Highmark Commercial Medical Policy - Pennsylvania

Medical Policy: I-56-025
Topic: Hydroxyprogesterone Caproate Injection as a Technique to Reduce Preterm Birth in High-Risk Pregnancies
Section: Injections
Effective Date: July 9, 2018
Issue Date: July 9, 2018
Last Reviewed: May 2018

Preterm labor and delivery is a major cause of neonatal morbidity and mortality. Women who have had a spontaneous preterm delivery are at increased risk for preterm delivery in subsequent pregnancies.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Any hydroxyprogesterone injection (e.g., Makena™) may be considered medically necessary in a pregnancy that meets All of the following conditions:

Hydroxyprogesterone injection is considered experimental/investigational and therefore not covered for all other indications not listed above. Scientific evidence does not support its use for other indications.

Procedure Codes
J1726, J1729

Dosage recommendations per the FDA label.

Professional Statements and Societal Positions

American College of Obstetricians and Gynecologists

  • In May 2014, the American College of Obstetricians and Gynecologists (ACOG) published a Practice Bulletin on multifetal gestations that included the following statement on progesterone therapy:
    • Progesterone treatment does not reduce the incidence of spontaneous preterm birth in unselected women with twin or triplet gestations and, therefore, is not recommended.
  • Previously, in October 2012, ACOG published a Practice Bulletin on prediction and prevention of preterm birth.The bulletin included the following recommendations (level A evidence) related to progesterone therapy in women with singleton pregnancies:
    • A woman with a singleton gestation and a prior spontaneous singleton birth should be offered progesterone supplementation starting at 16-24 weeks of gestation … to reduce the risk of recurrent spontaneous preterm birth. 

Society for Maternal-Fetal Medicine

  • A 2012 clinical guideline by the Society for Maternal-Fetal Medicine included the following conclusions and recommendations:
    • There is insufficient evidence to recommend the use of progestogens in singleton gestations with no prior PTB [preterm birth], and unknown CL [cervical length].
    • Progestogens have not been associated with prevention of PTB in multiple gestations, PTL [preterm labor], or PPROM [preterm premature rupture of membranes]. There is insufficient evidence to recommend the use of progestogens in women with any of these risk factors, with or without a short CL. Some experts offer 17P to women with a prior SPTB and a current multiple gestation, but there are insufficient data to evaluate the risks and benefits of this intervention in this population.
  • An updated Statement in 2017 by the Society for Maternal Fetal Medicine included the following statements and recommendations:
    • The Society for Maternal-Fetal Medicine (SMFM) continues to recommend that all women with a prior spontaneous preterm birth (PTB) of a singleton pregnancy be offered 17-alpha hydroxyprogesterone caproate (17OHP-C) therapy in a subsequent pregnancy with a singleton gestation. Data from several sources suggest that despite these recommendations, there remains continued underutilization of 17OHP-C for eligible patients.
    • The purpose of this statement is to reaffirm the choice of progestogen for women with a singleton gestation and a prior spontaneous PTB.

Place of Service: Outpatient

Experimental/Investigational (E/I) services are not covered regardless of place of service.

Hydroxyprogesterone Caproate Injection as a Technique to Reduce Preterm Birth in High-Risk Pregnancies is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

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U.S. Department of Health and Human Services
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Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

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