ModifiedCentenePolicy CP PMN.243

Progesterone (Crinone, Endometrin) — Coverage Criteria

Defines medical necessity and authorization criteria for Crinone and Endometrin (vaginal progesterone products) for ART, secondary amenorrhea, and prevention of preterm birth, and describes state-specific fertility/fertility preservation coverage notes affecting members.

Policy Summary

PayerCentene

PolicyProgesterone (Crinone, Endometrin) — Coverage Criteria

Policy CodePolicy CP PMN.243

Change TypeMaterial clinical updates

Effective DateSep 1, 2020

Next Review Date

Key ActionObtain prior authorization and submit clinical documentation demonstrating the member meets the listed initial or continued approval criteria for the requested indication and dosing limits.

SourceLink

POLICY UPDATE CHANGES

For prevention of preterm birth the policy was updated to define short cervix as cervical length < 25 mm per 2023 ACOG practice bulletin.

Removed criterion regarding concurrent use with Makena for prevention of preterm birth due to product discontinuation.

3Primary indications

<25 mmACOG short cervix threshold

300 mgEndometrin max dose

2Crinone strengths referenced

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.

6Secondary amenorrhea dosing episodes

Coverage Criteria

Initial Therapy — Assisted Reproductive Technology (ART)

Covered when ALL of the following are met:

ART Initial Approval: Member must have infertility coverage (optional pharmacy benefit); Age > 18 years; Request is for Crinone 8% or Endometrin; Prescribed as supplementation or replacement of progesterone as part of ART treatment for infertile women; Dose does not exceed specified maximumsCrinone 8%: 180 mg/day for up to 12 weeks; Endometrin: 300 mg/day for up to 10 weeks

All listed elements must be met

Initial Therapy — Secondary Amenorrhea

Covered when ALL of the following are met:

Secondary Amenorrhea Initial Approval: Diagnosis of secondary amenorrhea; Age >= 18 years; Request is for Crinone 4% or 8%; Failure of a progestin product (e.g., medroxyprogesterone, norethindrone) unless contraindicated or clinically significant adverse effects; Dose limits as listedCrinone 4%: 45 mg every other day for up to 6 doses; Crinone 8%: 90 mg every other day for up to 6 doses

For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395

Initial Therapy — Prevention of Preterm Birth (off-label)

Covered when ALL of the following are met:

Prevention of Preterm Birth Initial Approval: Prescribed for prevention of preterm birth (off-label); Age >= 18 years; Gestational age >= 16 weeks; Request is for Crinone 8% or Endometrin; Member has a short cervix (cervical length < 25 mm); Dose does not exceed specified maximumEndometrin: 200 mg/day (per some studies); Crinone 8%: 90 mg/day for prophylaxis (studies start 16–24 weeks and continue through 34–36 weeks)

Approval duration: 6 months

Continued Therapy — Continuation authorized when member meets one of the following and therapy limits not exceeded

Continuation authorized when member meets one of the following and therapy limits not exceeded:

Continued Therapy Conditions: a) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; b) Member is responding positively to therapy; plus indication-specific duration limits not exceededCrinone 8%: total not > 12 weeks; Endometrin: total not > 10 weeks; Crinone 4%/8% for secondary amenorrhea: not > 6 doses

If request is for prevention of preterm birth, therapy not continued beyond 37 weeks gestation (continue through 34–36 weeks per regimen)

Continued Therapy — Covered for continued therapy when ALL of the following are met

Covered for continued therapy when ALL of the following are met:

Continued therapy general: Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; member is responding positively to therapy; member is enrolled in a state/product with continuity of care if applicable.

Documentation must support prior initial approval, positive response, and continuity where applicable

Indication-specific duration and limits: If for ART: member has not exceeded 12 weeks of Crinone 8% (180 mg/day) or 10 weeks of Endometrin (300 mg/day); If for secondary amenorrhea: member has not yet received 6 doses of Crinone 4% or 8%; If for prevention of preterm birth: gestational age has not reached 37 weeks (continue through 34–36 weeks)Crinone 12 weeks; Endometrin 10 weeks; Secondary amenorrhea 6 doses; prevention through 34–36 weeks

If request is for a dose increase, new dose must not exceed listed maximums

Dose and Duration Limits

Covered when dosing and indication-specific limits are met:

ART dosing: Crinone 8%: 90 mg vaginally once daily for typical supplementation (maximum 90 mg/day; for partial/complete ovarian failure may be 90 mg BID up to 180 mg/day); Endometrin: 100 mg vaginally BID or TID (maximum 300 mg/day)Crinone max 180 mg/day; Endometrin max 300 mg/day

ART total duration limits: Crinone up to 12 weeks; Endometrin up to 10 weeks

Secondary amenorrhea dosing: Crinone 4%: 45 mg vaginally every other day up to a total of 6 doses; if 4% fails, Crinone 8%: 90 mg vaginally every other day up to a total of 6 doses6 doses total

Secondary amenorrhea total course typically 4 weeks

Prevention of preterm birth (off-label): Crinone 8%: 90 mg vaginally once daily starting 16–24 weeks gestation and continuing through 34 weeks gestation (some studies extend to 36 weeks); Endometrin: 200 mg vaginally nightly in some studies for prophylaxis

State laws and plan designs may limit coverage for infertility treatments and associated services. The policy notes that some states exclude coverage for procedures and medications intended to achieve conception (for example, artificial insemination, in‑vitro fertilization, GIFT, ZIFT, or other ovum harvesting/manipulation procedures) and that infertility benefits in many jurisdictions are restricted to diagnostic evaluation or to fertility preservation when iatrogenic infertility is anticipated. Providers should verify the member’s specific benefit plan and any state‑mandated fertility provisions prior to authorization.

Requests for non‑FDA approved indications that are not specifically addressed in this policy are excluded unless the provider supplies sufficient clinical evidence of efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for the marketplace, or CP PMN.53 for Medicaid) and the member’s evidence‑of‑coverage requirements.

Use of Crinone or Endometrin is contraindicated in patients with known sensitivity to progesterone or any product ingredient, known or suspected malignancy of the breast or genital organs, active thrombophlebitis or thromboembolic disorders (or a history of hormone‑associated thrombophlebitis/thromboembolism), missed abortion or ectopic pregnancy, liver dysfunction or disease, and for Crinone specifically, undiagnosed vaginal bleeding. These contraindications must be considered when determining medical necessity.

Coverage and payment determinations are governed by the member’s specific coverage documents and applicable contractual terms. This clinical policy is a guide to medical necessity and does not supersede the evidence‑of‑coverage, certificate of coverage, policy, contract of insurance, or other benefit document; providers should follow the Health Plan’s prior authorization procedures and confirm benefit applicability before delivering services.

Current evidence does not support the routine use of vaginal progesterone for prevention of preterm birth in women with multiple gestations or in singleton pregnancy without a short cervix. The policy follows ACOG guidance that vaginal progesterone is recommended when cervical length is ≤ 25 mm; it should not be routinely offered outside those parameters.

Coding and Product References

Product availability / NDC referenceNDC

NDCs not listed

Document lists product strengths and presentation (Crinone gel: 4% = 45 mg, 6 single-use applicators; Endometrin vaginal insert: 100 mg, 21 inserts with disposable applicators)

Short cervix — policy value

Short cervix valueLess than 25 mm (measured mid-pregnancy prior to 24 weeks)

Clinical trial referenceIn clinical trials, < 25 mm most frequently used to define short cervix

ACOG recommendationACOG recommends vaginal progesterone supplementation if cervical length is 25 mm or less

Cervical length threshold

Cervical length threshold<= 25 mm

Measurement timingMeasured mid-pregnancy (prior to 24 weeks gestation)

Use in criteria

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required — provider must demonstrate the member meets the listed initial approval criteria for the requested indication and submit documentation. Providers should follow plan-specific prior authorization processes and timelines when requesting coverage for Crinone or Endometrin.

Affected products: Crinone (4% and 8%) and Endometrin
Prior authorization required for ART treatment, secondary amenorrhea, and prevention of preterm birth per policy criteria

Prior Authorization

Prior Authorization for Continued Therapy

Prior authorization is required for continued therapy. Requests for renewal/continuation must document that the member previously met initial approval criteria and is responding positively to therapy. For ART, member should not have exceeded the maximum approved duration (Crinone 8% up to 12 weeks; Endometrin up to 10 weeks) unless otherwise specified in the continued therapy criteria.

Member has previously met initial approval criteria
Member is responding positively to therapy

Background

Vaginal progesterone formulations (Crinone gel and Endometrin inserts) are used clinically for progesterone supplementation in assisted reproductive technology (ART) cycles, for treatment of secondary amenorrhea when indicated per product labeling, and in selected off‑label use for prevention of preterm birth in patients with a short cervix. The policy aligns authorization criteria with FDA‑approved indications for Crinone and Endometrin and references ACOG guidance on the definition of a short cervix (< 25 mm) when considering therapy for preterm birth prevention.

Definitions

Assisted Reproductive Technology (ART) — definition

ART definition (short)Assisted Reproductive Technology: progesterone supplementation or replacement as part of an ART treatment for infertile women

Purpose in policyUsed to describe indication when Crinone or Endometrin are prescribed to support embryo implantation or corpus luteal function in ART

Products referencedCrinone and Endometrin noted as ART-supporting products

Short cervix — policy definition

Short cervix (policy definition)Cervical length < 25 mm for purposes of prevention of preterm birth criteria

Applied indicationUsed to authorize off-label prevention of preterm birth when other criteria met

Policy Summary

PayerCentene

PolicyProgesterone (Crinone, Endometrin) — Coverage Criteria

Policy CodePolicy CP PMN.243

Change TypeMaterial clinical updates

Effective DateSep 1, 2020

Next Review Date

Key ActionObtain prior authorization and submit clinical documentation demonstrating the member meets the listed initial or continued approval criteria for the requested indication and dosing limits.

SourceLink

On This Page

Start 16–24 weeks; continue through 34–36 weeks; Endometrin 200 mg/day (study-based)

Routine use for multiple gestations or singleton without short cervix is not supported

Threshold used for prevention of preterm birth coverage criteria

Duration limits: ART — Crinone 8%: up to 12 weeks; Endometrin: up to 10 weeks

Note

Prior Authorization Guidance

Policy guides medical necessity determinations used to inform coverage and prior authorization decisions. Coverage is subject to the member's evidence of coverage, contract terms, and applicable state/federal requirements. Providers are expected to exercise professional judgment and follow Health Plan processes.

This clinical policy is a guide to medical necessity and not a guarantee of payment
Coverage decisions subject to plan terms, exclusions, and state/federal law

Documentation Required

Provider must submit clinical documentation supporting that the member has met all approval criteria. Acceptable documentation includes office chart notes, relevant laboratory results, diagnostic reports, and prior authorization forms. Failure to submit supporting documentation may result in denial.

Examples: office chart notes, lab results, ART treatment records
Lack of supporting documentation may trigger denial

Denial Risk

Off-Label Indications Without Documentation

Requests for non–FDA-approved (off-label) indications that are not specifically addressed in this policy will be denied unless sufficient documentation of efficacy and safety is provided per the applicable off-label use policies (CP.CPA.09 for commercial, HIM.PA.154 for HIM, CP PMN.53 for Medicaid) or evidence of coverage documents.

Off-label requests must reference and meet applicable off-label policy requirements
Policy lists certain off-label use dosing (e.g., prevention of preterm birth) but non-addressed indications require off-label documentation

Documentation Required

Clinical Documentation

Clinical documentation must demonstrate the specific indication and supporting clinical facts per the criteria: e.g., diagnosis of secondary amenorrhea or documentation of infertility/ART plan, patient age (>18 where required), prior treatment history (including failure of a progestin for secondary amenorrhea unless contraindicated), prescribed product and dose, and response to therapy for continuation requests.

Document indication (ART, secondary amenorrhea, prevention of preterm birth)
Age and infertility coverage status where applicable
Prior treatment history (e.g., trial/failure of progestin for secondary amenorrhea)
Specify product (Crinone 4% or 8%; Endometrin) and dosing regimen

Step Therapy

Step Therapy for Secondary Amenorrhea

Step therapy for secondary amenorrhea: prior to approval, documentation must show failure of a progestin product (for example, medroxyprogesterone or norethindrone), unless the progestin is contraindicated or the member experienced clinically significant adverse effects. For Illinois HIM requests, step therapy bypasses may apply per IL HB 5395 as noted in state-specific policy modifications.

Required step: trial and failure of an oral progestin (e.g., medroxyprogesterone, norethindrone) unless contraindicated
If 4% Crinone fails, 8% Crinone may be attempted per dosing guidance
State modification: IL HIM step therapy bypass per HB 5395

Reference authorityAligned with ACOG and clinical trial definitions cited in policy

Assisted Reproductive Technology — short label

ART (short label)ART

Expanded termAssisted Reproductive Technology — supportive progesterone use in infertility treatment

Appendix referenceART listed in Appendix A abbreviations

Cervical length — short cervix threshold

Cervical length ≤ 25 mmDefined as short cervix when measured mid-pregnancy (prior to 24 weeks) and used to determine eligibility for progesterone to prevent preterm birth

TimingAssessment performed prior to 24 weeks gestation (mid-pregnancy)

Policy actionPresence of this measurement is required in prevention of preterm birth initial approval criteria

'Health Plan' definition

'Health Plan' definitionHealth Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan's affiliates.

ScopeDefinition applies to any health plan using this clinical policy

Policy contextCoverage decisions remain subject to the terms, conditions, exclusions, and limitations of the Health Plan's coverage documents