Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach.

The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was to develop an NIPD approach for couples at risk of transmitting dynamic mutations. This method includes targeted enrichment for linked-read libraries and targeted maternal plasma DNA sequencing. We also developed an innovative Bayesian procedure to integrate the Hoobari fetal genotyping model for inferring the fetal haplotype and the targeted gene variant status. Our method of directly resolving parental haplotypes through targeted linked-read sequencing was smoothly performed using blood samples from families with Huntington's disease or myotonic dystrophy type 1. The Bayesian analysis of transmission of parental haplotypes allowed defining the genotype of five fetuses. The predicted variant status of four of these fetuses was in agreement with the invasive prenatal diagnosis findings. Conversely, no conclusive result was obtained for the NIPD of fragile X syndrome. Although improvements should be made to achieve clinically acceptable accuracy, our study shows that linked-read sequencing and parental haplotype phasing can be successfully used for NIPD of triplet-repeat expansion diseases.Trial registration: NCT04698551_date of first registration: 07/01/2021.

Heat stress and sperm production in the domestic cat.

This study aimed to assess 1) the effect of high environmental temperatures on sperm production and 2) the effectiveness of a temperature-humidity index (THI) to predict the degree of thermal stress in a cat model. Semen collection was performed by electroejaculation for 18 mo in 20 tomcats maintained under controlled photoperiod. Still, temperature and humidity were not experimentally manipulated to describe the effect of natural climate conditions on seminal samples. Ejaculates (n = 512) were then grouped according to temperature records of the sampling day and compared by temperature and THI index. Significant lower sperm parameters and increase sperm tail abnormalities were observed during warm environments (temperature and THI). Concentration and total sperm count were the most affected parameters. Environmental temperatures of 28.5 °C with 54% relative humidity (THI = 77.07) and 27.9 °C with 66% humidity (THI = 77.84) were upper thresholds of moderate thermal stress. Moreover, days with relative humidity near 90% led to severe thermal stress with temperatures as low as 26.6 °C (THI = 78.88). The current study demonstrates the detrimental effect of high environmental temperatures on sperm quality in the domestic cat. This effect is observed at lower temperatures when high relative humidity is present. In this sense, the THI was a reliable predictor of the magnitude of thermal stress experienced by cats. Thus, cats from reproductive programs should be maintained under controlled photoperiod cycles with temperatures around 20 °C and humidity around 70% to avoid semen detrimental effects.

Effect of cat seminal plasma and purified llama ovulation-inducing factor (ß-NGF) on ovarian function in queens.

The present study aimed to determine the effect of cat seminal plasma and purified llama ovulation-inducing factor (ß-NGF) on ovarian activity in queens. Queens (n = 6) were used for all the treatments in a crossover design with an interval time between treatments of three interestrus intervals. Forty-eight hours after the detection of an estrus vaginal cytology, queens were given cat seminal plasma (subcutaneous or intramuscular), purified llama ovulation-inducing factor (15 or 35 µg), hCG (75 UI), saline, or were mated with a male. A total of 192 estrous cycles were observed. Estrus length and serum estradiol concentration were 6 ± 1 days (range 2-10 d) and 38 pg/mL (range 10-75 pg/mL), respectively. Queens mated and given hCG showed higher serum progesterone concentration and longer interestrus interval (47 ± 5 d) than that of controls (10 ± 3 d). Sixty-seven percent of queens (4/6) treated with subcutaneous cat seminal plasma, and 17% of those treated with purified llama ß-NGF showed high serum progesterone concentrations along with prolonged interestrus. However, intramuscular administration of cat seminal plasma produced interestrus intervals similar to controls (15 ± 5 d) and basal serum progesterone concentration (<0.50 ng/mL). This study demonstrates that the subcutaneous administration of cat seminal plasma induced ovulation in queens. Therefore, molecules present in cat seminal plasma, contribute to the induction of ovulation in queens. Identifying those molecules will improve the knowledge of queen's reproductive physiology. Also, it could offer a physiologic alternative to induce ovulation in queens when reproductive biotechnologies are used.

New device permitting non-invasive reversal of fetal endoscopic tracheal occlusion: ex-vivo and in-vivo study.

OBJECTIVE: One of the drawbacks of fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to re-establish airway patency. The 'Smart-TO' device is a new balloon for FETO that deflates spontaneously when placed in a strong magnetic field, therefore overcoming the need for a second procedure. The safety and efficacy of this device have not yet been demonstrated. The aim of this study was to investigate the reversibility, local side effects and occlusiveness of the Smart-TO balloon, both in a simulated in-utero environment and in the fetal lamb model. METHODS: First, the reversibility of tracheal occlusion by the Smart-TO balloon was tested in a high-fidelity simulator. Following videoscopic tracheoscopic balloon insertion, the fetal mannequin was placed within a 1-L water-filled balloon to mimic the amniotic cavity. This was held by an operator in front of their abdomen, and different fetal and maternal positions were simulated to mimic the most common clinical scenarios. Following exposure to the magnetic field generated by a 1.5-T magnetic resonance (MR) machine, deflation of the Smart-TO balloon was assessed by tracheoscopy. In cases of failed deflation, the mannequin was reinserted into a water-filled balloon for additional MR exposure, up to a maximum of three times. Secondly, reversibility, occlusiveness and local effects of the Smart-TO balloon were tested in vivo in fetal lambs. Tracheal occlusion was performed in fetal lambs on gestational day 95 (term, 145 days), either using the balloon currently used in clinical practice (Goldbal2) (n = 5) or the Smart-TO balloon (n = 5). On gestational day 116, the presence of the balloon was assessed by tracheoscopy. Deflation was performed by puncture (Goldbal2) or MR exposure (Smart-TO). Six unoccluded fetal lambs served as controls. Following euthanasia, the lung-to-body-weight ratio (LBWR), lung morphometry and tracheal circumference were assessed. Local tracheal changes were measured using a hierarchical histologic scoring system. RESULTS: Ex vivo, Smart-TO balloon deflation occurred after a single MR exposure in 100% of cases in a maternal standing position with the mannequin at a height of 95 cm (n = 32), 55 cm (n = 8) or 125 cm (n = 8), as well as when the maternal position was 'lying on a stretcher' (n = 8). Three out of eight (37.5%) balloons failed to deflate at first exposure when the maternal position was 'sitting in a wheelchair'. Of these, two balloons deflated after a second MR exposure, but one balloon remained inflated after a third exposure. In vivo, all Smart-TO balloons deflated successfully. The LBWR in fetal lambs with tracheal occlusion by a Smart-TO balloon was significantly higher than that in unoccluded controls, and was comparable with that in the Goldbal2 group. There were no differences in lung morphometry and tracheal circumference between the two balloon types. Tracheal histology showed minimal changes for both balloons. CONCLUSIONS: In a simulated in-utero environment, the Smart-TO balloon was effectively deflated by exposure of the fetus in different positions to the magnetic field of a 1.5-T MR system. There was only one failure, which occurred when the mother was sitting in a wheelchair. In healthy fetal lambs, the Smart-TO balloon is as occlusive as the clinical standard Goldbal2 system and has only limited local side effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[Evaluation of a measurement tool with real-time display of the standard value for fetal biometrics]. / Évaluation d'un outil de mesure avec affichage de la norme en temps réel pour les biométries fœtales.

OBJECTIVES: Most of the ultrasound machines include a tool allowing real-time display of the standard value of the biometric measurement being taken. Our hypothesis was that this tool influences the sonographer as measurements are taken, by inducing a normalization, thus a tendency towards the 50th percentile. The objective of this study was to evaluate the impact of a real-time display of the standard value in prenatal ultrasound screening. METHODS: We conducted an observational, prospective, controlled and open study including all patients who underwent a prenatal ultrasound scan in the 2nd or 3rd trimester at the University Hospitals in Strasbourg between December 2017 and June 2018. Exclusion criteria were the presence of a fetal morphological abnormality or a karyotypic abnormality. The tool being tested was the real-time display on screen of the gestational age, of which the measurement corresponds to the 50th percentile. The measurements were retrospectively transformed into Z-scores. The main end-point was to compare the distribution of Z-scores between the groups. RESULTS: We included 3551 ultrasound examinations: 696 performed with the tool and 2796 performed without. Fifty-nine scans were excluded due to morphological abnormalities. There was no statistically significant difference between the Z-scores distributions of measurements performed with or without the tool, regardless of the parameter studied. There was also no difference in the detection of pathological measurements: below the 10th percentile or above the 90th percentile. CONCLUSION: The use of such a tool does not seem to be detrimental to biometric screening, but on the other hand does not seem useful either.

Uterine endometrial cytology, biopsy, bacteriology, and serum C-reactive protein in clinically healthy diestrus bitches.

The aim of this work was to assess the agreement between endometrial cytology and uterine biopsy for the diagnosis of endometritis (END), the bacterial populations isolated from the vagina and uterus of bitches having END, and the measurement of C- reactive protein as a diagnostic tool for diagnosis of END in clinically healthy bitches. Fifty privately-owned intact, clinically healthy bitches, in diestrus, without a history of progestin administration, aged between 8 months and 6 years old and weighing between 5 and 28 kg were used in this study. Bitches were included in a program for breeding control at a municipal pet public shelter. Before ovariohysterectomy (OVX) samples for vaginal cytology and bacteriology, and blood samples were taken. After OVX endometrial cytology, bacteriological samples and biopsy were collected. Histologic examination was performed to confirm the uterine condition. Blood samples were centrifuged and stored at -20 °C until progesterone (P4) and C-reactive protein was measured. Samples for bacteriological culture were collected, and swabs were placed into Stuart's transport medium and transported to the laboratory. On histopathologic examination, the most common observation was END (27/50), followed by normal endometrium (NE; 18/50), cystic endometrial hyperplasia (CEH; 2/50), atrophy (2/50) and fibrosis with degeneration of the endometrial glands (1/50). Low degree of agreement was observed between results obtained by endometrial cytology samples and results obtained by biopsy in endometrial diagnosis (Kappa Coefficient: -0.19). In vaginal samples, ß-hemolytic Streptococcus, Staphylococcus spp., Escherichia coli, Proteus spp., Corynebacterium spp., and Klebsiella pneumoniae were the bacteria most often found. In uterine samples, only four samples from END showed bacterial grow. C-reactive protein frequency was higher in END (6/23, 23%) vs NE (0/16, 0%; Van der Waerden P-value = 0,0302). Our results support the hypothesis that END is a frequent finding in uterine biopsy and could be associated with subfertility and infertility in the bitch. A low degree of agreement was observed between the diagnostic results from the uterine biopsy and endometrial cytology. Bacteriology would not be recommended as a diagnostic tool because no bacteria highly associated with uterine diseases were isolated from bitches with END. Finally, the usefulness of C-reactive protein concentration as a marker for END in bitches could not be conclusively demonstrated.

[Outcome of in utero transfusion in case of fœtomaternal red blood cell incompatibility]. / Devenir obstétrical après transfusion in utero pour allo-immunisation fœto-maternelle.

OBJECTIVE: Erythrocyte allo-immunization's rate has decreased but without adapted treatment the prognosis is still poor. The aim of our study was to evaluate the fetal prognosis, the complication's rate and the risk factors of complications of the intrauterine transfusion. METHODS: Retrospective study about 37 fetus and 86 intrauterine transfusions between 2001 and 2017. Our main criterion in judging was the occurrence of procedure related complications: premature membrane rupture or premature delivery within seven days from the procedure, chorioamnionitis, abnormal fetal heart rate indicating an emergency ceasarean section within the 24hours from the procedure, in utero death or neonatal death related to the procedure. RESULTS: The survival rate was about 88.9% with a severe complication's rate of 5.8% per intrauterine transfusion and 13.5% per pregnancy. Intrauterine transfusions before 18 weeks of pregnancies was a complication risk factor: 50% of complications before 18 weeks vs. 1.3%, P=0.8×10-3. On the contrary, hydrops did not seem to be a complication risk factor (16.7% of complication with hydrops vs. 3.9%, P=0.27). The localisation of the needle insertion, intra-abdominal or placental insertion, had no effect on the fetal prognosis. CONCLUSION: Intrauterine transfusion complications are rare and it enhances the fetal prognosis. However, an early procedure is related to a higher rate of complications.

Expectant management and laser photocoagulation in isolated selective intra-uterine growth restriction: A single-center series.

INTRODUCTION: The objective was to report on a consecutive series of monochorionic diamniotic pregnancies complicated by selective Intra-Uterine Growth Restriction (sIUGR) and to describe perinatal outcomes based on whether or not there were umbilical Doppler findings, and specifically to study those pregnancies treated by laser. MATERIAL AND METHODS: This was a retrospective cohort study enrolling monochorionic diamniotic pregnancies presenting isolated sIUGR after 16 weeks' gestation (WG). RESULTS: Of the 25 cases of sIUGR, 16 were type I and 9 type II or III. Types II and III occurred earlier than type I (22.3 versus 24.3 WG), were more severe (discordance of 37% versus 23%), and delivered earlier (31.3 versus 33.9 WG). Survival was 12/18 (66.7%) for types II or III versus 32/32 (100%) for type I. Five laser photocoagulation procedures were attempted and allowed the survival of both twins in 2 cases. Overall survival after laser was 6/10 (60%). DISCUSSION: Isolated sIUGR is associated with high perinatal morbidity and mortality. Laser photocoagulation treatment is feasible and may enable survival of both twins in some cases, but may be technically difficult.

[Fetoscopic laser coagulation in 200 consecutive monochorionic pregnancies with twin-twin transfusion syndrome]. / Photocoagulation laser par fœtoscopie pour syndrome transfuseur-transfusé : analyse d'une série consécutive unicentrique de 200 cas.

OBJECTIVES: To report preoperative data, surgical characteristics, complications and perinatal outcome of twin-twin transfusion syndrome (TTTS) managed with laser ablation surgery, to analyze predictors of neonatal survival and to compare the 100 most recent cases with the older 100. MATERIALS AND METHODS: Observational cohort moncentric study of 200 cases of TTTS consecutively treated with fetoscopic laser coagulation between January 2004 and December 2014. RESULTS: There were 49 stage I, 88 stage II, 55 stage III and eight stage IV. Median gestation at time of laser was 20.1±3.0 weeks' gestation (WG) whereas median gestation at delivery was 31.6±5.4 WG. Overall perinatal survival rate was 68.0% and 84.0% have one or more surviving twins. Preterm premature rupture of membranes occurred in 39 cases with and the median gestational age for this complication was 28.8±4.6 SA. Predictive factors to have at least one living birth were Quintero stage and gestational age at delivery. In the most recent period, there were significantly more TTTS Quintero stage I treated with laser, more coagulation by the Solomon technique and a larger number of coagulated vessels. CONCLUSION: The neonatal survival of TTTS is improved by fetoscopic laser coagulation, preferely by using Solomon tecnhique. The use of active management of stage I is currently on research.

Sequential fetal serum ß2-microglobulin to predict postnatal renal function in bilateral or low urinary tract obstruction.

OBJECTIVE: Fetal serum ß2-microglobulin has been shown to predict postnatal renal outcome in cases of fetal obstructive uropathy. We assessed the value of serial measurements of fetal serum ß2-microglobulin in the prediction of postnatal renal outcome. METHODS: We retrospectively studied renal outcome in 42 fetuses with bilateral or low urinary tract obstruction that had fetal blood sampling on at least two occasions to assay serum levels of ß2-microglobulin. Amniotic fluid volume at the time of each sampling was recorded. We classified renal outcome as either favorable (when postnatal renal function was normal) or adverse (when postnatal chronic renal failure occurred or when renal dysplasia at autopsy was noted). A ß2-microglobulin cut-off of 5 mg/L and amniotic fluid index of 5 cm were used to predict postnatal renal outcome. RESULTS: Renal outcome was adverse in 28 cases and favorable in 14. In 12 (28.6%) cases, fetal serum ß2-microglobulin concentration differed between the first and last measurement. Prediction of postnatal renal outcome was correct in 11 of these cases based on the last ß2-microglobulin measurement. The sensitivity of ß2-microglobulin in predicting renal outcome was significantly higher (P = 0.005) when using the last rather than the first measurement (96.4% vs 64.3%), with similar specificity for both measurements (85.7% vs 78.6%, non-significant). The sensitivity of amniotic fluid volume was also significantly higher (P = 0.005) when using the last rather than the first measurement (75.0% vs 35.7%), with similar specificity for both measurements (64.3% vs 71.4%, non-significant). CONCLUSION: Sequential measurement of serum ß2-microglobulin, performed for adverse ultrasound findings, such as renal parenchymal abnormality or decreasing amniotic fluid volume, predicts postnatal renal outcome more accurately than does a single assay. This may be due to possible worsening of renal injury with increasing duration of urinary tract obstruction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Progesterone and ultrasonographic changes during aglepristone or cloprosternol treatment in queens at 21 to 22 or 35 to 38 days of pregnancy.

Progesterone (P4) is a requirement for pregnancy development. Previous reports observed a maximal value of serum P4 concentration on 21 days after the first mating after which it slowly declines throughout the rest of pregnancy. Ultrasound examination should be performed to ensure that pregnancy interruption is complete. Limited information is available on the ultrasonic appearance of conceptuses during pregnancy termination in cats The objective was to study serum P4 concentration and ultrasonographic changes during aglepristone (ALI) or cloprostenol (CLO) treatment and to evaluate the fertility after treatment. Two experiments (EXP) were carried out to accomplish this aim. Sixty queens, 12- to 36-month-old, were used. On Days 21 to 22 of pregnancy (EXP I) or 35 to 38 of pregnancy (EXP II), queens were divided into three groups (G). Queens in G1 received ALI (10 mg/kg, sc; EXP I, n = 10; EXP II, n = 10) for 2 consecutive days. Queens in G2 received CLO (5 µg/kg, sc; EXP I, n = 10; EXP II = 10) for 3 consecutive days. Queens in G3 received 1 mL of saline solution (PLA, sc; EXP I, n = 10; EXP II = 10). Blood samples were taken before treatment (Day 0) and every day during 10 days after the treatment to measure serum P4 concentrations. Likewise, after treatment, queens were monitored daily by ultrasonography for 10 days and weekly until the end of gestation to obtain gestational sacs measurements (GS), fetal measurements, and fetal biophysical profile. Data were analyzed by ANOVA. Serum P4 concentrations were significantly different on Day 6 (EXP I) and on Day 1 (EXP II) in ALI and CLO groups compared with PLA group (P < 0.05 and P < 0.01; respectively). The ultrasonographic monitoring during treatment allowed assessing changes in the GS and fetal measurements, embryo-fetal viability, and risk of pregnancy loss. In conclusion, the results from this study reported changes in serum P4 concentration and in ultrasonography measurements during pregnancy interruption with ALI or CLO treatment. Also it was observed that ALI and CLO are safe drugs and can preserve posttreatment queen fertility. Therefore, the results obtained in our work will be applied in feline reproduction practice.

Prolactin, Androstenedione and IGF1 Serum Concentrations During Induced Follicular Growth by eCG Administration in the Bitch.

The oestrus cycle in the domestic bitch, a monoestrous species, differs considerably from that of other veterinary domestic animals species. In the bitch the combined use of eCG and hCG is effective to induce oestrus predictably and safely (Stornelli et al., Theriogenology, 78, 2012 and 1056). Although several studies were done to describe the hormonal changes during the canine oestrus cycle, to our knowledge none was done to describe the hormonal changes during induced follicular growth after the administration of eCG. The aim of this work was to study prolactin (PRL), insulin-like growth factor (IGF1) and androstenedione (ANDR) serum concentrations during follicular growth induced by a single dose of eCG administered to late anoestrous bitches. PRL and ANDR concentrations were lower before than after eCG TRT (before eCG vs pro-oestrus, oestrus and dioestrus; 4.3 ± 1.8 ng/ml vs 6.5 ± 1.6 ng/ml, p < 0.05; 0.08 ± 0.2 ng/ml vs 0.42 ± 0.16 ng/ml, p < 0.05). Conversely, IGF1 concentrations were similar before and after eCG TRT (286.0 ng/ml ±32.2, p > 0.53). Additionally, PRL concentrations were similar before oestrus compared to during oestrus and dioestrus (6.9 ± 1.7 ng/ml, p > 0.19). Furthermore, IGF1 concentrations were higher before and during oestrus compared to first day of dioestrus (286.1 ± 29.8vs 200.4 ± 29.2 ng/ml, p < 0.01). On the contrary, ANDR concentrations were lower before and during oestrus compared to first day of diestrum (0.35 ± 0.17 ng/ml and 0.38 ± 0.15 vs 0.68 ± 0.17 ng/ml, p < 0.05). These results show that treatment with a single injection of 50 IU/kg of eCG in late anoestrous bitches successfully induced changes in follicular growth which were paralleled with changes in PRL, IGF1 and ANDR serum concentration similar to those occurring during a normally occurring oestrous cycle. In addition, our results suggest that IGF1 in the bitch could play an important role in ovarian folliculogenesis.

[Accuracy of placenta accreta prenatal diagnosis by ultrasound and MRI in a high-risk population]. / Diagnostic anténatal des placentas accreta : apport de l'échographie et de l'IRM dans une population à risque.

OBJECTIVES: Main objective was to compare accuracy of ultrasonography and MRI for antenatal diagnosis of placenta accreta. Secondary objectives were to specify the most common sonographic and RMI signs associated with diagnosis of placenta accreta. MATERIAL AND METHODS: This retrospective study used data collected from all potential cases of placenta accreta (patients with an anterior placenta praevia with history of scarred uterus) admitted from 01/2010 to 12/2014 in a level III maternity unit in Strasbourg, France. High-risk patients beneficiated antenatally from ultrasonography and MRI. Sonographic signs registered were: abnormal placental lacunae, increased vascularity on color Doppler, absence of the retroplacental clear space, interrupted bladder line. MRI signs registered were: abnormal uterine bulging, intraplacental bands of low signal intensity on T2-weighted images, increased vascularity, heterogeneous signal of the placenta on T2-weighed, interrupted bladder line, protrusion of the placenta into the cervix. Diagnosis of placenta accreta was confirmed histologically after hysterectomy or clinically in case of successful conservative treatment. RESULTS: Twenty-two potential cases of placenta accreta were referred to our center and underwent both ultrasonography and MRI. All cases of placenta accreta had a placenta praevia associated with history of scarred uterus. Sensibility and specificity for ultrasonography were, respectively, 0.92 and 0.67, for MRI 0.84 and 0.78 without significant difference (p>0.05). The most relevant signs associated with diagnosis of placenta accreta in ultrasonography were increased vascularity on color Doppler (sensibility 0.85/specificity 0.78), abnormal placental lacunae (sensibility 0.92/specificity 0.55) and loss of retroplacental clear space (sensibility 0.76/specificity 1.0). The most relevant signs in MRI were: abnormal uterine bulging (sensitivity 0.92/specificity 0.89), dark intraplacental bands on T2-weighted images (sensitivity 0.83/specificity 0.80) or placental heterogeneity (sensitivity 0.92/specificity 0.89). Association of two sonographic or MRI signs had the best sensitivity/specificity ratio. DISCUSSION AND CONCLUSION: Ultrasonography and RMI represent two interesting and complementary diagnostic tools for antenatal diagnosis of placenta accreta. Because of its cost and accessibility, ultrasonography remains the first in line to be used for diagnosis. Use of an analytical grid for diagnosis of placenta accreta could be helpful.

[Performance and indications of noninvasive prenatal testing using cell free circulating fetal DNA (cffDNA) for the detection of fetal trisomy 21, 18 and 13 in France]. / Performance et indication du dépistage des trisomies 21, 18 et 13 en France par l'analyse de l'ADN fœtal dans le sang maternel.

OBJECTIVES: To evaluate de performances of noninvasive prenatal testing using cell free circulating fetal DNA (cffDNA) for the detection of fetal trisomy 21, 18 and 13 in a French population. MATERIALS AND METHODS: cffDNA analysis was performed by massive parallel sequencing during a multicenter, non interventional, prospective study and the results were compared with a standard fetal karyotype. RESULTS: Results were available for 886 patients who have been classified as high- or moderate-risk depending on the presence of fetal abnormalities on ultrasound examination. For the high-risk group (n=376), the sensitivity and specificity of the test were 100% and 99.9% for trisomy 21, 88% and 99.9% for trisomy 18 and 100% and 99.9% for trisomy 13. The rate of other pathogenic chromosomal abnormalities with a negative NIPT was 7.9%. In the low-risk group (n=510), the sensitivity was 100% and the specificity 99.8% for trisomy 21, and only 0.4% of pathogenic chromosomal abnormalities were revealed by fetal karyotyping but not detected by cffDNA analysis. CONCLUSION: Noninvasive prenatal testing using cffDNA for high risk patients without fetal anomalies at ultrasound could be recommended in France after counseling on the possible risk of undiagnosed anomalies.

Technical aspects and effectiveness of percutaneous fetal therapies for large sacrococcygeal teratomas: cohort study and literature review.

OBJECTIVES: The objectives of this study were to evaluate the efficacy of minimally invasive ablation of high-risk large sacrococcygeal teratomas (SCT) and to compare the efficacy of vascular and interstitial tumor ablation. METHODS: This was a retrospective multicenter study including a cohort of fetuses with high-risk large SCTs between 2004 and 2010. In addition, we performed a systematic literature review of all cases that underwent tumor ablation in order to compare the survival rates after 'vascular' and 'interstitial' ablation. Statistical analysis was conducted using Bayesian methods. RESULTS: In our cohort, a total of 13 fetuses had high-risk large SCT and five of them underwent tumor ablation. The estimated difference in hydrops resolution rate between the fetal intervention and the no fetal intervention groups was 44.6% (95% credibility interval, 1.5 to 81.0%; Pdiff> 0 = 97.9%). The estimated difference in survival rate between the fetal intervention and the no fetal intervention groups was 31.0% (13.9 to 48.1%; Pdiff> 0 = 99.9%). We analyzed our five cases together with 28 cases from the literature and estimated the difference in survival rate between the vascular and interstitial ablation groups as 19.8% (-13.1 to 50.1%; Pdiff> 0 = 88.3%). The estimated difference in hydrops resolution rate between the vascular and the interstitial ablation groups was 36.7% (-5.7 to 72.7%; Pdiff> 0 = 95.5%). CONCLUSION: Minimally invasive surgery seems to improve perinatal outcome in cases of high-risk large fetal SCT. Our findings suggest that 'vascular' ablation may improve outcome and may be more effective than 'interstitial' tumor ablation, but this hypothesis needs further investigation in a larger multicenter prospective study. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

[Fetal therapy and fetoscopy: A reality in clinical practice in 2015]. / Thérapie fœtale et fœtoscopie : une réalité clinique en 2015.

Both the improvement of pathophysiological knowledge of major fetal anomalies and the development of therapeutic tools have allowed in some specific cases in utero therapy by foetoscopy. We discuss the state of art and recent advances for four major anomalies: twin-to-twin transfusion syndrome, congenital diaphragmatic hernia, myelomeningocele and lower urinary tract obstruction. Fetoscopic laser surgery for twin-to-twin transfusion syndrome has become the gold standard for treatment of TTS. In terms of fetal surgery, severe congenital diaphragmatic hernia and myelomeningocele are the two main indications, even if open fetal surgery is still the gold standard for management of myelomeningocele. New techniques using fetal cystoscopy are currently under development. Although the maternal morbidity associated with foetoscopy is low, preterm rupture of membranes and preterm delivery remain an important problem. Long-term evaluation of those neonates remains mandatory.