After in vitro fertilization with a single embryo, the parents learned about being pregnant with twins in the 10th week with various indications that an embryonic mix-up could have taken place. The affected couple thus expressed the urgent desire for a clarification of parenthood considering an abortion. However, the prenatal test results would not have been available until the 14/15th week of pregnancy. Legally, then, severe physical or mental distress of the pregnant woman must be claimed by physicians to justify an abortion after the twelfth week. However, a lack of genetic relatedness could lead to serious psychological distress for the parents, making a pregnancy termination possible even after the twelfth week, which is discussed in this case study alongside the interdisciplinary team\'s ethical, legal, and medical considerations.For the invasive relationship testing, cultivated chorionic villi samples (CVS) from both unborn and saliva samples from the putative parents were genetically analyzed using classical short tandem repeats (STR) analysis. The perfect match of both CVS profiles suggested the occurrence of an unusual late twin shaft, for which, fortunately, parenthood could be confirmed. To our knowledge, this is the first report on a prenatal investigation of a suspected embryo mix-up after assisted reproductive technology (ART), in which parenthood should be fixed. We want to draw attention to this unthinkable scenario, which may increase in the future with ART-induced rising multiple pregnancies.

To evaluate cell-free non-invasive prenatal testing (cfNIPT) in pregnancies affected by mosaicism.
We assessed paired cfNIPT and chorionic villus sample (CVS) results from the same pregnancies in a case series of mosaicism detected in Central and North Denmark Regions from April 2014 to September 2018. Indications for the clinically obtained CVS, pregnancy markers and outcome were retrieved from The Danish Fetal Medicine Database.
Mosaicisms in CVS involved common aneuploidy, n = 14; sex chromosomal aneuploidies, n = 14; rare autosomal trisomies (RATs), n = 16 and copy number variants (CNVs) >5Mb, n = 9. Overall, 24/53 (45.3%; CI 95%: 31.8%-59.4%) of cases with mosaicism were detected by cfNIPT; highest for RATs (56%) and lowest for CNVs (22%). CfNIPT more commonly detected high-level than low-level mosaic cases (p = 0.000). CfNIPT detected 7/16 (43.8%; CI 95%: 21%-69%) clinically significant mosaic cases, either true fetal mosaicism or confined placental mosaicisms with adverse pregnancy outcome. There was a trend toward a higher risk for adverse outcome in pregnancies where mosaicism was detected by cfNIPT compared to pregnancies where mosaicism was not detected by cfNIPT (p = 0.31).
CfNIPT has a low detection rate of mosaicism, including pregnancies with clinically significant mosaicism. However, abnormal cfNIPT results may be a predictor of adverse pregnancy outcomes.

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UNASSIGNED: Congenital ichthyosis represents a wide spectrum of diseases. This article reviews prenatal testing for ichthyosis.
UNASSIGNED: We used pubmed.ncbi.nlm.nih.gov to search for 38 types of congenital ichthyosis combined with 17 words related to prenatal testing.
UNASSIGNED: Search resulted in 408 publications covering 13 types of ichthyoses and four types of tests.
UNASSIGNED: Biochemical testing is diagnostic in trichothiodystrophy, but nonspecific in X-linked ichthyosis and Refsum syndrome. Except in X-linked ichthyosis, biochemical testing requires invasive procedures to obtain fetal skin biopsy, amniocytes, or chorionic villus samples. It is superior to histological and cytological examination of fetal skin biopsy or amniocytes because keratinization occurs later in pregnancy and microscopy cannot differentiate between ichthyosis types. Imaging is more acceptable due to noninvasiveness and routine use, although ultrasonography is operator-dependent, nonspecific, and captures abnormalities at late stage. Molecular tests are described in at-risk pregnancies but testing of free fetal DNA was not described.

Complete trisomy 5 is a rare and lethal abnormality. Mosaic trisomy 5 presents in various phenotypes, ranging from a clinically normal fetus to fetuses presenting uterine growth restriction, congenital heart anomalies, multiple dysmorphic features and psychomotor development abnormalities. Although rare, there are cases of a normal psychomotor development regardless of the associated low fetal growth frequently associated with mosaic trisomy 5. This is the first case report to date of a live fetus with complete trisomy 5 reported in chorionic villus sampling and mosaic trisomy 5 in amniotic fluid with a concomitant Ebstein anomaly. Diagnosis of mosaic trisomy 5 represents a challenge for the clinical team and patients, as the information regarding this syndrome is scarce and based mostly on case reports of liveborns, which may introduce a selection bias when counselling the parents.

BACKGROUND: Chorionic villus sampling (CVS) remains essential for first-trimester genetic diagnosis, yet clinical volume may be insufficient to train new clinicians in the technique. Available simulation models are expensive, require animal parts or specialized resins, and cannot be stored for repeated use.
METHODS: We present a model for trans-abdominal CVS (TA-CVS) which is constructed from readily available materials costing less than $10 and can be refrigerated and re-used to train maternal-fetal medicine fellows in CVS.
RESULTS: All three attending physicians performing TA-CVS at our institution described the model as an accurate visual and tactile simulation, prompting its integration into our fellowship curriculum. To date, two senior fellows have achieved competency on the simulator and begun to perform clinical CVS under supervision, one of whom is an author on this paper. Both fellows and attendings indicated that the simulator provided a valuable tool for repeated practice prior to clinical CVS. Simulators are now maintained on the unit and have been re-used for 3 months and dozens of simulated procedures each without any apparent qualitative degradation in performance.
CONCLUSIONS: We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS.

OBJECTIVE: To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis.
METHODS: From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs.
RESULTS: The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask.
CONCLUSIONS: The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.

In 2011, it was decided to implement chromosomal microarray in prenatal testing in the Central Denmark Region, mainly due to the expected higher diagnostic yield. Chromosomal microarray was introduced gradually for an increasing number of pregnancies and without a transition period where both karyotyping and chromosomal microarray were performed: first malformations (2011), then large nuchal translucency (2013), then high risk at combined first trimester risk screening (2016) and finally for all indications (2018). This retrospective study summarizes 11 years of using chromosomal microarray in invasive prenatal testing and presents the effect on diagnostic yield and turnaround time. Furthermore, the concerns when introducing chromosomal microarray are presented and discussed.
Registry data from the Danish Fetal Medicine Database, the regional fetal medicine database, the Danish Cytogenetic Central Register and the local laboratory database at Department of Clinical Genetics were all combined, and a cohort of 147 158 singleton pregnancies with at least one ultrasound examination was established RESULTS: Of the 147 158 pregnancies, invasive sampling was performed (chorionic villi or amniocytes) in 8456, corresponding to an overall invasive rate of 5.8%. Between 2016 and 2018, 3.4% (95% confidence interval [CI] 2.8-4.2%; n = 86) of the invasive samples (n = 2533) had a disease causing copy number variant and 5.3% (95% CI 4.4-6.2%; n = 133) had trisomies and other aneuploidies. The turnaround time more than halved from 14 days to an average of 5.5 days for chorionic villus sampling.
Chromosomal microarray identified 5.3% trisomies and 3.4% copy number variants, thereby increased the diagnostic yield by more than 64% compared with karyotype only and it also more than halved the turnaround time. Some preliminary concerns proved real, eg prenatal counseling complexity, but these have been resolved over time in a clinical path with expert consultations.

OBJECTIVE: We present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a positive non-invasive prenatal testing (NIPT) result suspicious of trisomy 13, a chorionic villus sampling (CVS) result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.
METHODS: A 29-year-old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation because of a positive NIPT result (Z-score = 20.9, positive ≥3) suspicious of trisomy 13 at 11 weeks of gestation and a CVS result of mosaic trisomy 13 at 14 weeks of gestation. At 14 weeks of gestation, CVS revealed the multiplex ligation-dependent probe amplification (MLPA) result of rea X,Y (P095) × 1, 13 (P095) × 3, 18,21 (P095) × 2/X,Y (P095) × 1, 13,18,21 (P095) × 2 and a karyotype of 48,XY,+13,+mar [9]/47,XY,+mar[16]. She was referred to the hospital for genetic counseling at 15 weeks of gestation, and cytogenetic analysis of parental blood revealed 47,XY,+mar in the father and 46, XX in the mother. Fluorescence in situ hybridization (FISH) analysis on the paternal blood showed that the extra dicentric marker was derived from chromosome 15 without the locus SNRPN (15q11.2), and the result was 47,XY,+mar.ish dic(15) (D15Z1++, SNRPN-, PML-)[20]. Amniocentesis at 20 weeks of gestation revealed a karyotype of 47,XY,+mar pat (20/20). Simultaneous interphase FISH analysis on uncultured amniocytes revealed 32% (32/100 cells) mosaicism for trisomy 13. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis using the DNA extracted from the parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 13. Prenatal ultrasound findings were normal. The woman was advised to continue the pregnancy, and a phenotypically normal 2708-g male baby was delivered at 38 weeks of gestation, The cord blood, umbilical cord and placenta had the karyotypes of 47,XY,+mar pat and did not have UPD 13. When follow-up at age two months, the neonate was phenotypically normal. FISH analysis on buccal mucosal cells detected 5.3% (5/95 cells) mosaicism for trisomy 13, compared with 0% in the normal control.
CONCLUSIONS: Low-level mosaic trisomy 13 at amniocentesis can be associated with a positive NIPT result suspicious of trisomy 13, a CVS result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy 2 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) and chorionic villus sampling (CVS) results for trisomy 2, maternal uniparental disomy (UPD) 2, perinatal progressive decrease of the aneuploid cell line, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, intrauterine growth restriction (IUGR) and a favorable fetal outcome.
METHODS: A 35-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because both NIPT at 9 weeks of gestation and CVS at 11 weeks of gestation revealed trisomy 2. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). Amniocentesis revealed a karyotype of 47,XY,+2[11]/46,XY[19]. Prenatal ultrasound findings were normal. She was referred to the hospital for genetic counseling at 20 weeks of gestation, and repeat amniocentesis performed at 24 weeks of gestation revealed a karyotype of 46,XY (22/22 colonies). The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods revealed maternal uniparental heterodisomy of chromosome 2. Simultaneous molecular cytogenetic analysis on uncultured amniocytes showed the results of arr 2p25.3q37.3 × 2.4 with a log2 ratio = 0.26, consistent with 40% mosaicism for trisomy 2 by array comparative genomic hybridization (aCGH), and 28% (28/100 cells) mosaicism for trisomy 2 by interphase fluorescence in situ hybridization (FISH). Despite IUGR on fetal ultrasound, the woman was advised to continue the pregnancy, and a 2252-g phenotypically normal male baby was delivered at 38 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY (40/40 colonies), 46,XY (40/40 colonies) and 47,XY,+2[9]/46,XY[31], respectively. QF-PCR analysis on cord blood, umbilical cord and placenta confirmed uniparental heterodisomy of chromosome 2 in the cord blood and umbilical cord, and maternal origin of trisomy 2 in the placenta. FISH analysis on buccal mucosal cells at age 1.5 months revealed 8.7% (9/104 cells) mosaicism for trisomy 2. When follow-up at age four months, the neonate manifested a normal phenotype except intermittent hypoventilation. Molecular analysis of the PHOX2B gene revealed a normal result. When follow-up at age one year, he manifested normal development.
CONCLUSIONS: Mosaic trisomy 2 at prenatal diagnosis should alert the possibility of UPD 2 and include a UPD 2 testing. Low-level mosaic trisomy 2 at amniocentesis can be associated with perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.