ModifiedmhnPolicy CP.PMN.243

Progesterone (Crinone, Endometrin) prior authorization

Defines medical necessity criteria and prior authorization requirements for Crinone (4% and 8%) and Endometrin vaginal progesterone products for assisted reproductive technology, secondary amenorrhea, and prevention of preterm birth across applicable lines of business.

Policy Summary

Payermhn

PolicyProgesterone (Crinone, Endometrin) prior authorization

Policy CodePolicy CP.PMN.243

Change TypeMaterial updates — HIM EOC addedMakena concurrent use removed

Effective DateSep 1, 2020

Next Review Date

Key ActionSubmit prior authorization with supporting clinical documentation demonstrating the member meets the indication-specific criteria and dosing/duration limits.

SourceLink

POLICY UPDATE CHANGES

For prevention of preterm birth, removed criterion regarding concurrent usage with Makena due to product discontinuation.

Evidence of coverage language for infertility/fertility preservation was added for multiple HIM states including NC.

3covered indications

180 mgART max Crinone 8%

300 mgART max Endometrin

≤25 mmshort cervix threshold

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

NCstate addendum referenced

Coverage Criteria

inv-01: Initial Approval Criteria

Coverage is authorized when the specified criteria for the chosen indication are fully met.

A. Assisted Reproductive Technology (ART) Treatment

ART-1: Member must have infertility coverage (optional pharmacy benefit).
ART-2: Age ≥ 18 years.
ART-3: Request is for Crinone 8% or Endometrin.
ART-4: Prescribed as supplementation or replacement of progesterone as part of ART treatment for infertile women.
ART-5 Dose limits
- ART-5a: Crinone 8%: 180 mg per day for up to 12 weeks.
- ART-5b: Endometrin: 300 mg per day for up to 10 weeks.

B. Secondary Amenorrhea

SA-1: Diagnosis of secondary amenorrhea.
SA-2: Age ≥ 18 years.
SA-3: Request is for Crinone 4% or 8%.
SA-4: Failure of a progestin product (e.g., medroxyprogesterone, norethindrone), unless contraindicated or clinically significant adverse effects are experienced.
SA-5 Dose limits
- SA-5a:

C. Prevention of Preterm Birth (off-label)

PTB-1: Prescribed for prevention of preterm birth.
PTB-2: Age ≥ 18 years.
PTB-3: Request is for Crinone 8% or Endometrin.
PTB-4: Gestational age is ≥ 16 weeks.≥ 16 weeks gestation
PTB-5: Member has a short cervix as defined as a cervical length ≤ 25 mm.

inv-04: All Indications (Section I)

Covered when ALL of the following are met:

Section I All Indications: 1) Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria, or (b) currently receiving medication and enrolled in a state/product with continuity of care regulations (refer to state addendums CC.PHARM.03A and CC.PHARM.03B); 2) Member is responding positively to therapy; 3) Indication-specific limits: (a) ART: member has infertility coverage and has not exceeded 12 weeks of therapy (Crinone 8%) or 10 weeks of therapy (Endometrin); (b) Secondary amenorrhea: member has not yet received 6 doses of Crinone 4% or 8%; (c) Prevention of preterm birth: week 37 (through 36 weeks, 6 days) of gestation or delivery has not yet been reached; 4) If request is for a dose increase, the new dose does not exceed the indication-specific maximums: ART (Crinone 8% up to 180 mg/day for up to 12 weeks; Endometrin up to 300 mg/day for up to 10 weeks), Secondary amenorrhea (Crinone 4% 45 mg QOD up to 6 doses; Crinone 8% 90 mg QOD up to 6 doses), Prevention of preterm birth (Crinone 8% 90 mg/day; Endometrin 200 mg/day).see text

inv-05: Dosing and duration

Dosing and maximums by indication:

ART dosing: Crinone 8%: 90 mg QD; for partial/complete ovarian failure Crinone 8%: 90 mg BID (maximum 180 mg/day). Endometrin: 100 mg BID or TID (maximum 300 mg/day). Approvals for ART limited per approval duration policies (see Section I).max doses as stated

Secondary amenorrhea dosing: Crinone 4%: 45 mg every other day up to a total of 6 doses; if Crinone 4% fails, Crinone 8%: 90 mg every other day up to a total of 6 doses. Approval duration: 4 weeks.6 doses

Prevention of preterm birth dosing: Crinone 8%: 90 mg vaginally QD starting at 16–24 weeks gestation and continuing through 34 weeks (some studies to 36 weeks); maximum 90 mg/day. Endometrin: 200 mg vaginally nightly starting 16–24 weeks and continuing through 34 weeks; maximum 200 mg/day. Approval duration: 6 months.gestational age window 16–34 wks

inv-02: Continuation Therapy

Renewal approvals require continued response and limits on cumulative duration/doses depending on indication.

Continuation Criteria

Continuation-1: Member currently receiving medication via Centene benefit or previously met initial approval criteria OR member is currently receiving medication and is enrolled in a state/product with continuity of care regulations.
Refer to state addendums for CC.PHARM.03A and CC.PHARM.03B
Continuation-2: Member is responding positively to therapy.
Continuation-3
- ART-cont: Crinone 8%: not more than 12 weeks total; Endometrin: not more than 10 weeks total.Crinone 8% ≤ 12 weeks; Endometrin ≤ 10 weeks

inv-03: Other diagnoses/indications

Requests not matching the listed indications or recent label changes are handled per formulary/non-formulary or off-label policies.

Other Indications: If the drug has undergone a recent label change (within the last 6 months) not reflected in this policy, refer to the formulary/no-coverage or non-formulary policies for the relevant line of business as specified in policy (e.g., CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16).

Off-label referral: If the requested use is not specifically listed under Section III (Diagnoses/Indications not authorized) and criterion 1 does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

For states not otherwise specified in this policy, infertility drugs that are not listed on the formulary are not payable under this benefit provision unless they are specifically listed on the formulary. Providers should verify formulary status and applicable state addenda when submitting requests or prior authorization documentation.

Requests for use of progesterone products for indications that are not FDA‑approved and are not addressed in this policy will be excluded unless the provider supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policy for the member’s line of business (for example, CP.CPA.09 for commercial, HIM.PA.154 for marketplace, or CP.PMN.53 for Medicaid) or per the evidence of coverage.

When state Medicaid coverage provisions conflict with this clinical policy, the state Medicaid provisions take precedence. Providers and reviewers should consult the applicable state Medicaid manual for specific coverage rules that supersede the clinical policy.

American College of Obstetricians and Gynecologists (ACOG) guidance notes that vaginal progesterone is recommended when a mid‑pregnancy cervical length is ≤ 25 mm. Conversely, ACOG does not support routine use of progesterone for multiple gestations and advises that for a singleton pregnancy with a prior spontaneous preterm birth, vaginal progesterone should not be offered for prevention in the absence of a shortened cervix (per the April 2023 practice advisory).

Coding

Cervical length for short cervix — value used in policy

Cervical length used in policy≤ 25 mm is used as the definition of a short cervix for preterm birth prevention eligibility.

Evidence sourceACOG and clinical trials most frequently use < 25 mm measured mid‑pregnancy (prior to 24 weeks).

Policy applicationRequired for eligibility under the Prevention of Preterm Birth indication in Section I.

Cervical length threshold — ≤ 25 mm

Threshold valueCervical length ≤ 25 mm

Measurement timingMeasured mid‑pregnancy (prior to 24 weeks) per ACOG guidance.

Use in criteria

Provider Actions & Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit required information for Crinone and Endometrin when requesting coverage.

Affected products: Crinone 4% and 8%, Endometrin

Prior Authorization

Prior Authorization and Approval Durations

Approvals are time-limited and issued per indication. Secondary amenorrhea approvals are valid for 4 weeks total; ART treatment approvals are valid for 6 months total; prevention of preterm birth approvals are valid for 6 months total.

Secondary amenorrhea: 4 weeks
ART treatment: 6 months
Prevention of preterm birth: 6 months

Definitions

Short cervix definition used in policy — cervical length ≤ 25 mm

Definition usedShort cervix defined as cervical length ≤ 25 mm.

Measurement contextDefinition applies to mid‑pregnancy cervical length assessment (prior to 24 weeks).

Policy useRequired criterion for Prevention of Preterm Birth indication in this policy.

FDA-approved indications — Crinone 4%/8% and Endometrin intended uses

Crinone 4% indicationIndicated for treatment of secondary amenorrhea.

Crinone 8% indicationsIndicated for progesterone supplementation/replacement as part of ART and for secondary amenorrhea if Crinone 4% failed.

Background

Vaginal progesterone preparations (Crinone and Endometrin) are used primarily for progesterone supplementation in assisted reproductive technology (ART), for treatment of secondary amenorrhea (Crinone 4% FDA‑approved), and off‑label for prevention of preterm birth in patients with a short cervix. A short cervix in this policy is defined as a cervical length ≤ 25 mm. Dosing and duration vary by indication and product (see dosing table), and prior authorization is required for Crinone (4% and 8%) and Endometrin when criteria apply.

Revision History

2025-06-27revisionLatest

Removed prevention-of-preterm-birth criterion requiring concurrent use with Makena due to Makena product discontinuation; added multiple HIM line-of-business evidence-of-coverage (infertility/fertility preservation) updates and added state-specific changes including IL HIM step therapy bypass and GA fertility preservation statutory language.

2024-05-13revision

Removed Milprosa from the policy due to product discontinuation and added evidence-of-coverage language for infertility/fertility preservation for HIM line-of-business (AR, CA, IL, LA, NV, NJ, NC and other states).

Policy Summary

Payermhn

PolicyProgesterone (Crinone, Endometrin) prior authorization

Policy CodePolicy CP.PMN.243

Change TypeMaterial updates — HIM EOC addedMakena concurrent use removed

Effective DateSep 1, 2020

Next Review Date

Key ActionSubmit prior authorization with supporting clinical documentation demonstrating the member meets the indication-specific criteria and dosing/duration limits.

SourceLink

On This Page

Crinone 4%: 45 mg every other day for up to 6 doses.

SA-5b: Crinone 8%: 90 mg every other day for up to 6 doses.

cervical length ≤ 25 mm

PTB-6 Dose limits

PTB-6a: Crinone 8%: 90 mg per day.90 mg/day
PTB-6b: Endometrin: 200 mg per day.200 mg/day

SA-cont: Secondary amenorrhea: patient has not yet received 6 doses of Crinone 4% or 8%.≤ 6 doses

PTB-cont: Prevention of preterm birth: therapy prior to week 37 or delivery (through 36 weeks, 6 days).before 37 weeks gestation

Operational note: Approvals and renewals must be supported by documentation (office chart notes, lab results, or other clinical information) demonstrating continued positive response and that dosing/duration limits are not exceeded.

Member must have a short cervix (≤ 25 mm) to meet Prevention of Preterm Birth criteria.

Gestational age window for prophylaxis — start/continue timing

Start windowBegin prophylaxis at 16–24 weeks gestation

Continue throughContinue through 34 weeks gestation (some studies extend to 36 weeks).

Products/dosing contextCrinone 8%: 90 mg QD; Endometrin: 200 mg nightly (max 200 mg/day) for preterm birth prophylaxis.

Documentation Required

Documentation Requirement — Submit Supporting Clinical Records

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) that supports the member has met all approval criteria. Failure to provide required documentation may result in denial of the request.

Examples of supporting documentation: office notes, lab results, prior authorization history demonstrating prior approvals or current therapy response
Requests for non‑FDA indications must include sufficient evidence per off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53)

Step Therapy

Step Therapy for Secondary Amenorrhea

Step therapy applies for secondary amenorrhea: request for Crinone 4% or 8% requires prior failure of an alternative progestin (e.g., medroxyprogesterone, norethindrone) unless contraindicated or clinically significant adverse effects occurred. Specific state-level exceptions may bypass this requirement.

Step required: failure of an alternative progestin prior to Crinone, unless contraindicated
IL HIM: step therapy bypass added per IL HB 5395 (effective 1/1/2026)

Step Therapy

Step Therapy and Formulary Cross-Reference

Formulary and state/product-specific step therapy exceptions and bypasses may apply. Refer to the plan formulary and applicable state addenda for continuity of care and step therapy bypass provisions.

Check formulary policies and state addendums (e.g., CC.PHARM.03A, CC.PHARM.03B) for continuity of care and bypass rules
State-specific legislative changes (e.g., IL HB 5395) may add bypasses

Step Therapy

Step Therapy — Additional/Not Specified

No other step therapy requirements are specified in this policy beyond those noted for secondary amenorrhea and state-specific exceptions. Verify any additional plan- or state-level requirements before submission.

If unspecified, assume no additional step therapy applies beyond documented criteria and state exceptions

Note

Binding of Providers and Representatives

Providers and their representatives are bound by the terms and conditions of this clinical policy through their contractual relationship with the Health Plan. Where no contract exists, submission of services or claims constitutes agreement to be bound by these terms. Unauthorized copying or distribution of this policy is prohibited.

Providers are independent contractors and not agents of the Health Plan
Submitting claims or providing services indicates agreement to policy terms when no contract exists

Denial Risk

Medicaid Precedence May Affect Denials

For Medicaid members, state Medicaid coverage provisions take precedence when they conflict with this clinical policy. Refer to the applicable state Medicaid manual for coverage determinations; state provisions may change denials or approval outcomes.

State Medicaid rules override this policy when conflicts exist
Consult the state Medicaid manual for specific coverage provisions

Endometrin indication

Indicated to support embryo implantation and early pregnancy as part of an ART treatment program.

Assisted Reproductive Technology (ART) definition

DefinitionAssisted Reproductive Technology (ART)

Context in policyART denotes fertility treatments where progesterone supplementation may be used to support implantation and early pregnancy.

Related appendixAppendix A lists ART as an abbreviation used in the policy.

Short cervix clinical threshold per ACOG — cervical length ≤ 25 mm (mid-pregnancy prior to 24 weeks)

ACOG clinical thresholdCervical length ≤ 25 mm (measured mid‑pregnancy prior to 24 weeks) is used to define a short cervix per ACOG.

Policy linkageThis ACOG threshold is applied in the policy as the requirement for Prevention of Preterm Birth eligibility.

Evidence noteClinical trials most frequently use < 25 mm to define short cervix; ACOG recommends vaginal progesterone when cervical length is ≤ 25 mm.

administrative_update

Applied template changes to 'Other diagnoses/indications' and 'Continuation therapy' sections and updated references.

2021-03-23administrative_update

Updated HIM off-label use reference to HIM.PA.154 and reviewed/updated references (3Q 2021 annual review).