Significant decrease in miscarriages after preimplantation genetic diagnosis (PGD) for recurrent pregnancy loss using array comparative genome hybridization (Array CGH)

Abstract

Array CGH can analyze all chromosomes for aneuploidy and may further reduce the risk of miscarriage in patients suffering from recurrent pregnancy loss (RPL). The objective of this study was to determine any beneficial effects of PGD by array CGH for RPL patients in comparison to their expected loss rate and to PGD by FISH results. Multicenter retrospective study. The study included 177 cycles of couples with idiopathic RPL (defined as 3 or more miscarriages), average maternal age of 36.3 years, undergoing ART at multiple fertility centers. PGD was done using day-3 biopsy (n = 143) or day-5 biopsy (n = 34), followed by analysis by aCGH. Each PGD patient was matched with their expected loss rate for RPL patients (Brigham et al. 1999). An ongoing pregnancy was defined as past second trimester. In total 1517 embryos were analyzed, of which 33% were normal, 63% were abnormal and 4% none analyzable (no nucleus or no DNA amplification). Of the 176 cycles, pregnancy data was available for 154, of which 66 (43%) became pregnant with an implantation rate of 45% (95 sacs / 212 replaced embryos) and 62 cycles (40%) are ongoing past second trimester or delivered. We would expect a 34.9% miscarriage rate in this specific group of patients, but the miscarriage rate found was only 6% (4/66) (P<0.001). Previous PGD results using FISH showed that the miscarriage rate in idiopathic RPL patients was significantly reduced from 26% to 10% in patients younger than 35, and from 39% to13% in older patients. Current PGD results with aCGH indicate a significant decrease in the miscarriage rate of idiopathic RPL patients and high pregnancy rates for the current average maternal age of 36. These data suggest that aCGH further improves the results previously obtained by FISH. Furthermore, this confirms that idiopathic recurrent miscarriage is mostly caused by embryonic chromosome abnormalities.