Download PDF
Semin Reprod Med 2015; 33(03): 161-168
DOI: 10.1055/s-0035-1552586
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Novel Strategies for the Management of Recurrent Pregnancy Loss

William H. Kutteh
1   Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
2   St. Jude Children's Hospital, Memphis, Tennessee
› Author Affiliations
Further Information

Publication History

Publication Date:
02 June 2015 (online)

   Permissions and Reprints

Abstract

This article discusses the current trends in the diagnosis and treatment of recurrent pregnancy loss. Genetic testing of the miscarriage tissue by 23-chromosome microarray and the ability to identify maternal cell contamination have increased our awareness of the role of aneuploidy as a cause of recurrent pregnancy loss. This increasing influence and the role of genetic testing in developing a strategy for the evaluation of recurrent pregnancy loss are described and discussed. The most common questions that practicing physicians ask about recurrent pregnancy loss include how many losses are needed to make the diagnosis, what counts as a pregnancy loss, what constitutes a full workup, should we get karyotypes on the parents and the miscarriage, and what is the prognosis for a live birth? This review attempts to answer those questions based on current research and clinical experience to expand our current understanding of recurrent pregnancy loss.

Keywords

recurrent pregnancy loss - antiphospholipid antibodies - uterine anomalies - recurrent miscarriage
 

  • References

  • 1 Kutteh WH, Pasquarette MM. Recurrent pregnancy loss. Adv Obstet Gynecol 1995; 2: 147-177
    PubMedGoogle Scholar
  • 2 Saravelos SH, Regan L. Unexplained recurrent pregnancy loss. Obstet Gynecol Clin North Am 2014; 41 (1) 157-166
    CrossrefPubMedGoogle Scholar
  • 3 Hassold T, Chen N, Funkhouser J , et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet 1980; 44 (Pt 2) 151-178
    CrossrefPubMedGoogle Scholar
  • 4 Pellestor F, Andréo B, Arnal F, Humeau C, Demaille J. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes. Hum Genet 2003; 112 (2) 195-203
    PubMedGoogle Scholar
  • 5 American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). Int J Gynaecol Obstet 2002; 78 (2) 179-190
    CrossrefPubMedGoogle Scholar
  • 6 Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 2012; 98 (5) 1103-1111
    CrossrefPubMedGoogle Scholar
  • 7 National Collaborating Centre for Women's and Children's Health (UK). Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. London: Royal College of Obstetrics and Gynecology; 2012 December (NICE Clinical Guidelines, No. 154)
    PubMedGoogle Scholar
  • 8 Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril 2010; 93 (4) 1234-1243
    CrossrefPubMedGoogle Scholar
  • 9 Christiansen OB. Evidence-based investigations and treatments of recurrent pregnancy loss. Curr Opin Obstet Gynecol 2006; 18 (3) 304-312
    CrossrefPubMedGoogle Scholar
  • 10 Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2006; 21 (9) 2216-2222
    CrossrefPubMedGoogle Scholar
  • 11 Silver RM, Branch DW, Goldenberg R, Iams JD, Klebanoff MA. Nomenclature for pregnancy outcomes: time for a change. Obstet Gynecol 2011; 118 (6) 1402-1408
    CrossrefPubMedGoogle Scholar
  • 12 Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC. Williams Obstetrics. 19th ed. Norwalk, CT: Appleton and Lange; 1993: 661-690
    Google Scholar
  • 13 Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol 2004; 104 (1) 50-55
    CrossrefPubMedGoogle Scholar
  • 14 American College of Obstetricians and Gynecologists Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 118: antiphospholipid syndrome. Obstet Gynecol 2011; 117 (1) 192-199
    CrossrefPubMedGoogle Scholar
  • 15 American College of Obstetricians and Gynecologists Women's Health Care Physicians. ACOG Practice Bulletin No. 138. Inherited thrombophilias in pregnancy. Obstet Gynecol 2013; 122 (3) 706-717
    CrossrefPubMedGoogle Scholar
  • 16 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) 1076-1082
    PubMedGoogle Scholar
  • 17 Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 2004; 81 (2) 367-373
    CrossrefPubMedGoogle Scholar
  • 18 Carp H, Guetta E, Dorf H, Soriano D, Barkai G, Schiff E. Embryonic karyotype in recurrent miscarriage with parental karyotypic aberrations. Fertil Steril 2006; 85 (2) 446-450
    CrossrefPubMedGoogle Scholar
  • 19 Neri G, Serra A, Campana M, Tedeschi B. Reproductive risks for translocation carriers: cytogenetic study and analysis of pregnancy outcome in 58 families. Am J Med Genet 1983; 16 (4) 535-561
    CrossrefPubMedGoogle Scholar
  • 20 Engels H, Eggermann T, Caliebe A , et al. Genetic counseling in Robertsonian translocations der(13;14): frequencies of reproductive outcomes and infertility in 101 pedigrees. Am J Med Genet A 2008; 146A (20) 2611-2616
    CrossrefPubMedGoogle Scholar
  • 21 Brigham SA, Conlon C, Farquharson RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod 1999; 14 (11) 2868-2871
    CrossrefPubMedGoogle Scholar
  • 22 Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril 2000; 73 (2) 300-304
    CrossrefPubMedGoogle Scholar
  • 23 Carp H, Toder V, Aviram A, Daniely M, Mashiach S, Barkai G. Karyotype of the abortus in recurrent miscarriage. Fertil Steril 2001; 75 (4) 678-682
    CrossrefPubMedGoogle Scholar
  • 24 Hassold TJ. A cytogenetic study of repeated spontaneous abortions. Am J Hum Genet 1980; 32 (5) 723-730
    PubMedGoogle Scholar
  • 25 Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17 (2) 446-451
    CrossrefPubMedGoogle Scholar
  • 26 Kearns WG, Pen R, Graham J , et al. Preimplantation genetic diagnosis and screening. Semin Reprod Med 2005; 23 (4) 336-347
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Tobler KJ, Brezina PR, Benner AT, Du L, Xu X, Kearns WG. Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. J Assist Reprod Genet 2014; 31 (7) 843-850
    CrossrefPubMedGoogle Scholar
  • 28 Li G, Jin H, Xin Z , et al. Increased IVF pregnancy rates after microarray preimplantation genetic diagnosis due to parental translocations. Syst Biol Reprod Med 2014; 60 (2) 119-124
    CrossrefPubMedGoogle Scholar
  • 29 Brezina PR, Kutteh WH. Classic and cutting-edge strategies for the management of early pregnancy loss. Obstet Gynecol Clin North Am 2014; 41 (1) 1-18
    CrossrefPubMedGoogle Scholar
  • 30 Jaslow CR, Kutteh WH. Effect of prior birth and miscarriage frequency on the prevalence of acquired and congenital uterine anomalies in women with recurrent miscarriage: a cross-sectional study. Fertil Steril 2013; 99 (7) 1916-1922.e1
    CrossrefPubMedGoogle Scholar
  • 31 Bailey AP, Jaslow CR, Kutteh WH. Minimally invasive surgical options for congenital and acquired uterine factors associated with recurrent pregnancy loss. Womens Health (Lond Engl) 2015; 11 (2) 161-167
    PubMedGoogle Scholar
  • 32 Coulam CB, Acacio B. Does immunotherapy for treatment of reproductive failure enhance live births?. Am J Reprod Immunol 2012; 67 (4) 296-304
    CrossrefPubMedGoogle Scholar
  • 33 Wong LF, Porter TF, Scott JR. Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev 2014; 10: CD000112
    PubMedGoogle Scholar
  • 34 Egerup P, Lindschou J, Gluud C, Christiansen OB. The effects of immunotherapy with intravenous immunoglobulins versus no intervention, placebo, or usual care in patients with recurrent miscarriages: a protocol for a systematic review with meta-analyses, trial sequential analyses, and individual patient data meta-analyses of randomised clinical trials. Syst Rev 2014; 3: 89
    CrossrefPubMedGoogle Scholar
  • 35 Kutteh WH. Antiphospholipid antibody syndrome and reproduction. Curr Opin Obstet Gynecol 2014; 26 (4) 260-265
    CrossrefPubMedGoogle Scholar
  • 36 Salmon JE, Girardi G, Lockshin MD. The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients. Nat Clin Pract Rheumatol 2007; 3 (3) 140-147 , quiz 1, 187
    CrossrefPubMedGoogle Scholar
  • 37 Je S, Girardi G. The role of complement in the antiphospholipid syndrome. Curr Dir Autoimmun 2004; 7: 33-48
    PubMedGoogle Scholar
  • 38 Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 1996; 174 (5) 1584-1589
    CrossrefPubMedGoogle Scholar
  • 39 Lund M, Kamper-Jørgensen M, Nielsen HS, Lidegaard Ø, Andersen AM, Christiansen OB. Prognosis for live birth in women with recurrent miscarriage: what is the best measure of success?. Obstet Gynecol 2012; 119 (1) 37-43
    CrossrefPubMedGoogle Scholar