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Updated Clinical Guidance for the Use of Progesterone Supplementation for the Prevention of Recurrent Preterm Birth

  • Practice Advisory PA
  • April 2023

This Practice Advisory was developed by the American College of Obstetricians and Gynecologists with the assistance of Hyagriv N. Simhan, MD, MS; Allison Bryant, MD, MPH; Manisha Gandhi, MD; and Mark Turrentine, MD.

This Practice Advisory serves as an update to Practice Bulletin No. 234, Prediction and Prevention of Spontaneous Preterm Birth, originally published in 2021 1 .

This Practice Advisory is provided to address the April 6, 2023, decision by the U.S. Food and Drug Administration (FDA) to withdraw approval of Makena and its generics (17-alpha hydroxyprogesterone caproate [17-OHPC]) 2 . Additionally, this Practice Advisory serves to update the current evidence and recommendations for the use of progesterone for the prevention of recurrent preterm birth.

The American College of Obstetricians and Gynecologists (ACOG) guidance regarding the use of progesterone for the prevention of preterm birth is included in ACOG Practice Bulletin No. 234, “Prediction and Prevention of Spontaneous Preterm Birth” 1 . Updated recommendations are:

  • Vaginal progesterone may be considered as a treatment option for patients with a history of preterm birth, singleton gestation, and a shortened cervix. However, vaginal progesterone has not been proven effective in the absence of a shortened cervix and should not be considered as an alternative to 17-OHPC. 
  • Intramuscular 17-OHPC is not recommended for the primary prevention of preterm birth in patients with a history of spontaneous preterm birth.
  • Dependent upon cervical length measurement, prior pregnancy history, and past treatment, a discussion of the range of interventions available to prevent a recurrent preterm birth should occur and a collaborative action plan should be developed.

With regard to the use of prophylactic 17-OHPC specifically for the prevention of recurrent preterm birth, the FDA’s assessment of the current body of evidence concluded that there were not sufficient data to indicate that this was an effective treatment in the broad population it was originally approved for—all pregnant people with a prior spontaneous preterm birth between 20 and 37 weeks of gestation. Whether this intervention would be useful in a subset of people requires future study. The FDA does not seem to base its decision on safety concerns. Although compounding remains an option, the FDA’s decision to withdraw approval of Makena will significantly impact access to and availability of 17-OHPC for the prevention of preterm birth.

Another important update to the evidence pertains to the use of vaginal progesterone for prevention of recurrent preterm birth in asymptomatic people. The results of a meta-analysis and an additional recently published study evaluating vaginal progesterone to prevent recurrent preterm birth found that vaginal progesterone was not associated with a reduction in recurrent preterm birth 3 4 . As a result, ACOG’s guidance is updated via this Practice Advisory to recommend that in the setting of a singleton pregnancy with a history of prior spontaneous preterm birth, and in the absence of a shortened cervix, vaginal progesterone should not be offered as a prevention option. The table from the Practice Bulletin is updated and is included in this Practice Advisory Table 1.

In summary, at this time, the body of evidence is equivocal regarding the effectiveness of 17-OHPC, and the referenced FDA action will limit access to 17-OHPC for patients. Furthermore, the body of evidence does not indicate that vaginal progesterone is effective for the prevention of recurrent preterm birth in singleton pregnancies with a prior preterm birth between 20 and 37 weeks of gestation in the absence of a shortened cervix 3 4 . As described in Practice Bulletin No. 234, patients with a singleton pregnancy and prior spontaneous preterm birth should be assessed with serial endovaginal ultrasound cervical length measurement  1 . Dependent upon cervical length measurement, prior pregnancy history, and past treatment, a discussion of the range of interventions available to prevent a recurrent preterm birth should occur and a collaborative action plan should be developed Table 1.

Preterm birth remains a significant public health issue and more evidence for effective interventions is urgently needed.  The American College of Obstetricians and Gynecologists will continue to monitor the evidence as it evolves and advocate for prevention strategies for preterm birth that are effective and accessible to all patients.

Table 1. Screening and Interventions for Prevention of Preterm Birth. Updated from Table 1 in Prediction and prevention of spontaneous preterm birth. ACOG Practice Bulletin No. 234. American College of Obstetricians and Gynecologists. Obstet Gynecol 2021;138:e65–90.

   

Access the Society for Maternal-Fetal Medicine statement.

Please contact [email protected] with any questions.

Access ACOG’s FAQs on Use of Progesterone for the Prevention of Recurrent Preterm Birth.

References

  1. Prediction and prevention of spontaneous preterm birth. ACOG Practice Bulletin No. 234. American College of Obstetricians and Gynecologists. Obstet Gynecol 2021;138:e65-90. doi: 10.1097/AOG.0000000000004479
    Article Locations:
    Article LocationArticle LocationArticle Location
  2. . U.S. Food and Drug Administration. FDA Commissioner and Chief Scientist announce decision to withdraw approval of Makena. FDA; 2023. Accessed April 6, 2023. Available at: https://www.fda.gov/news-events/press-announcements/fda-commissioner-and-chief-scientist-announce-decision-withdraw-approval-makena
    Article Locations:
    Article Location
  3. Conde-Agudelo A, Romero R. Vaginal progesterone does not prevent recurrent preterm birth in women with a singleton gestation, a history of spontaneous preterm birth, and a midtrimester cervical length >25 mm. Am J Obstet Gynecol 2022;227:923-6. doi: 10.1016/j.ajog.2022.07.054
    Article Locations:
    Article LocationArticle Location
  4. Nelson DB, Lafferty A, Venkatraman C, McDonald JG, Eckert KM, McIntire DD, et al. Association of vaginal progesterone treatment with prevention of recurrent preterm birth. JAMA Netw Open 2022;5:e2237600. doi: 10.1001/jamanetworkopen.2022.37600
    Article Locations:
    Article LocationArticle Location

The American College of Obstetricians and Gynecologists recognizes and supports the gender diversity of all patients who seek obstetric and gynecologic care. In original portions of this document, authors seek to use gender-inclusive language or gender-neutral language. When describing research findings, this document uses gender terminology reported by investigators. To review ACOG’s policy on inclusive language, see https://www.acog.org/clinical-information/policy-and-position-statements/statements-of-policy/2022/inclusive-language.

A Practice Advisory is a brief, focused statement issued to communicate a change in ACOG guidance or information on an emergent clinical issue (eg, clinical study, scientific report, draft regulation). A Practice Advisory constitutes ACOG clinical guidance and is issued only online for Fellows but may also be used by patients and the media. Practice Advisories are reviewed periodically for reaffirmation, revision, withdrawal, or incorporation into other ACOG guidelines. This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary. This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It is not intended to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology. The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its publications may not reflect the most recent evidence. Any updates to this document can be found on www.acog.org/clinical.

on acog.org/clinical. While ACOG makes every effort to present accurate and reliable information, this publication is provided “as is” without any warranty of accuracy, reliability, or otherwise, either express or implied. ACOG does not guarantee, warrant, or endorse the products or services of any firm, organization, or person. Neither ACOG nor its officers, directors, members, employees, or agents will be liable for any loss, damage, or claim with respect to any liabilities, including direct, special, indirect, or consequential damages, incurred in connection with this publication or reliance on the information presented.

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The American College of Obstetricians and Gynecologists (ACOG) is the nation’s leading group of physicians providing evidence-based obstetric and gynecologic care. As a private, voluntary, nonprofit membership organization of more than 60,000 members, ACOG strongly advocates for equitable, exceptional, and respectful care for all women and people in need of obstetric and gynecologic care; maintains the highest standards of clinical practice and continuing education of its members; promotes patient education; and increases awareness among its members and the public of the changing issues facing patients and their families and communities. www.acog.org

Topics
17 alpha-Hydroxyprogesterone Caproate High risk pregnancy Premature birth Preterm birth Progesterone Recurrent preterm birth Short cervix Spontaneous preterm birth
Figures & Tables

Figures & Tables

Table 1. Screening and Interventions for Prevention of Preterm Birth. Updated from Table 1 in Prediction and prevention of spontaneous preterm birth. ACOG Practice Bulletin No. 234. American College of Obstetricians and Gynecologists. Obstet Gynecol 2021;138:e65–90.

Table 1. Screening and Interventions for Prevention of Preterm Birth. Updated from Table 1 in Prediction and prevention of spontaneous preterm birth. ACOG Practice Bulletin No. 234. American College of Obstetricians and Gynecologists. Obstet Gynecol 2021;138:e65–90.

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