Evaluation of couples with recurrent pregnancy loss

INTRODUCTION

Couples with recurrent pregnancy loss (RPL) require empathy and understanding as early pregnancy loss is an emotionally traumatic experience, similar to that associated with stillbirth or neonatal death. In addition, evaluation can be frustrating and difficult because the etiology of their RPL may not be determined and there are few evidence-based diagnostic and treatment strategies [1,2].

CANDIDATES FOR EVALUATION

RPL is classically defined as the occurrence of three or more consecutive losses of clinically recognized pregnancies prior to the 20th week of gestation (ectopic and molar pregnancies are not included). (See "Definition and etiology of recurrent pregnancy loss".)

There is a general consensus that healthy women should not undergo extensive evaluation after a single first trimester or early second trimester spontaneous miscarriage, given these are relatively common, sporadic events: miscarriage occurs in about 10 to 15 percent of clinically recognized pregnancies under 20 weeks of gestation [3]. In prospective studies, the overall risk of miscarriage in the next pregnancy remains about 15 percent after one miscarriage, but rises to 17 to 31 percent after two consecutive miscarriages and to 25 to 46 percent after three or more miscarriages. Based on these and similar data, most experts initiate evaluation and treatment of RPL after either two or three consecutive miscarriages [3-5].

It is important to remember that most women with RPL have a good prognosis for eventually having a successful pregnancy, even when a definitive diagnosis is not made and no treatment initiated. In one representative study, the overall live birth rates after normal and abnormal diagnostic evaluations for RPL were 77 and 71 percent, respectively [6]. In another study, 8 of 17 women with six or more consecutive unexplained miscarriages subsequently achieved a successful pregnancy outcome [7].

HISTORY AND PHYSICAL EXAMINATION

The minimum diagnostic workup of couples with RPL consists of a complete medical, surgical, genetic, and family history and a physical examination.

                    

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Oct 2014. | This topic last updated: Aug 22, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Trott EA, Russell JB, Plouffe L Jr. A review of the genetics of recurrent pregnancy loss. Del Med J 1996; 68:495.
  2. Plouffe L Jr, White EW, Tho SP, et al. Etiologic factors of recurrent abortion and subsequent reproductive performance of couples: have we made any progress in the past 10 years? Am J Obstet Gynecol 1992; 167:313.
  3. Stirrat GM. Recurrent miscarriage. Lancet 1990; 336:673.
  4. American College of Obstetricians and Gynecologists. Management of recurrent early pregnancy loss. ACOG practice bulletin no. 24, American College of Obstetricians and Gynecologists, Washington, DC 2001.
  5. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril 2010; 93:1234.
  6. Laufer MR, Ecker JL, Hill JA. Pregnancy outcome following ultrasound-detected fetal cardiac activity in women with a history of multiple spontaneous abortions. J Soc Gynecol Investig 1994; 1:138.
  7. Clifford K, Rai R, Regan L. Future pregnancy outcome in unexplained recurrent first trimester miscarriage. Hum Reprod 1997; 12:387.
  8. Clark DA, Daya S, Coulam CB, Gunby J. Implication of abnormal human trophoblast karyotype for the evidence-based approach to the understanding, investigation, and treatment of recurrent spontaneous abortion. The Recurrent Miscarriage Immunotherapy Trialists Group. Am J Reprod Immunol 1996; 35:495.
  9. Carp H, Guetta E, Dorf H, et al. Embryonic karyotype in recurrent miscarriage with parental karyotypic aberrations. Fertil Steril 2006; 85:446.
  10. Tharapel AT, Tharapel SA, Bannerman RM. Recurrent pregnancy losses and parental chromosome abnormalities: a review. Br J Obstet Gynaecol 1985; 92:899.
  11. De Braekeleer M, Dao TN. Cytogenetic studies in couples experiencing repeated pregnancy losses. Hum Reprod 1990; 5:519.
  12. Hassold T, Jacobs PA, Pettay D. Cytogenetic studies of couples with repeated spontaneous abortions of known karyotype. Genet Epidemiol 1988; 5:65.
  13. Carp H, Feldman B, Oelsner G, Schiff E. Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril 2004; 81:1296.
  14. Schaeffer AJ, Chung J, Heretis K, et al. Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet 2004; 74:1168.
  15. Fritz B, Hallermann C, Olert J, et al. Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous abortions. Eur J Hum Genet 2001; 9:539.
  16. ACOG Committee Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol 2009; 114:1161.
  17. Goldberg JM, Falcone T, Attaran M. Sonohysterographic evaluation of uterine abnormalities noted on hysterosalpingography. Hum Reprod 1997; 12:2151.
  18. Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography in patients with uterine cavity diseases. Fertil Steril 2000; 73:406.
  19. Keltz MD, Olive DL, Kim AH, Arici A. Sonohysterography for screening in recurrent pregnancy loss. Fertil Steril 1997; 67:670.
  20. Homer HA, Li TC, Cooke ID. The septate uterus: a review of management and reproductive outcome. Fertil Steril 2000; 73:1.
  21. Reuter KL, Daly DC, Cohen SM. Septate versus bicornuate uteri: errors in imaging diagnosis. Radiology 1989; 172:749.
  22. Malhotra N, Sood M. Role of hysteroscopy in infertile women. J Indian Med Assoc 1997; 95:499, 525.
  23. Pellerito JS, McCarthy SM, Doyle MB, et al. Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography. Radiology 1992; 183:795.
  24. Ansari AH, Kirkpatrick B. Recurrent pregnancy loss. An update. J Reprod Med 1998; 43:806.
  25. Caliskan E, Ozkan S, Cakiroglu Y, et al. Diagnostic accuracy of real-time 3D sonography in the diagnosis of congenital Mullerian anomalies in high-risk patients with respect to the phase of the menstrual cycle. J Clin Ultrasound 2010; 38:123.
  26. Bermejo C, Martínez Ten P, Cantarero R, et al. Three-dimensional ultrasound in the diagnosis of Müllerian duct anomalies and concordance with magnetic resonance imaging. Ultrasound Obstet Gynecol 2010; 35:593.
  27. Roubey RA. Update on antiphospholipid antibodies. Curr Opin Rheumatol 2000; 12:374.
  28. Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril 1996; 66:24.
  29. Vinatier D, Dufour P, Cosson M, Houpeau JL. Antiphospholipid syndrome and recurrent miscarriages. Eur J Obstet Gynecol Reprod Biol 2001; 96:37.
  30. Negro R, Schwartz A, Gismondi R, et al. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab 2010; 95:E44.
  31. Chen L, Hu R. Thyroid autoimmunity and miscarriage: a meta-analysis. Clin Endocrinol (Oxf) 2011; 74:513.
  32. Thangaratinam S, Tan A, Knox E, et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 2011; 342:d2616.
  33. Trout SW, Seifer DB. Do women with unexplained recurrent pregnancy loss have higher day 3 serum FSH and estradiol values? Fertil Steril 2000; 74:335.
  34. Cervera R, Balasch J. Autoimmunity and recurrent pregnancy losses. Clin Rev Allergy Immunol 2010; 39:148.
  35. Harger JH, Rabin BS, Marchese SG. The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses: a prospective controlled study. Obstet Gynecol 1989; 73:419.
  36. Coulam CB. Immunologic tests in the evaluation of reproductive disorders: a critical review. Am J Obstet Gynecol 1992; 167:1844.
  37. Laird SM, Tuckerman EM, Cork BA, et al. A review of immune cells and molecules in women with recurrent miscarriage. Hum Reprod Update 2003; 9:163.
  38. Clark DA. Is there any evidence for immunologically mediated or immunologically modifiable early pregnancy failure? J Assist Reprod Genet 2003; 20:63.
  39. Ogasawara M, Kajiura S, Katano K, et al. Are serum progesterone levels predictive of recurrent miscarriage in future pregnancies? Fertil Steril 1997; 68:806.
  40. Peters AJ, Lloyd RP, Coulam CB. Prevalence of out-of-phase endometrial biopsy specimens. Am J Obstet Gynecol 1992; 166:1738.