The Only Treatment for Idiopathic Recurrent Pregnancy Loss

Peter Kovacs, MD, PhD


September 28, 2018

Recurrent Pregnancy Loss

A miscarriage occurs in 15%-25% of clinically recognized pregnancies. Most pregnancy losses are due to random chromosome errors. When a woman loses two or more pregnancies under similar conditions, the diagnosis of recurrent pregnancy loss can be made. Recurrent pregnancy losses account for 3%-5% of all pregnancy losses.[1,2]

Risk factors for pregnancy loss are well established. Women aged over 35 years, men aged over 50 years, stress, smoking, increased alcohol or coffee consumption, environmental effects, and chronic endometritis have all been identified as risk factors.[3]

Recurrent pregnancy loss requires a thorough evaluation. This usually involves genetic, hematologic, endocrine, and immunologic testing as well as an assessment of the uterine cavity. When a problem is identified, specific treatment can be offered. In at least 50% of cases, however, no factors responsible for the pregnancy loss are found and the diagnosis of idiopathic pregnancy loss is made. The various approaches to preventing pregnancy loss that have been evaluated for these patients were summarized in a recent meta-analysis.[4]

Meta-analysis Findings

The meta-analysis is based on findings of randomized controlled trials evaluating the benefits of treatments in couples with three or more consecutive pregnancy losses. The primary outcome was live birth after 22 weeks' gestation. Findings of the meta-analysis included:

  • Two small trials evaluated the effect of aspirin and the evidence was insufficient to draw conclusions.

  • On the basis of three studies, there was no benefit from low-molecular-weight heparin (risk ratio [RR], 1.47; 95% confidence interval [CI], 0.83-2.61).

  • Two large studies with different designs tested the benefits of progesterone. One found no benefit, whereas the other reported a higher live birth rate with progesterone use.

  • No randomized trials were done on steroid use.

  • Intravenous immunoglobulin had no significant impact on live birth rates based on the findings of six randomized trials (RR, 1.07; 95% CI, 0.91-1.26).

  • Immunization with paternal leukocytes was shown to improve live birth rates based on five small studies (RR, 1.8; 95% CI, 1.34-2.41). Pregnancy rates in the control groups, however, were unusually low.

  • No randomized controlled trials tested the effect of intralipid or preimplantation genetic screening

According to this meta-analysis, the only treatment that can be recommended for the management of idiopathic recurrent pregnancy loss is progesterone, starting from the time of ovulation.


Recurrent pregnancy loss is frustrating for both patients and providers, particularly when no cause can be identified. Even if the evaluation reveals abnormalities, the efficacy of most available treatments is not well proven.

Congenital or acquired uterine abnormalities can be corrected surgically, which will improve the outcome of a subsequent pregnancy. Severe endocrine abnormalities (hypothyroidism, hyperthyroidism, hyperprolactinemia) can be corrected medically.[3]

The role of hematologic abnormalities is questionable. Heparin was shown to influence trophoblast invasion, but a beneficial role in recurrent pregnancy loss has not been shown. In the case of antiphospholipid syndrome, the combination of aspirin and heparin improves clinical outcomes.[2,3]

In cases of parental chromosome abnormalities, in vitro fertilization with preimplantation genetic screening can be offered.[2] The potential role of the immune system and treatments modifying the immune response have been extensively studied, but overall, no benefit has been found.[2,3]

Couples affected by recurrent pregnancy loss are desperate and willing to try any treatment to improve their chance to have a child. It should not be forgotten that the prognosis with no treatment in case of unexplained recurrent pregnancy loss is favorable. Most will conceive without any specific therapy.[5]

This meta-analysis supports only one treatment for idiopathic recurrent pregnancy loss: the use of progesterone. In all other cases, appropriate counseling, explaining the prognosis without treatment, and "tender, loving care" should be offered instead of treatments with potential side effects but no proven efficacy.


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