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Recurrent Miscarriages: Evaluation and Testing to Prevent Pregnancy Loss

Recurrent pregnancy loss (RPL), defined by the American Society of Reproductive Medicine (ASRM) as 2 or more failed clinical pregnancies, may affect as many as 5% of couples who are trying to conceive (2, 3). The harsh reality is that up to 15% of all clinically recognized pregnancies end in spontaneous miscarriage (1), and despite the heartbreaking experience, many miscarriages may not be preventable. But in certain cases there are contributing factors that can, and should, be treated. At some point we need to begin asking the right questions. Given that the risk of future miscarriage is similar whether a couple has had 2 or 3 prior successive losses, current guidelines recommend evaluation to begin after two consecutive spontaneous miscarriages (2). In this article, we will summarize the major known causes of miscarriage, and what can be done to prevent them.

Categories

Recurrent pregnancy loss can be broken down into the following categories:

  • Chromosomal factors

    Chromosomal abnormalities are the most common cause of miscarriage and account for as many as 80% of first trimester losses. There are certain tests, including parental karyotyping or preimplantation genetic screening (during IVF) which can detect risk or occurrence of chromosomal changes in embryos.

  • Anatomical factors

    Anatomical or structural abnormalities, (such as uterine septa or adhesions, fibroids or polyps) may be implicated in as many as 10-15% of cases of RPL and are thought to cause miscarriage by disrupting the formation of the placenta (1). Although not all fibroids will be problematic, intramural fibroids larger than 5 cm or submucosal fibroids of any size are the most likely to be implicated in RPL (1). When indicated, surgical removal of fibroids, or resection of intrauterine adhesions or septa can dramatically improve pregnancy outcomes (1). With smaller fibroids, nutritional interventions and acupuncture is often a useful approach.

  • Endocrine (hormonal) changes

    Endocrine factors may be to blame in as many as 17-20% of RPL cases (1), and there are quite a number of hormones that could be implicated. PCOS, or Polycystic ovarian syndrome, is thought to be the most common of these conditions, and has been implicated in as many as 40% of women who experience RPL (1). Other important endocrine disturbances to rule out in RPL include diabetes or insulin resistance, thyroid dysfunction or thyroid autoimmunity, hyperprolactinemia and luteal phase defect. Specific testing to evaluate an underlying endocrine etiology may include blood tests for TSH, thyroid antibodies, prolactin, progesterone, ovarian reserve testing, and more rarely, an endometrial biopsy (1). Treatment options range, depending on the underlying diagnosis. In cases of thyroid disorders or hyperprolactinemia, medication may be required. First-line treatment for PCOS involves lifestyle modification and weight loss when indicated. A recent Cochrane review article has found evidence of benefit for the use of progesterone in early pregnancy among all women with a history of recurrent miscarriage (4).

  • Clotting disorders

    Thrombophilias, or clotting disorders, play a more controversial role in RPL, and testing for these conditions is often overlooked. Testing may involve screening for factor V Leiden, protein C and protein S deficiencies and MTHFR mutations.

  • Autoimmune infertility

    In order for implantation to occur, the mother’s immune system must tolerate the embryo, whose genetic material is not identical to her own. For this reason, the role of immunologic factors in RPL has long been proposed. Currently a consensus on the appropriate diagnostic interventions and therapy in this area is lacking. Perhaps the most well recognized cause of autoimmune infertility is antiphospholipid syndrome (APS). Screening tests to rule out autoimmune infertility, such as APS include anticardiolipin antibodies and lupus anticoagulant (1). Treatment recommendations for autoimmune causes of RPL commonly include low-dose aspirin or heparin (1), among other therapies.

  • Infectious causes

    Infectious causes of RPL, such as ureaplasma, mycoplasma, Chlamydia, L monocytogenes and HSV, are less common (1), but should still be screened for in women who are trying to conceive, especially with a history of miscarriage.

  • Environmental/lifestyle factors

    Certain exposures and environmental factors also pose a risk for miscarriage. The most well documented exposures include excessive caffeine consumption (3 or more cups per day), alcohol consumption (more than 3 drinks per week), and cigarette smoking (1). Nicotine from cigarette smoke acts as a vasoconstrictor, which reduces uterine and placental blood flow, thereby increasing the risk of spontaneous pregnancy loss.

Seeking answers and options for treatment

Given the similar probability of miscarriage after 2 or 3 losses, all women with a history of two miscarriages and no prior live births should receive a rigorous evaluation and work-up. Fifty percent of the time, there is an underlying etiology to pregnancy loss that can be detected and treated. Even in cases where the cause of RPL remains elusive, there are certain treatment options that still remain valid. Progesterone has shown benefit at decreasing the subsequent miscarriage rate among women who have experienced at least 3 pregnancy losses (1). Another potential therapy for unexplained RPL is low dose aspirin, which has proven to offer most benefit to women with previous miscarriages beyond 13 weeks gestation (1). An often overlooked, but effective approach for patients with unexplained RPL is counselling and psychological support. One study found that weekly counselling sessions during the first trimester was shown to increase subsequent pregnancy success rates to 86% as compared to 33% in women who did not receive pre-conception care (5). In our clinic we recognize the emotional toll on women and couples who are trying to conceive, especially those who have suffered a prior miscarriage. Our comprehensive approach to care takes into account the psychological factors, as well as evaluates for potential underlying complications to carrying to term. Addressing lifestyle factors to improve not only pregnancy outcomes, but also fetal health, by way of evidenced based natural medicine is what we strive to do best.

Despite the devastating effects on a couple suffering a miscarriage, the relative probability of carrying to term in the next pregnancy is increased. The proper evaluation, management, and options for advanced care should begin to add light at the end of the tunnel for these couples.

References for this article

  1. Ford HB, Schust DJ. Recurrent pregnancy loss: Etiology, diagnosis and therapy. Reviews in Obstetrics & Gynecology 2009; 2(2): 76-83.
  2. The Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertility and Sterility 2012; 98 (5): 0015-0282.
  3. Garrido-Gimenez C, Alijotas-Reig J. Recurrent miscarriage: causes, evaluation and management. Postgrad Med J 2015; 91(1073): 151-62.
  4. Haas DM, Ramsey PS. Progesterone for preventing miscarriage. Cochrane Database Syst Rev 2013; 10: CD003511.
  5. Stray-Pedersen B, Stray-Pedersen S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol. 1984;148(2):140-6.

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