Abnormal non-invasive prenatal test results concordant with karyotype of cytotrophoblast but not reflecting abnormal fetal karyotype.

We present a unique case in which non-invasive and invasive prenatal diagnoses showed abnormal, but discordant, results. A patient with abnormal non-invasive prenatal test (NIPT) results, indicating a 99% risk for monosomy X, was referred to our center for genetic counseling and confirmatory studies. Cytogenetic analysis of uncultured mesenchymal core of chorionic villi (CV) revealed a mosaic male karyotype consisting of two abnormal cell lines: one with monosomy X and the other with an isodicentric chromosome Y. Array analysis of the trophoblast confirmed the NIPT results. Based on the CV results, the patient opted for termination of pregnancy. After extensive counseling by a clinical geneticist about the possible outcomes and by a gynecologist about the risk of a second-trimester abortion procedure, the patient agreed to undergo early amniocentesis. Amniocentesis confirmed that the fetus had a male karyotype with an isodicentric chromosome Y, and the single nucleotide polymorphism (SNP) array profile suggested absence of the monosomy X cell line. The male infant was expected to be infertile. The patient finally decided to continue the pregnancy. Our case confirms that NIPT results are comparable with those of short-term cultured CV investigating the cytotrophoblast. Our patient was not aware that the NIPT results reveal the placental karyotype, which sometimes may be different from the fetal karyotype. Pretest counseling and providing the risk figures for false-positive and false-negative NIPT results are of great importance in order to discourage women from terminating pregnancies based on NIPT results alone.

Prevalence of tetraploid metaphases in semidirect and cultured chorionic villi.

OBJECTIVE: Investigation of the normal frequency of tetraploid metaphases in semidirect (STC) and cultured (LTC) chorionic villi. METHODS: Fifty metaphases in STC- and in LTC-villi slides of 100 women of advanced maternal age were screened for tetraploidy. RESULTS: Up to three tetraploid metaphases were encountered in 27% of the STC-villi preparations; the scores fitted a Poisson distribution. In all LTC-villi preparations tetraploid cells were seen; the scores fitted a log-Gaussian distribution. CONCLUSIONS: On the basis of these distributions, we propose a protocol for the management of tetraploid metaphases in chorionic villi, strongly reducing the number of prenatal follow-up investigations.

Abnormal karyotypes in semi-direct chorionic villus preparations of women with different cytogenetic risks.

Among 3499 cytogenetically investigated semi-direct chorionic villus samples, 219 (6.3 per cent) abnormal karyotypes were encountered. The karyotypes were considered certainly abnormal (generalized abnormal with high probability) in 109 cases (3.1 per cent), and in 110 cases (3.1 per cent) uncertainly abnormal (potentially confined to the placenta), requiring further investigation. Of these 110 uncertain abnormalities, the cytogenetic result turned out to be finally abnormal representing generalized abnormality in 36 cases (32.7 per cent), finally normal representing confined placental mosaicism (CPM) in 69 cases (62.7 per cent), and remained undetermined in 5 instances (4.5 per cent). The rate of the numbers of certainly abnormal and all (certainly + uncertainly) abnormal results, the certainty rate, and that of generalized abnormalities and all abnormalities (generalized abnormalities + CPM cases), the predictive value, are strongly correlated with the cytogenetic risk. Therefore, we advise chorionic villus sampling for cytogenetic investigation only in women with a cytogenetic risk equal to or exceeding that of a 40-year-old pregnant woman. Because of the high rate of prenatal follow-up investigations after the finding of uncertain results in semi-direct villi, semi-direct and cultured villi should be karyotyped simultaneously.

Chorionic villus sampling and materno-fetal transfusions: an immunological pathogenesis of vascular disruptive syndromes?

Experimental materno-embryonic transfusions with serum that is immunologically active against blood group antigens cause congenital malformations in the rat embryo. In view of the possible increased incidence of vascular disruptive syndromes after chorionic villus sampling (CVS), we investigated the occurrence of materno-fetal transfusions (MFTs) in this procedure. In 18 pregnant women experiencing two needle introductions at CVS, we looked immunohistochemically at the presence of haemoglobin A1-containing maternal erythrocytes in the fetal circulation of the separately collected first and second chorionic villus samples. In 4 of 18 patients (22 per cent), a significant increase of maternal cells was observed in the second sample compared with the first sample, indicating the occurrence of MFT by CVS. On the rare occasion of maternal immunization against fetal antigens, a CVS-associated MFT might provoke immunological damage to the fetus.