Meta-analysis Supports Progesterone for Recurrent Pregnancy Loss

Peter Kovacs, MD, PhD


April 17, 2017

Supplementation With Progestogens in the First Trimester of Pregnancy to Prevent Miscarriage in Women With Unexplained Recurrent Miscarriage: A Systematic Review and Meta-analysis of Randomized, Controlled Trials

Saccone G, Schoen C, Franasiak JM, Scott RT Jr, Berghella V
Fertil Steril. 2017;107:430-438


Many factors increase the risk for pregnancy loss; these include cytogenetic, uterine, endocrine, hematologic, metabolic, and certain immunologic abnormalities. In about one half of all cases of pregnancy loss, even a detailed evaluation will fail to identify a modifiable risk factor. In such cases, empirical treatments, such as aspirin, heparin, and progestogens, are often used.

This systematic review analyzed the evidence behind the use of progestogen in unexplained recurrent pregnancy loss (RPL), which is diagnosed when a woman miscarries more than two subsequent pregnancies.[1]


This meta-analysis included 10 randomized controlled trials with 1586 patients and evaluated natural progesterone or synthetic progestogens compared with no treatment or placebo. Women receiving progestogen in the first trimester had a lower risk for pregnancy loss (relative risk, 0.72; 95% confidence interval, 0.53-0.97). Supplementation with progestogen had no impact on the incidence of preterm birth, neonatal mortality, or fetal genital abnormalities.

Subgroup analysis revealed that oral, intramuscular, and synthetic progestogens were associated with lower risk for miscarriage. Vaginal progestogen and natural progesterone, however, did not affect miscarriage rates. Intramuscular 17-alpha hydroxyprogesterone caproate and oral dydrogesterone were both associated with significant reduction in miscarriage risk.

On the basis of these findings, the authors concluded that synthetic progestogens, but not natural progesterone, are associated with lower miscarriage risk among women with unexplained RPL.


Progesterone secreted by the corpus luteum and then by the placenta is a key hormone during pregnancy and is required for implantation and maintenance of pregnancy.[2] In addition, it has some immunomodulatory effects that could further influence endometrial receptivity.[3] This meta-analysis supports the use of synthetic progestogens in women with unexplained RPL.

Important aspects of this treatment need to be studied further, however. When should progesterone be started? Which preparation should be given: synthetic or natural? What is the optimal dose and duration of treatment? These questions need to be answered to be able to provide adequate supportive care. But until such findings become available, synthetic progestogens should still be given to women with unexplained RPL, starting from when their pregnancy is confirmed.



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