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Semin Reprod Med 2011; 29(6): 463-469
DOI: 10.1055/s-0031-1293200
© Thieme Medical Publishers

First Trimester Miscarriage Evaluation

Ruth B. Lathi1 , Florette K. Gray Hazard2 , Amy Heerema-McKenney2 , Joanne Taylor4 , Jane Tsung Chueh3
  • 1Department of Obstetrics and Gynecology, Recurrent Pregnancy Loss Program, Stanford University, Stanford, California
  • 2Department of Pathology, Stanford University, Stanford, California
  • 3Department of Obstetrics & Gynecology, Maternal & Fetal Medicine, Stanford University, Stanford, California
  • 4Department of Perinatal Genetic Counseling, Lucile Packard Children's Hospital at Stanford, Stanford, California
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Publication History

Publication Date:
08 December 2011 (online)

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ABSTRACT

Miscarriage is a relatively common occurrence for otherwise healthy women. Despite its frequency, evaluation for cause is rare. The most common cause of miscarriage is sporadic chromosome errors. Chromosomal analysis of the miscarriage offers an explanation in at least 50% of cases. Conventional cytogenetic evaluation can only be done on fresh tissue, so it is critical that the treating physician consider genetic testing at the time of the miscarriage. Ultrasound can estimate the gestational age at the time of miscarriage and identify major abnormalities in some embryos. A careful pathological examination can add to the evaluation by ruling out rare disorders with the highest recurrence risk. A multidisciplinary approach to miscarriage evaluation is essential to understanding the cause and risk of recurrence. A thorough evaluation of a miscarriage, in combination with emotional support, can often provide the necessary reassurance and confidence as the patient prepares for her next pregnancy.

KEYWORDS

Miscarriage - ultrasound - aneuploidy - pathology - pregnancy loss

REFERENCES

  • 1 Goldstein S R. Early detection of pathologic pregnancy by transvaginal sonography.  J Clin Ultrasound. 1990;  18 (4) 262-273
    Google Scholar
  • 2 Sauerbrei E, Cooperberg P L, Poland B J. Ultrasound demonstration of the normal fetal yolk sac.  J Clin Ultrasound. 1980;  8 (3) 217-220
    Google Scholar
  • 3 Timor-Tritsch I E, Farine D, Rosen M G. A close look at early embryonic development with the high-frequency transvaginal transducer.  Am J Obstet Gynecol. 1988;  159 (3) 676-681
    Google Scholar
  • 4 Bradley W G, Fiske C E, Filly R A. The double sac sign of early intrauterine pregnancy: use in exclusion of ectopic pregnancy.  Radiology. 1982;  143 (1) 223-226
    Google Scholar
  • 5 Nyberg D A, Laing F C, Filly R A, Uri-Simmons M, Jeffrey Jr R B. Ultrasonographic differentiation of the gestational sac of early intrauterine pregnancy from the pseudogestational sac of ectopic pregnancy.  Radiology. 1983;  146 (3) 755-759
    Google Scholar
  • 6 Stiller R J, Haynes de Regt R, Blair E. Transvaginal ultrasonography in patients at risk for ectopic pregnancy.  Am J Obstet Gynecol. 1989;  161 (4) 930-933
    Google Scholar
  • 7 Kadar N, Bohrer M, Kemmann E, Shelden R. The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study.  Fertil Steril. 1994;  61 (6) 1016-1020
    Google Scholar
  • 8 Romero R, Kadar N, Jeanty P et al.. Diagnosis of ectopic pregnancy: value of the discriminatory human chorionic gonadotropin zone.  Obstet Gynecol. 1985;  66 (3) 357-360
    Google Scholar
  • 9 Levi C S, Lyons E A, Lindsay D J. Early diagnosis of nonviable pregnancy with endovaginal US.  Radiology. 1988;  167 (2) 383-385
    Google Scholar
  • 10 Brown D L, Emerson D S, Felker R E, Cartier M S, Smith W C. Diagnosis of early embryonic demise by endovaginal sonography.  J Ultrasound Med. 1990;  9 (11) 631-636
    Google Scholar
  • 11 Rowling S E, Coleman B G, Langer J E, Arger P H, Nisenbaum H L, Horii S C. First-trimester US parameters of failed pregnancy.  Radiology. 1997;  203 (1) 211-217
    Google Scholar
  • 12 Achiron R, Tadmor O, Mashiach S. Heart rate as a predictor of first-trimester spontaneous abortion after ultrasound-proven viability.  Obstet Gynecol. 1991;  78 (3 Pt 1) 330-334
    Google Scholar
  • 13 Laboda L A, Estroff J A, Benacerraf B R. First trimester bradycardia. A sign of impending fetal loss.  J Ultrasound Med. 1989;  8 (10) 561-563
    Google Scholar
  • 14 Howe R S, Isaacson K J, Albert J L, Coutifaris C B. Embryonic heart rate in human pregnancy.  J Ultrasound Med. 1991;  10 (7) 367-371
    Google Scholar
  • 15 Falco P, Milano V, Pilu G et al.. Sonography of pregnancies with first-trimester bleeding and a viable embryo: a study of prognostic indicators by logistic regression analysis.  Ultrasound Obstet Gynecol. 1996;  7 (3) 165-169
    Google Scholar
  • 16 Doubilet P M, Benson C B. Outcome of first-trimester pregnancies with slow embryonic heart rate at 6-7 weeks gestation and normal heart rate by 8 weeks at US.  Radiology. 2005;  236 (2) 643-646
    Google Scholar
  • 17 Bromley B, Harlow B L, Laboda L A, Benacerraf B R. Small sac size in the first trimester: a predictor of poor fetal outcome.  Radiology. 1991;  178 (2) 375-377
    Google Scholar
  • 18 Pedersen J F, Mantoni M. Prevalence and significance of subchorionic hemorrhage in threatened abortion: a sonographic study.  AJR Am J Roentgenol. 1990;  154 (3) 535-537
    Google Scholar
  • 19 Bennett G L, Bromley B, Lieberman E, Benacerraf B R. Subchorionic hemorrhage in first-trimester pregnancies: prediction of pregnancy outcome with sonography.  Radiology. 1996;  200 (3) 803-806
    Google Scholar
  • 20 Odeh M, Tendler R, Kais M, Grinin V, Ophir E, Bornstein J. Gestational sac volume in missed abortion and anembryonic pregnancy compared to normal pregnancy.  J Clin Ultrasound. 2010;  38 (7) 367-371
    Google Scholar
  • 21 Ball E, Robson S C, Ayis S, Lyall F, Bulmer J N. Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion.  J Pathol. 2006;  208 (4) 528-534
    Google Scholar
  • 22 Novak R W, Malone J M, Robinson H B. The role of the pathologist in the evaluation of first trimester abortions.  Pathol Annu. 1990;  25 (Pt 1) 297-311
    Google Scholar
  • 23 Jindal P, Regan L, Fourkala E O et al.. Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.  Hum Reprod. 2007;  22 (2) 313-316
    Google Scholar
  • 24 Boyd T K, Redline R W. Chronic histiocytic intervillositis: a placental lesion associated with recurrent reproductive loss.  Hum Pathol. 2000;  31 (11) 1389-1396
    Google Scholar
  • 25 Marchaudon V, Devisme L, Petit S, Ansart-Franquet H, Vaast P, Subtil D. Chronic histiocytic intervillositis of unknown etiology: clinical features in a consecutive series of 69 cases.  Placenta. 2011;  32 (2) 140-145
    Google Scholar
  • 26 Boyd T K, Redline R W. Chronic histiocytic intervillositis: a placental lesion associated with recurrent reproductive loss.  Hum Pathol. 2000;  31 (11) 1389-1396
    Google Scholar
  • 27 Katzman P J, Genest D R. Maternal floor infarction and massive perivillous fibrin deposition: histological definitions, association with intrauterine fetal growth restriction, and risk of recurrence.  Pediatr Dev Pathol. 2002;  5 (2) 159-164
    Google Scholar
  • 28 Sebire N J, Backos M, El Gaddal S, Goldin R D, Regan L. Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients.  Obstet Gynecol. 2003;  101 (2) 258-263
    Google Scholar
  • 29 Redline R W, Zaragoza M, Hassold T. Prevalence of developmental and inflammatory lesions in nonmolar first-trimester spontaneous abortions.  Hum Pathol. 1999;  30 (1) 93-100
    Google Scholar
  • 30 Rushton D I. Simplified classification of spontaneous abortions.  J Med Genet. 1978;  15 (1) 1-9
    Google Scholar
  • 31 Waters B L, Ashikaga T. Significance of perivillous fibrin/oid deposition in uterine evacuation specimens.  Am J Surg Pathol. 2006;  30 (6) 760-765
    Google Scholar
  • 32 Oyer C E, Cai R, Coughlin J J, Singer D B. First trimester pregnancy loss associated with varicella zoster virus infection: histological definition of a case.  Hum Pathol. 1998;  29 (1) 94-95
    Google Scholar
  • 33 Redline R W, Abramowsky C R. Clinical and pathologic aspects of recurrent placental villitis.  Hum Pathol. 1985;  16 (7) 727-731
    Google Scholar
  • 34 Russell P, Atkinson K, Krishnan L. Recurrent reproductive failure due to severe placental villitis of unknown etiology.  J Reprod Med. 1980;  24 (2) 93-98
    Google Scholar
  • 35 Edmondson N, Bocking A, Machin G, Rizek R, Watson C, Keating S. The prevalence of chronic deciduitis in cases of preterm labor without clinical chorioamnionitis.  Pediatr Dev Pathol. 2009;  12 (1) 16-21
    Google Scholar
  • 36 Novak R, Agamanolis D, Dasu S et al.. Histologic analysis of placental tissue in first trimester abortions.  Pediatr Pathol. 1988;  8 (5) 477-482
    Google Scholar
  • 37 Bayraktar M R, Ozerol I H, Gucluer N, Celik O. Prevalence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in pregnant women.  Int J Infect Dis. 2010;  14 (2) e90-e95
    Google Scholar
  • 38 Check J H. A practical approach to the prevention of miscarriage: Part 3—Passive immunotherapy.  Clin Exp Obstet Gynecol. 2010;  37 (2) 81-83
    Google Scholar
  • 39 Ville Y, Khalil A, Homphray T, Moscoso G. Diagnostic embryoscopy and fetoscopy in the first trimester of pregnancy.  Prenat Diagn. 1997;  17 (13) 1237-1246
    Google Scholar
  • 40 Philipp T, Kalousek D K. Generalized abnormal embryonic development in missed abortion: embryoscopic and cytogenetic findings.  Am J Med Genet. 2002;  111 (1) 43-47
    Google Scholar
  • 41 Philipp T, Feichtinger W, Van Allen M I, Separovic E, Reiner A, Kalousek D K. Abnormal embryonic development diagnosed embryoscopically in early intrauterine deaths after in vitro fertilization: a preliminary report of 23 cases.  Fertil Steril. 2004;  82 (5) 1337-1342
    Google Scholar
  • 42 Philipp T, Philipp K, Reiner A, Beer F, Kalousek D K. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies.  Hum Reprod. 2003;  18 (8) 1724-1732
    Google Scholar
  • 43 Philipp T, Kalousek D K. Morphology of the 45,X embryo: an embryoscopic study.  Am J Med Genet A. 2003;  120A (3) 314-319
    Google Scholar
  • 44 Philipp T, Grillenberger K, Separovic E R, Philipp K, Kalousek D K. Effects of triploidy on early human development.  Prenat Diagn. 2004;  24 (4) 276-281
    Google Scholar
  • 45 Pauli R M. Stillbirth: fetal disorders.  Clin Obstet Gynecol. 2010;  53 (3) 646-655
    Google Scholar
  • 46 Hogge W A, Byrnes A L, Lanasa M C, Surti U. The clinical use of karyotyping spontaneous abortions.  Am J Obstet Gynecol. 2003;  189 (2) 397-400, discussion 400–402
    Google Scholar
  • 47 Simpson J L. Causes of fetal wastage.  Clin Obstet Gynecol. 2007;  50 (1) 10-30
    Google Scholar
  • 48 Bell K A, Van Deerlin P G, Haddad B R, Feinberg R F. Cytogenetic diagnosis of “normal 46,XX” karyotypes in spontaneous abortions frequently may be misleading.  Fertil Steril. 1999;  71 (2) 334-341
    Google Scholar
  • 49 Lomax B, Tang S, Separovic E et al.. Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions.  Am J Hum Genet. 2000;  66 (5) 1516-1521
    Google Scholar
  • 50 Peng H H, Chao A S, Wang T H, Chang Y L, Chang S D. Prenatally diagnosed balanced chromosome rearrangements: eight years' experience.  J Reprod Med. 2006;  51 (9) 699-703
    Google Scholar
  • 51 Gardner R JM, Sutherland G R eds.. Chromosome Abnormalities and Genetic Counseling. 3rd ed. New York, NY: Oxford University Press; 2004
    Google Scholar
  • 52 Sugiura-Ogasawara M, Aoki K, Fujii T et al.. Subsequent pregnancy outcomes in recurrent miscarriage patients with a paternal or maternal carrier of a structural chromosome rearrangement.  J Hum Genet. 2008;  53 (7) 622-628
    Google Scholar
  • 53 Franssen M T, Korevaar J C, Leschot N J et al.. Selective chromosome analysis in couples with two or more miscarriages: case-control study.  BMJ. 2005;  331 (7509) 137-141
    Google Scholar
  • 54 Tharapel A T, Tharapel S A, Bannerman R M. Recurrent pregnancy losses and parental chromosome abnormalities: a review.  Br J Obstet Gynaecol. 1985;  92 (9) 899-914
    Google Scholar
  • 55 Stephenson M D, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement.  Hum Reprod. 2006;  21 (4) 1076-1082
    Google Scholar
  • 56 Klock S C, Chang G, Hiley A, Hill J. Psychological distress among women with recurrent spontaneous abortion.  Psychosomatics. 1997;  38 (5) 503-507
    Google Scholar

Ruth B. LathiM.D. 

Department of Obstetrics and Gynecology, Recurrent Pregnancy Loss Program, Stanford University

300 Pasteur Drive HH333, Stanford, CA 94305

Email: rlathi@stanford.edu