Incidence and spectrum of chromosome abnormalities in spontaneous abortions: New insights from a 12-year study

Abstract

Purpose: Despite advances in harvesting and culturing techniques, analysis of the impact of these improvements on the observed frequency of chromosomal abnormalities in spontaneous abortions (SAB) has not been determined. We sought to evaluate the effect of these refinements on the success rate of our cultures and on the resulting frequency of detected chromosomal abnormalities. Methods: Between 1990 and 2002, 2301 specimens obtained from the products of conception (POC) of SABs were submitted to our laboratory for cytogenetic analysis.Due to refinements in specimen processing and culture techniques introduced at the end of 1997, our data were analyzed for two periods: Period A from 1990 through 1997 with 907 eligible specimens and Period B from 1998 through 2002 with 1273 eligible specimens. Results: Modifications in physician communication and sample processing contributed to significant improvements in the culture success rate and in the ratio of male-to-female cases with normal karyotypes. Additionally, increased detection of trisomic, triploid, and multiple aneuploid cases in Period B resulted in a significant increase in the percentage of cases with abnormal karyotypes (42.8% in Period A vs. 65.8% in Period B). Monosomy X accounted for Ͻ 10% of all abnormalities in Period B. Eighty five multiple aneuploid karyotypes, including 57 double trisomies, comprised 7.7% of our 1099 abnormal cases. These karyotypes were detected predominantly in POCs from the older women in our study. This collection of multiple aneuploidies is the largest published to date and includes abnormalities not reported in prior studies. We also present a table empirically derived from the data in Period B that indicates the likelihood of a specific abnormal karyotype based on maternal age. The table can be utilized by health care providers, who counsel patients after a spontaneous miscarriage. Conclusion: Improvements in laboratory technique have led to reduced contamination and growth failure of POCs, irrespective of maternal age. This in turn has led to a more balanced male-to-female ratio and to the detection of an increased number of abnormal cases. Genet Med 2005:7(4):251-263. Key Words: cytogenetics, spontaneous abortion, aneuploidy, karyotype, chromosome abnormalityA correlation between chromosomal abnormalities and spontaneous abortions (SABs) has been observed since the 1960s. 1 This correlation was strengthened in the 1970s when Boue et al. 2 published one of the earliest large cytogenetic studies. In the study, almost 1500 samples of fetal tissue were karyotyped and an abnormality rate of over 60% was found. Subsequent large studies using harvested products of conception (POC) failed to match this abnormality rate, with rates of 32%-54% reported. [3][4][5][6][7][8][9] Furthermore, a large number of specimens in these studies failed to grow successfully in culture and thus could not be evaluated for abnormalities. The data culled from these studies have served as the basis for the estimated abnormality rates in the general popu...

Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: A retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization

“…However, as three cases were observed by FISH, it is possible that a more complex chromosome abnormality or a simple deletion of the chromosome 21 locus tested by FISH was identified. Our data are similar to that of Menasha et al, 30 where 11 of 13 autosomal monosomies involved chromosome 21. Monosomy 21 has also been described prenatally 38,39 and in liveborns.…”

“…1). To improve success and abnormality rates, the use of only chorionic villi has been recommended 30 ; however, we continue to test fetal and unidentified tissue in an attempt to identify a genetic cause for the fetal demise. For fetal tissue specimens, the percent abnormal for both chromosome and FISH analyses was identical (17%).…”

“…It is well established that approximately 50% of first-trimester SA is chromosomally abnormal. 6,8,10,30 Chromosome analysis is the current gold standard for detection of chromosome aberrations; however, approximately 20% of POC samples fail to yield a chromosome result due to culture failure, often attributable to microbial contamination or nonviable tissue.…”

Cytogenetic analysis in various tissues of pregnancy loss

“…We recently surveyed five years of data. Although our numbers are small, we did obtain results similar to those recently reported by Menasha et al, 1 in that these findings reflect a change in the type of specimens we receive and/or our preparation of these tissues.…”

“…We also identified two cases with multiple aneuploidy; trisomies 3 and 15, and trisomies 2, 8, 17 and 20, neither of which have been previously reported. 1 Our findings agree with Menasha et al 1 that the type of tissue received by the cytogenetics laboratory is important for success of growth and karyotyping, and hence, the information that can be provided to couples. Any methodology that optimizes the viability of specimens analyzed in the cytogenetics laboratory would increase the amount of clinically useful information provided to clinicians, thereby increasing quality of care for the patient.…”