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...

These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.