Termination of pregnancy for foetal indication in the French context analysis of decision-making in a Multidisciplinary Centre For Prenatal Diagnosis.

OBJECTIVE: In France, termination of pregnancy (TOP) for medical reasons is legal, regardless of the term, after authorisation by a Multidisciplinary Centre for Prenatal Diagnosis (MCPD). This study analyses the elements supporting the TOP decision-making process faced with a foetal pathology. STUDY DESIGN: Medical records of one MCPD were analysed for the period 2013 and 2014 and semi-structured interviews with MCPD members were conducted. RESULTS: Out of 265 files concerning foetal indications, all but one resulted in a decision for TOP. The main indications in number for TOP were malformations and chromosomal abnormalities. For indications such as trisomy 21, authorisations are generally given without discussion. Our results underline the importance that professionals attach to the collegiality of decisions, particularly in situations of uncertainty. CONCLUSION: This study provides information about the activity of MCPDs within the field of prenatal diagnosis and shows the importance of these structures in supporting women and couples whilst respecting their autonomy. At present, the role of the MCPD is in the process of evolving and could become an information and advisory board for women, based on collegial expertise to guide their decision-making.

Single Circulating Fetal Trophoblastic Cells Eligible for Non Invasive Prenatal Diagnosis: the Exception Rather than the Rule.

Non-Invasive Prenatal Diagnosis (NIPD), based on the analysis of circulating cell-free fetal DNA (cff-DNA), is successfully implemented for an increasing number of monogenic diseases. However, technical issues related to cff-DNA characteristics remain, and not all mutations can be screened with this method, particularly triplet expansion mutations that frequently concern prenatal diagnosis requests. The objective of this study was to develop an approach to isolate and analyze Circulating Trophoblastic Fetal Cells (CFTCs) for NIPD of monogenic diseases caused by triplet repeat expansion or point mutations. We developed a method for CFTC isolation based on DEPArray sorting and used Huntington's disease as the clinical model for CFTC-based NIPD. Then, we investigated whether CFTC isolation and Whole Genome Amplification (WGA) could be used for NIPD in couples at risk of transmitting different monogenic diseases. Our data show that the allele drop-out rate was 3-fold higher in CFTCs than in maternal cells processed in the same way. Moreover, we give new insights into CFTCs by compiling data obtained by extensive molecular testing by microsatellite multiplex PCR genotyping and by WGA followed by mini-exome sequencing. CFTCs appear to be often characterized by a random state of genomic degradation.

Evaluation of a new balloon for fetal endoscopic tracheal occlusion in the nonhuman primate model.

OBJECTIVE: We developed a new balloon called "Smart-TO," which allows noninvasive and easy unplugging, thanks to a magnetic valve actuated by the magnetic fringe field of a magnetic resonance imaging (MRI) scanner. The objective of this feasibility study was to evaluate the operation of this new balloon in a nonhuman primate model. METHODS: Four pregnant rhesus monkeys underwent fetal endoscopic tracheal occlusion using the "Smart-TO" balloon. The pregnant monkeys were simply carried around the perimeter of an MRI scanner a few days later. Study outcomes were feasibility of fetal tracheal occlusion using the "Smart-TO" balloon, persistence of the balloon in the fetal trachea, and deflation of the balloon when subjected to the magnetic fringe field of an MRI. RESULTS: At the time of the unplug procedure, in all cases, the balloon was still in a correct position, and its shape did not change based on their ultrasound appearance. After bringing the pregnant monkeys into the fringe field of the MRI scanner, the balloon deflated in all cases. CONCLUSION: The balloon we developed allows noninvasive, easily triggered, and externally controlled reversal occlusion, based on the nonhuman primate model. Further tests evaluating occlusiveness and potential adverse effects are necessary.

Experimental fetal endoscopic tracheal occlusion in rhesus and cynomolgus monkeys: nonhuman primate models.

OBJECTIVE: The monkey model is the best model to investigate some physiological response to the fetal transitory tracheal occlusion but it has never been described in Macaca monkeys. The aim of this study was to evaluate the feasibility of fetal endoscopic tracheal occlusion (FETO) in a non-human primate model. METHODS: Pregnant rhesus monkeys and cynomolgus were tested as a potential experimental model for FETO in the third trimester of pregnancy, by performing fetal tracheoscopies with and without tracheal occlusion. RESULTS: A total of 22 pregnancies were followed in 16 monkeys and underwent fetal surgery. Percutaneous endoscopic access to the uterine cavity was possible in 20 cases (91%). Of these 20 pregnant monkeys, fetal tracheoscopy could be achieved in 15 cases (75%). In rhesus monkeys, the time between the onset of endoscopy and tracheal penetration decreases as operator experience increases. Neither maternal morbidity nor mortality was related to surgery. Two fetal losses were possibly due to the procedure. CONCLUSION: FETO is feasible in the non-human primate, which closely reflects procedures in humans. The non-human primate model for FETO, specially the rhesus monkeys, may be useful for future studies concerning the mechanisms related to the lung growth after transitory fetal tracheal occlusion.