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Journal of Assisted Reproduction and Genetics logoLink to Journal of Assisted Reproduction and Genetics
. 1999 May;16(5):253–258. doi: 10.1023/A:1020315529090

Implications of Sperm Chromosome Abnormalities in Recurrent Miscarriage

Carmen Rubio 1, Carlos Simón 1,2, Joan Blanco 3, Francesca Vidal 3, Yolanda Mínguez 1, José Egozcue 3, Juana Crespo 1, José Remohí 1,2, Antonio Pellicer 1,2,
PMCID: PMC3455708  PMID: 10335472

Abstract

Purpose:Our purpose was to assess the existence of sperm chromosome abnormalities in recurrent pregnancy loss in an assisted reproduction program.

Methods:In this prospective study, 12 sperm samples from couples undergoing in vitro fertilization with two or more first-trimester spontaneous abortions were analyzed. Diploidy and disomy in decondensed sperm nuclei were assessed for chromosomes 13, 18, 21, X, and Y using two- and three-color fluorescence in situ hybridization.

Results:Sex chromosome disomy in sperm samples from recurrent abortion couples was significantly increased compared to that from internal controls (0.84% vs 0.37%). In a subpopulation of seven couples who underwent oocyte donation, mean frequencies for sex chromosome disomy (1%) were even higher and diploidy (0.43%) was also significantly increased.

Conclusions:These results suggest an implication of sperm chromosome abnormalities in some cases of recurrent pregnancy loss.

Keywords: unexplained recurrent miscarriage, chromosome abnormalities, sperm, nuclei, fluorescence in situ hybridization

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REFERENCES

  • 1.Stirrat GM. Recurrent miscarriage I: Definition and epidemiology. Lancet. 1990;336:673–675. doi: 10.1016/0140-6736(90)92159-f. [DOI] [PubMed] [Google Scholar]
  • 2.Tulppala M, Palosuo T, Ramsay T, Miettinen A, Salonen R, Ylikorkala O. A prospective study of 63 couples with a story of recurrent spontaneous abortion: Contributing factors and outcome of subsequent pregnancies. Hum Reprod. 1993;8:764–770. doi: 10.1093/oxfordjournals.humrep.a138137. [DOI] [PubMed] [Google Scholar]
  • 3.Berry CW, Brambati B, Eskes TKAB, Exalto N, Fox H, Geraedts JP, Gerhard I, Gonzales Gomes F, Grudzinskas JG, Hustin J. The Euro-Team Early Pregnancy (ETEP)* protocol for recurrent miscarriage. Hum Reprod. 1995;10:1516–1520. doi: 10.1093/humrep/10.6.1516. [DOI] [PubMed] [Google Scholar]
  • 4.Boué J, Boué A, Lazar P. Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions. Teratology. 1975;12:11. doi: 10.1002/tera.1420120103. [DOI] [PubMed] [Google Scholar]
  • 5.Hassold TJ, Matsuyama A, Newlands IM, Matsuura JS, Jacobs PA, Manuel B, Tsuei J. A cytogenetic study of spontaneous abortions in Hawaii. Ann Hum Genet. 1978;41:443–454. doi: 10.1111/j.1469-1809.1978.tb00914.x. [DOI] [PubMed] [Google Scholar]
  • 6.Gerneri S, Betio D, Simoni G, et al. Prevalence and distribution of chromosome abnormalities in a sample of first trimester internal abortions. Hum Reprod. 1987;2:735–739. doi: 10.1093/oxfordjournals.humrep.a136623. [DOI] [PubMed] [Google Scholar]
  • 7.Eiben B, Bartels I, Bahr-Porch S, Borgmann S, Gatz G, Gellert G, Goebel R, Hammans W, Hentemann M, Osmers R, et al. Cytogenetic analysis of 750 spontaneous abortions with the direct preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. Am J Hum Genet. 1990;47:656–663. [PMC free article] [PubMed] [Google Scholar]
  • 8.Strom CM, Ginsberg N, Applebaum M, Bozorgi N, White M, Caffarelli M, Verlinsky Y. Analysis of 95 first-trimester spontaneous abortions by chorionic villus sampling and karyotype. J Assist Reprod Genet. 1992;9:458–461. doi: 10.1007/BF01204052. [DOI] [PubMed] [Google Scholar]
  • 9.Strobino B, Fox HE, Kline J, Stein Z, Susser M, Warburton D. Characteristics of women with recurrent spontaneous abortion and women with favourable reproductive histories. Am J Publ Health. 1986;76:986–991. doi: 10.2105/ajph.76.8.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.De Braekeleer M, Dao TN. Cytogenetic studies in couples experiencing repeated pregnancy losses. Hum Reprod. 1990;5:519–528. doi: 10.1093/oxfordjournals.humrep.a137135. [DOI] [PubMed] [Google Scholar]
  • 11.Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of recurrent miscarriage: Preliminary experience of 500 consecutive cases. Hum Reprod. 1994;9:1328–1332. doi: 10.1093/oxfordjournals.humrep.a138703. [DOI] [PubMed] [Google Scholar]
  • 12.Delhanty JDA, Handyside AH. The origin of genetic defects in the human and their detection in preimplantation embryo. Hum Reprod Update. 1995;1:201–215. doi: 10.1093/humupd/1.3.201. [DOI] [PubMed] [Google Scholar]
  • 13.Zenzes MT, Casper RF. Cytogenetics of human oocytes, zygotes, and embryos after in vitro fertilization. Hum Genet. 1992;88:367–375. doi: 10.1007/BF00215667. [DOI] [PubMed] [Google Scholar]
  • 14.Cowchock FS, Gibas ZG, Jackson LG. Chromosome errors as a cause of spontaneous abortion: The relative importance of maternal age and obstetric history. Fertil Steril. 1993;59:1011–1014. doi: 10.1016/s0015-0282(16)55920-2. [DOI] [PubMed] [Google Scholar]
  • 15.Munné S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril. 1995;64:382–391. [PubMed] [Google Scholar]
  • 16.Egozcue J, Templado C, Vidal F, Navarro J, Morer-Fargas F, Marina S. Meiotic studies in a series of 1100 infertile and sterile men. Hum Genet. 1983;65:185–187. doi: 10.1007/BF00286660. [DOI] [PubMed] [Google Scholar]
  • 17.Speed RM, Chandley AC. Prophase of meiosis in human spermatocytes analysed by EM microspreading in infertile men and their controls and comparisons with human oocytes. Hum Genet. 1990;84:547–554. doi: 10.1007/BF00210808. [DOI] [PubMed] [Google Scholar]
  • 18.Blanco J, Egozcue J, Vidal F. Incidence of chromosome 21 disomy in human spermatozoa as determined by fluorescent in-situ hybridization. Hum Reprod. 1996;4:722–726. doi: 10.1093/oxfordjournals.humrep.a019241. [DOI] [PubMed] [Google Scholar]
  • 19.Blanco J, Rubio C, Simón S, Egozcue J, Vidal F. Increased incidence of disomic sperm nuclei in a 47,XYY male assessed by fluorescent in situ hybridization (FISH) Hum Genet. 1997;99:413–416. doi: 10.1007/s004390050381. [DOI] [PubMed] [Google Scholar]
  • 20.Simón C, Gutierrez A, Vidal A, de los Santos MJ, Tarin JJ, Remohi J, Pellicer A. Outcome of patients with endometriosis in assisted reproduction: Results from in vitro fertilization and oocyte donation. Hum Reprod. 1994;9:725–729. doi: 10.1093/oxfordjournals.humrep.a138578. [DOI] [PubMed] [Google Scholar]
  • 21.Remohí J, Gallardo E, Levy M, Valbuena D, de los Santos MJ, Simon C, Pellicer A. Oocyte donation in women with recurrent pregnancy loss. Hum Reprod. 1996;11:2048–2051. doi: 10.1093/oxfordjournals.humrep.a019541. [DOI] [PubMed] [Google Scholar]
  • 22.Vidal F, Moragas M, Catalá V, Torello MJ, Santalo J, Calderon G, Gimenez C, Barri PN, Egozcue J, Veiga A. Sephadex filtration and human serum albumin gradients do not select spermatozoa by sex chromosome: A fluorescent in situ hybridization study. Hum Reprod. 1993;8:1740–1743. doi: 10.1093/oxfordjournals.humrep.a137926. [DOI] [PubMed] [Google Scholar]
  • 23.Byrd JR, Asked DE, McDonough PG. Cytogenetic findings in fifty-five couples with recurrent fetal wastage. Fertil Steril. 1977;28:246–250. doi: 10.1016/s0015-0282(16)42433-7. [DOI] [PubMed] [Google Scholar]
  • 24.Sbracia M, Cozza G, Grasso JA, Mastrone M, Scarpellini F. Semen parameters and sperm morphology in men in unexplained recurrent spontaneous abortion, before and during a 3 year follow-up period. Hum Reprod. 1996;11:117–120. doi: 10.1093/oxfordjournals.humrep.a019002. [DOI] [PubMed] [Google Scholar]
  • 25.Egozcue J, Blanco J, Vidal F. Chromosome studies in human sperm nuclei using fluorescence in-situ hybridization (FISH) Hum Reprod. 1997;3:441–452. doi: 10.1093/humupd/3.5.441. [DOI] [PubMed] [Google Scholar]
  • 26.Spriggs EL, Rademaker AW, Martin RH. Aneuploidy in human sperm: The use of multicolor FISH to test various theories of nondisjunction. Am J Hum Genet. 1996;58:356–362. [PMC free article] [PubMed] [Google Scholar]
  • 27.Williams BJ, Ballenger CA, Malter H, Bishop F, Tucker M, Zwingman TA, Hassold TJ. Non-disjunction in human sperm: Results of fluorescence in situ hybridizaton studies using two and three probes. Hum Mol Genet. 1996;2:1929–1936. doi: 10.1093/hmg/2.11.1929. [DOI] [PubMed] [Google Scholar]
  • 28.Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S. Predictive value of abnormal sperm morphology in “in vitro” fertilization. Fertil Steril. 1988;49:112–117. doi: 10.1016/s0015-0282(16)59660-5. [DOI] [PubMed] [Google Scholar]
  • 29.Kiefer D, Check JH, Katsoff D. Evidence that oligoasthenozoospermia may be an etiologic factor for spontaneous abortion after in vitro fertilization-embryo transfer. Fertil Steril. 1997;68:545–548. doi: 10.1016/s0015-0282(97)00235-5. [DOI] [PubMed] [Google Scholar]
  • 30.Pang MG, Zackowsky JL, Hoegerman SF, Moon SY, Cuticchia AJ, Acosta AA, Kearns WG. Detection by fluorescence in situ hybridization of chromosome 7, 11, 12, 18, X and Y abnormalities from oligoasthenoteratozoospermic patients of an vitro fertilization program. J Assist Reprod Genet. 1995;12(Suppl):53S. [Google Scholar]
  • 31.In't Velt P, Broekmans F, de France H, Pearson PL, Pieters MH, van Kooij RJ. Intracytoplasmic sperm injection (ICSI) and chromosomally abnormal spermatozoa. Hum Reprod. 1997;12:752–754. doi: 10.1093/humrep/12.4.752. [DOI] [PubMed] [Google Scholar]
  • 32.Vidal F, Giménez C, Rubio C, Simon C, Pellicer A, Santalo J, Egozcue J. FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy wastage. J Assist Reprod Genet. 1998;15:309–312. doi: 10.1023/A:1022552713015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Simón C, Rubio C, Vidal F, Gimenez C, Moreno C, Parrilla JJ, Pellicer A. Increased chromosome abnormalities in human preimplantation embryos after in-vitro fertilization in patients with recurrent miscarriage. Reprod Fertil Dev. 1998;10:1–6. doi: 10.1071/r98030. [DOI] [PubMed] [Google Scholar]

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