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    Recurrent pregnancy loss



    Any issues that arise as a result of the analyses in Table 2 should be addressed. All patients with modifiable risk factors should be counseled appropriately. As noted, some observational data suggest that there is an association between obesity and pregnancy loss,35,36 although other studies have not confirmed this link.37 Given this putative link and the known deleterious effect of obesity on overall health, overweight and obese women should be counseled on weight loss and exercise. Similarly an association has been documented between cigarette smoking and pregnancy loss,38 and tobacco is a known carcinogen with multiple negative health effects. Women who smoke should be counseled at every visit on the importance of cessation.

    Otherwise, women should consider starting folic acid supplementation (4 mg daily), because it has been demonstrated to decrease the risk of aneuploidy and subsequent pregnancy loss.12,13 Progesterone supplementation during the luteal phase and early pregnancy should be undertaken only after a discussion with the patient regarding its uncertain benefits. We recommend empiric treatment for women with recurrent pre-embryonic losses (eg, chemical pregnancies).

    No data exist to support the use of heparin or aspirin outside of the context of APAS for the prevention of RPL. Screening for inherited thrombophilias is not indicated. The presence of mid-pregnancy hemorrhagic losses should prompt an evaluation for bleeding dyscrasias (eg, hypofibrinogenemia, dysfibrinogenemia, and factor XIII deficiency).


    Recurrent pregnancy loss is a psychologically stressful diagnosis for couples, and in approximately 50% of cases, no cause will be found.2 The number of evidence-based practices available for guidance is limited. This confluence of factors presents a challenge for clinicians. However, in studies of interventions aimed at reducing rates of miscarriage in women with otherwise unexplained RPL, control groups experience a live birth rate of up to 87% with no intervention.39 Thus, one of the most significant things we can do when caring for these complex patients is to offer them emotional support and accurate information.

    As more work is done in this emerging area of inquiry, we will be able to shed more light on this complex problem.



    1. Practice Committee, American Society for Reproductive Medicine: Definitions of infertility and recurrent pregnancy loss. Fertil Steril. 2008; 90: S60.

    2. Warren JE, Silver RM. Genetics of Pregnancy Loss. Clinical Obstetrics and Gynecology. 2008;51(1):84-95.

    3. Rai R, Regan L: Recurrent miscarriage. Lancet. 2006;768 (9535):601-611.

    4. Rink BD, Lockwood CJ. Recurrent Pregnancy Loss. In: Creasy RJ, ed. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice, 7th Ed. Philadelphia, PA: Elsevier; 2013: 707-718.

    5. Silver RM, Branch DW, Goldenberg R, et al. Nomenclature for pregnancy outcomes: time for a change. Obstet Gynecol. 2011;118(6):1402-1408. PMID:22105271

    6. Murugappan G, Gustin S, Lathi RB. Separation of miscarriage tissue from maternal decidua for chromosome analysis. Fertil Steril. 2014;102:e9-10.

    7. Bell KA, Van Deerlin PG, Haddad BR, Feinberg RF. Cytogenetic diagnosis of “normal 46, XX” karyotypes in spontaneous abortions may be misleading. Fertil Steril 1999;71:334-341.

    8. Romero ST, Geiersbach KB, Paxton CN, et al. Differentiation of genetic abnormalities in early pregnancy loss. Ultrasound Obstet Gynecol. 2015;45(1):89-94.

    9. Dhillon RK, Hillman SC, Morris RK, et al. Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG 2014;121:11-21.

    10.Reddy UM, Page GP, Saade GR et al. Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med 2012;367:2185-2193.

    11. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy.Nat Rev Genet. 2001;2(4):280-291.

    12.George L, Mills JL, Johansson ALV et al. Plasma folate levels and risk of spontaneous abortion. JAMA. 2002;288:1867-1873.

    13. Gaskins AJ, Rich-Edwards JW, Hauser R. Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth. Obstet Gynecol. 2014;124(1):23-31.


    Charles J. Lockwood, MD, MHCM
    Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South ...


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