title: 1(st) trimester miscarriage: four decades of study.
abstract: Miscarriage is a very common occurrence in humans. This paper sets out to present published data on research that has provided increased understanding of pregnancy failure. Clarification of definitions, exploring the range of failures from preclinical to later pregnancy losses, and the scientific tools employed to find information on the losses have been documented. What is now understood, which tools work best, and the associated limitations are all discussed. Early studies used cytogenetic methods and tissue culture to obtain results. Improvements in laboratory tools such as better tissue culture incubators, inverted microscopes, laminar flow hoods, improvements in culture media, all contributed to obtaining more results for patients. These studies demonstrated the significant contribution of unbalanced chromosomal karyotypes to pregnancy failure. Maternal age as a contributing factor in trisomy was clearly demonstrated. First trimester miscarriage exhibits very high cytogenetic abnormality; in contrast to very low rates in later losses. Combining data across all time periods of pregnancy will affect the significance of chromosomal error in the early pregnancy failures. Cytogenetic methods investigate whole genomes, and are considered to represent the standard against which new methods must be validated. New molecular genetic methods provide the opportunity to examine samples without the necessity of tissue culture. Techniques may be site-specific or whole genome. Fluorescent in situ hybridisation (FISH), comparative genomic hybridisation (CGH), array-based CGH, single nucleotide polymorphism (SNP) detection, quantitative polymerase chain reaction (qPCR), and quantitative fluorescent PCR (QF-PCR), have all been utilised. In comparison studies with classical/conventional cytogenetics, each newer method offers advantages and limitations. At the present time, a combined approach using conventional and molecular methods will elucidate the cause of miscarriage for almost all samples. In a clinical setting this would be optimum.
authors.affiliation: Cyto Labs Pty Ltd, Bentley, Western Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Hardy
authors.affiliation: Cyto Labs Pty Ltd, Bentley, Western Australia.
authors.forename: Philip John
authors.initials: PJ
authors.lastname: Hardy
keywords: 1st trimester miscarriage; Cytogenetics; molecular cytogenetics; recurrent miscarriage
references.citation: Obstet Gynecol Sci. 2014 Nov;57(6):518-25
references.pmid: 25469342
references.citation: Am J Hum Genet. 2000 Mar;66(3):1149-52
references.pmid: 10712226
references.citation: Prenat Diagn. 1998 Jul;18(7):659-68
references.pmid: 9706646
references.citation: Ann Hum Genet. 1978 May;41(4):443-54
references.pmid: 655633
references.citation: Hum Reprod. 2005 Nov;20(11):3008-11
references.pmid: 16006453
references.citation: J Med Genet. 1987 Jan;24(1):60-4
references.pmid: 3806641
references.citation: Fertil Steril. 2001 Feb;75(2):374-9
references.pmid: 11172842
references.citation: Hum Reprod. 2001 Jun;16(6):1100-3
references.pmid: 11387276
references.citation: Hum Genet. 1979 Feb 15;46(3):285-94
references.pmid: 155642
references.citation: Hum Genet. 1997 Jul;100(1):1-21
references.pmid: 9225963
references.citation: Prenat Diagn. 2000 Jul;20(7):582-6
references.pmid: 10913958
references.citation: Int J Fertil. 1990 Sep-Oct;35(5):266-70
references.pmid: 1980661
references.citation: Am J Hum Genet. 1995 Oct;57(4):867-74
references.pmid: 7573048
references.citation: Prenat Diagn. 1997 Feb;17(2):180-3
references.pmid: 9061769
references.citation: Am J Hum Genet. 1984 Nov;36(6):1349-56
references.pmid: 6517056
references.citation: Fertil Steril. 2000 Feb;73(2):300-4
references.pmid: 10685533
references.citation: Cytogenet Cell Genet. 2000;90(3-4):219-26
references.pmid: 11124518
references.citation: Mol Cytogenet. 2014 Jun 24;7:43
references.pmid: 25013457
references.citation: Prenat Diagn. 1989 May;9(5):339-47
references.pmid: 2471183
references.citation: Hum Reprod. 2002 May;17(5):1166-70
references.pmid: 11980734
references.citation: Rev Med Chil. 1997 Mar;125(3):317-22
references.pmid: 9460269
references.citation: Fertil Steril. 2014 May;101(5):1349-52
references.pmid: 24636399
references.citation: Am J Med Genet. 1990 Feb;35(2):165-73
references.pmid: 2178414
references.citation: Obstet Gynecol. 1991 Mar;77(3):394-8
references.pmid: 1992406
references.citation: Am J Hum Genet. 1980 Sep;32(5):723-30
references.pmid: 7424911
references.citation: Am J Hum Genet. 2000 May;66(5):1516-21
references.pmid: 10741955
references.citation: Am J Obstet Gynecol. 1998 Dec;179(6 Pt 1):1654
references.pmid: 9855612
references.citation: Eur J Obstet Gynecol Reprod Biol. 1992 Nov 19;47(2):117-20
references.pmid: 1459324
references.citation: Mol Cytogenet. 2014 Jun 05;7:38
references.pmid: 24976865
references.citation: Am J Hum Genet. 2000 Jun;66(6):1807-20
references.pmid: 10801385
references.citation: Fertil Steril. 1998 Feb;69(2):274-7
references.pmid: 9496341
references.citation: Am J Hum Genet. 1992 Mar;50(3):544-50
references.pmid: 1347192
references.citation: Mol Cytogenet. 2012 Jul 16;5(1):33
references.pmid: 22794168
references.citation: Eur J Hum Genet. 2001 Jul;9(7):539-47
references.pmid: 11464246
references.citation: J Assist Reprod Genet. 2012 Aug;29(8):817-20
references.pmid: 22618194
references.citation: Hum Reprod. 2002 Feb;17(2):446-51
references.pmid: 11821293
references.citation: Am J Med Genet. 1997 Jan 10;68(1):98
references.pmid: 8986286
references.citation: Prenat Diagn. 1997 Mar;17(3):271-5
references.pmid: 9110372
references.citation: Clin Genet. 1999 Jul;56(1):103-4
references.pmid: 10466428
references.citation: Am J Med Genet. 1987 Oct;28(2):353-60
references.pmid: 3322004
references.citation: Biochim Biophys Acta. 2012 Dec;1822(12):1951-9
references.pmid: 22796359
references.citation: Am J Med Genet. 2001 Mar 1;99(2):152-3
references.pmid: 11241476
references.citation: Am J Med Genet A. 2012 Aug;158A(8):2050-2
references.pmid: 22753013
references.citation: Prenat Diagn. 1998 Dec;18(12 ):1308-15
references.pmid: 9885025
references.citation: J Reprod Fertil Suppl. 1988;36:73-81
references.pmid: 3193408
references.citation: Prenat Diagn. 1999 Feb;19(2):100-4
references.pmid: 10215063
references.citation: Am J Hum Genet. 1973 Sep;25(5):539-47
references.pmid: 4741848
references.citation: Am J Hum Genet. 1991 Jan;48(1):65-71
references.pmid: 1824668
references.citation: Mol Hum Reprod. 1997 May;3(5):445-50
references.pmid: 9239730
references.citation: Prenat Diagn. 1999 Jul;19(7):601-3
references.pmid: 10419605
references.citation: Hum Genet. 1991 Jun;87(2):239-40
references.pmid: 2066117
references.citation: Am J Hum Genet. 1992 Sep;51(3):516-25
references.pmid: 1386710
references.citation: Am J Hum Genet. 1989 Oct;45(4):599-605
references.pmid: 2577470
references.citation: Hum Genet. 1993 Jun;91(5):409-15
references.pmid: 8314552
references.citation: Hum Pathol. 1995 Feb;26(2):201-9
references.pmid: 7860050
references.citation: Hum Genet. 1985;70(1):11-7
references.pmid: 3997148
references.citation: Ann Genet. 1981;24(1):32-3
references.pmid: 6971614
references.citation: Eur J Hum Genet. 2001 Dec;9(12):910-6
references.pmid: 11840192
references.citation: Hereditas. 1972;71(1):160-3
references.pmid: 4680642
references.citation: Br J Obstet Gynaecol. 1975 Nov;82(11):849-57
references.pmid: 1191598
references.citation: Cytogenet Cell Genet. 1984;38(3):200-5
references.pmid: 6541559
references.citation: Fertil Steril. 1999 Feb;71(2):334-41
references.pmid: 9988408
references.citation: Ann Genet. 1981;24(1):34-6
references.pmid: 6971615
references.citation: Clin Genet. 2009 Feb;75(2):133-40
references.pmid: 19215247
references.citation: Obstet Gynecol. 1996 Oct;88(4 Pt 1):616-9
references.pmid: 8841229
references.citation: Prenat Diagn. 1999 Feb;19(2):181-2
references.pmid: 10215081
references.citation: Pediatr Pathol. 1987;7(4):363-94
references.pmid: 3444789
references.citation: Am J Med Genet. 1997 Oct 31;72(3):297-301
references.pmid: 9332658
references.citation: Hum Genet. 1984;66(1):77-84
references.pmid: 6698558
references.citation: Am J Med Genet. 1991 Sep 1;40(3):316-8
references.pmid: 1951436
references.citation: Fertil Steril. 1996 Feb;65(2):250-3
references.pmid: 8566242
references.citation: Hum Reprod. 2005 May;20(5):1235-43
references.pmid: 15760965
references.citation: Hum Reprod. 1995 Oct;10 (10 ):2696-9
references.pmid: 8567795
references.citation: Prenat Diagn. 1997 Jul;17(7):689-90
references.pmid: 9249873
references.citation: Eur J Obstet Gynecol Reprod Biol. 1992 Sep 23;46(2-3):129-36
references.pmid: 1451889
references.citation: Ann Hum Genet. 1980 Jul;44(Pt 1):29-36
references.pmid: 7198887
references.citation: Am J Hum Genet. 1996 Mar;58(3):628-33
references.pmid: 8644722
references.citation: Teratology. 1985 Oct;32(2):297-315
references.pmid: 4049288
references.citation: J Med Genet. 1975 Sep;12(3):265-8
references.pmid: 1177277
references.citation: Fertil Steril. 2014 Jan;101(1):178-82
references.pmid: 24182409
references.citation: Prenat Diagn. 2001 Dec;21(12):1034-48
references.pmid: 11746161
references.citation: BJOG. 2014 Jan;121(1):11-21
references.pmid: 23859082
references.citation: Am J Hum Genet. 1996 Jul;59(1):176-84
references.pmid: 8659524
references.citation: Ann Genet. 1993;36(2):107-10
references.pmid: 8215215
references.citation: N Engl J Med. 1987 Jan 15;316(3):121-4
references.pmid: 3796682
references.citation: Hum Reprod. 1994 Feb;9(2):366-73
references.pmid: 8027299
references.citation: Am J Obstet Gynecol. 1990 Nov;163(5 Pt 1):1505-10
references.pmid: 2240097
references.citation: Hum Genet. 1983;64(1):24-7
references.pmid: 6683706
references.citation: Am J Med Genet. 1991 Jun 1;39(3):314-6
references.pmid: 1867283
references.citation: Hum Genet. 1991 Feb;86(4):383-7
references.pmid: 1999340
references.citation: Prenat Diagn. 1998 Jul;18(7):737-41
references.pmid: 9706657
references.citation: Ann Hum Genet. 1980 Oct;44(Pt 2):151-78
references.pmid: 7316468
references.citation: Hum Genet. 1997 Dec;101(3):339-45
references.pmid: 9439664
references.citation: BMC Med. 2013 Jun 26;11:154
references.pmid: 23803387
references.citation: Prenat Diagn. 1998 Jun;18(6):633-4
references.pmid: 9664613
references.citation: Ann Hum Genet. 1984 May;48(Pt 2):129-44
references.pmid: 6234852
references.citation: Am J Hum Genet. 1987 Sep;41(3):465-83
references.pmid: 3631080
references.citation: Am J Hum Genet. 1986 Jul;39(1):68-78
references.pmid: 3752082
references.citation: Obstet Gynecol. 1994 Aug;84(2):294-7
references.pmid: 8041550
references.citation: Hum Reprod. 1998 Apr;13(4):805-9
references.pmid: 9619528
references.citation: BMC Med Genet. 2009 Sep 14;10:89
references.pmid: 19751515
references.citation: Prenat Diagn. 1997 Dec;17(13):1299-311
references.pmid: 9509547
references.citation: Hum Reprod. 1997 Apr;12 (4):823-6
references.pmid: 9159449
references.citation: Ann Hum Genet. 1988 Jul;52(Pt 3):227-35
references.pmid: 2977936
references.citation: Genet Med. 2011 Jan;13(1):46-51
references.pmid: 21102343
references.citation: Hum Pathol. 1998 May;29(5):505-11
references.pmid: 9596275
references.citation: Hum Genet. 1980;55(1):87-98
references.pmid: 7450760
references.citation: Am J Hum Genet. 1997 Jul;61(1):23-32
references.pmid: 9245981
references.citation: Lancet. 1980 Jan 26;1(8161):167-9
references.pmid: 6101630
references.citation: BMJ. 2000 Jun 24;320(7251):1708-12
references.pmid: 10864550
references.citation: Genet Med. 2011 Jun;13(6):545-52
references.pmid: 21415758
references.citation: J Med Genet. 1987 Dec;24(12):725-32
references.pmid: 2892938
references.citation: Am J Reprod Immunol. 1991 Aug;26(1):23-7
references.pmid: 1741935
references.citation: J Ment Defic Res. 1977 Dec;21(4):299-308
references.pmid: 146744