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
Open accessAbstract
Introduction The use of chromosome analysis on products of conception from spontaneous abortions is recommended to identify a genetic etiology. However, 20% of products of conception cultures are unsuccessful due to microbial contamination or lack of viable dividing cells. Our laboratory implemented a reflex fluorescent in situ hybridization (FISH) assay to detect numeric chromosome abnormalities for unsuccessful cultures.Materials and methods All products of conception samples were simultaneously processed for both chromosome analysis and FISH analysis. If the chromosome analysis was unsuccessful, interphase FISH was performed for chromosomes 13, 16, 18, 21, 22, X, and Y. To assess the performance of the FISH assay, a 3-year retrospective comparative analysis of the FISH results versus chromosome results was performed.Results Of 5555 total specimens, 4189 (75%) represented chorionic villi/fetal tissue and 1366 (25%) represented tissue of unidentified origin. Of the 1189 tissues of unidentified origin with chromosome or FISH results, 1096 (92%) were XX, indicating that the majority of these tissues are likely maternal in origin. Of the 3361 successful chromosome studies on the chorionic villi/fetal tissue specimens, 1734 (52%) samples had a chromosome abnormality. Of the 762 successful FISH studies on chorionic villi/fetal tissue specimens that were unsuccessful by chromosome studies, 181 (25%) had an abnormal result with the targeted FISH panel. Overall, the FISH panel detected approximately 70% of the chromosome abnormalities in products of conception detectable by karyotype. When the FISH panel results were combined with chromosome analysis for the 4189 chorionic villi/fetal tissue specimens, the overall abnormality rate is 47%.Conclusions Our reflex FISH assay proved useful for the detection of common chromosome aneuploidies in products of conception samples that failed conventional chromosome analysis. Because of its limited view of the genome, cautious interpretation of FISH results is required for all samples, in particular, trisomy of an acrocentric chromosome, which may represent a Robertsonian translocation. An algorithmic approach to the genetic evaluation of products of conception specimens, with the potential for initial evaluation by a FISH panel, may be warranted.
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Cites
A cytogenetic study of 1000 spontaneous abortions
Hassold, T. J., Chen, N., Funkhouser, J. G., et al. (1980) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1980.tb00955.x · Cited by 686 · see citing works
Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions
Boué, J., Boué, A., & Lazar, P. (1975) · Teratology · doi:10.1002/tera.1420120103 · Cited by 666 · see citing works
Estimates of human fertility and pregnancy loss
Zinaman, M. J., Clegg, E. D., Brown, C., O’Connor, J., & Selevan, S. G. (1996) · Fertility and Sterility · doi:10.1016/s0015-0282(16)58144-8 · Cited by 606 · see citing works
Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy
Hassold, T., & Chiu, D. (1985) · Human Genetics · doi:10.1007/bf00389450 · Cited by 481 · see citing works
Delaying childbearing: effect of age on fecundity and outcome of pregnancy.
van Noord‐Zaadstra, B. M., Looman, C. W. N., Alsbach, H., Habbema, J. D. F., Velde, E. R. T., & Karbaat, J. (1991) · BMJ · doi:10.1136/bmj.302.6789.1361 · Cited by 446 · see citing works
Menasha, J. D., Levy, B., Hirschhorn, K., & Kardon, N. B. (2005) · Genetics in Medicine · doi:10.1097/01.gim.0000160075.96707.04 · Cited by 309 · see citing works
Anatomic and chromosomal anomalies in 639 spontaneous abortuses
Kajii, T., Ferrier, A., Niikawa, N., Takahara, H., Ohama, K., & Avirachan, S. (1980) · Human Genetics · doi:10.1007/bf00329132 · Cited by 308 · see citing works
Slama, R. (2002) · Human Reproduction · doi:10.1093/humrep/17.2.503 · Cited by 308 · see citing works
Philipp, T. (2003) · Human Reproduction · doi:10.1093/humrep/deg309 · Cited by 288 · see citing works
Eiben, B., Bartels, I., Bähr-Porsch, S., Borgmann, S., Gatz, G., Gellert, G., Goebel, R., Hammans, W., Hentemann, M. A., & Osmers, R. (1990) · Europe PMC (PubMed Central) · Cited by 278 · see citing works
Fetal loss in Down syndrome pregnancies
Morris, J. K., Wald, N. J., & Watt, H. (1999) · Prenatal Diagnosis · doi:10.1002/(sici)1097-0223(199902)19:2 · Cited by 215 · see citing works
Schaeffer, A. J., Chung, J., Heretis, K., Wong, A., Ledbetter, D. H., & Martin, C. L. (2004) · The American Journal of Human Genetics · doi:10.1086/421250 · Cited by 207 · see citing works
Lomax, B. L., Tang, S., Separovic, E. R., Phillips, D., Hillard, E., Thomson, T., & Kalousek, D. K. (2000) · The American Journal of Human Genetics · doi:10.1086/302878 · Cited by 161 · see citing works
Multiplex interphase FISH as a screen for common aneuploidies in spontaneous abortions
Jobanputra, V. (2002) · Human Reproduction · doi:10.1093/humrep/17.5.1166 · Cited by 148 · see citing works
Spontaneous and recurrent abortion
Bennett, M. J., Edmonds, D. K., & Dewhurst, J. (1987) · Medical Entomology and Zoology · Cited by 124 · see citing works
Chromosomal anomalies in first‐trimester miscarriages
Ljunger, E., Cnattingius, S., Lundin, C., et al. (2005) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/j.0001-6349.2005.00882.x · Cited by 118 · see citing works
Benkhalifa, M., Kasakyan, S., Clément, P., Baldi, M., Tachdjian, G., Demi̇rol, A., Gürgan, T., Fiorentino, F., Mohammed, M., & Qumsiyeh, M. Β. (2005) · Prenatal Diagnosis · doi:10.1002/pd.1230 · Cited by 116 · see citing works
Diego‐Álvarez, D., de Alba, M. R., Cardero‐Merlo, R., et al. (2007) · Prenatal Diagnosis · doi:10.1002/pd.1777 · Cited by 116 · see citing works
Guerneri, S., Bettio, D., Simoni, G., Brambati, B., LANZANI, A., & Fraccaro, M. (1987) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a136623 · Cited by 113 · see citing works
Diagnosis of miscarriages by molecular karyotyping: Benefits and pitfalls
Robberecht, C., Schuddinck, V., Fryns, J., & Vermeesch, J. R. (2009) · Genetics in Medicine · doi:10.1097/gim.0b013e3181abc92a · Cited by 108 · see citing works
Double trisomy revisited—a multicenter experience
Micale, M. A., Insko, J., Ebrahim, S. A. D., et al. (2009) · Prenatal Diagnosis · doi:10.1002/pd.2429 · Cited by 95 · see citing works
Analyses of 95 first-trimester spontaneous abortions by chorionic villus sampling and karyotype
Strom, C. M., Ginsberg, N. A., Applebaum, M., Bozorgi, N., White, M., Caffarelli, M. A., & Verlinsky, Y. (1992) · Journal of Assisted Reproduction and Genetics · doi:10.1007/bf01204052 · Cited by 82 · see citing works
The Principles of Clinical Cytogenetics
Gersen, S. L., & Keagle, M. B. (2005) · Humana Press eBooks · doi:10.1385/1592598331 · Cited by 81 · see citing works
Menten, B., Swerts, K., Chiaie, B. D., Janssens, S., Buysse, K., Philippé, J., & Speleman, F. (2009) · BMC Medical Genetics · doi:10.1186/1471-2350-10-89 · Cited by 69 · see citing works
Spurbeck, J. L., Carlson, R. O., Allen, J. E., & Dewald, G. W. (1988) · Cancer Genetics and Cytogenetics · doi:10.1016/0165-4608(88)90312-3 · Cited by 68 · see citing works
Genetics in Obstetrics and Gynecology
Blackburn, S. (2004) · The Journal of Perinatal & Neonatal Nursing · doi:10.1097/00005237-200401000-00011 · Cited by 67 · see citing works
Shimokawa, O., Harada, N., Miyake, N., Satoh, K., Mizuguchi, T., Niikawa, N., & Matsumoto, N. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31421 · Cited by 63 · see citing works
Diego‐Álvarez, D., García‐Hoyos, M., Trujillo, M. J., et al. (2005) · Human Reproduction · doi:10.1093/humrep/deh781 · Cited by 59 · see citing works
Bruno, D. L., Burgess, T., Ren, H., et al. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31552 · Cited by 55 · see citing works
Cytogenetic analysis of 1508 spontaneous abortions originating from south Slovakia
Dejmek, J., Vojtaššák, J., & Malová, J. (1992) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/0028-2243(92)90257-y · Cited by 53 · see citing works
Warren, J. E., Turok, D. K., Maxwell, T. M., Brothman, A. R., & Silver, R. M. (2009) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e3181bc6ab0 · Cited by 46 · see citing works
Full monosomy 21: A clinically recognizable syndrome?
Fryns, J. P., D'Hondt, F., Goddeeris, P., et al. (1977) · Human Genetics · doi:10.1007/bf00393578 · Cited by 46 · see citing works
Cytogenetics of Spontaneous Abortion
Pflueger, S. (2005) · Humana Press eBooks · doi:10.1385/1-59259-833-1:323 · Cited by 42 · see citing works
Pegoraro, E., Carelli, V., Zeviani, M., Cortelli, P., Montagna, P., Barboni, P., Angelini, C. I., & Hoffman, E. P. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960202)61:4 · Cited by 39 · see citing works
Cytogenetic studies in spontaneous abortion: the Calgary experience
Lin, C. C., Braekeleer, M. D., & Jamro, H. (1985) · Canadian Journal of Genetics and Cytology · doi:10.1139/g85-083 · Cited by 39 · see citing works
Monosomy 21: a new case confirmed by in situ hybridization
Pellissier, M. C., Philip, N., Voelckel-Baeteman, M. A., et al. (1987) · Human Genetics · doi:10.1007/bf00273852 · Cited by 38 · see citing works
Mori, M. Á., Lapunzina, P. D., Delicado, A., et al. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20622 · Cited by 38 · see citing works
A female infant with monosomy 21
Dziuba, P., Dziekanowska, D., & H�bner, H. (1976) · Human Genetics · doi:10.1007/bf00270866 · Cited by 29 · see citing works
Prenatal diagnosis of JAK3 deficient SCID
Schumacher, R. F., Mella, P., Lalatta, F., Fiorini, M., Giliani, S. C., VILLA, A. M., Candotti, F., & Notarangelo, L. D. (1999) · Prenatal Diagnosis · doi:10.1002/(sici)1097-0223(199907)19:7 · Cited by 27 · see citing works
FULL MONOSOMY 21, PRENATALLY DIAGNOSED BY FLUORESCENTIN SITU HYBRIDIZATION
Joosten, A. M. S., VOS, S. D., Opstal, D. V., et al. (1997) · Prenatal Diagnosis · doi:10.1002/(sici)1097-0223(199703)17:3 · Cited by 27 · see citing works
Bowen, P., & Lee, C. S. N. (1969) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(69)90688-7 · Cited by 25 · see citing works
Lescoat, D., Jouan, H., Loeuillet-Olivo, L., & Le Calvé, M. (2005) · Prenatal Diagnosis · doi:10.1002/pd.1132 · Cited by 21 · see citing works
21-Monosomy in a liveborn male infant
Herva, R., Koivisto, M., & Sepp�nen, U. (1983) · European Journal of Pediatrics · doi:10.1007/bf00661907 · Cited by 15 · see citing works
Examination of trisomy 13, 18 and 21 foetal tissues at different gestational ages using FISH
Moore, G. E., Ruangvutilert, P., Chatzimeletiou, K., et al. (2000) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200436 · Cited by 11 · see citing works
Garzicić, B., Guć-Sćekić, M., Pilic-Radivojevic, G., et al. (1988) · PubMed · Cited by 11 · see citing works
Fejgin, M. D., Pomeranz, M., Liberman, M., Fishman, A., & Amiel, A. (2005) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/j.0001-6349.2005.00757.x · Cited by 10 · see citing works
Separating monosomy-21 from the "arthrogryposis basket".
Cs, H., & Ae, C. (1981) · PubMed · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Warburton D, Stein Z, Kline J, Susser M. Chromosome abnormalities in spontaneous abortion: data from the New York city study. In: Porter IH, Hook EB, editors. Embryonic and fetal death. New York: Academic Press, 1980:261-287.
- Daniely M, Barkai G, Goldman B, Aviram-Goldring A. Detection of nu- merical chromosome aberrations by comparative genomic hybridization. Prenat Diagn 1999;19:100 -104.
- Spurbeck JL, Zinsmeister AR, Meyer KJ, Jalal SM. Dynamics of chromo- some spreading. Am J Med Genet 1996;61:387-393.
- Sanchez JM, Franzi L, Collia F, De Diaz SL, Panal M, Dubner M. Cytoge- netic study of spontaneous abortions by transabdominal villus sampling and direct analysis of villi. Prenat Diagn 1999;19:601-603.
- Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counselling, 2nd ed. Oxford: Oxford University Press, 1996.
Cited by
Sorted by citations
van den Berg, M. M. J., van Maarle, M. C., van Wely, M., & Goddijn, M. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.07.001 · Cited by 282 · see citing works
Recurrent MiscarriageGreen‐top Guideline No. 17
Regan, L., Rai, R., Saravelos, S., Li, T., & the Royal College of Obstetricians and Gynaecologists (2023) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.17515 · Cited by 158 · see citing works
Fertility after recurrent miscarriages: results of an observational cohort study
Kling, C., Hedderich, J., & Kabelitz, D. (2018) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-017-4532-4 · Cited by 31 · see citing works
- Authors
- Shearer, B. M., Thorland, E. C., Carlson, A. W., Jalal, S. M., & Ketterling, R. P.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Ketterling, Rhett P.
- ORCID
- Ketterling, Rhett P.
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 13
- Issue
- 6
- Pages
- 545-552
- ISSN
- 1098-3600 (ISSN-L)
- OpenAlex
- W1992858592
- Cited by
- 72
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- products of conception, miscarriage, aneuploidy, interphase FISH, chorionic villi, fetal tissue, Robertsonian translocation
- MeSH terms
- Abortion, Spontaneous, Aneuploidy, Female, Fertilization, Fetus, Humans, Pregnancy, Retrospective Studies, In Situ Hybridization, Fluorescence, Cytogenetic Analysis
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