Pharmacy Prior Authorization Criteria

Gonadotropins - PA, NF

Indications for Prior Authorization

Follistim AQ (follitropin beta)

• For diagnosis of Ovulation Induction
  Indicated for the induction of ovulation and pregnancy in anovulatory infertile women in whom the cause of infertility is functional and not due to primary ovarian failure.

• For diagnosis of Spermatogenesis Induction
  Indicated for the induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism (HH) in whom the cause of infertility is not due to primary testicular failure.

• For diagnosis of Ovarian Stimulation in association with Assisted Reproductive Technology
  Indicated for pregnancy in normal ovulatory women undergoing controlled ovarian stimulation as part of an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle.

Gonal-F (follitropin alfa)

• For diagnosis of Ovulation Induction
  Indicated for the induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure.

• For diagnosis of Ovarian Stimulation in association with Assisted Reproductive Technology
  Indicated for the development of multiple follicles in ovulatory infertile women as part of an assisted reproductive technology (ART) cycle.

• For diagnosis of Spermatogenesis Induction
  Indicated for the induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism for whom the cause of infertility is not due to primary testicular failure.

Gonal-F RFF (follitropin alfa)

• For diagnosis of Ovarian Stimulation in association with Assisted Reproductive Technology [1-5]
  Indicated for the development of multiple follicles in ovulatory infertile women as part of an assisted reproductive technology (ART) cycle.

• For diagnosis of Ovulation Induction
  Indicated for the induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure.

• For diagnosis of Spermatogenesis Induction [6, 7]
  Used for the treatment of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.

Gonal-F RFF Redi-ject (follitropin alfa)

• For diagnosis of Ovarian Stimulation in association with Assisted Reproductive Technology [1-5]
  Indicated for the development of multiple follicles in ovulatory women as part of an assisted reproductive technology (ART) cycle.

• For diagnosis of Ovulation Induction
  Indicated for the induction of ovulation and pregnancy in oligo-anovulatory women in whom the cause of infertility is functional and not due to primary ovarian failure.

• For diagnosis of Spermatogenesis Induction [6, 7]
  Used for the treatment of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.

Menopur (menotropins)

• For diagnosis of Ovarian Stimulation in association with Assisted Reproductive Technology
  Indicated for the development of multiple follicles and pregnancy in ovulatory women as part of an Assisted Reproductive Technology (ART) cycle.

• For diagnosis of Ovulation Induction [6, 7]
  Used for the treatment of ovulation induction in patients with polycystic ovary syndrome who failed on clomiphene. The ovulation rate compared to Gonal-f was non-inferior, at rates of 85.7% and 85.5% respectively. [8] In other studies, rates of ovulation of 95% and pregnancy rates of 58% to 72% are demonstrated. Because of its high cost, higher incidence of serious side effects, and difficult of administration menotropins are usually reserved to treat patients who have failed to respond to therapy with clomiphene. [9]

• For diagnosis of Spermatogenesis Induction [6, 7]
  Used for the treatment of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure.

Criteria

Follistim AQ

Prior Authorization

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Ovulation Induction

• Provided it is not a benefit exclusion
AND
• Diagnosis of anovulatory infertility
AND
• Infertility is not due to primary ovarian failure
AND
• For induction of ovulation
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Gonal-f, Gonal-f RFF, Gonal-f RFF Redi-ject, Menopur (off-label)

Prior Authorization

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Ovulation Induction

• Provided it is not a benefit exclusion
AND
• Diagnosis of anovulatory infertility
AND
• Infertility is not due to primary ovarian failure
AND
• For induction of ovulation
AND
• One of the following:
• Trial and failure, intolerance, or contraindication to Follistim AQ (follitropin beta) [A]
OR
• Patient has a condition that requires use of drug that contains both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (applies to Menopur only)
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Gonal-f, Gonal-f RFF, Gonal-f RFF Redi-ject

Non Formulary

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Ovulation Induction

• Provided it is not a benefit exclusion
AND
• Submission of medical records (e.g., chart notes) confirming diagnosis of anovulatory infertility
AND
• Submission of medical records (e.g., chart notes) confirming infertility is not due to primary ovarian failure
AND
• For induction of ovulation
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming trial and failure, intolerance, or contraindication to Follistim AQ (follitropin beta) [A]
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Follistim AQ

Prior Authorization

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Ovarian Stimulation

• Provided it is not a benefit exclusion
AND
• Diagnosis of infertility
AND
• For the development of multiple follicles (ovarian stimulation) in an ovulatory female patient participating in an Assisted Reproductive Technology (ART) program
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Gonal-f, Gonal-f RFF, Gonal-f RFF Redi-ject, Menopur

Prior Authorization

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Ovarian Stimulation

• Provided it is not a benefit exclusion
AND
• Diagnosis of infertility
AND
• For the development of multiple follicles (ovarian stimulation) in an ovulatory female patient participating in an Assisted Reproductive Technology (ART) program
AND
• One of the following:
• Trial and failure, intolerance, or contraindication to Follistim AQ (follitropin beta) [B]
OR
• Concomitant use with Follistim AQ is required (applies to Menopur only)
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Gonal-f, Gonal-f RFF, Gonal-f RFF Redi-ject

Non Formulary

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Ovarian Stimulation

• Provided it is not a benefit exclusion
AND
• Submission of medical records (e.g., chart notes) confirming diagnosis of infertility
AND
• For the development of multiple follicles (ovarian stimulation) in an ovulatory female patient participating in an Assisted Reproductive Technology (ART) program
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming trial and failure, intolerance, or contraindication to Follistim AQ (follitropin beta) [B]
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Follistim AQ

Prior Authorization

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Male Hypogonadotropic Hypogonadism

• Provided it is not a benefit exclusion
AND
• One of the following:
• Diagnosis of male primary hypogonadotropic hypogonadism
• Diagnosis of male secondary hypogonadotropic hypogonadism
AND
• For induction of spermatogenesis
AND
• Infertility is not due to primary testicular failure
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Gonal-f, Gonal-f RFF (off-label), Gonal-f RFF Redi-ject (off-label), Menopur (off-label)

Prior Authorization

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Male Hypogonadotropic Hypogonadism

• Provided it is not a benefit exclusion
AND
• One of the following:
• Diagnosis of male primary hypogonadotropic hypogonadism
• Diagnosis of male secondary hypogonadotropic hypogonadism
AND
• For induction of spermatogenesis
AND
• Infertility is not due to primary testicular failure
AND
• Trial and failure, intolerance, or contraindication to Follistim AQ (follitropin beta) [C]
AND
• Prescribed by or in consultation with a reproductive endocrinologist

Gonal-f, Gonal-f RFF (off-label), Gonal-f RFF Redi-ject (off-label)

Non Formulary

Length of Approval: 2 months [D] (or per plan benefit design)
For diagnosis of Male Hypogonadotropic Hypogonadism

• Provided it is not a benefit exclusion
AND
• Submission of medical records (e.g., chart notes) confirming one of the following:
• Diagnosis of male primary hypogonadotropic hypogonadism
• Diagnosis of male secondary hypogonadotropic hypogonadism
AND
• For induction of spermatogenesis
AND
• Submission of medical records (e.g., chart notes) confirming infertility is not due to primary testicular failure
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming trial and failure, intolerance, or contraindication to Follistim AQ (follitropin beta) [C]
AND
• Prescribed by or in consultation with a reproductive endocrinologist

P & T Revisions

2025-06-27, 2024-08-19, 2023-09-21, 2022-09-22, 2022-07-25, 2022-04-19, 2021-12-01, 2021-09-23, 2020-07-20

References

1. Gonal-F prescribing information. EMD Serono, Inc. Rockland, MA. November 2023.
2. Gonal-F RFF prescribing information. EMD Serono, Inc. Rockland, MA. November 2023.
3. Gonal-F RFF Redi-ject prescribing information. EMD Serono, Inc. Rockland, MA. May 2024.
4. Follistim AQ prescribing information. Organon USA LLC. Jersey City, NJ. July 2023.
5. Menopur prescribing information. Ferring Pharmaceuticals, Inc. Parsippany, NJ. May 2018.
6. DRUGDEX System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically. Accessed July 29, 2024.
7. Lexicomp Online [Internet database]. Waltham, MA: UpToDate, Inc.; July 30, 2021. https://online.lexi.com. Accessed July 29, 2024.
8. Platteua P, Andersen AN, Balen A, et al. Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study. Hum. Reprod. 2006;21:1798-1804.
9. Kelly AC, Jewlewicz R. Alternate regimens for ovulation induction in polycystic ovarian disease. Fertil Steril. 1990;54;195-202.
10. Lawson R, El-Toukhy T, Kassab, A. Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: a life table analysis. Human Reprod. 2003;18: 327-533
11. Fasouliotis SJ, Simon A, Laufer N. Evaluation and treatment of low responders in assisted reproductive technology: a challenge to meet. J Assist Reprod Genet. 2000;17(7)357-73.
12. Warne, DW, Decosterd G, Okada H, et al. A Combined analysis of data to identify predictive factors for spermatogenesis with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril. 2009 Aug; 92(2):592-604.
13. Wei Z, Cheng X, Li H, et al. Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization. Reprod Biol Endoctrinol 2010;8:26.
14. Mahutte NG, Arici A. Role of gonadotropin-releasing hormone antagonist in poor responders Fertil Steril. 2007 Feb;87(2):241-98.
15. Surrey ES, Schoolcraft WB. Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques. Fertil Steril. 200 Apr; 73(4):667-76.:
16. Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94(3):801-8.
17. The Practice Committee of the American Society for Reproductive Medicine. Use of exogenous gonadotropins in anovulatory women: a technical bulletin. Fertil Steril. 2008;90:S7-12.
18. Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients - 2002 update. Endocr Pract. 2002;8:440-456.
19. Liu PY, Turner L, Rushford D, et al. Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men. Hum Reprod. 1999;14:1540-1545.
20. Per clinical consult with reproductive endocrinologist, April 10, 2013.

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End Notes

1. There is no consensus definition of poor responder to gonadotropins in the setting of ovulation induction. [10-11, 13-15] One study looked at ovulation induction failure with gonadotropin specifically. [10] Poor response in this study was defined as maximum dose of 450 IU gonadotropin daily for 9 days and either: (i) < 4 oocytes obtained at oocyte retrieval, or (ii) cycle cancellation prior to oocyte retrieval because of poor follicular development (< 3 follicles of > 14 mm after 9-12 days of stimulation).
2. There is no consensus definition of poor responder to gonadotropins in the setting of ovarian stimulation in association with ART. [10-11, 13-15] The most cited definition of poor responders was: number of mature follicles < 2-5; number of mature oocytes retrieved < 3: single dominant follicle; mean daily gonadotropin dose > 300 IU; and total gonadotropin dose > 40 ampules. [10]
3. There is no consensus definition of poor responder to gonadotropins in the setting of spermatogenesis induction in men with hypogonadotropic hypogonadism. Outcomes measured for response include time to achieve first sperm, time to conception, and sperm concentration, but poor response was not well-defined. [12, 16] A combined analysis looked at four clinical trials and used the common efficacy outcome of spermatozoa concentration of greater than or equal 1.5 x 10^6 /mL. [12]
4. Sixty days would be a reasonable length of authorization for all of the indications. [20]

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Revision History

• 2025-06-27: June Medispan Off-cycle GPI reclassification
• 2024-08-19: 2024 annual review: updated NF criteria to require submission of medical records confirming diagnosis for all indications, confirming infertility is not due to primary ovarian failure for ovulation induction, and confirming infertility is not due to primary testicular failure for hypogonadotropic Hypogonadism. Background updates.
• 2023-09-21: 2023 Annual review: Updated "controlled ovarian hyperstimulation" to "ovarian stimulation" per standard medical terminology with no change in intent. Background updates.
• 2022-09-22: Annual review: Updated embedded step for "ovulation induction" and "controlled ovarian stimulation" indications to add bypass to trial requirement for Menopur. Removed obsolete GPIs (Follistim AQ 75 and 150, Repronex).
• 2022-07-25: Add embedded step through Follistim AQ for Menopur
• 2022-04-19: GPI Reclassification
• 2021-12-01: Program update to include NF criteria
• 2021-09-23: Removed Bravelle as a target as product is now obsolete and updated references section.
• 2020-07-20: Updated references.

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