Hydroxyprogesterone Caproate Injection as a Technique to Reduce Preterm Birth in High-Risk Pregnancies

Policy ID: I-56-028

Section: Injections

Effective Date: October 01, 2020

Revised Date: March 04, 2022

Revision Effective Date: May 01, 2022

Last Reviewed: March 23, 2022

Applies To: Commercial Only

Description

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.

Hydroxyprogesterone caproate (Makena^TM) is a synthetic progestin used to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. Hydroxyprogesterone caproate (Makena) binds extensively to plasma proteins including albumin and corticosteroid binding globulins. The mechanism by which hydroxyprogesterone caproate reduces the risk of recurrent preterm birth is not known.

Criteria

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

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Hydroxyprogesterone caproate (Makena) may be considered medically necessary in a pregnancy that meets ALL of the following criteria:

Current pregnancy; and
Pregnancy is between 16 weeks, 0 days and 20 weeks, 6 days; and
History of spontaneous preterm birth (less than 37 weeks, 0/7 days) but no preterm labor in the current pregnancy.

Hydroxyprogesterone caproate (Makena) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Procedure Codes

J1726

J1729

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services(CMS) and other peer reviewed resources or evidence-based guidelines.

Diagnosis Codes

Covered Diagnosis Codes for Procedure Codes J1726 and J1729

O09.211

O09.212

O09.213

O09.219

O34.40

O34.41

O34.42

O34.43

O47.00

O47.02

O47.03

Z87.51

Professional Statements and Societal Positions Guidelines

American College of Obstetricians and Gynecologists - 2019

In October 2019, the American College of Obstetricians and Gynecologists (ACOG) published a Practice Advisory on Clinical guidance for integration of the findings of the PROLONG study: Progestin’s Role in Optimizing Neonatal Gestation:
- Current guidelines in the United States recommend the use of progesterone supplementation in women with prior spontaneous preterm birth.
- Consideration for offering 17-OHPC to women at risk of recurrent preterm birth should continue to take into account the body of evidence for progesterone supplementation, the values and preferences of the pregnant woman, the resources available, and the setting in which the intervention will be implemented.
- ACOG is not changing their clinical recommendations at this time and continues to recommend offering hydroxyprogesterone caproate as outlines in Practice Bulletin # 130, Prediction and Prevention of Preterm Birth.

Society for Maternal-Fetal Medicine - 2017

A 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 individuals.
- The purpose of this statement is to reaffirm the choice of progestogen for women with a singleton gestation and a prior spontaneous PTB.
An updated statement in 2019 by SMFM: Use of 17-alpha hydroxyprogesterone caproate for prevention of recurrent preterm birth
- Based on the evidence of effectiveness in the Meis study, which is the trial with the largest number of US individuals, and given the lack of demonstrated safety concerns, SMFM believes that it is reasonable for providers to use 17-OHPC in women with a profile more representative of the very high-risk population reported in the Meis trial.
- For all women at risk of recurrent sPTB, the risk/benefit discussion should incorporate a shared decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.
- The lack of benefit from 17-OHPC seen in the PROLONG trial raises questions regarding the efficacy of 17-OHPC, and additional studies are needed to identify populations in which administration of 17-OHPC may provide needed benefit in the reduction of recurrent sPTB.
- SMFM will continue to closely follow advances in this area to assure optimal care for women and to provide guidance for maternal-fetal medicine subspecialists.

An updated statement in 2021 by SMFM: Response to EPPPIC and considerations for the use of progestogens for the preventions of preterm birth:
- The data presented in the EPPPIC meta-analysis reaffirms SMFM’s current guidelines to consider the use of 17-OHPC in women with a singleton gestation and a history of sPTB between 20 and 36 6/7 weeks of gestation. For singleton pregnancies in women with prior sPTB or short cervical length, prescription of progestogen treatment should follow a process of shared decision-making with a discussion of the benefits, potential risks, patient values, cost, limitations of the data, and logistics (eg, choice of progestogen) to maximize patient compliance and optimize pregnancy outcomes
- In singleton pregnancies at high-risk for PTB due to prior sPTB or short cervix, both 17-OHPC and vaginal progesterone reduced the risk of PTB before 34 weeks of gestation and improved other birth and neonatal outcomes. However, there was no clear evidence to support one intervention’s effectiveness over the other in reducing PTB before 34 weeks of gestation, serious neonatal complication, overall maternal complications, or perinatal death.
- The underlying risk of preterm birth is greater at shorter cervical lengths, absolute risk reductions are greater for women with a shorter cervix, and treatment might be most useful for this subpopulation.
- SMFM will continue to review the recent and evolving evidence on the use of progestogens for the prevention of preterm birth.

ND Committee Review

Internal Medical Policy Committee 9-21-2020 adopted policy

Internal Medical Policy Committee 9-21-2021 Annual Review

Internal Medical Policy Committee 3-23-2022 Updated E/I statement, updated Professional Statements and Societal Positions Section

Links

References (PDF)

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and the Company reserves the right to review and update medical policy periodically.

Policy ID: I-56-027

Section: Injections

Effective Date: October 01, 2020

Revised Date: September 21, 2020

Last Reviewed: September 21, 2021

Archived Date: April 30, 2022

Applies To: Commercial Only

Description

Criteria

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

Hydroxyprogesterone caproate (Makena) may be considered medically necessary in a pregnancy that meets ALL of the followingcriteria:

Current pregnancy; and
Pregnancy is between 16 weeks, 0 days and 20 weeks, 6 days; and
History of spontaneous preterm birth (less than 37 weeks, 0/7 days) but no preterm labor in the current pregnancy.

Hydroxyprogesterone caproate (Makena) is considered experimental/investigational and therefore not covered for allother indications not listed above. Scientific evidence does not support its use for other indications.

Procedure Codes

J1726

J1729

Diagnosis Codes

Covered Diagnosis Codes for Procedure Codes J1726 and J1729

O09.211

O09.212

O09.213

O09.219

O34.40

O34.41

O34.42

O34.43

O47.00

O47.02

O47.03

Z87.51

Professional Statements and Societal Positions Guidelines

American College of Obstetricians and Gynecologists

In October 2019, the American College of Obstetricians and Gynecologists (ACOG) published a Practice Advisory on Clinical guidance for integration of the findings of the PROLONG study: Progestin’s Role in Optimizing Neonatal Gestation:
- Current guidelines in the United States recommend the use of progesterone supplementation in women with prior spontaneous preterm birth.
- Consideration for offering 17-OHPC to women at risk of recurrent preterm birth should continue to take into account the body of evidence for progesterone supplementation, the values and preferences of the pregnant woman, the resources available, and the setting in which the intervention will be implemented.
- ACOG is not changing their clinical recommendations at this time and continues to recommend offering hydroxyprogesterone caproate as outlines in Practice Bulletin # 130, Prediction and Prevention of 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.
An updated statement in 2019 by SMFM: Use of 17-alpha hydroxyprogesterone caproate for prevention of recurrent preterm birth
- Based on the evidence of effectiveness in the Meis study, which is the trial with the largest number of US patients, and given the lack of demonstrated safety concerns, SMFM believes that it is reasonable for providers to use 17-OHPC in women with a profile more representative of the very high-risk population reported in the Meis trial.
- For all women at risk of recurrent sPTB, the risk/benefit discussion should incorporate a shared decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.
- The lack of benefit from 17-OHPC seen in the PROLONG trial raises questions regarding the efficacy of 17-OHPC, and additional studies are needed to identify populations in which administration of 17-OHPC may provide needed benefit in the reduction of recurrent sPTB.
- SMFM will continue to closely follow advances in this area to assure optimal care for women and to provide guidance for maternal-fetal medicine subspecialists.

ND Committee Review

Internal Medical Policy Committee 9-21-2020 adopted policy

Internal Medical Policy Committee 9-21-2021 Annual Review

Links

References (PDF)

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