Hysteroscopy pp 151-159 | Cite as

The Role of Hysteroembryoscopy in the Management of Spontaneous and Repeated Pregnancy Loss

  • Vasilios Tanos
  • Demetra Georgiou
  • Marios Neofytou
  • Eleftherios Meridis
  • Minas Paschopoulos


Hystero-embryoscopy (HEpy) can be used for an in situ autopsy of an embryo in spontaneous as well as in repeated pregnancies loss (RPL). Such an autopsy of a miscarriage embryo can provide useful information regarding the morphology of the embryo, ruling out anatomical defects and collecting the embryo under direct vision anticipating an accurate embryo karyotyping. In this prospective study the cause of a spontaneous miscarriage (SM) and RPL was investigated. Many RPL cases that have been diagnosed and treated may experience a consequent miscarriage during next pregnancy. This constituted a major interest in our research. Embryo autopsy was performed by hysteroscopy technique using 2.9–5 mm hysteroscopes, 5Fr graspers and scissors and normal saline as distending medium. The embryo morphology results were correlated with the genetic results and compared with the patients’ diagnosis and treatment during the last miscarriage. Chromosomal abnormalities diagnosed in 70% of both SM and RPL cases while morphological defects observed in 51% and 15.7% respectively. In 10.6% of the SM and 5.9% of the RPL cases HEpy failed to diagnose a clear cause of the miscarriage indicating other etiological factors, probably due to myometrial dysfunction. Embryoscopy seems to be a valuable method for accurate diagnosis of the miscarriage cause during first trimester SM and RPL and can be especially useful for future treatment purposes. Standardization of RPL patients’ clinical characteristics criteria and treatment protocols are imperative to perform studies with reliable results. The combination of 4D sonography, in situ embryo autopsy together with embryo genetic analysis will probably enlighten our knowledge about the cause of SM and RPL.


Hysteroscopy Embryoscopy Hystero-embryoscopy Repeated pregnancies loss Spontaneous miscarriage 


  1. 1.
    Crotti L, Tester DJ, White WM, et al. Long QT syndrome—associated mutations in intrauterine fetal death. JAMA. 2013;309(14). doi: 10.1001/jama.2013.3219.
  2. 2.
    Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod. 2006;21(4):1076–82. doi: 10.1093/humrep/dei417. CrossRefPubMedGoogle Scholar
  3. 3.
    Robberecht C, Pexsters A, Jan D, Fryns JP, D’Hooghe T, Vermeesch JR. Cytogenetic and morphological analysis of early products of conception following hystero-embryoscopy from couples with recurrent pregnancy loss. Prenat Diagn. 2012;32:933–42.CrossRefPubMedGoogle Scholar
  4. 4.
    Carp HJA, Toder V, Orgad S, Aviram A, Danieli M, Mashiach S, Barkai G. Karyotype of the abortus in recurrent miscarriage. Fertil Steril. 2001;75:678–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case–control study. Hum Reprod. 2002;17:446–51.CrossRefPubMedGoogle Scholar
  6. 6.
    Warburton D, Neugut RH, Lustenberger A, Nicholas A, Kline J. No association between spennicide use and trisomy at prenatal diagnosis. New Engl J Med. 1987.Google Scholar
  7. 7.
    Frias AE Jr, Luikenaar RA, Sullivan AE, Lee RM, Porter TF, Branch DW, Silver RM. Poor obstetric outcome in subsequent pregnancies in women with prior fetal death. Obstet Gynecol. 2004;104(3):521–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Canhao P, Falcao F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis. 2003;15:159–66.CrossRefPubMedGoogle Scholar
  9. 9.
    Hill MA. Embryology BGDA lecture—development of the embryo/fetus 1. 2017.
  10. 10.
    Rosenfeld JA, Oppenheim S, DeSalle R. A whole genome gene content phylogenetic analysis of anopheline mosquitoes. Mol Phylogenet Evol. PMID: 27866013. doi:  10.1016/j.ympev.2016.11.006.
  11. 11.
    Qin J-Z, Pang L-H, Li M-Q, Xu J, Zhou X (2013) Risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology: a meta-analysis. PLoS ONE8(10): e75953.
  12. 12.
    Simpson JL, Bombard AT. Chromosomal abnormalities in spontaneous abortion: frequency, pathology and genetic counseling. In: KBMJ E, editor. Spontaneous abortion. London: Blackwell; 1987. p. 51–76.Google Scholar
  13. 13.
    Goddijn M, Leschot NJ. Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14:855–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Hassold TJ. A cytogenetic study of repeated spontaneous abortions. Am J Hum Genet. 1980;32(5):723–30.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Benadiva CA, Kligman I, Munne S. Aneuploidy 16 in human embryos increases significantly with maternal age. Fertil Steril. 1996;66:248–55.CrossRefPubMedGoogle Scholar
  16. 16.
    Angell RR Aneuploidy in older women. Higher rates of aneuploidy in oocytes from older women. Hum Reprod 1994; 9: 1199–2000.Google Scholar
  17. 17.
    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280–91.CrossRefPubMedGoogle Scholar
  18. 18.
    Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril. 1995;64:382–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Nasseri A, Mukherjee T, Grifo JA, Noyes N, Krey L, et al. Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy. Fertil Steril. 1999;71:715–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Farr SL, Schieve LA, Jamieson DJ. Pregnancy loss among pregnancies conceived through assisted reproductive technology. Am J Epidemiol. 2007;165:1380–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Nicolaides P, Petersen M. Origin and mechanisms of non-disjunction in human autosomal trisomies. Hum Reprod. 1998;13:313–9.CrossRefGoogle Scholar
  22. 22.
    Kim JW, Lee WS, Yoon TK, Seok HH, Cho JH, et al. Chromosomal abnormalities in spontaneous abortion after assisted reproductive treatment. BMC Med Genet. 2010;11:153.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wang Y, Cheng Q, Meng L, Luo C, Hu H, Zhang J, Cheng J, Xu T, Jiang T, Liang D, Hu P, Xu Z. Clinical application of SNP array analysis in first-trimester pregnancy loss: a prospective study. Clin Genet. 2016.Google Scholar
  24. 24.
    Angiolucci M, Murru R, Melis G, et al. Association between different morphological types and abnormal karyotypes in early pregnancy loss. Ultrasound Obstet Gynecol. 2011;37:219–25.CrossRefPubMedGoogle Scholar
  25. 25.
    European Stroke Initiative Executive Committee; EUSI Writing Committee, Olsen TS, Langhorne P, Diener HC, Hennerici M, Ferro J, Sivenius J, Wahlgren NG, Bath P. European Stroke Initiative recommendations for stroke management-update 2003. Cerebrovasc Dis. 2003;16(4):311–37.CrossRefGoogle Scholar
  26. 26.
    Branch DW, Gibson M, Silver RM. Clinical practice. Recurrent miscarriage. N Engl J Med. 2010;363(18):1740–7. doi: 10.1056/NEJMcp1005330.CrossRefPubMedGoogle Scholar
  27. 27.
    Meza-Espinoza JP, Anguiano LO, Rivera H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest. 2008;66(4):237–40. Epub 2008 Jul 22.CrossRefPubMedGoogle Scholar
  28. 28.
    Laurino MY, et al. Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2005;14(3):165–81.CrossRefPubMedGoogle Scholar
  29. 29.
    Philipp T, Philipp K, Reiner A, Beer F, Kalousek DK. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum Reprod. 2003;18:1724–32.CrossRefPubMedGoogle Scholar
  30. 30.
    Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. 2000;73:300–4. doi: 10.1016/S0015-0282(99)00495-1.CrossRefPubMedGoogle Scholar
  31. 31.
    Franssen MTM, et al. Selective chromosome analysis in couples with two or more miscarriages: case-control study. BMJ. 2005;331: 137–41. PMC: Web 10 Feb 2017.Google Scholar
  32. 32.
    Kavalier F. Investigation of recurrent miscarriages. BMJ. 2005;331(7509):121–2.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Yoshino O, Nishii O, Osuga Y, Asada H, Okuda S, Orisaka M, Hayashi T. Myomectomy decreases abnormal uterine peristalsis and increases pregnancy rate. J Minim Invasive Gynecol. 2012;19(1):63–7. doi: 10.1016/j.jmig.2011.09.010.CrossRefPubMedGoogle Scholar
  34. 34.
    Toth B, Würfel W, Bohlmann MK, Gillessen-Kaesbach G, Nawroth F, Rogenhofer N, Tempfer C, Wischmann T, von Wolff M. Recurrent miscarriage: diagnostic and therapeutic procedures. Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), German Society of Gynecology and Obstetrics, guideline of the DGGG (S1-Level, AWMF Registry No. 015/050, December 2013).Google Scholar
  35. 35.
    Kristiina R, Liina N, Maris L. Genetics of recurrent miscarriage: challenges, current knowledge, future directions. Front Genet. 2012;3. doi:  10.3389/fgene.2012.00034, ISSN: 1664-8021.
  36. 36.
    Daher S, Mattar R, Gueuvoghlanian-Silva BY, Torloni MR. Genetic polymorphisms and recurrent spontaneous abortions: an overview of current knowledge. Am J Reprod Immunol. 2012;67:341–7. doi: 10.1111/j.1600-0897.2012.01123.x.CrossRefPubMedGoogle Scholar
  37. 37.
    Kaare M. Genetic studies on recurrent miscarriage. Doctoral dissertation (article-based), University of Helsinki, Faculty of Medicine, Haartman Institute Folkhälsan Institute of Genetics. 2009.

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Vasilios Tanos
    • 1
  • Demetra Georgiou
    • 2
  • Marios Neofytou
    • 3
  • Eleftherios Meridis
    • 4
  • Minas Paschopoulos
    • 5
  1. 1.St. George’s Medical School, Nicosia University and Aretaeio HospitalNicosiaCyprus
  2. 2.Department of CytogeneticsMak III. HospitalNicosiaCyprus
  3. 3.eHealth Laboratory, Computer Science DepartmentUniversity of CyprusNicosiaCyprus
  4. 4.Emvryomed GlyfadaAthensGreece
  5. 5.Obstetrics and Gynaecology, Medical School, Ioannina UniversityIoanninaGreece

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