The majority of miscarriages are sporadic and most result from genetic causes that are greatly influenced by maternal age. Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies, and up to 50% of cases of RPL will not have a clearly defined etiology.
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PMID 22835448 22835448 DOI 10.1016/j.fertnstert.2012.06.048 10.1016/j.fertnstert.2012.06.048
Cite this article
Reproductive Endocrinology Precis (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertility and sterility, 98(5), 1103-1111. https://doi.org/10.1016/j.fertnstert.2012.06.048
Reproductive Endocrinology Precis. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98(5):1103-1111. doi:10.1016/j.fertnstert.2012.06.048
Reproductive Endocrinology Precis. "Evaluation and treatment of recurrent pregnancy loss: a committee opinion." Fertility and sterility, vol. 98, no. 5, 2012, pp. 1103-1111.
Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).
Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Reproductive Endocrinology and Infertility, 2026·Fertility and sterility
Luteal phase deficiency (LPD) is a clinical diagnosis associated with abnormal luteal phase length of ≤10 days. Potential etiologies of LPD include inadequate progesterone duration, inadequate progesterone levels, or endometrial progesterone resistance. Luteal phase deficiency has been described in association with medical conditions, but also in fertile, normally menstruating women. Although progesterone is important for the process of implantation and early embryonic development, LPD has not been proven to be an independent entity causing infertility or recurrent pregnancy loss. Controversy exists regarding the multiple proposed measures for diagnosing LPD, and assuming it can be diagnosed accurately, whether treatment improves outcomes. This document replaces the document of the same name, last published in 2021 (Fertil Steril 2021;115(6):1416-23).
Practice Committee of the American Society for Reproductive Medicine, 2026·Fertility and Sterility
Current strategies for the assessment and treatment of recurrent pregnancy loss are discussed. This replaces the previous document, titled, "Evaluation and treatment a committee opinion," last published in 2012.
This narrative review examines the evidence for medical optimization of inflammatory conditions, vitamin deficiencies, endocrine disorders, immune dysregulation, oligo-ovulation, and luteal phase factors to improve fertility outcomes in women attempting to conceive through natural or timed intercourse. Overall, there is a paucity of data with respect to these categories among patients pursuing timed intercourse, precluding our ability to draw strong recommendations. However, there is strong evidence supporting treatment of endocrine disorders, specifically overt thyroid dysfunction and hyperprolactinemia, as well as oligo-ovulation. Conversely, treatment of subclinical hypothyroidism is not recommended. The current data are insufficient to support empiric use of antiinflammatory medications, corticosteroids, thyroid hormones, or vitamins or supplements to improve chances of pregnancy in a general infertility population.