Background

Most IUIs include ovarian stimulation through oral medications such as clomiphene citrate and letrozole. Occasionally, physicians will prescribe gonadotropins, which are injectable exogenous hormones such as Follicle Stimulating Hormone (FSH) and human menopausal gonadotropin (hMG), which help stimulate ovulation of one egg. The goal of gonadotropin treatment for ovulation induction is to promote the development of a single mature follicle. Monofollicular development decreases the risk of multiple gestation and Ovarian Hyperstimulation Syndrome (OHSS). However, monofollicular development can be difficult to achieve and the risk of multiple gestation and OHSS cannot be eliminated with gonadotropins. Ovulation induction, hormonal therapy (medication) used to stimulate oocyte production, maturation, and/or ovulation should be closely monitored by all physicians.

Gonadotropin Intrauterine Insemination (IUI)

All IUI cycles where gonadotropins are prescribed require preapproval. Gonadotropin IUI cycles should be managed by a physician (reproductive endocrinologist) with the requisite training and experience.

CPT Codes Impacted by Policy:

Progyny CPT Code	CPT Code Definition
S4035	Stimulated IUI
S4017	Cancelled IUI

Medication Impacted by Policy:

Formulary Medication	Non-Formulary Medication
Menopur	Follistim
Gonal F	Ganirelix

It is not clinically appropriate to pursue IUI with Gonadotropin, if the member has not attempted treatment in past with clomiphene citrate, if member has not attempted treatment in past with letrozole. If the member has attempted treatment in past with clomiphene citrate or letrozole and developed a dominant (follicle 13mm or larger in diameter) follicle. If member has not first been counseled about treatment option of IVF as well as risks of gonadotropin therapy including but not limited to multiple pregnancies. If the member is at higher than average risk of complications from a multiple pregnancy.

Consideration shall be provided to the following clinical scenarios if all of the following conditions are present and validated upon a review of submitted medical records:

1. Each of the following is true and documentation verifying such has been provided:

   1. Patient has polycystic ovarian syndrome as a cause of infertility; has attempted separate treatments using clomiphene citrate (up to a daily 5 -7 day course of 150mg daily dosage) and separately letrozole (up to a daily dose of 7.5mg for 5-7 days); AND
   2. Patient has failed to recruit/without dominant follicle formation/ovulation with oral medication; AND
   3. Patient has reviewed the option of IVF with single embryo transfer with provider and has been fully informed on the risks of multiple gestation; AND
   4. Patient has declined IVF/SET as next step treatment.

2. Each of the following is true and documentation verifying such has been provided:

   1. Patient has hypothalamic amenorrhea as a cause of infertility; AND
   2. Patient has attempted treatment with clomiphene citrate (to a dose of at least 100mg daily for 5 days or more) and separate treatment with letrozole (up to a dose of at least 5mg daily for 5 days or more)
   3. Patient has failed to recruit a dominant follicle with oral medication; AND
   4. Provider has reviewed the option of IVF with Single embryo transfer with patient and discussed the risks of multiple gestation; AND
3. Patient has declined IVF/SET as next step treatment.

Authorization requests will not be granted where the patient has other diagnosed cause of infertility that would not be appropriately treated through the use of gonadotropins: including but not limited to patient has tubal occlusion; severe male factor; Mullerian anomaly (including but not limited to septum (partial or complete); unicornuate; bicornuate; didelphic uterus or a prior history of preterm delivery or loss

Documentation Required

1. Obstetric medical history, stim sheet, including number of prior pregnancies and gamete source of prior pregnancy, compared to current requesting attempt. Pregnancy outcomes, history of pregnancy loss
2. Provider must submit all prior stimulation sheets where clomiphene; letrozole; or gonadotropins were used for fertility treatments.

References

1. Practice Committees of the American Society for Reproductive Medicine and Society for Reproductive Endocrinology and Infertility. Use of exogenous gonadotropins for ovulation induction in anovulatory women: a committee opinion. Fertility and Sterility. January, 2020.
2. Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertility and Sterility. February, 2020.
3. Practice Committee of the Society for Reproductive Endocrinology and Infertility, Quality Assurance Committee of the Society for Assisted Reproductive Technology, and the Practice Committee of the American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: a committee opinion. Fertility and Sterility. March, 2022.
4. Akhtar MA, Saravelos SH, Li TC, Jayaprakasan K, on behalf of the Royal College of Obstetricians and Gynaecologists. Reproductive Implications and Management of Congenital Uterine Anomalies. Scientific Impact Paper No. 62. British Journal of Obstetrics and Gynecology 2020; 127:e1-e13.
5. Colicchia LC, Simhan HN. Optimizing Subsequent Pregnancy Outcomes for Women with a Prior Preterm Birth. American Journal of Perinatology. February, 2016.