Subject: Infertility

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
Gonadotropin releasing hormone (GnRH)
NP	Factrel®  (gonadorelin)	X
NP	Lutrepulse®  (gonadorelin)	X
Gonadotropin releasing hormone antagonist
NP	Ganirelix®  (ganirelix acetate)	X
NP	Cetrotide®  (cetrorelix acetate)	X
Human chorionic gonadotropin
P	chorionic gonadotropin	X
P	chorex-10 (chorionic gonadotropin)	X
P	pregnyl (chorionic gonadotropin)	X
P	novarel (chorionic gonadotropin)	X
NP	Profasi HP®  (chorionic gonadotropin)	X
NP	Ovidrel®  (choriogonadotropin alfa)	X
Gonadotropins
P	Bravelle®  (uFSH-follitropin)	X
P	Follistim AQ®  (rFSH-follitropin beta)	X
P	Gonal-F®  (rFSH-follitropin alfa)	X
P	Menopur®  (LH and FSH menotropins)	X
P	Repronex®  (LH and FSH menotropins)	X
NP	Metrodin®  (uFSH-follitropin)	X
NP	Fertinex®  (uFSH-follitropin)	X
NP	Pergonal®  (LH and FSH menotropins)	X

Policy:

For the purpose of this policy, the criteria below applies to plans that have elected to use Aetna Pharmacy to manage the fulfillment and the precertification of specialty drugs.

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Lutrepulse, Factrel Ganirelix and Cetrotide are subject to precertification.  If precertification requirements apply Aetna considers these drugs to be medically necessary for those members who meet the following precertification criteria:

For Lutrepulse and Factrel

Female Members

A.     Documented with diagnosis of infertility and she is unable to conceive or produce conception after one year of frequent, unprotected heterosexual sexual intercourse, or six months of frequent, unprotected heterosexual sexual intercourse if the female partner is over age 35 years. Alternately, a woman without a male partner may be considered infertile if she is unable to conceive or produce conception after at least twelve cycles of donor insemination (six cycles for women age 35 or older). However, this definition of infertility may vary due to state mandates and plan customization; please check plan documents.



 AND

B.  A documented diagnosis of the following:

1. For use, in addition to gonadotropin stimulation, in pituitary down-regulation as part of in vitro fertilization treatment  OR
2. Pulsatile administration of gonadotropin-releasing hormone is considered medically necessary in women with WHO Group I ovulation disorders (hypothalamic pituitary failure, characterized by hypothalamic amenorrhea or hypogonadotropic hypogonadism) (see appendix for WHO classification of ovulation disorders)

Male Members

A. A documented diagnosis of hypogonadotropic hypogonadism male infertility


For Ganirelix and Cetrotide

Female Members

A. Documented with diagnosis of inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation

Male Members

A. A documented diagnosis of hypogonadotropic hypogonadism male infertility

 

Under some plans, including plans that use an open or closed formulary, novarel,  pregnyl, Profasi HP, chorex, chorionic gonadotropin, Ovidrel, Pergonal, Menopur, Repronex, Gonal-F, Follistim AQ, Urofollitropin, Bravelle, Metrodin and Fertinex are subject to precertification.  If precertification requirements apply Aetna considers these drugs to be medically necessary for those members who meet the following precertification criteria:

Female Members

A.  Documented with diagnosis of infertility and she is unable to conceive or produce conception after one year of frequent, unprotected heterosexual sexual intercourse, or six months of frequent, unprotected heterosexual sexual intercourse if the female partner is over age 35 years. Alternately, a woman without a male partner may be considered infertile if she is unable to conceive or produce conception after at least twelve cycles of donor insemination (six cycles for women age 35 or older). However, this definition of infertility may vary due to state mandates and plan customization; please check plan documents.

AND

B.  A documented diagnosis of the following:

1. Women with WHO Group II ovulation disorders such as polycystic ovary sundrome who do not ovulate with clomiphene citrate or tamoxifen. (See definitions below for WHO classification of ovulation disorders.) OR
2. For use in pituitary down-regulation as part of in vitro fertilization treatment  OR
3. Pulsatile administration of gonadotropins are considered medically necessary for women with WHO Group I ovulation disorders (hypothalamic pituitary failure, characterized by hypothalamic amenorrhea or hypogonadotropic hypogonadism). OR
4. Clomiphene plus gonadotropins may be considered medically necessary in women who do not ovulate using clomiphene alone.


Note: Growth hormone for infertility treatment is considered experimental and investigational. There is inadequate evidence that the use of adjuvant growth hormone treatment during ovulation induction improves pregnancy rates. 

Note: Intravenous immunoglobulins are considered experimental and investigational for treatment of infertility.

Male Members

A. A documented diagnosis of hypogonadotropic hypogonadism male infertility

Note: The above medications are not considered medically necessary for idiopathic male infertility (i.e., for men without documented hypogonadotropic hypogonadism) because they have not been found to be effective for this indication.

Definitions:

For purposes of this policy, the following definitions will be used:

Classification of ovulatory disorders

Anovulation and oligo-ovulation are ovulatory disorders that are estimated to cause 21% of female fertility problems. The World Health Organization classifies ovulation disorders into three groups.

• Group I: hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism). 
• Group II: hypothalamic pituitary dysfunction (predominately polycystic ovary syndrome). 
• Group III: ovarian failure.
  

Place of Service:

Outpatient

The above policy is based on the following references:

1. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. 2006.
2. USP DI® Drug Information For The Health Care Professional - 26th Ed. (online from www.statref.com) Thomson Micromedex, Greenwood Village, CO. 2006.
3. AHFS Drug Information® with AHFSfirstReleases®. (online from www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. 2006.
4. DRUGDEX^® System: Klasco RK (Ed):DRUGDEX^® System. Online edition. Thomson Micromedex, Greenwood Village, CO.
5. American Society for Reproductive Medicine (ASRM). Guidelines for the provision of infertility dervices. ASRM Guidelines. Birmingham, AL: ASRM; July 1996.
6. American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertil Steril. 2005;83(6):1622-1628.
7. World Health Organization (WHO). WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. 4^th ed. Cambridge, UK: Cambridge University Press; May 1999.
8. World Health Organization (WHO). WHO Manual for the Standardized Investigation, Diagnosis and Management of the Infertile Male. Cambridge, UK: Cambridge University Press; 2000.
9. World Health Organization (WHO). Current Practices and Controversies in Assisted Reproduction. Report of a Meeting on “Medical, Ethical and Social Aspects of Assisted Reproduction”, WHO Headquarters, Geneva, Switzerland, 17-21 September 2001. E Vayena, PJ Rowe, PD Griffin, eds. Geneva, Switzerland: WHO; 2002. Available at: http://www.who.int/reproductive-health/infertility/
   report_content.htm. Accessed June 16, 2005.
10. Howles CM, Saunders H, Alam V, Engrand P; The FSH Treatment Guidelines Clinical Panel. Predictive factors and a corresponding treatment algorithm for controlled ovarian stimulation in patients treated with recombinant human follicle stimulating hormone (follitropin alfa) during assisted reproduction technology(ART) procedures. An analysis of 1378 patients. Curr Med Res Opin. 2006;22(5):907-18.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

January 01, 2007