CurrentCignaPolicy 1012

Injectable fertility medications (gonadotropins, hCG, leuprolide, menotropins)

This Cigna coverage policy governs medical necessity review and authorization of injectable fertility medications (including follitropins, hCG, leuprolide, and menotropins) when benefits are available under a member's plan; it affects providers requesting coverage and members receiving these agents.

Policy Summary

PayerCigna

PolicyInjectable fertility medications (gonadotropins, hCG, leuprolide, menotropins)

Policy CodePolicy 1012

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionDocument a complete clinical evaluation and required monitoring (including ultrasound and serum estradiol) and submit that documentation with any prior authorization request.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Up to 12 monthsInitial and reauthorization approval duration

MultipleNamed injectable agents covered when criteria met

Experimental/Not coveredOther uses

MultipleFDA‑labeled products discussed

OHSS warningsOHSS precautions repeated

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.

Medical Necessity and Coverage Criteria

Product-specific Medical Necessity Criteria

Covered when the listed product-specific criteria are met:

Chorionic Gonadotropin (Novarel, Pregnyl, chorionic gonadotropin): Considered medically necessary when ONE of the following are met: 1) Ovulation induction in females undergoing infertility treatment; 2) Ovulation induction in females undergoing fertility preservation; 3) Males with documented hypogonadotropic hypogonadism.1 of 3

Follistim AQ (follitropin beta): Considered medically necessary when BOTH of the following are met: 1) ONE of: a) Ovulation induction in females undergoing infertility treatment; b) Ovulation induction in females undergoing fertility preservation; c) Males with documented hypogonadotropic hypogonadism; AND 2) ONE of: a) Documentation of failure with Gonal-f; b) Patient has been started on a current cycle of therapy with Follistim AQ.all of the two conditions

Gonal-f (follitropin alfa): Considered medically necessary when ONE of the following are met: 1) Ovulation induction in females undergoing infertility treatment; 2) Ovulation induction in females undergoing fertility preservation; 3) Males with documented hypogonadotropic hypogonadism.1 of 3

Leuprolide acetate / Lupron (various formulations): Considered medically necessary when there is documentation that the medication is being used for treatment of female infertility.documentation of use for female infertility

Menopur (menotropins): Considered medically necessary when ONE of the following are met: 1) Ovulation induction in females undergoing infertility treatment; 2) Ovulation induction in females undergoing fertility preservation; 3) Males with documented hypogonadotropic hypogonadism.1 of 3

Ovidrel (choriogonadotropin alfa): Considered medically necessary when ONE of the following are met: 1) Ovulation induction in females undergoing infertility treatment; 2) Ovulation induction in females undergoing fertility preservation.1 of 2

Reauthorization

Continuation covered when:

Reauthorization of injectable fertility medications: Continuation is considered medically necessary when the above medical necessity criteria continue to be met.criteria still met

FDA-indicated coverage criteria and monitoring prerequisites

Coverage-aligned indications and required conditions (presented as FDA/clinical prerequisites):

Female reproductive indications: Induction of ovulation and development of multiple follicles for ART: prior to initiation perform a complete gynecologic and endocrinologic evaluation; exclude primary ovarian failure; exclude pregnancy; demonstrate tubal patency when applicable; and evaluate the fertility status of the male partner.N/A

See product-specific dosing and OHSS precautions.

Male reproductive indications: Induction of spermatogenesis in men with hypogonadotropic hypogonadism in whom infertility is not due to primary testicular failure: perform a complete medical and endocrinologic evaluation; confirm hypogonadotropic hypogonadism and exclude primary testicular failure; normalize serum testosterone with hCG prior to combined FSH therapy when indicated.N/A

Treatment response may take months; dosing individualized.

OHSS and monitoring:

Dosing, monitoring, and trigger criteria

Covered when ALL of the following dosing and monitoring conditions are met:

Dosing initiation and population: Begin gonadotropin therapy on cycle day 2 or 3 with recommended starting dose individualized by age and pituitary suppression status (examples: Gonal-f RFF 150 IU/day for women <35 whose endogenous gonadotropins are suppressed; Gonal-f RFF 225 IU/day for women ≥35 when suppressed; Menopur initial 225 IU/day when suppressed).

References: product dosing guidance

Monitoring for response: Adjust dose based on ultrasound evaluation of follicular growth combined with serum estradiol measurements; document ovarian response and estradiol prior to dose changes. Do not make additional dosage adjustments more frequently than specified (Gonal-f: not more frequently than every 3–5 days and by no more than 75–150 IU per adjustment; Menopur: not more frequently than every 2 days and not by more than 150 IU per adjustment).

Dose adjustment intervals and magnitude per product labeling.

Duration limits: Limit therapy duration according to product guidance (Gonal-f RFF: therapy should not exceed about 10 days in most cases; Menopur: therapy should not exceed 20 days).

Injectable fertility medications (including follitropins, menotropins, hCG, and leuprolide) are governed by this medical necessity policy and are covered only when the specific product-level criteria in this policy are met. These agents are specifically excluded under most benefit plans; providers must confirm benefit availability in the applicable plan document and meet the policy’s stated medical necessity requirements for coverage.

Human chorionic gonadotropin (hCG) has not been demonstrated to be effective as an adjunctive therapy for obesity or for weight-loss indications. hCG is not effective for weight loss and should not be used for obesity management or related indications.

Administration of hCG (including Ovidrel or urinary chorionic gonadotropin preparations) must be withheld when ovarian monitoring indicates an excessive ovarian response. Examples include multiple follicular development, clinically significant ovarian enlargement, or excessive estradiol production. Additionally, when using Menopur, withhold hCG on the last day of Menopur therapy if monitoring suggests an increased risk of ovarian hyperstimulation syndrome (OHSS).

Any use of injectable fertility medications that is not listed in the policy’s medical necessity criteria is considered not medically necessary, experimental, investigational, or unproven and may be denied.

When dosing Menopur (alone or in combination with Bravelle), do not administer daily doses that exceed 450 International Units. Dose adjustments should follow the product guidance and documented monitoring.

Billing Codes and Drug Presentations

Considered Medically Necessary when criteria metHCPCSCovered

J0725	Injection, chorionic gonadotropin, per 1,000 USP units.
J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J3355	Injection, urofollitropin, 75 IU.
J3490	Unclassified drugs.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.
S0122	Injection, menotropins, 75 IU.
S0126	Injection, follitropin alfa, 75 IU.
S0128	Injection, follitropin beta, 75 IU.

Drug presentations and strengthsmixed

175 IU per 0.210 mL; 350 IU per 0.420 mL; 650 IU per 0.780 mL; 975 IU per 1.170 mL	Follistim AQ cartridge presentations (follitropin beta).
600 IU or 1200 IU vials	Gonal-f lyophilized multiple dose vial (follitropin alfa) — yields 450 IU and 1050 IU FSH after reconstitution.
82 IU vial → delivers 75 IU	Gonal-f RFF single-dose vial (after reconstitution).
300 IU, 450 IU, 900 IU	Gonal-f RFF Redi-ject prefilled disposable delivery systems.
250 µg in 0.5 mL	Ovidrel prefilled syringe choriogonadotropin alfa.
10,000 USP units per vial	Chorionic gonadotropin multiple dose vial.
5,000 or 10,000 USP units	Novarel vial presentations.
75 IU FSH + 75 IU LH per vial	Menopur lyophilized powder presentation.
Leuprolide acetate 14 mg/2.8 mL; Lupron Depot 3.75 mg	Leuprolide depot presentations.

Dose adjustment interval — Adjust dose after specified days; frequency limits

Dose adjustment timing (Gonal‑f RFF)Adjust the dose after 5 days based on ovarian response (ultrasound + serum estradiol); do not adjust more frequently than every 3–5 days or by more than 75–150 IU per adjustment.

Dose adjustment timing (Menopur)Adjust the dose after 5 days based on ovarian response (ultrasound + serum estradiol); do not make additional dosage adjustments more frequently than every 2 days or by more than 150 IU per adjustment.

Basis for adjustmentsDose adjustments must be guided by ultrasound assessment of follicular growth combined with serum estradiol measurements; document response prior to changes.

Maximum daily Menopur — 450 International Units

Maximum daily MenopurDo not administer daily doses of Menopur or Menopur combined with Bravelle that exceed 450 International Units.

Provider Requirements, Documentation, and Authorization

Prior Authorization

Prior authorization and codes

Certain injectable fertility medications may require review under the medical benefit. Depot leuprolide codes (e.g., J1950, J9217) may apply when the medical benefit is used.

When covered by medical benefit, pre-certification is not required for some depot leuprolide codes (see coding guidance).
Relevant HCPCS: J1950, J9217.

Documentation Required

Clinical prerequisites and monitoring

Documented clinical evaluation and monitoring consistent with product labeling must be submitted to support authorization. This includes exclusion of primary ovarian or testicular failure and appropriate endocrine/gynecologic assessments.

Exclude primary ovarian failure (women) or primary testicular failure (men) prior to therapy.
Provide gynecologic and endocrinologic evaluation notes and pregnancy exclusion for women.

Background and Scope

Injectable fertility therapies in this policy include several pharmacologic classes with distinct clinical roles: follitropins (recombinant or urinary FSH preparations such as Gonal‑f and Follistim AQ) are used to induce ovulation, stimulate follicular development for assisted reproductive technology (ART), and to stimulate spermatogenesis in men with hypogonadotropic hypogonadism; menotropins (e.g., Menopur) provide combined FSH and LH activity to support follicular development in ovulation induction and ART; human chorionic gonadotropin (hCG) (urinary products such as Novarel/Pregnyl and recombinant choriogonadotropin alfa, Ovidrel) mimics luteinizing hormone to trigger final follicular maturation and support the corpus luteum; and GnRH agonists (leuprolide/Lupron) are used to suppress pituitary gonadotropin release to prevent premature ovulation during controlled ovarian stimulation. These agents are used in ovulation induction, ART cycles, fertility preservation, and in men to induce spermatogenesis when hypogonadotropic hypogonadism is documented.

Definitions and Drug Class Descriptions

Follitropins — FSH preparations description and clinical use

DefinitionFollitropins are FSH preparations (recombinant or urinary) used to induce ovulation, stimulate follicular development for IVF/ICSI, and stimulate spermatogenesis in males with hypogonadotropic hypogonadism.

Product typesIncludes urofollitropin (urinary FSH) and recombinant follitropin alfa and beta produced in CHO cells; these preparations contain no LH activity.

Clinical useUsed in anovulatory/oligoovulatory patients, patients with unexplained infertility, and patients undergoing ART; typically used with GnRH agonists to prevent premature ovulation and with hCG to trigger ovulation after follicular maturation.

Leuprolide (GnRH agonist) — Mechanism and use to prevent premature ovulation

MechanismLeuprolide is a synthetic GnRH analog that initially increases FSH and LH secretion but with continuous administration (1–3+ weeks) causes pituitary down-regulation and marked suppression of FSH and LH.

Policy Summary

PayerCigna

PolicyInjectable fertility medications (gonadotropins, hCG, leuprolide, menotropins)

Policy CodePolicy 1012

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionDocument a complete clinical evaluation and required monitoring (including ultrasound and serum estradiol) and submit that documentation with any prior authorization request.

SourceLink

On This Page

During treatment and for a two-week post-treatment period, assess at least every other day for signs of excessive ovarian stimulation; withhold hCG and consider stopping FSH if ovarian monitoring suggests an increased risk of ovarian hyperstimulation syndrome (OHSS).

Assess every other day during treatment and two-week post-treatment period

Multiple product entries repeat this precaution.

hCG trigger criteria: Administer hCG trigger (e.g., Ovidrel prefilled syringe 250 µg or 5,000–10,000 IU urinary hCG per labeling) only when adequate follicular development is evident by ultrasound and serum estradiol; withhold hCG if monitoring suggests excessive ovarian response or increased OHSS risk.

Dose maxima: Do not exceed maximum daily doses where specified (for example, do not administer daily doses of Menopur alone or in combination with Bravelle that exceed 450 International Units).

Combination dosing noteWhen Menopur is combined with Bravelle, total initial combined doses should not exceed product-specified limits and daily combined dosing must remain ≤450 IU.

Therapy duration limitTherapy with Menopur should not exceed 20 days.

Provide fertility status evaluation of male partner when applicable.

Note

Drug availability to support authorization

Provide exact product presentation and strength for the drug requested to support authorization (NDC or descriptive presentation acceptable).

Follistim AQ cartridges: 175 IU, 350 IU, 650 IU, 975 IU.
Gonal-f: single-dose vials and Redi-ject presentations (75 IU per reconstituted vial; 300, 450, 900 IU Redi-ject).
Ovidrel: prefilled syringe 250 µg; Novarel/Pregnyl: 5,000 or 10,000 USP units; Menopur: 75 IU FSH/75 IU LH vials.
Lupron/Lupron Depot presentations as listed.

Step Therapy

Product-specific prior trial requirement

Some products require documentation of prior trial or prior start of therapy before coverage (product-specific). Include documentation of prior failure or current-cycle start where required.

Follistim AQ: documentation of failure with Gonal-f OR documentation that patient has been started on current cycle of therapy with Follistim AQ.
Include dates and outcomes of prior therapy trials when applicable.

Documentation Required

hCG pretreatment before FSH in men

For men with hypogonadotropic hypogonadism, pretreatment with hCG to normalize testosterone is required prior to initiating FSH therapy (per labeling). Provide serum testosterone levels and hCG dosing history.

Initial hCG dosing example: 1,500 IU twice weekly (or 1,000–2,250 USP units two to three times weekly per Gonal-f labeling) until testosterone normalizes.
If testosterone not normalized after specified period, document dose escalation and duration.

Step Therapy

Stepwise individualized dosing

Dosing must follow a stepwise, individualized titration plan with defined starting doses and scheduled adjustments supported by monitoring data.

Follistim AQ example (anovulatory): start 50 IU daily for ≥7 days; adjust by 25–50 IU at weekly intervals; maximum individualized daily dose 250 IU (or per formulation guidance).
Gonal‑f RFF Redi‑ject (ART): start 150 IU daily (or 225 IU if ≥35 and suppressed); adjust after 5 days; do not change more frequently than every 3–5 days or by >75–150 IU at each adjustment.
Menopur (ART): typical start 225 IU, adjust after 5 days; do not adjust more frequently than every 2 days or by >150 IU per adjustment; do not exceed 450 IU daily.

Documentation Required

Required clinical documentation

Required clinical documentation must be submitted with authorization requests, including baseline and monitoring data per product labeling.

Complete gynecologic and endocrinologic evaluation (women) and exclusion of primary ovarian failure.
Documentation of tubal patency and fertility evaluation of male partner when indicated.
Baseline and follow-up monitoring data (ultrasound follicular measurements, serum estradiol, serum testosterone for men) and dates of assessments.

Documentation Required

Pre-treatment evaluations

Pre-treatment evaluations specified in FDA labeling must be completed and documented prior to initiation of therapy.

Women: complete gynecologic and endocrinologic evaluation, exclude pregnancy, demonstrate tubal patency, evaluate male partner fertility.
Men: thorough medical and endocrinologic evaluation, confirm hypogonadotropic hypogonadism, exclude primary testicular failure, document gonadotropin levels.

Documentation Required

Document ultrasound and estradiol for dose adjustments

Dose adjustments and treatment continuation must be based on ultrasound assessment of follicular growth and serum estradiol measurements; document values and dates.

Provide serial ultrasound follicle measurements and serum estradiol levels used to justify dose changes.
Document frequency of monitoring and any protocol to reduce/stop dosing in high responders.

Denial Risk

Unsupported Indications

Uses not specified in the coverage criteria or FDA indications are considered experimental/investigational and may be denied.

Any indication not listed as medically necessary in the applicable product criteria should be considered not covered.
Include supporting clinical rationale if requesting consideration for atypical use.

Documentation Required

OHSS monitoring requirement

Ovarian Hyperstimulation Syndrome (OHSS) risk must be actively monitored; withhold hCG trigger when monitoring suggests increased OHSS risk and document monitoring results and decisions.

Withhold hCG on the last day of Follistim AQ, Gonal‑f RFF, Menopur, or other follicle‑stimulating therapy when ultrasound/estradiol indicate increased OHSS risk.
Document signs of excessive ovarian response (multiple follicles, ovarian enlargement) and elevated estradiol values leading to withholding of hCG.
Advise clinical follow-up frequency during treatment and for two weeks post-treatment as recommended.

Denial Risk

Withhold hCG if excessive ovarian response / Withhold hCG for OHSS risk

Specific operational instruction: withhold hCG (including Ovidrel) when excessive ovarian response or OHSS risk is identified; document the decision.

Ovidrel should be withheld when monitoring indicates excessive response (multiple follicles, significant ovarian enlargement, or excessive estradiol).
Menopur guidance: withhold hCG on last day of therapy if monitoring suggests increased OHSS risk.

Physiologic effect timelineTransient hormone rise in the first week followed by suppression to castrate or postmenopausal levels within 2–3 weeks; normal function typically returns within ~3 months after stopping therapy.

Clinical useUsed to suppress the pituitary and prevent premature ovulation during controlled ovarian stimulation protocols (GnRH agonist co-treatment).

Human Chorionic Gonadotropin (hCG) — Role as LH mimic and product forms

RolehCG is a placentally-derived hormone that mimics pituitary LH activity and is used to trigger ovulation and support corpus luteum function.

Product formsAvailable as urinary-derived chorionic gonadotropin (Novarel, Pregnyl) and recombinant choriogonadotropin alfa (Ovidrel prefilled syringe 250 µg).

Mechanism notehCG stimulates gonadal steroid production by acting like LH and has minor FSH activity; it substitutes for the mid-cycle LH surge to induce ovulation.

Hypogonadotropic hypogonadism (HH) — Definition and relevance to spermatogenesis induction

DefinitionHypogonadotropic hypogonadism (HH) is a form of secondary hypogonadism characterized by low gonadotropin levels (FSH/LH) where infertility is due to hypothalamic or pituitary dysfunction rather than primary testicular failure.

Relevance to treatmentInduction of spermatogenesis in men with HH is accomplished with hCG (to normalize testosterone) and concomitant FSH or HMG therapy; primary testicular failure must be excluded before treatment.

Treatment sequencingMen should have HH confirmed and achieve normalization of serum testosterone with hCG pretreatment prior to initiating combined FSH therapy for spermatogenesis.

Ovarian Hyperstimulation Syndrome — Definition and contraindication for hCG trigger

DefinitionOvarian Hyperstimulation Syndrome (OHSS) is a clinically significant excessive ovarian response marked by multiple follicular development, ovarian enlargement, and/or excessive estradiol production.

Clinical implicationAdministration of hCG (e.g., Ovidrel) should be withheld when monitoring indicates an excessive ovarian response or increased risk of OHSS; withhold hCG if monitoring suggests increased OHSS risk on the last day of stimulation.

Trigger administration criteriaDo not administer hCG until adequate follicular development is confirmed by serum estradiol and vaginal ultrasonography; withhold when excessive response is evident.