Fertility Problems and Infertility Treatment Options

Fertility problems are possible for both men and women. The cause can be found through physical exam, extensive medical and sexual history. Depending on the cause of infertility, there are different treatment options.

Medications are one of the infertility treatment options available for both men and women. Medications can help correct ovulation problems in women and hormone problems in men. When treatment options, including injectable infertility agents, exceed the comfort level of a provider, the member should be referred to a specialist with expertise in diagnosis and treatment of infertility (e.g., reproductive endocrinologist)

NOTE: Coverage of injectable fertility medications varies depending on a member’s benefit policy.

1. Please refer to the applicable benefit plan document to determine benefit availability and the terms and conditions of coverage.
2. Please refer to Oscar’s Medical Clinical Guideline Number CG016 - Diagnosis and Treatment of Infertility for medical coverage criteria of infertility diagnostic and treatment services.
3. This Clinical Guideline only applies to members whose plan covers injectable agents listed in Table 1 for infertility treatments.

• The Plan requires that members be unable to use, or have tried and failed preferred agent(s) first.
• The use of these agents for other indications (e.g., cancer treatments, gender dysphoria treatments) may also be addressed in separate Clinical Guidelines.

Table 1: Infertility Injectable Agents

Drug Name | Brand Name | Classification

Follitropin beta | Follistim AO | Gonadotropins

Follitropin alfa | Gonal-F | Gonadotropins

Follitropin alfa | Gonal-f RFF | Gonadotropins

Follitropin alfa | Gonal-f RFF Redi-ject Pen | Gonadotropins

Chorionic Gonadotropin (Human) | Novarel | Gonadotropins

Chorionic Gonadotropin (Recombinant) | Ovidrel | Gonadotropins

Chorionic Gonadotropin (Human) | Pregnyl | Gonadotropins

Human Chorionic Gonadotropin, HCG | Not Listed | Gonadotropins

Menotropins | Menopur | Gonadotropins

Leuprolide Acetate | Not Listed | GnRH Agonists

Cetrorelix Acetate | Cetrotide | GnRH Antagonists

Ganirelix Acetate | Not Listed | GnRH Antagonists

Definitions

“Infertility” is a disease or condition characterized by the incapacity to impregnate another person or to conceive, defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or therapeutic donor insemination, or after six (6) months of regular, unprotected sexual intercourse or therapeutic donor insemination for a female 35 years of age or older. Earlier evaluation and treatment may be warranted based on a Member’s medical history or physical findings. Infertility may be caused by disease, dysfunction, or malformation.

“Iatrogenic Infertility” refers to an impairment of fertility by surgery, radiation, chemotherapy or other medical treatment affecting reproductive organs or processes.

Medical Necessity Criteria for Initial Authorization

The Plan considers Infertility Injectable Agents medically necessary when ALL of the following criteria are met:

1. The requested medication is prescribed by or in consultation with a specialist with expertise in diagnosis and treatment of infertility (e.g., reproductive endocrinologist); AND
2. ONE of the following:

• The member is a female and meets ALL of the following:
  1. Is 18 years of age or older; and
  2. The medication is being used for ONE of the following FDA approved or compendia supported indications:
  1. induction of ovulation; or
  2. inhibition of premature luteinizing hormone surges; or
  3. multiple follicle development;

• preservation of fertility when a medical treatment will directly or indirectly lead to iatrogenic infertility; and
• For induction of ovulation, has tried and failed or is unable to use clomiphene citrate or comparable estrogen modulators such as letrozole due to ONE of the following:
  1. a documented trial and failure, intolerance to, or contraindication; or
  2. risk factor(s) for poor response; or
  3. not clinically appropriate; or
  4. member is 37 years of age or older; and
• Clinical chart documentation is submitted showing ALL of the following:
  1. complete gynecologic and endocrinologic evaluation and diagnosis of cause of infertility; and
  2. member is currently not pregnant; and
  3. a diagnosis of primary ovarian failure has been excluded; and
  4. the fertility status of the male partner has been evaluated; and
  5. medical conditions preventing pregnancy have been excluded or adequately treated (medical conditions preventing pregnancy may include blocked fallopian tubes, hyperprolactinemia, thyroid, or adrenal disorders); OR
• The member is a male and meets BOTH of the following:
  1. The medication is being used for ONE of the following FDA approved or compendia supported indications:
     • induction of spermatogenesis; or
     • hypogonadotropic hypogonadism; or
     • prepubertal cryptorchidism; and
  2. Clinical chart documentation is submitted showing BOTH of the following:
     1. complete medical and endocrinologic evaluation and diagnosis of cause of infertility; and
     2. the fertility status of the female partner has been evaluated; AND
• The use of medication at the requested dosage or quantity, frequency, site of administration, and duration of therapy is supported by Food and Drug Administration (FDA) approved dosing or evidence-based literature.

If the above prior authorization criteria are met, the requested Infertility Injectable Agents will be approved for:

• 3 months for females; or
• 6 months for males

Medical Necessity Criteria for Reauthorization

All members (including new members) requesting authorization for continuation of therapy must meet all initial authorization criteria.

If the above prior authorization criteria are met, the requested Infertility Injectable Agents will be reauthorized for:

• 3 months for females; or
• 6 months for males

Experimental or Investigational / Not Medically Necessary

Infertility Injectable Agents for any other fertility problems is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. "Clinical Pharmacology [database on the Internet]." Elsevier Inc., 2023, www.clinicalpharmacology.com. Accessed June 2023.
2. "DailyMed. Package Inserts." U.S. National Library of Medicine, National Institutes of Health (NIH), 2023, dailymed.nlm.nih.gov/dailymed/index.cfm. Accessed June 2023.
3. "Lexicomp Online Database [database on the Internet]." Lexicomp Inc., 2023, online.lexi.com. Accessed June 2022.
4. "Micromedex Solutions [database on the Internet]." Truven Health Analytics, 2023, micromedex.com. Accessed June 2023.
5. Birnbaum, S. "Approach to the Infertile Couple." Primary Care Medicine: Office Evaluation and Management of the Adult Patient. 8th ed., Wolters Kluwer, 2021, pp. 1049-1056.
6. Klipstein, S., et al. "Fertility Preservation for Pediatric and Adolescent Patients with Cancer: Medical and Ethical Considerations." Pediatrics, vol. 145, no. 3, 2020, e20193994. DOI: 10.1542/peds.2019-3994. (Reaffirmed 2022 Jul)
7. Lafferty, K., et al. "Infertility: Understanding Investigation and Treatment Options." InnovAiT, vol. 13, no. 7, 2020, pp. 394-401. DOI: 10.1177/1755738020923714.
8. Legro, R.S., et al. "Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome." N Engl J Med, vol. 371, 2014, pp. 119-129.
9. Lindsay, T.J., Vitrikas, K.R. "Evaluation and Treatment of Infertility." American Family Physician, vol. 91, no. 5, 2015, pp. 308-14.
10. Lobo, R.A. "Infertility: Etiology, Diagnostic Evaluation, Management, Prognosis." Comprehensive Gynecology.

11. Practice Committee of the American Society for Reproductive Medicine. "Evidence-Based Treatments for Couples with Unexplained Infertility: A Guideline." Fertil Steril, vol. 113, 2020, pp. 305-22.
12. Practice Committee of the American Society for Reproductive Medicine. "Fertility Evaluation of Infertile Women: A Committee Opinion." Fertility and Sterility, vol. 116, no. 5, 2021, pp. 1255-1265. DOI: 10.1016/j.fertnstert.2021.08.038. (Reaffirmed 2022 Jul)
13. Reindollar, R., et al. "A Randomized Clinical Trial to Evaluate Optimal Treatment for Unexplained Infertility: The Fast Track and Standard Treatment (FASTT) Trial." Fertil Steril, vol. 94, 2010, pp. 888-899.
14. Schlegel, P.N., et al. "Diagnosis and Treatment of Infertility in Men." AUA/ASRM Guideline.

Clinical Guideline Revision / History Information

Original Date: 06/23/2022

Reviewed/Revised: 06/29/2023