Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

About 2 per cent of specimens from chorionic villus sampling (CVS) analysed either on direct preparation of cytotrophoblast cells or after culture of mesenchymal stroma reveal confined placental mosaicism (CPM), most commonly involving chromosomal trisomy. A significantly higher rate of prenatal loss (22 per cent) as well as the presence of intrauterine growth retardation (IUGR) has been reported among pregnancies with CPM. To evaluate more precisely the effect of these aneuploid cell lines confined to the placenta on intrauterine fetal growth and fetal survival, we have studied 34 term placentae from pregnancies with CPM diagnosed on CVS and confirmed identical mosaicism in 17 of these placentae. There was a direct correlation between a high number of aneuploid cells present at CVS and a high likelihood of their detection in term placenta. Also, the proportion of aneuploid cells in the mosaic term placentae correlated with that observed in CVS specimens. Among 17 gestations with confirmed CPM at delivery, there were six cases of IUGR identified, five in liveborns and one associated with intrauterine death.

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To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.

We prospectively studied the ability of acrosome reaction (AR) inducibility to predict fertilization success in a group of 232 infertile patients presenting sequentially for in-vitro fertilization (IVF). The median percentage of eggs fertilized for the overall patient population was 25% (interquartile range 5-58%), with one to 29 oocytes available for insemination (median, five oocytes). The median percentage of eggs fertilized at IVF increased as the percentage of spermatozoa able to undergo AR became greater: spermatozoa with a failed AR (< or = 5%) fertilized only 12% of eggs, while spermatozoa with AR values > 9% fertilized 50% of eggs. The assay had a specificity of 0.75, a sensitivity of 0.55 and an odds ratio of 2.9; thus, AR-positive patients are 2.9 times more likely to achieve fertilization than patients with a failed AR. Receiver operator characteristic (ROC) curves were constructed for AR, sperm concentration and percentage of normal forms in semen. All three parameters proved to be potentially useful in predicting the occurrence of fertilization, although AR and morphology appeared to be better than sperm concentration by ROC analysis. Patients were divided into four clearly defined subgroups according to their traditional semen characteristics, including morphology. The median percentage of eggs fertilized decreased as traditional semen characteristics deteriorated, from a median of 46% for patients with excellent sperm concentration, motility and morphology, to a median of 29% for patients with suboptimal semen quality and a median of 0% for patients with severely impaired semen.(ABSTRACT TRUNCATED AT 250 WORDS)

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Preimplantation genetic testing provides a means for couples at risk for spinal muscular atrophy type I to reduce their chance of initiating an affected pregnancy.

Four cases having mosaicism for a small marker or ring [45,X/46,X,+mar or 45,X/46,X,+r] chromosome were ascertained following cytogenetic studies requested because of minor anomalies (cases 1, 3, and 4) and/or short stature (cases 2 and 4). While all 4 cases had traits typical of Ullrich-Turner syndrome (UTS), cases 1, 3, and 4 had manifestations not usually present in UTS, including unusual facial appearance, mental retardation/developmental delay (MR/DD) (cases 3 and 4), and syndactylies (case 1). The facial appearances of cases 1 and 3 were similar yet distinct from that of case 4. Using fluorescence in situ hybridization (FISH), each of the markers in these 4 cases was identified as having been derived from an X chromosome. The level of mosaicism for the mar/r(X) cell line in these cases varied from 70% (case 1) to 16% (case 4) but was not apparently correlated with the presence of MR/DD. Replication studies demonstrated a probable early replication pattern for the mar/r(X) in cases 1, 3, and 4, while the marker in case 2 was apparently late replicating. To date, 41 individuals having mosaicism for a small mar/r(X) chromosome have been described. Interestingly, most of the 14 individuals having a presumedly active mar/r(X) demonstrated clinical findings atypical of UTS, including abnormal facial changes (11) and MR/DD (13). MR was noted most frequently in those cases having at least 50% mosaicism for the marker or ring. In contrast, atypical UTS facial appearance or MR/DD was not noted in 14 of the 16 cases with UTS who carried a probable late replicating marker or ring. In conclusion, although the phenotype of 45,X/46,X,mar/r(X) individuals appears to be influenced by the genetic content and degree of mosaicism for the mar/r(X), the most significant factor associated with MR/DD appears to be the activity status of the mar/r(X) chromosome. Thus, our 4 cases provide further support for the hypothesis that a lack of inactivation of a small mar/r(X) chromosome may be a factor leading to the MR and other phenotypic abnormalities seen in this subset of individuals having atypical UTS.