Seven cases of trisomy 3 mosaicism in chorionic villi

This paper describes seven cases of confined chorionic mosaicism with trisomy 3. The chromosomally abnormal cell line in chorionic villi was revealed in three cases at diagnostic CVS and in four cases at the evacuation of the uterine cavity after a missed abortion had been diagnosed by ultrasound. In two of these cases, the abortion occurred after apparently normal development of the fetus during the second trimester of pregnancy. An evaluation of the effect of confined chorionic mosaicism with trisomy 3 on the viability of the conceptus has been attempted.     

Chromosome mosaicism and maternal cell contamination in chorionic villi

While chorionic villus sampling allows both early and rapid prenatal diagnosis of chromosome disorders, the accuracy of this technique has not been fully established. Maternal cell contamination and pseudomosaicism represent two major sources of diagnostic error. Combined use of both direct chromosome preparations and villus cultures is important in overcoming these problems. Direct preparations of villus tissue allow recognition of maternal cell contamination of villus cultures. Conversely, villus cultures yield higher resolution chromosomes and may be helpful in differentiating between true versus pseudomosaicism when two or more cell lines are identified in direct chromosome preparations. Preliminary data suggest that analysis of direct preparations from multiple individually processed villus fragments may also be of value in this regard. Until more experience is gained, mid-trimester amniocentesis should be offered to CVS patients when mosaicism is encountered.     

Trisomy 14 mosaicism leading to cytogenetic discrepancies in chorionic villi sampled at different times

Short- and long-term cultures of chorionic villi obtained in the 11th week of pregnancy revealed trisomy 14. After induced abortion trisomy 14 mosaicism was established in fetal skin and umbilical cord tissue while a second long-term culture of chorionic villi exhibited a normal karyotype. The results of the pathological investigations are discussed with respect to the cytogenetic findings.     

The dilemma of chromosomal mosaicism in chorionic villus sampling--'direct' versus long-term cultures

Chromosomal mosaicism is one of several unanswered dilemmas in first-trimester prenatal diagnosis. We report the course of a pregnancy in which a normal karyotype was detected on direct CVS preparation and fetal blood, 100 per cent trisomy 21 in one long-term CVS culture, and low-rate trisomy 21 mosaicism in a second long-term CVS culture and amniocentesis. The phenotypically normal infant had a 6 per cent mosaicism of trisomy 21. It appears that a persistent low-rate mosaicism in different tissues may be indicative of the true status of the fetus.     

Variations in chromosomal aneuploidy rates in IVF blastocysts and early spontaneous abortion chorionic villi

Journal of Assisted Reproduction and Genetics - To compare chromosomal aberrations and aneuploidy features in (i) blastocysts following intracytoplasmic sperm injection (ICSI) and trophectoderm...     

Puncture of the chorionic villi. Technic--experiences--risks

Chorion villi biopsy is a recently introduced method for first trimester prenatal diagnosis. Based on 435 cases of chorionic villi biopsies, obtained during a 3 year period, we report our experiences with the technique of chorionic villi sampling, chromosomal analysis from trophoblast tissue and possibly associated complications, such as spontaneous abortions, vaginal bleeding, and chromosomal mosaicism. The rate of spontaneous abortions in our group of patients was 3%. This appears low, considering the high overall spontaneous abortion rate in early pregnancy of women over 35 years. The cytogenetic diagnosis is complicated by a high rate (2.8%) of chromosomal mosaicism, which were found to be not representative for the fetus, but required control amniocentesis. From our experiences with this method we conclude that chorion villi biopsy can be offered as a reliable alternative method to amniocentesis in the hands of an experienced team of obstetric surgeons and cytogenetists.     

Immunocytochemistry of human chorionic gonadotropin in human chorionic villi

The immunocytochemical localization of human chorionic gonadotropin was investigated in chorionic villi from the seventh to twelfth week of gestation. By the light microscopic peroxidase-antiperoxidase technique, positive reactions of human chorionic gonadotropin were found exclusively in the syncytiotrophoblast. Immunoelectron microscopy by means of the protein A-gold technique reveals localization of the immunoreactive gold particles in two kinds of membrane-bound granular inclusions in this cell; one type is granules of 200 to 300 nm in diameter with moderate electron density and the other is large electron-dense bodies of 500 to 1000 nm. The former seems to be Golgi-derived secretory granules that play a role in the release of human chorionic gonadotropin from the syncytiotrophoblast. Although the origin of the latter is still uncertain, a certain amount of this hormone might be stored or treated by lysosomal digestion in the large bodies during these stages.     

A practical assessment of ultrasound-guided transcervical aspiration of chorionic villi and subsequent chromosomal analysis

Summary. Aspiration biopsy of trophoblastic villi was performed on 56 patients immediately preceding suction termination of pregnancy, using a malleable metal cannula and ultrasound guidance. Villi were obtained from 47 patients (84%), with sampling success rising to 93% after experience. Immediate complications were noted in 14% of patients and correlated with placental positions situated furthest from the cervical canal. Karyotyping from cultured and/or direct preparations was attempted on the villus samples and was successful in 42. Clarity of the karyotypes obtained from direct preparations in this series was not found to be adequate for diagnostic purposes. A number of practical suggestions which facilitate chorion villus sampling are described.     

A practical assessment of ultrasound-guided transcervical aspiration of chorionic villi and subsequent chromosomal analysis

Aspiration biopsy of trophoblastic villi was performed on 56 patients immediately preceding suction termination of pregnancy, using a malleable metal cannula and ultrasound guidance. Villi were obtained from 47 patients (84%), with sampling success rising to 93% after experience. Immediate complications were noted in 14% of patients and correlated with placental positions situated furthest from the cervical canal. Karyotyping from cultured and/or direct preparations was attempted on the villus samples and was successful in 42. Clarity of the karyotypes obtained from direct preparations in this series was not found to be adequate for diagnostic purposes. A number of practical suggestions which facilitate chorion villus sampling are described.     

Incidence and outcome of chromosomal mosaicism found at the time of chorionic villus sampling

OBJECTIVE: Chromosomal mosaicism has been reported in about 1% to 3% of chorionic villus sampling specimens. This report provides incidence and outcome information that should be useful in counseling patients found to have mosaicism on chorionic villus sampling.STUDY DESIGN: A retrospective analysis of 11,200 consecutive patients undergoing chorionic villus sampling at the University of California, San Francisco, during the period from Jan. 1, 1984, to June 1, 1996, was undertaken.RESULTS: A total of 140 cases of mosaicism were identified for an incidence of 1.3%. Follow-up information was available for 130 cases, 26 of which (20%) were confirmed in fetal tissue. Confirmation rates for specific types of mosaicism were as follows: autosomal trisomy 7.6%, sex chromosome 25%, structural abnormality 27.3%, and marker chromosome 77.8%. Neonatal outcome was normal in all cases for which pregnancy continued.CONCLUSION: The data indicate that in most cases of chromosomal mosaicism found by chorionic villus sampling the mosaicism is unlikely to be clinically significant in the fetus. (Am J Obstet Gynecol 1997;176:1349-53.)     

Chromosomal mosaicism in chorionic villus sampling

The observation of multiple, chromosomally distinct cell lines in chorionic villus samples is not an unusual finding and occurs in 1 per 100 samples. This frequency is ten times greater than the level of mosaicism observed in newborn surveys and, thus, must reflect phenomenon other than true fetal mosaicism. Indeed, only 23% of mosaicism detected at CVS is confirmed in the fetus (2.3 per 1,000 CVS), which is much closer to the newborn rate (1 per 1,000). This indicates that most mosaicism encountered in CVS is unrelated to the fetal karyotype and as such is an inaccurate prediction of the fetal genotype, the purpose of prenatal diagnosis. Most of the mosaicism detected in CVS is due to confined placental mosaicism. Either as a result of error-prone cell division generating an excess of abnormal cells in extraembryonic tissues or reduced selection against aneuploid cells in these tissues allowing their persistence, chorionic villi and placenta appear to show much higher levels of mosaicism than seen in fetuses. This explains the more frequent finding of multiple cell lines in CVS than in amniocentesis or liveborn individuals. The discrepancy between levels of mosaicism present in chorionic villi and fetal tissues means that most instances of mosaicism detected in CVS are not associated with a fetal abnormality and should be evaluated by further prenatal testing, i.e., amniocentesis or fetal blood sampling. Because of the frequency of chromosomal mosaicism in CVS and its attendant need for further testing, a discussion of mosaicism should be included in counseling prior to CVS. The higher frequency of discrepant results in direct CVS preparation emphasizes the prudence of delaying decision making until the results of the CVS culture have been obtained. Although the observation of mosaicism clearly complicates genetic counseling and decision making, it does not appear to be associated with an adverse fetal outcome. Whereas most of the mosaicism observed in CVS is the result of confined placental mosaicism, other types of discrepancies also occur. Maternal cell contamination occurs in about 1% of cases, but is easily evaluated by examining the direct preparation and analyzing chromosome polymorphism. The incidence of pseudomosaicism in CVS cultures is unclear but probably low. Interestingly, CVS analysis has suggested that twinning may be a more common phenomenon at conception than reported at birth and that some discrepancies may reflect the nonviability of twins with abnormal karyotypes. Chorionic villi sampling remains a viable alternative to amniocentesis for early prenatal diagnosis. An understanding of the origins of mosaicism in CVS is necessary for     

The distinction between arylsulphatases in chorionic villi

The relatively high activity of arylsulphatase C (ASC) in the placenta is a potential risk for the misdiagnosis of arylsulphatase A (ASA) or arylsulphatase B (ASB) deficiency in chorionic villus sampling when assayed by synthetic substrates. A clear distinction between these enzymes can be achieved in either the direct villi or the cultured villi cells. Interestingly, the activity of ASC differed significantly in cultured villi cells when prepared by two different methods, namely, minced villi versus treatment with trypsin and collagenase, while ASA and ASB were not affected by these treatments. Whether ASC was directly affected by one of these treatments or whether a selection of cells with different ASC levels was achieved is not yet clear, but this phenomenon clearly indicates the importance of precise definition of CVS preparations to correlate with the enzyme activity data.     

Chromosome banding in direct preparations of chorionic villi

Chorionic villus sampling (CVS) is now currently offered for first trimester prenatal diagnosis of genetic disorders. Chromosome analysis of CVS in direct and culture preparations is possible using modifications of standard banding techniques. We summarize our experience in applying QFQ, GTG, RBG, CBG, DA/DAPI, NOR, and SC differentiation protocols to direct preparations. Characteristic chromosome regions are properly labelled by these techniques, and analysis of 300 band stage karyotypes is consistently achievable on GTG banded direct preparations. However, banding of CVS direct chromosomes has proved to be difficult, and the analysis needs to be backed up by culture preparations.