Infertility is a multifactorial issue affecting both men and women

characterized by the inability to conceive after 12 months or more of regular unprotected intercourse or therapeutic donor insemination. Early evaluation and treatment are warranted after 6 months for women over age 35 years. The cause can be identified through physical examinations, detailed medical and sexual history, and relevant laboratory investigations.

Depending on the cause, various treatment options are available, which may include medications, surgery, assisted reproductive technologies, or a combination of these. If infertility management exceeds the expertise of a healthcare provider, the patient should be referred to a specialist with experience in diagnosing and treating infertility, such as a reproductive endocrinologist.

Clomiphene (Clomid) is a nonsteroidal fertility agent approved by the FDA to induce ovulation in women who ovulate infrequently or who are anovulatory, including patients with polycystic ovary syndrome (PCOS). Clomiphene is effective in stimulating ovulation in patients with a functioning hypothalamic-pituitary-ovarian axis and ovaries capable of normal functioning. In addition to its role in inducing ovulation, clomiphene is also used to evaluate ovarian reserve and to regulate ovulation timing in patients receiving donor insemination. While not an FDA-approved use, clomiphene has been utilized to increase sperm counts in men with infertility due to idiopathic oligospermia (low sperm count or inadequate sperm functionality). Clomiphene is available as an oral tablet.

NOTE: Coverage for infertility treatments may vary based on an individual's benefit policy.

• Please refer to the specific benefit plan document to determine the extent and terms of coverage.
• This Clinical Guideline is applicable only to members whose plans cover infertility treatments.
• For medical coverage criteria regarding infertility diagnostic and treatment services, please refer to Oscar’s Medical Clinical Guideline Number CG016 - Diagnosis and Treatment of Infertility.

Definitions

"Compendia" are summaries of drug information and medical evidence to support decision-making about the appropriate use of drugs and medical procedures.

"FDA" refers to the Food and Drug Administration.

"Infertility" is defined by the failure to achieve a successful pregnancy after 12 months or more of appropriate, timed unprotected intercourse or therapeutic donor insemination. Earlier evaluation and treatment may be justified based on medical history and physical findings and is warranted after 6 months for women over age 35 years.

Medical Necessity Criteria for Authorization

The Plan considers clomiphene (Clomid) medically necessary when ALL of the following criteria are met:

1. The requested medication is prescribed by or in consultation with a clinician experienced in management of gynecologic and endocrine disorders; AND
2. The member is 18 years of age and older; AND
3. The member has a diagnosis of female infertility; AND
4. The medication is not being used for induction of ovulation associated with in vitro fertilization programs; AND
5. Clinical chart documentation is submitted showing ALL of the following:
   • a. complete gynecologic and endocrinologic evaluation and diagnosis of cause of infertility; and
   • b. the member has demonstrated ovulatory dysfunction; and
   • c. the member is currently not pregnant, confirmed by a negative pregnancy test; and
   • d. the member has normal liver function; and
   • e. complete pelvic examination and endometrial biopsy have been performed, and neoplastic lesions have been ruled out; and
   • f. Medical conditions that could prevent pregnancy have been excluded or adequately treated (medical conditions preventing pregnancy may include blocked fallopian tubes, hyperprolactinemia, thyroid, or adrenal disorders); and
   • g. the fertility status of the male partner has been evaluated; and
   • h. The member does not have ANY of the following:
   • i. ovarian cysts or ovarian enlargement, unless enlargement is due to PCOS; or
   • ii. primary pituitary or ovarian failure; or
   • iii. unexplained vaginal bleeding.

If the above prior authorization criteria are met, clomiphene (Clomid) will be approved for 6 months.

Experimental or Investigational / Not Medically Necessary

The use of clomiphene (Clomid) for any indication that is not FDA approved or compendia supported is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. American Society for Reproductive Medicine. (2013). Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertility and Sterility, 99(1), 63.
2. Anawalt BD and Page ST. Treatments for male infertility. UpToDate.com [online]. Last Updated Feb 2020. Last Reviewed Aug 2021. Accessed Sept 2021. Available at: https://www.uptodate.com/contents/treatments-for-male-infertility.

4. Clinical Pharmacology [online]. Elsevier. 2021. Accessed Sept 2021. Available at: http://www.clinicalpharmacology.com
5. Clomid (clomiphene) [prescribing information]. South Plainfield, NJ: Cosette Pharmaceuticals Inc; May 2022.
6. Clomiphene [prescribing information]. Chestnut Ridge, NY: Par Pharmaceutical; June 2016.
7. Huijben M, Lock MTWT, de Kemp VF, de Kort LMO, van Breda HMK. Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis. Andrology. 2022;10(3):451-469. doi:10.1111/andr.13146
8. Practice Committee of the American Society for Reproductive Medicine (ASRM). Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril. 2013;100(2):341-348.
9. Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634-1647. doi: 10.1016/j.fertnstert.2016.08.048.
10. Puia D, Pricop C. Effectiveness of clomiphene citrate for improving sperm concentration: a literature review and meta-analysis. Cureus. 2022;14(5):e25093. doi:10.7759/cureus.25093
11. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II. Fertil Steril. 2021;115(1):62-69. doi:10.1016/j.fertnstert.2020.11.016
12. Shmorgun D, Claman P. No-268-The diagnosis and management of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can. 2017;39(11):e479-e486. doi:10.1016/j.jogc.2017.09.003
13. Smithson DS, Vause TDR, Cheung AP. No. 362-ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can. 2018;40(7):978-987. doi:10.1016/j.jogc.2017.12.004
14. Snyder PJ. Induction of fertility in men with secondary hypogonadism. UpToDate.com [online]. Last Updated Aug 2019. Last Reviewed Aug 2021. Accessed Sept 2021. Available at: https://www.uptodate.com/contents/induction-of-fertility-in-men-with-secondary-hypogonadism
15. Teede HJ, Misso ML, Costello MF, et al; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364-379. doi:10.1016/j.fertnstert.2018.05.004

Clinical Guideline Revision / History Information

• Original Date: 10/14/2021
• Reviewed/Revised: 12/01/2021, 06/23/2022, 06/29/2023