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
Further Information

Publication History

Publication Date:
08 December 2011 (online)

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.

REFERENCES

  • 1 Goldstein S R. Early detection of pathologic pregnancy by transvaginal sonography.  J Clin Ultrasound. 1990;  18 (4) 262-273
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 9 Levi C S, Lyons E A, Lindsay D J. Early diagnosis of nonviable pregnancy with endovaginal US.  Radiology. 1988;  167 (2) 383-385
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 30 Rushton D I. Simplified classification of spontaneous abortions.  J Med Genet. 1978;  15 (1) 1-9
  • 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
  • 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
  • 33 Redline R W, Abramowsky C R. Clinical and pathologic aspects of recurrent placental villitis.  Hum Pathol. 1985;  16 (7) 727-731
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 45 Pauli R M. Stillbirth: fetal disorders.  Clin Obstet Gynecol. 2010;  53 (3) 646-655
  • 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
  • 47 Simpson J L. Causes of fetal wastage.  Clin Obstet Gynecol. 2007;  50 (1) 10-30
  • 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
  • 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
  • 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
  • 51 Gardner R JM, Sutherland G R eds.. Chromosome Abnormalities and Genetic Counseling. 3rd ed. New York, NY: Oxford University Press; 2004
  • 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
  • 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
  • 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
  • 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
  • 56 Klock S C, Chang G, Hiley A, Hill J. Psychological distress among women with recurrent spontaneous abortion.  Psychosomatics. 1997;  38 (5) 503-507

Ruth B. Lathi, M.D. 

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

300 Pasteur Drive HH333, Stanford, CA 94305

Email: [email protected]