the gold standard in screening for trisomy 21. Despite the advantages that cfDNA offers in screening for common trisomies, it must be recognized that it does not address many other chromosomal disorders and any of the structural fetal anomalies. In the first trimester, the optimal approach is to combine an ultrasound assessment of the fetus, which includes an NT measurement, with cfDNA testing. If fetal structural defects are detected or if the NT thickness is increased, an amniocentesis or a CVS with at least chromosomal microarray should be offered.

Objective: The aim of the objective was to compare the detection rate for trisomy 21 of universal cell free DNA (cfDNA) screening with contingent screening. Methods: Retrospective study was carried out at 3 German centers. The study included euploid and trisomy 21 pregnancies where cfDNA and first trimester (FT) screening assessment was carried out. The FT risk for trisomy 21 was computed based on combined screening and stratified into the following classes: high risk ≥1:10, intermediate risk 1:11–1,000, low risk ≤1,001. For universal cfDNA screening, the cfDNA test results were examined. For the contingent screening model, the result of the cfDNA test was taken into account in case of an intermediate FT risk. Different strategies combining maternal age, nuchal translucency, nasal bone, beta-hCG, and PAPP-A were evaluated. Screen positivity was defined as either a high risk after FT screening or a cfDNA test indicating a high-risk result. An inconclusive cfDNA test was also considered as screen positive. Results: The search of the database identified 2,255 euploid and 163 affected pregnancies. All affected fetuses were identified by universal cfDNA screening. 1.3% of the euploid fetuses were classified as screen positive due to final inconclusive cfDNA test result. The detection and false-positive rate of a contingent approach that is based on combined screening and cfDNA screening in the intermediate group would be 98.4% and 0.7%, respectively. With this approach, cfDNA screening would be necessary in only about 27% of all pregnancies. Conclusion: This study demonstrates that a contingent approach provides similar detection rates for trisomy 21 as universal cfDNA screening, by a reduction of 73% the number of cfDNA tests.

Gynecological sonography is the central and most frequently used technical examination method used by gynecologists. Its focus is on the clarification of masses of the uterus and the adnexa, fertility diagnosis, clarification of bleeding disorders and chronic and acute pelvic problems, pelvic floor and incontinence diagnosis as well as the differential diagnosis of disturbed early pregnancy. The indication for diagnostic and therapeutic interventions, preoperative planning and postoperative controls are largely based on the findings of gynecological sonography. These examinations are particularly dependent on the experience of the examiner.Based on the proven multi-stage concept of obstetric diagnostics, gynecological sonography should primarily be performed by an experienced and specialized examiner in patients for whom the initial gynecological examinations have not yet led to a sufficient assessment of the findings. So that the expert status required for this has an objective basis, the Gynecology and Obstetrics Section of DEGUM in cooperation with ÖGUM and SGUM implemented the option of acquiring DEGUM Level II for gynecological sonography. The effectiveness of the care in the multi-level concept depends on the quality of the ultrasound examination at level I. Quality requirements for the basic examination and the differentiation between the basic and further examination have therefore already been defined by DEGUM/ÖGUM. The present work is intended to set out quality requirements for gynecological sonography of DEGUM level II and for the correspondingly certified gynecologists.Common pathologies from gynecological sonography and requirements for imaging and documentation are described.Die gynäkologische Sonografie ist das zentrale und am häufigsten angewandte apparative Untersuchungsverfahren der Frauenärzt*innen. Ihre Schwerpunkte sind die Abklärung von Raumforderungen des Uterus und der Adnexen, die Fertilitätsdiagnostik, Abklärung von Blutungsstörungen und chronischen wie akuten Unterbauchbeschwerden, die Beckenboden- und Inkontinenzdiagnostik sowie die Differentialdiagnostik der gestörten Frühschwangerschaft. Die Indikation zu diagnostischen und therapeutischen Interventionen, die präoperative Planung und die postoperativen Kontrollen beruhen maßgeblich auf Befunden der gynäkologischen Sonografie. Diese Untersuchungen sind im besonderen Maße von der Erfahrung des Untersuchers abhängig.In Anlehnung an das bewährte Mehrstufenkonzept der geburtshilflichen Diagnostik sollte daher bei Patientinnen, in denen die frauenärztlichen Erstuntersuchungen noch nicht zu einer ausreichenden Einschätzung der Befunde führen, primär eine gynäkologische Sonografie durch einen erfahrenen und spezialisierten Untersucher erfolgen. Damit der hierfür erforderliche Expertenstatus eine objektivierbare Grundlage bekommt, wurde von der Sektion Gynäkologie und Geburtshilfe der DEGUM in Kooperation mit der ÖGUM und SGUM die Möglichkeit des Erwerbs der DEGUM-Stufe II für die gynäkologische Sonografie implementiert. Die Effektivität der Versorgung im Mehrstufenkonzept lebt aber von der Qualität der Ultraschalluntersuchung auf Stufe I. Qualitätsanforderungen für die Basisunteruntersuchung und die Differenzierung zwischen Basis- und weiterführender Untersuchung wurden daher bereits von der DEGUM/ÖGUM definiert. Die vorliegende Arbeit soll Qualitätsanforderungen an eine gynäkologische Sonografie der DEGUM-Stufe II und an die entsprechend zertifizierten Frauenärztinnen und Frauenärzte darlegen.Häufige Pathologien aus der gynäkologischen Sonografie und Anforderungen an die Bildgebung und Dokumentation werden beschrieben.

BackgroundFetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.MethodsWe performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature.ResultsWe identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the kinesin family member 21A gene (KIF21A) was found.ConclusionOur study underlines the broad locus heterogeneity of FA with well-established and atypical genotype–phenotype associations. We describe KIF21A as a new factor implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia and facial dysmorphisms. This hypothesis is further corroborated by a recent report on overlapping phenotypes observed in Kif21a null piglets., publishedVersion

ZusammenfassungNach dem Zweiten Weltkrieg wurden weltweit Zwillingskohorten aufgebaut, die inzwischen ca. 1,5 Mio. Zwillinge umfassen und zwischen 1950 und 2012 über 2748 Zwillingsstudien hervorgebracht haben. Diese Zahl steigt jedes Jahr um weitere 500 bis 1000. Die Unterrepräsentanz deutscher Zwillingsstudien in diesen Datenbanken lässt sich nicht allein durch den Missbrauch medizinischer Forschung im Nationalsozialismus erklären. Entwicklung und Ausbau großer Zwillingskohorten sind ethisch und datenschutzrechtlich eine Herausforderung. Zwillingskohorten ermöglichen jedoch die Langzeit- und Echtzeiterforschung vieler medizinischer Fragestellungen; und die Zwillingsstudien tragen auch nach der Entschlüsselung des Humangenoms erheblich zur Beantwortung der Frage nach Anlage oder Umwelt als mögliche Erkrankungsauslöser bei.Derzeit gibt es 2 deutsche Zwillingskohorten: die biomedizinische Kohorte HealthTwiSt mit ca. 1500 Zwillingspaaren und TwinLife, eine soziologisch-psychologische Kohorte mit ca. 4000 Zwillingspaaren. Daneben gibt es krankheitsspezifische Kohorten. 2016 startete das TwinHealth-Konsortium der Medizinischen Fakultät der Universität Tübingen mit dem Ziel, eine forschungsoffene und nachhaltige Zwillingsforschung am Standort Tübingen zur Bearbeitung unterschiedlicher Fragestellungen zu etablieren.Der Artikel bietet mithilfe einer systematischen Literaturrecherche und einer medizinhistorischen Betrachtung einen Überblick über die weltweite und nationale Entwicklung von Zwillingsstudien und -datenbanken der letzten 100 Jahre. Anhand der Tübinger TwinHealth-Initiative beleuchtet er den Aufbau eines Zwillingskollektivs und dessen juristische, ethische und Datenschutzaspekte.

Assistenzsysteme in der Pranatalmedizin konnen die tagliche Arbeit erheblich unterstutzen. Den simpelsten Ansatz stellt die Bereitstellung von Referenzkurven dar. Die weiteren heute ublicherweise eingesetzten Verfahren fuhren wohl zu einer Arbeitserleichterung, sind aber im Vergleich zu den Moglichkeiten, die sich mit der Implementierung der kunstlichen Intelligenz ergeben, von untergeordneter Bedeutung. Die Einfuhrung von Assistenzsystemen, die auf kunstlicher Intelligenz beruhen, hat das Potenzial, die sonographische Untersuchung bezuglich Effektivitat und Qualitat grundlegend zu verandern.

Das Ersttrimesterscreening (ETS) beinhaltet eine ausfuhrliche Ultraschalluntersuchung sowie biochemische oder genetische Analysen und ermoglicht eine individuelle Risikoeinschatzung hinsichtlich Chromosomenstorungen, Fehlbildungen und Praeklampsie. Zahlreiche Fehlbildungen konnen im ersten Trimester erkannt werden, und die Detektionsrate kann durch die Beurteilung der Nackentransparenz oder Zusatzmarker gesteigert werden. Entsprechend der Erkennbarkeit sind die strukturellen Fehlbildungen grundsatzlich in 3 Kategorien unterteilt: die (so gut wie) immer erkennbaren, die potenziell erkennbaren und die nie oder selten erkennbaren Fehlbildungen. Im Rahmen des ETS werden in der Regel letale oder schwerwiegende genetische oder strukturelle Fehlbildungen diagnostiziert. Die fruhe Detektion dieser Fehlbildungen erleichtert die Entscheidungsfindung der Eltern und ermoglicht eine adaquate Planung der weiteren Untersuchungen, Beratungen und Therapien. Die zellfreie DNA-Untersuchung kann nach einer unauffalligen Ultraschalluntersuchung als Zusatzmethode zur Detektion fur Trisomien 21, 18 und 13 angeboten werden.

Objective To examine the efficacy of hyperimmunoglobulin (HIG) treatment in women with a recent primary cytomegalovirus (CMV) infection up to 14 weeks' gestation. Methods This is an ongoing observational study conducted at the prenatal medicine departments of the University Hospitals of Tubingen, Bonn, Cologne and Erlangen, Germany, as well as at the Laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tubingen, Tubingen, Germany. Enrolment criteria were the presence of confirmed recent primary CMV infection in the first trimester and a gestational age at first HIG administration of ≤ 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-immunoglobulin (Ig)-G levels, low anti-CMV-IgG avidity in the presence of a positive CMV-IgM test and no positive reactivity or just seroconversion anti-gB2-IgG-reactivity. HIG administration was started as soon as possible within a few days after the first visit. HIG was administered intravenously at a dose of 200 IU/kg maternal body weight and repeated every 2 weeks until about 18 weeks' gestation. The primary outcome was maternal-fetal transmission at the time of amniocentesis. Multivariate logistic regression analysis was used to determine significant covariates that could predict maternal-fetal transmission. Results We included 149 pregnancies (153 fetuses) that completed the treatment. Median maternal age and weight were 32.0 years and 65.0 kg, respectively. Median gestational age at the time of first referral to one of the four centers was 9.4 weeks. Median anti-CMV-IgG level, anti-CMV-IgM index and CMV-IgG avidity were 5.7 U/mL, 2.5 and 22.3%, respectively. HIG treatment was started at a median gestational age of 10.6 weeks and ended at a median of 17.9 weeks. Within this time frame, HIG was administered on average four times in each patient. Amniocentesis was carried out at a median gestational age of 20.4 weeks. In 143 (93.5%) of the 153 cases, the fetus was not infected. Maternal-fetal transmission occurred in 10 cases (6.5% (95% CI, 3.2-11.7%)). On uni- and multivariate logistic regression analysis, the level of anti-IgM index was the only factor associated significantly with maternal-fetal transmission at amniocentesis. However, only four (40.0%) of the 10 cases with maternal-fetal transmission had an anti-IgM index above 11.4, which corresponds to the 95th centile of pregnancies without transmission. Conclusions HIG is a treatment option to prevent maternal-fetal transmission in pregnancy with a primary CMV infection. However, HIG treatment seems to be beneficial primarily in women with a recent primary infection in the first trimester or during the periconceptional period, and when it is administered at a biweekly dose of 200 IU/kg. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound has become an essential diagnostic tool in gynecology, and every practicing gynecologist must be able to differentiate normal from pathologic findings, such as benign or malignant pelvic masses, adnexal torsion, pelvic inflammation disease, endometriosis, ectopic pregnancies, and congenital uterine malformations at least on a basic level. A standardized approach to the correct settings of the ultrasound system, the indications for gynecologic ultrasound investigations, and the sonographic appearance of normal anatomy and common pathologic findings in the standard planes are important prerequisites for safe and confident clinical management of gynecologic patients. Based on current publications and different national and international guidelines, updated DEGUM, ÖGUM, and SGUM recommendations for the performance of basic gynecologic ultrasound examinations were established.Die sonografische Basisuntersuchung in der Gynäkologie umfasst Diagnostik und Differenzialdiagnostik in der täglichen Praxis: Gesundheitsvorsorge, Abgrenzung der Normalbefunde von pathologischen Befunden wie kongenitale Fehlbildungen, benigne und maligne Tumoren, Adnextorsionen, entzündliche Erkrankungen des inneren Genitals, Endometriose, gestörte Frühgraviditäten und Tubargraviditäten sowie Fragestellungen zu Kontrazeption und Fertilität. Die Standardisierung der Untersuchungstechnik sowie die genaue Definition der Leistungsinhalte für die Basisdiagnostik und für die weiterführende Diagnostik (DEGUM-Stufe II) analog des schon seit Jahren in der pränatalen Diagnostik bewährten Mehrstufenkonzepts der DEGUM sind inzwischen auch in die gynäkologische Sonografie implementiert worden. Als Grundlage für eine strukturierte Aus- und Weiterbildung im Rahmen dieses Stufenkonzepts haben DEGUM, ÖGUM und SGUM die Qualitätsanforderungen und die Leistungsinhalte für gynäkologische sonografische Basisuntersuchungen (DEGUM-Stufe I) entsprechend dem gegenwärtigen Kenntnisstand sowie anhand nationaler und internationaler Standards und Empfehlungen aktualisiert.

Die vorgeburtliche Primar-Infektion mit dem Zytomegalievirus gehort zu den relevantesten Infektionen in der Schwangerschaft. Sie kann zu einer erheblichen Entwicklungsstorung des Kindes fuhren, kann aber auch folgenlos bleiben. Fur die Risikobeurteilung ist der Zeitpunkt der mutterlichen Infektion und konsekutiv die Wahrscheinlichkeit der maternofetalen Transmission zur zentraler Bedeutung. Mit zunehmender Schwangerschaftswoche steigt die Transmissionshaufigkeit, gleichzeitig sinkt aber die Wahrscheinlichkeit einer fetalen Schadigung. Therapeutische Ansatze beinhalten die Pravention der mutterlichen Infektion durch Hygienemasnahme, die Pravention der Transmission durch Hyperimmunglobulin und die Therapie des Feten mit Valaciclovir.

In the last decades, abnormal placentation and umbilical cord insertion have become an increasingly relevant and feared pathology in obstetrics with increased morbidity and mortality for mother and child. In addition to several increasingly common risk factors, such as assisted reproduction, the main reason for the increased occurrence is the greater frequency of Cesarean sections. Correct diagnosis, which is primarily determined sonographically, is essential for targeted perinatal management. In particular, the diagnostic criteria and current management recommendations are described in the following article. Storungen der Plazentation und Nabelschnurinsertion haben sich in den letzten Jahrzehnten zu einer zunehmend relevanten und gefurchteten Pathologie der Geburtshilfe mit erhohter Morbiditat und Mortalitat fur Mutter und Kind entwickelt. Neben einigen zunehmend haufigeren Risikofaktoren wie beispielsweise assistierte Reproduktion liegt die Hauptursache fur das vermehrte Auftreten in der angestiegenen Haufigkeit der Sectio caesarea. Essenziell fur ein gezieltes perinatales Management ist die korrekte Diagnosestellung, welche vorrangig sonografisch erfolgt. Im folgenden Artikel sollen insbesondere die diagnostischen Kriterien und aktuellen Managementempfehlungen vorgestellt werden.

Objective To determine whether the frontomaxillary facial (FMF) angle and the prefrontal space ratio (PFSR) are helpful in screening for open spinal defects by ultrasound in the second and third trimesters of pregnancy. Methods The FMF angle and the PFSR were measured in fetuses with spina bifida according to standardized protocols. The normal range of the PFSR was previously published by our group. To determine the normal values for the FMF angle in the second and third trimesters of pregnancy, we used the same stored images from the above-mentioned study. Results 71 affected and 279 normal fetuses were included in this study. Median gestational ages in the two groups were 21.1 weeks and 21.6 weeks, respectively. In fetuses with spina bifida, the FMF angle was significantly smaller than in the normal population (72.9° versus 79.6°). However, the measurement was below the fifth centile in only 22.5% of the affected fetuses. The PFSR was similar in both groups. Conclusions The FMF angle is smaller in second and third trimester fetuses with open spina bifida. However, the difference is not large enough to implement this marker in current screening programs.

Der Fokus der Ultraschalldiagnostik liegt in der Beurteilung der fetalen und plazentaren Sonomorphologie mittels B‑Bild-Darstellung. Die ermittelten Schnittbilder werden mit den normalen Schnittebenen verglichen, um so die intrauterine Entwicklung des Feten und der Plazenta beurteilen zu konnen. Fur manche Organsysteme, etwa fur das Urogenitalsystem, lasst sich aus der B‑Bild-Darstellung eine Funktionsbeurteilung ableiten. Eine weitere Moglichkeit der pranatalen Funktionsbeurteilung ist die Dopplersonographie. Mit ihr lassen sich Flussigkeitsbewegungen – in aller Regel Blutstrome – hinsichtlich ihrer Richtung und Geschwindigkeit untersuchen und so Ruckschlusse auf die fetale Herzleistung, auf Compliance und Stromungswiderstande in einem fetalen bzw. plazentaren Gefasabschnitt oder auch auf die fetale Erythrozytenkonzentration ziehen. Obwohl das Verfahren schon einige Jahrzehnte alt ist, finden sich auch heute noch Innovationen in der dopplersonographischen Beurteilung der Schwangerschaft, so etwa Neuerungen im Bereich der „twin anemia polycythemia sequence“ (TAPS) bei monochorialen Gemini, in der Beurteilung der Ductus-venosus-Blutstromung zur Detektion von Herzfehlern im ersten Trimenon, in der Bewertung der Dopplerbefunde bei spater Wachstumsretardierung sowie bei der Beurteilung von maternaler Gefascompliance und Stromungswiderstande bei einer Praeklampsie.

Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis.This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial.In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters.Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced.Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Sex hormones such as estradiol (E2) have long-lasting influence on brain architecture. Recent studies indicate further structural changes during hormonal transition periods including pregnancy, when women experience the greatest increase in sex hormone levels across their life span. In the present study, three groups of women (n = 44) with different levels of E2 underwent structural magnetic resonance imaging: (1) first-time pregnant women (n = 13, 'extreme E2 group'); (2), nulliparous, naturally cycling women who received 12 mg of E2 valerate (n = 16, 'high E2 group'); and (3) nulliparous, naturally cycling women receiving a placebo and hence low E2 (n = 15, 'low E2 group'). Blood samples were taken to assess hormonal levels. Moreover, parameters for cognition, emotion regulation and affect were assessed. On the neuronal level, the extreme E2 compared to the high E2 group showed a reduced gray matter volume in the left putamen. However, no significant differences were found between the low vs. high E2 groups, nor between the low E2 and extreme E2 groups. Cognitive performance was reduced in the extreme E2 group, although a positive affect was increased compared to the high E2 and low E2 groups. Furthermore, regression analyses revealed several associations between cognition, subjective measures of affect, emotion regulation and gray matter volume. A volume reduction of the left putamen during pregnancy further supports the notion that the female brain is shaped by hormonal transition phases, possibly preparing women for their future roles (e.g., pregnant women for their role as mothers).

To determine whether the prefrontal space ratio (PSFR), inferior facial (IFA) and maxilla-nasion-mandible angle (MNM), and the fetal profile line (FPL) are helpful in identifying fetuses with Robin sequence (RS) in cases with isolated retrognathia, and thus better predict the likelihood of immediate need for postnatal respiratory support.This was a retrospective matched case-control study of fetuses/infants with isolated retrognathia with or without RS receiving pre- and postnatal treatment at the University Hospital of Tübingen, Germany between 2008 and 2020. The PFSR, IFA, MNM, and FPL were measured in affected and normal fetuses according to standardized protocols. Cases were stratified into isolated retrognathia and RS.21 (n=7 isolated retrognathia, n=14 RS) affected fetuses and 252 normal fetuses were included. Their median gestational age at ultrasound examination was 23.6 and 24.1 weeks, respectively. In fetuses with isolated retrognathia and RS, the PSFR, IFA, and FPL were significantly different from the normal population. At a false-positive rate of 5%, the detection rate was 76.2% for the PFSR, 85.7% for the IFA, and 90.5% for both parameters combined. However, all parameters failed to distinguish between isolated retrognathia and RS.PSFR and IFA are simple markers for identifying retrognathia prenatally. However, they are not helpful for the detection of RS in fetuses with isolated retrognathia. Therefore, delivery should take place in a center experienced with RS and potentially life-threatening airway obstruction immediately after birth.Es sollte bestimmt werden, ob das präfrontale Raumverhältnis (PSFR), der inferiore faziale Winkel (IFA) und der Maxilla-Nasion-Mandibula-Winkel (MNM) oder die fetale Profillinie (FPL) bei der Identifizierung von Föten mit Robin-Sequenz (RS) in Fällen mit isolierter Retrognathie hilfreich sind, um so die Wahrscheinlichkeit eines unmittelbaren Bedarfs an postnataler Atmungsunterstützung besser vorherzusagen zu können.Dies war eine retrospektive, gematchte Fall-Kontroll-Studie von Föten/Kindern mit isolierter Retrognathie mit oder ohne RS, die zwischen 2008 und 2020 im Universitätsklinikum Tübingen, Deutschland prä- und postnatal behandelt wurden. Die PFSR, IFA, MNM und FPL wurden bei betroffenen und normalen Föten nach standardisierten Protokollen gemessen. Die Patienten wurden in isolierte Retrognathie und RS unterteilt.21 (n=7 isolierte Retrognathie, n=14 RS) betroffene und 252 normale Föten wurden eingeschlossen. Das mediane Gestationsalter bei der Ultraschalluntersuchung betrug 23,6 bzw. 24,1 Wochen. Bei Föten mit isolierter Retrognathie und RS unterschieden sich die PSFR, IFA und FPL signifikant von der normalen Population. Bei einer Falsch-Positiv-Rate von 5% betrug die Erkennungsrate 76,2% für die PFSR, 85,7% für die IFA und 90,5% für beide Parameter zusammen. Alle Parameter konnten jedoch nicht zwischen isolierter Retrognathie und RS unterscheiden.PSFR und IFA sind einfache Marker zur pränatalen Identifizierung von Retrognathien. Sie sind jedoch nicht hilfreich für die Erkennung von RS bei Föten mit isolierter Retrognathie. Daher sollte die Entbindung in einem Zentrum erfolgen, das Erfahrung mit RS und einer potenziell lebensbedrohlichen Atemwegsobstruktion unmittelbar nach der Geburt hat.

Wolf-Hirschhorn syndrome (WHS) is a common genetic condition and prenatal diagnosis is difficult due to heterogeneous expression of this syndrome and rather non-specific ultrasound findings. Objective of this study was to examine the prenatal ultrasound findings in fetuses with Wolf-Hirschhorn syndrome (WHS).Retrospective assessment of 18 pregnancies that were seen at three tertiary referral centers (Universities of Bonn, Tuebingen and Nuernberg / Germany). Findings of prenatal ultrasound examinations, genetic results and outcome were compared. Additionally, findings of our study were compared to previous small case series from the literature and then compared to data on postnatal frequencies and abnormalities in affected patients.Median gestational age at the time of examination was 23 + 1 weeks' (range: 13 + 4 to 29 + 1 weeks') with female-to-male ratio of 2.5:1. Most frequent ultrasound findings were facial abnormalities, symmetric IUGR and microcephaly that presented in 94.4, 83.3 and 72.2% of cases, respectively. The combination of microcephaly and hypoplastic nasal bone was a particularly characteristic finding. Growth retardation presented in all fetuses 20 weeks, but not below. Other frequent abnormalities included cardiac anomalies in 50 and single umbilical artery (SUA) in 44.4% of fetuses.WHS should be considered in the presence of symmetric IUGR together with microcephaly, hypoplastic nasal bone and facial abnormalities on prenatal ultrasound. Genetic testing by chromosomal microarray analysis (CMA) is strongly recommended in this context.

Optimal mode of birth for twins, in particular monochorionic twins, has been the subject of much debate. This retrospective study compared maternal and newborn outcomes after vaginal birth in monochorionic and dichorionic twins, utilizing a large institutional database.Retrospective analysis focusing on 98 monochorionic-diamniotic (MC-DA) and 540 dichorionic-diamniotic (DC-DA) twin births extracted from the perinatal database of a large German hospital. Pregnancies ≥36 weeks of gestation with two viable foetuses born between 2004 and 2014 divided into planned vaginal and planned caesarean delivery were included. Descriptive analysis was performed for maternal characteristics. Odds ratios (OR) with 95% confidences intervals (CI) tested the predictive effect of vaginal birth on neonatal and maternal outcomes.51.0% MC-DA and 46.7% DC-DA twin pregnancies were planned vaginal births and 44.0% MC-DA mothers and 43.7% DC-DA mothers actually gave birth vaginally. The overall rate of caesarean section (CS) during the years under observation was 79.6% for MC-DA and 77.0% for DC-DA pregnancies. There were no significant differences in neonatal outcome between the subsamples, although acidosis was observed more often in the second DC-DA twin and Apgar scores 7 were observed more often in MC-DA twins.Vaginal birth may be recommended as an option to women with monochorionic twins as no significant differences in outcomes were found between MC-DA and DC-DA twins. However, over half of planned vaginal twin births resulted in CS.

Objectives: The aims of the study were to assess the false-positive and uninformative test rate with first trimester cell-free DNA (cfDNA) screening for common trisomies and microdeletion 22q11.2 (22q11.2DS) and to examine women’s attitudes toward such an approach. Methods: This is a prospective study at the Prenatal Medicine Department of the University of Tübingen, Germany, at 11–13 weeks. In all pregnancies, a detailed ultrasound examination was carried out, followed by a cfDNA analysis for common trisomies and 22q11.2DS. In cases where the cfDNA analysis indicated 22q11.2DS, invasive prenatal diagnostic testing and parental testing were performed. After delivery, a detailed neonatal clinical examination was carried out including further genetic testing. Prior to counselling about the study, we asked the pregnant women who were potentially eligible for the study to anonymously report on their knowledge about 22q11.2DS. Results: A total of 1,127 pregnancies were included in the final analysis of the study. The first cfDNA test was uninformative in 15 (1.33%) pregnancies. In 10 (0.89%) cases, the test remained uninformative, even after the second blood sample. There were 3 (0.27%) cases with a positive cfDNA test for 22q11.2DS. In all, 983 women returned the anonymous questionnaire prior to study participation. Only 80 (8.1%) women responded that they felt familiar or very familiar with 22q11.2DS. Conclusion: The addition of 22q11.2DS in first trimester cfDNA screening for common trisomies is feasible. The uninformative test rate for common trisomies and 22q11.2DS is 0.9%, and the false-positive rate for 22q11.2DS is 0.3%. Awareness and education around 22q11.2DS should be improved.

To analyze copy number variants (CNVs) in subjects with small for gestational age (SGA) in China. A total of 85 cases with estimated fetal weight (EFW) or birth weight below the 10th percentile for gestational age were recruited, including SGA associated with structural anomalies (Group A, n = 20) and isolated SGA (Group B, n = 65). In all cases, cytogenetic karyotyping and infection screening were normal. We examined DNA from fetuses (amniocentesis or cordocentesis) and newborns (cord blood) to detect CNVs using a single nucleotide polymorphism (SNP, n = 75) array or low-pass whole-genome sequencing (WGS, n = 10). Of 85 total cases, 3 (4%) carried pathogenic chromosomal abnormalities, including 2 cases with pathological CNVs and 1 case with upd(22)pat. In Group A, the mean gestational age at the time of diagnosis was 26.8 (SD 4.1) weeks and mean EFW/birth weight was 907.2 (SD 567.8) g. In Group B, the mean gestational age at the time of diagnosis was 34.1 (SD 5.8) weeks. Mean EFW/birth weight was 1879.2 (SD 714.5) g. The pathologic detection rate was 10% (2/20) in Group A and 2% (1/65) in Group B. It was inclined that the lower the EFW percentile, the more frequent the occurrence of CNVs. Pathological subchromosomal anomalies were detected by CMA or low-pass WGS in 10% and 2% of SGA subjects with and without malformation, respectively. SGA fetuses with structural anomalies presented with higher pathological subchromosomal anomalies. The molecular genetic analysis is not recommended for isolated SGA pregnancies without other abnormal findings.

Aim To investigate the changes of modified myocardial performance index (Mod‐MPI) in early‐onset and late‐onset fetal growth restriction (FGR) cases, and its association with adverse perinatal outcome. Methods This was a prospective study on 77 early‐onset and 100 late‐onset FGR cases. Hundred normal fetuses were matched as control groups for early‐onset and late‐onset FGR groups, respectively. Mod‐MPI and vessel Doppler parameters including umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) were measured. Perinatal outcomes were followed up. Mod‐MPI of FGR cases were compared in normal Doppler, abnormal Doppler, and control groups. The association of Mod‐MPI and perinatal outcome was investigated, and further efficacy of Mod‐MPI predicting adverse outcome was studied. Results Compared with control groups, both abnormal and normal Doppler groups showed increased Mod‐MPI in early‐onset and late‐onset FGR, respectively. Mod‐MPI had no significant difference between abnormal and normal Doppler groups. Mod‐MPI was associated with adverse outcome in early‐onset FGR (OR = 3.307) and late‐onset FGR (OR = 3.412). The sensitivity and specificity of Mod‐MPI predicting adverse outcome were 60% and 80% when cutoff value was 0.47 in early‐onset FGR. And they were 65% and 70% when cutoff value was 0.50 in late‐onset FGR. Conclusion Fetal growth restriction fetuses had increased Mod‐MPI. Mod‐MPI could be used to predict adverse perinatal outcome of FGR fetuses. Mod‐MPI was an effective parameter to supplement vessels’ Doppler parameters in monitoring FGR.

Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.We performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature.We identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in theOur study underlines the broad locus heterogeneity of FA with well-established and atypical genotype-phenotype associations. We describe

The worldwide development of twin cohorts began after World War II. These cohorts now include around 1.5 million twins, and more than 2748 twin studies have been published between 1950 and 2012. Each year, the number of twin publications increases by another 500 to 1000. The underrepresentation of German twin studies cannot be solely explained by the abuse of medical research under National Socialism. Developing and expanding large twin cohorts is a challenge in terms of both ethics and data protection. However, twin cohorts enable long-term and real-time research on many medical issues and contribute to answer the question of predisposition or environment as possible disease triggers - even after the sequencing of the human genome.There are currently two German twin cohorts: the biomedical cohort HealthTwiSt, with around 1500 pairs of twins, and TwinLife, a sociological-psychological cohort with around 4000 pairs of twins. There are also disease-specific cohorts. The TwinHealth Consortium in the Faculty of Medicine at the University of Tübingen was established in 2016 with the aim of enabling open-ended and sustainable twin research in Tübingen to answer various scientific questions.With the help of systematic literature research and medical history, this article gives an overview of the worldwide development of twin studies and databases over the last 100 years. The example of the Tübingen TwinHealth Initiative illuminates the structure of a twin cohort and its legal, ethical, and data protection aspects.Nach dem Zweiten Weltkrieg wurden weltweit Zwillingskohorten aufgebaut, die inzwischen ca. 1,5 Mio. Zwillinge umfassen und zwischen 1950 und 2012 über 2748 Zwillingsstudien hervorgebracht haben. Diese Zahl steigt jedes Jahr um weitere 500 bis 1000. Die Unterrepräsentanz deutscher Zwillingsstudien in diesen Datenbanken lässt sich nicht allein durch den Missbrauch medizinischer Forschung im Nationalsozialismus erklären. Entwicklung und Ausbau großer Zwillingskohorten sind ethisch und datenschutzrechtlich eine Herausforderung. Zwillingskohorten ermöglichen jedoch die Langzeit- und Echtzeiterforschung vieler medizinischer Fragestellungen; und die Zwillingsstudien tragen auch nach der Entschlüsselung des Humangenoms erheblich zur Beantwortung der Frage nach Anlage oder Umwelt als mögliche Erkrankungsauslöser bei.Derzeit gibt es 2 deutsche Zwillingskohorten: die biomedizinische Kohorte HealthTwiSt mit ca. 1500 Zwillingspaaren und TwinLife, eine soziologisch-psychologische Kohorte mit ca. 4000 Zwillingspaaren. Daneben gibt es krankheitsspezifische Kohorten. 2016 startete das TwinHealth-Konsortium der Medizinischen Fakultät der Universität Tübingen mit dem Ziel, eine forschungsoffene und nachhaltige Zwillingsforschung am Standort Tübingen zur Bearbeitung unterschiedlicher Fragestellungen zu etablieren.Der Artikel bietet mithilfe einer systematischen Literaturrecherche und einer medizinhistorischen Betrachtung einen Überblick über die weltweite und nationale Entwicklung von Zwillingsstudien und -datenbanken der letzten 100 Jahre. Anhand der Tübinger TwinHealth-Initiative beleuchtet er den Aufbau eines Zwillingskollektivs und dessen juristische, ethische und Datenschutzaspekte.

Purpose To examine if the uterocervical angle (UCA) can be used to predict preterm delivery in women with painful and regular uterine contractions and a cervical length of 25 mm or less. Methods Retrospective study at the perinatal unit of the University Hospital of Tuebingen, Germany. Women with singleton gestation and preterm contractions between 24 + 0 and 33 + 6 weeks’ gestation were included. For the UCA measurement, a line is placed from the internal os to the external os irrespective of whether the cervix is straight or curved. A second line is drawn to delineate the lower uterine segment. The angle between the two lines is the UCA measurement. The measurements were taken on stored images from our database. Results The study consisted of 213 singleton pregnancies. At the time of UCA measurement, median maternal and gestational age was 31.4 years and 29.7 weeks’ gestation. Median gestational age at delivery was 35.3 weeks and the corresponding birth weight 2480 g, respectively. The UCA measurement in women who delivered within 2 days, between 3–7 days and after 7 days was not helpful to distinguish between these three groups [median UCA measurements: 108.5°, 108.0° and 107.3° (Kruskal–Wallis test p = 0.576)]. Uni- and multivariate logistic multiple regression analysis demonstrated that the delivery within 2 days was only dependent on the gestational age and the cervical length at the time of presentation. Conclusion The measurement of UCA is not useful in predicting preterm birth in the subsequent 7 days after an episode of preterm contractions.

Objective To examine the positive predictive value (PPV) of cfDNA screening for sex chromosome aneuploidies (SCA) in a large series of over 90 000 patients. Methods Retrospective study based on samples that were sent to Cenata, a private laboratory which uses the Harmony Prenatal Test. The SCA high-risk results were stratified according to the method of diagnostic testing and according to karyotype result. Results The study population consisted of 144 cases. The CfDNA test indicated monosomy X, XXX, XXY, and XYY in 62, 37, 40, and 5 cases, respectively. The overall PPV was 38.9% (30.9-47.4), 29.0% (18.2-42.9) for monosomy X, 29.7% (15.9-47.9) for 47,XXX, 57.5% (40.9-73.0) for 47,XXY, and 80.0% (28.4-99.5) for 47,XYY). A total of 112 (77.8%) women with a high-risk result for SCAs opted for prenatal karyotyping. In this group, there were significant differences in the PPV if the karyotype was assessed by amniocentesis or by CVS: 29.5% vs 50.0%. This significant difference was driven by the monosomy X result which shows a significantly higher PPV in CVS (54.6% (23.4-83.3) vs 17.1% (6.6-33.6)). For the other SCAs, the differences were not significant. Conclusion PPV of an abnormal cfDNA test for SCAs is low, particularly for monosomy X. The confirmation rate depends on the type of confirmatory test.

BACKGROUND Human reproductive issues affecting fetal and maternal health are caused by numerous exogenous and endogenous factors, of which the latter undoubtedly include genetic changes. Pathogenic variants in either maternal or offspring DNA are associated with effects on the offspring including clinical disorders and nonviable outcomes. Conversely, both fetal and maternal factors can affect maternal health during pregnancy. Recently, it has become evident that mammalian reproduction is influenced by genomic imprinting, an epigenetic phenomenon that regulates the expression of genes according to their parent from whom they are inherited. About 1% of human genes are normally expressed from only the maternally or paternally inherited gene copy. Since numerous imprinted genes are involved in (embryonic) growth and development, disturbance of their balanced expression can adversely affect these processes. OBJECTIVE AND RATIONALE This review summarises current our understanding of genomic imprinting in relation to human ontogenesis and pregnancy and its relevance for reproductive medicine. SEARCH METHODS Literature databases (Pubmed, Medline) were thoroughly searched for the role of imprinting in human reproductive failure. In particular, the terms ‘multilocus imprinting disturbances, SCMC, NLRP/NALP, imprinting and reproduction’ were used in various combinations. OUTCOMES A range of molecular changes to specific groups of imprinted genes are associated with imprinting disorders, i.e. syndromes with recognisable clinical features including distinctive prenatal features. Whereas the majority of affected individuals exhibit alterations at single imprinted loci, some have multi-locus imprinting disturbances (MLID) with less predictable clinical features. Imprinting disturbances are also seen in some nonviable pregnancy outcomes, such as (recurrent) hydatidiform moles, which can therefore be regarded as a severe form of imprinting disorders. There is growing evidence that MLID can be caused by variants in the maternal genome altering the imprinting status of the oocyte and the embryo, i.e. maternal effect mutations. Pregnancies of women carrying maternal affect mutations can have different courses, ranging from miscarriages to birth of children with clinical features of various imprinting disorders. WIDER IMPLICATIONS Increasing understanding of imprinting disturbances and their clinical consequences have significant impacts on diagnostics, counselling and management in the context of human reproduction. Defining criteria for identifying pregnancies complicated by imprinting disorders facilitates early diagnosis and personalised management of both the mother and offspring. Identifying the molecular lesions underlying imprinting disturbances (e.g. maternal effect mutations) allows targeted counselling of the family and focused medical care in further pregnancies.

Objective To examine whether in fetuses with trisomy 21 (T21), the ductus venosus (DV) flow differs in presence of a major cardiac defect (congenital cardiac defect [CHD]) and whether this affects the risk distribution in first trimester screening for T21. Methods This retrospective study included pregnant women who underwent first trimester screening. This involves an examination of the crown-rump length, the nuchal translucency, the ductus venosus (DV) flow, and the heart. Three groups of fetuses were examined: euploid without CHD, T21 with CHD, and T21 without CHD. We examined the DV pulsatility index for veins, the direction of the a-wave, and ratios of velocities: v/S, v/D, a/S, a/D, and S/D. Results The study population consisted of 410 euploid fetuses and 136 with T21 (51 with CHD and 85 without CHD). In the 3 groups, the a-wave was reversed in 3.2%, 66.7%, and 57.6%. The DV flow ratios in T21 with and without CDH were significantly different compared with normal fetuses. When comparing the ratios between the 2 T21 groups, only the a/S and a/D ratio were significantly different. The risk distributions in screening for T21 with and without CDH were similar. Conclusion There are some small differences in the DV flow of T21 fetuses with and without CHD, but they are not clinically useful.

Objective Prospective randomized trial to compare the performance of first trimester combined screening (FTCS) with an approach that uses the combination of a detailed ultrasound examination and cfDNA analysis. Methods Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks’ gestation (fetal NT ≤3.5 mm and no fetal defects) were randomized into two groups. In the first group, the risk of aneuploidy was assessed using FTCS based on the most recent FMF UK algorithm. In the second group, the risk assessment was based on ultrasound findings and cfDNA screening (Harmony® Prenatal Test). An additional tube of blood was collected for FTCS in case the cfDNA analysis remained uninformative. The false positive rate in screening for trisomy 21 was defined as primary outcome parameter. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. The results were compared using 95% confidence intervals using Clopper and Pearson method. Results Between October 2015 and December 2016, 1,518 women with singleton pregnancies were referred for first trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (>3.5 mm) and/or fetal defects. Eighty-seven (5.9%) women declined randomization. Out of the remaining 1400 women, 699 were randomized into the FTCS arm and 701 into the ultrasound + cfDNA analysis arm. In 24 cases the outcome could not be obtained. Thus, there were 688 pregnancies in each study arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, the use of assisted reproduction, and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10,000. None of the cases had a risk above 1:100 [95% CI 0.0 – 0.5%]. In the FTCS arm, the median risk for trisomy 21 was 1 in 3,786 and in 17 cases, the risk was higher than 1:100 which corresponds to 2.5% [95% CI 1.5 – 3.9%] of the FTCS study-arm population. Conclusion Our study has shown that first trimester screening for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false positive rate compared to FTCS. This approach obviates the need for maternal serum free beta hCG and PAPP-A in screening for fetal aneuploidy.

Facial clefts and Robin sequence (RS) share the timing of the diagnosis during the course of pregnancy, their association with genetic diseases and the subsequent management following the initial diagnosis. If a suspicion of a facial cleft or RS is made, a detailed anatomical examination of the fetus should be carried out to identify further anomalies. This may also involve genetic testing including a microarray or an exome analysis. Interdisciplinary counseling, including pre- and postnatal experts with sufficient experience in the management of such neonates, should be involved in this counseling. Parents should be informed about disease-specific therapeutic options and postnatal outcome. Delivery should take place in a center with experience in craniofacial malformations where clinicians are prepared for potentially life-threatening airway obstruction immediately after birth.

To contribute to establishing donor selection criteria based on our experience with two successful living-donor human uterus transplantations (UTx) and an aborted attempt. This interventional study included three patients with uterine agenesis, aged 23, 34, and 23 years, scheduled for UTx, and their uterus-donating mothers, aged 46, 61, and 46 years, respectively. Interventions included preoperative investigations, donor surgery, back-table preparation, and recipient surgery. Preoperative imaging, surgical data, histopathology, menstrual pattern, and uterine blood flow were the main outcome measures. In the first case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 12.12/5.95 h. Regular spontaneous menstruations started 6-week post-transplantation, continuing at 24–28-day intervals throughout the 6-month observation period. Repeated follow-up cervical biopsies showed no signs of rejection. In the second case (61-year-old donor), surgery lasted 13.10 h; attempts to flush the retrieved uterus failed due to extreme resistance of the left uterine artery (UA) and inability to perfuse the right UA. Transplantation was aborted to avoid graft vessel thrombosis or insufficient blood flow during potential pregnancy. Histopathology revealed intimal fibrosis and initial sclerosis (right UA), extensive intimal fibrosis (parametric arterial segments), and subtotal arterial stenosis (myometrial vascular network). In the third case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 9.05/4.52 h. Menstruations started 6-week post-transplantation. Repeated cervical biopsies showed no signs of rejection during the initial 12-week follow-up period. Meticulous preoperative evaluation of potential living uterus donors is essential. This may include selective contrast-enhanced UA angiograms and limitation of donor age, at least in donors with risk factors for atherosclerosis. ClinicalTrials.gov Identifier: NCT03048396.

Im Lauf der letzten Jahrzehnte hat sich das Ersttrimesterscreening (ETS) zu einem komplexen Test entwickelt, der auf zahlreiche Komplikationen abzielt. Durch die zellfreie DNA-Analyse (cfDNA) ist nun fur die haufigsten Chromosomenstorungen ein weiteres nichtinvasives Testverfahren mit beeindruckender Detektions- und Falsch-positiv-Rate verfugbar. Da seine Testgute besser ist als die des ETS wird zunehmend ein Wechsel auf die cfDNA-Analyse diskutiert. Sollte des ETS durch die cfDNA-Analyse abgelost werden? Auch wenn die Testgute der cfDNA-Analyse im Screening auf Trisomie 21 besser ist als die des ETS, sollte doch die Relevanz des ETS nicht unterschatzt werden. Die dem ETS vorangestellte eingehende Ultraschalluntersuchung ermoglicht es, das Risiko fur andere, nicht durch die cfDNA-Analyse erkennbare Chromosomenstorungen zu beurteilen. Als Hinweiszeichen sind vor allem die erhohte Nackentransparenzdicke (NT) und das Vorliegen fetaler Fehlbildungen zu nennen; in diesen Fallen sollte eine diagnostische Punktion erwogen werden. Zudem ist die fruhe Diagnose von Fehlbildungen per se sinnvoll, um bei der Planung nicht in Zeitdruck zu geraten. Des Weiteren gewinnt das Praeklampsiescreening im Rahmen des ETS zunehmend an Bedeutung, da mit Acetylsalicylsaure auch eine Therapieoption zur Verfugung steht. Daneben sollten der unschatzbare Wert der Bestimmung des Gestationsalters sowie das Erkennen von Mehrlingen und deren Chorionizitat durch das ETS nicht unerwahnt bleiben. Das Screening auf Trisomie 21 wird absehbar mithilfe der cfDNA-Analyse erfolgen. Dennoch ist das vorangestellte ETS mit seinen Moglichkeiten von groser Bedeutung fur das Management der Schwangerschaft und sollte auch kunftig weiter Bestand haben.