A retrospective study of preimplantation embryos diagnosed with monosomy by fluorescence in situ hybridization (FISH)

Abstract

This report is a retrospective study of preimplantation embryos diagnosed with monosomy for chromosomes 13, 15, 16, 18, 21, 22, X and Y on day 3 to determine the rate of true positives, false positives and/or mosaicism and to assess if these embryos are suitable for in vitro fertilization (IVF) transfer. In a one year period, 80 patients went through preimplantation genetic diagnosis for aneuploidy screening (PGD-AS). Monosomy was diagnosed in 51 embryos. Fluorescence in situ hybridization (FISH) was then performed on the blastomeres at day 5–7 with commercially available probes using the same probe set that initially identified monosomy for chromosomes 13, 16, 21 and 22 or chromosomes 15, 18, X and Y. Based on FISH analysis, the monosomy diagnosed during routine PGD-AS analysis was confirmed in 17 of the 51 embryos. A euploid result for the specific chromosomes tested was observed in 16 of the 51 embryos while mosaicism was found in the remaining 18 embryos. This results in an estimated false positive rate of 3.8% for a diagnosis of monosomy. Reanalysis of these embryos demonstrates that the majority of monosomy diagnoses represents true monosomy or mosaicism and should be excluded for transfer in IVF. Furthermore, improved understanding from recent emerging data regarding the fate of oocytes in women with advanced maternal age undergoing IVF to the development of early embryos may provide a valuable insight into the mechanism of chromosome mosaicism.

Developmental potential of clinically discarded human embryos and associated chromosomal analysis

“…Using an SNP array for clinically discarded embryos, we found that whole chromosome loss is the most frequently occurring abnormal event, consistent with a previous report 42 . In addition, whole chromosome gain and segmental deletions were also frequently observed as previously reported 43 44 45 .…”

“…Following the use of SNP array-based 24 chromosome aneuploidy screening, two out of 3,401 blastocysts demonstrated isodisomy in human 2PN-derived blastocysts after trophoblast cell biopsy, with an associated frequency of UPD of 0.06% 42 . In our previous study, the percentage of UPD in human clinically discarded blastocysts was 3.7% 46 , consistent with data generated as part of the present study (2.7%).…”

Chromosomal integrity of human preimplantation embryos at different days post fertilization

“…A significant difference was found in our research between monosomy and trisomy rate. The cause for that difference might be technical elements (FISH interpretations) but it may also suggest that chromosome loss is more common in aneuploid embryo [9].…”

Prevalence of chromosomal mosaicism in pregnancies from couples with infertility

“…Munne et al (27) in 1997 reported that IVF culture conditions and/or hormone stimulation protocols may induce chromosomal mosaicism. More recently, mosaicism has been found in 16% to 67% of embryos after preimplantation genetic diagnosis (PGD) in couples requiring ART (28,29). Because, in many cases, preimplantation genetic diagnosis is conducted in patients with infertility and potential mosaics are not transferred, there is no available cytogenetic followup evaluation to determine the actual prevalence and consequence of these mosaics.…”