This document addresses the use of oral, injectable and topical infertility drugs, including protocols used to treat women with ovulation disorders, drugs used as part of an Assisted Reproductive Technology (ART) treatment (most commonly through in vitro fertilization [IVF]), intrauterine insemination, and as treatment of male infertility with gonadotropins.
Note: Please see the following documents for additional information:
CG-DRUG-15 Gonadotropin Releasing Hormone (GnRH) Analogs
CG-SURG-35 Intracytoplasmic Sperm Injection (ICSI)
I. Clomiphene Citrate
Clomiphene citrate for a maximum of 6 cycles of therapy is considered medically necessary for ovulation induction in individuals who meet any of the following criteria:
- Women with normogonadotropin anovulatory dysfunction such as polycystic ovary syndrome (PCOS); or
- Young women with unexplained infertility of short duration, with normal levels of luteal progesterone and a normal hysterosalpingogram; or
- Stage I or II endometriosis.
Not Medically Necessary:
Clomiphene citrate is considered not medically necessary for ovulation induction in individuals who meet ANY of the following criteria:
- Women with primary ovarian failure or tubal occlusion; or
- Women with hypogonadotropic anovulatory disorders or hypopituitarism; or
- Greater than 6 cycles of therapy.
II. Ovulation Stimulation Alone or With Intrauterine Insemination - Injectable Low Dose Follicle Stimulating Hormone (FSH) (Bravelle™, Follistim AQ®, Gonal-f®, Gonal-f®-RFF) or Menotropins (Repronex® and Menopur®)
Ovulation induction with a maximum of 3 cycles of injectable low dose FSH or menotropins, with or without intrauterine insemination, is considered medically necessary in individuals who meet ANY of the following criteria:
- Women with hypogonadotropic anovulatory disorders or hypopituitarism - these women will not respond to FSH alone, but will require additional therapy with luteinizing hormone (LH) containing product, either human chorionic gonadotropins (hCG) or recombinant LH (Luveris®); or
- Women with normogonadotropin anovulatory disorders (that is, polycystic ovary syndrome) or those with unexplained infertility who have not ovulated or conceived after a prior trial of three cycles of clomiphene.
Not Medically Necessary:
Ovulation induction with injectable low dose FSH or menotropins is considered not medically necessary in any of the following individuals:
- Women receiving more than 3 ovulatory cycles of therapy; or
- Women with tubal occlusion or primary ovarian failure.
III. Ovarian Stimulation in Conjunction with In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) (Bravelle, Follistim AQ, Gonal-f, Gonal-f RFF, Menopur, Recombinant hCG (Ovidrel) or, Repronex, urinary derived hCG (Pregnyl, Novarel and generics), with GnRH agonists (Lupron Depot, generic leuprolide) or antagonists (Cetrotide, Ganirelix)
A maximum of 3 cycles of ovarian stimulation in conjunction with IVF or ICSI is considered medically necessary in individuals who meet ANY of the following criteria:
- Couples with severe male factor infertility; or
- Women with bilateral tubal occlusion; or
- Unexplained infertility that has not responded to ovarian induction therapy.
Not Medically Necessary:
Ovarian stimulation in conjunction with IVF or ICSI is considered not medically necessary in individuals with greater than 3 cycles of therapy.
IV. Gonadotropins for Male Infertility Associated with Hypogonadotropic Hypogonadism (Follistim AQ, Gonal-f)
Follistim AQ or Gonal-f in combination with hCG, are considered medically necessary for infertile men with hypogonadotropic hypogonadism with onset prior to completion of pubertal development.
The use of hCG alone or in combination with FSH is considered medically necessary to maintain spermatogenesis for infertile men with post-pubertal acquired hypogonadotropic hypogonadism who have previously had normal sperm production.
The use of hCG alone or in combination with FSH is considered medically necessary to maintain spermatogenesis for infertile men with partial gonadotropin deficiency.
Not Medically Necessary:
The use of gonadotropins for male infertility associated with hypogonadotropic hypogonadism is considered not medically necessary when the criteria above are not met.
V. Progesterone Vaginal Supplementation or Replacement for Infertility Treatment (Crinone 8% gel, Endometrin vaginal insert, Prochieve 8% gel)
Progesterone vaginal insert or 8% gel is considered medically necessary as part of an Assisted Reproductive Technology (ART) treatment for infertile women who require progesterone supplementation.
Not Medically Necessary:
The use of progesterone vaginal insert or 8% gel for infertile women is considered not medically necessary when the criteria above are not met.
The use of progesterone 4% gel is considered not medically necessary as part of an ART treatment for infertile women who require progesterone supplementation.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. A draft of future ICD-10 Coding (effective 10/01/2014) related to this document, as it might look today, is included below for your reference. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
|J0725||Injection, chorionic gonadotropin; per 1,000 USP units [Novarel, Pregnyl]|
|J1950||Injection, leuprolide acetate (for depot suspension); per 3.75 mg [Lupron]|
|J3355||Injection, urofollitropin, 75 IU [Bravelle]|
|J3490||Unclassified drugs [when specified as lutropin alfa (Luveris), cetrorelix acetate (Cetrotide), Ovidrel or other injectable for infertility treatment]|
|J8499||Prescription drug, oral, non-chemotherapeutic, NOS [when specified as clomiphene citrate (Clomid, Serophene)]|
|S0122||Injection, menotropins; 75 IU [Menopur, Repronex]|
|S0126||Injection, follitropin alfa; 75 IU [Gonal-F]|
|S0128||Injection, follitropin beta; 75 IU [Follistim ]|
|S0132||Injection, ganirelix acetate; 250 mcg [Antagon]|
|No code||Progesterone vaginal insert or gel [Crinone 8%, Endometrin, Prochieve 8%, Crinone 4%, Prochieve 4%]|
| || |
|ICD-9 Diagnosis|| |
| ||All diagnoses|
| || |
|ICD-10 Diagnosis||ICD-10-CM draft codes; effective 10/01/2014:|
| ||All diagnoses|
| || |
The American Society for Reproductive Medicine (ASRM) (2008) defines infertility and states:
Infertility is a disease, defined by the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse. 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.
Drugs used to enhance infertility include the gonadotropin releasing hormone (GnRH), gonadotropins, human chorionic gonadotropins (hCG), and other ovulation stimulating agents such as the anti-estrogens. These agents may be used for the induction of ovulation, superovulation to produce more than one developing follicle or to stimulate multiple follicular developments in assisted reproductive techniques. Exogenous gonadotropins, in particular, have been used for ovulatory dysfunction, luteal phase defects, unexplained infertility, male factor infertility and assisted reproductive techniques (i.e., in vitro fertilization [IVF]). There are several types of gonadotropins available. Follicle stimulating hormone (FSH) is available commercially in both recombinant (Gonal-f, Gonal-f RFF and Follistim AQ) and a urinary-derived preparation (Bravelle). Products containing both FSH and LH are also available (Menopur, Repronex). A pure luteinizing hormone product (Luveris) is commercially available for the treatment of individuals with hypogonadotropin anovulatory disorders or hypopituitarism.
Categories of infertility drugs with pharmacologic actions are summarized in the following table:
|Menotropins: FSH and LH(Repronex, Menopur)|
- The FSH and LH present in menotropin products produce ovarian follicular growth and maturation in women without primary ovarian failure.
Follitropin and Urofollitropins: FSH (Follistim AQ, Gonal-f/ RFF, Bravelle)
- The FSH present in follitropin and urofollitropin products produce ovarian follicular growth and maturation in women without primary ovarian failure.
|Lutropin alfa: r-LH|
- In the ovaries, during the follicular phase, LH stimulates the cells to secrete androgens which in turn facilitate the production of estradiol. Estradiol helps support FSH-induced follicular development. LH is also thought to help with embryo implantation. Exogenous LH is administered with follitropin or urofollitropins in ART protocols or in infertile women with a documented LH deficiency.
Human chorionic gonadotropins (hCG) Urinary-derived hCG (Pregnyl, Novarel and generics) Recombinant hCG (Ovidrel)
- Sole use of menotropins, follitropins or urofollitropins will result in an undesirable endogenous LH surge and premature egg release. Administration of hCG after treatment with these products will suppress the LH surge, thus facilitating final follicular development, maturation and ovulation.
- Gonadotropin-releasing hormone (GnRH) antagonists are used to suppress premature luteinizing hormone (LH) surges during ART. LH surge suppression prevents eggs from being released prematurely. Protocols using GnRH antagonists are referred to as "short protocols" as these agents allow for shorter treatment times.
GnRH analogs or agonists
(Lupron Depot® and generic leuprolide acetate)
- Administration results in an initial release of endogenous LH and FSH release, but chronic daily administration (as in ART) results in suppression of endogenous LH and FSH release. Pre-treatment with GnRH analogs in ART prevents the endogenous LH surge which would occur if menotropins, follitropin or urofollitropin were used alone. Protocols using GnRH analogs are referred to as "long protocols" as use of these agents results in longer treatment times.
(Clomid®, Serophene® and generics)
- Clomiphene binds to estrogenic receptors and thus decreases the number of available receptors. The hypothalamus and pituitary respond to this antiestrogenic effect by releasing additional LH, FSH and gonadotropins, resulting in ovarian stimulation.
|Progesterone vaginal supplementation or replacement (Crinone 8% gel, Endometrin vaginal inserts, Prochieve 8% gel)|
- Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone functions to maintain the pregnancy. Vaginal supplementation or replacement of progesterone is used in ART protocols for infertile women who require progesterone supplementation.
FSH= Follicle stimulating hormone; LH= luteinizing hormone; r-LH= recombinant luteinizing hormone; hCG= human chorionic gonadotropins; ART= assisted reproductive technology; GnRH = gonadotropin releasing hormone
For women with ovulation failure, or in those with unexplained infertility, typically the initial therapy focuses on ovarian stimulation with clomiphene citrate (CC), with or without intrauterine insemination (IUI). There is a lack of evidence in support of having two IUI's on successive days as compared to a single well timed IUI.
Women with stage I-II endometriosis who undergo IUI and controlled ovarian hyperstimulation are typically more likely to conceive than those who try conceiving without such assistance. The ASRM (2012) in an opinion paper on endometriosis and infertility issued conclusions including the following:
- In younger women (under 35 years of age) with stage I-II endometriosis associated infertility, expectant management or super ovulation/intrauterine insemination (SO/IUI) can be considered as first line therapy.
- For women age 35 years and older more aggressive treatment such as SO/IUI or in vitro fertilitzation (IVF) may be considered.
In 2013, the ASRM (2013) reported the following summary and conclusions regarding the use of CC in women:
- Clomiphene citrate is an effective first-line treatment for the majority of women with anovulatory infertility.
- Clomiphene citrate treatment combined with intercourse does not increase cycle fecundity in couples with unexplained infertility compared with expectant management.
- Clomiphene citrate treatment in combination with IUI seems to increase cycle fecundity in couples with unexplained infertility compared with expectant management.
- Side effects of CC treatment generally are mild and well tolerated. The principal risk of CC treatment is an increased incidence of multifetal gestation (<10%).
- Failure to conceive after 3 to 4 successful CC-induced ovulation cycles is indication for further evaluation to exclude other contributing causes of infertility, particularly in women >35 years of age.
- Combination therapies involving CC and other agents (metformin, glucocorticoids, and exogenous gonadotropins) may be effective when treatment with CC alone fails to induce ovulation.
- Clomiphene citrate treatment should be monitored (menstrual calendar, serum progesterone concentration, urinary LH excretion) to ensure its effectiveness in ovulation induction.
- The choice of monitoring should be tailored to the needs of the specific patient.
In addition, the ASRM (2013) stated that if CC is used to induce ovulation, pregnancy is most likely to occur in the first 3 to 6 cycles, and therapy beyond 6 cycles is generally not recommended. ACOG (2002) advises that there is no benefit to increasing the dosage of clomiphene once ovulation has occurred or to continuing beyond six months of treatment.
Zain and colleagues (2009) reported on a randomized controlled trial comparing clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with PCOS. The authors concluded their study demonstrated that clomiphene citrate is superior to metformin in inducing ovulation in anovulatory women with PCOS.
IVF procedures require initial ovarian stimulation with menotropins, FSH products, either gonadotropin release hormone (GnRH) agonists or antagonists to prevent the normal endogenous LH surge, and finally human urinary or recombinant chorionic gonadotropin at the end of the cycle to cause final follicle maturation. Protocols vary, and during the last decade the trend in infertility management has been toward a greater use of recombinant products. For example, recombinant FSH (rFSH) products (Gonal-f, Gonal f- RFF, Follistim AQ) are now available and are an alternative to the purified urine-derived FSH (Bravelle) and the urine-derived menotropins (Repronex, Menopur). It was anticipated that the use of rFSH products would result in better, more consistent clinical outcomes, such as clinical pregnancy rate and live birth rate, the final health outcome. However, a recent Cochrane review reported that there was no significant difference in live birth rates or other secondary outcomes, including number of oocytes retrieved. Safety and tolerability of urine-derived and recombinant products appear to be similar (Van Wely, 2005). All gonadotropin cycles should be carefully monitored with ultrasound to decrease the risk of multiple pregnancies and ovarian hyperstimulation syndrome (Aboulghar, 2001; ACOG 2002; Dickey, 2005; Eijkemans, 2003; Hughes, 2003; Yang, 1998). Protocols may include the use of either urine derived formulations of FSH (Bravelle) or menotropins containing FSH and LH (Repronex, Menopur) or recombinant FSH products (Gonal-f, Gonal-f RFF, Follistim AQ). Reviews and meta-analysis have shown that urine derived and recombinant products have equivalent outcomes (clinical pregnancy, live birth rate, number of oocytes retrieved). The safety and tolerability are also similar (Al-Inany, 2005; Von Welty, 2005).
Another key component of an IVF cycle is suppression of the normal endogenous LH surge in order to suppress premature release of eggs. As noted in the above table, either GnRH agonists or antagonists can be used. When agonists are used, the protocol is known as a "long protocol," since longer treatment times are required, compared to the use of GnRH antagonists, known as a "short protocol." In the United States, leuprolide (Lupron Depot) is the only available GnRH agonist, while two GnRH antagonist products (Cetrotide, Ganirelix) are available. The use of GnRH antagonists is associated with a shorter treatment cycle compared to agonists (i.e., short vs. long protocol), however, recent reviews have reported that use of GnRH antagonists (i.e., short protocol) is associated with a lower clinical pregnancy rate compared to GnRH agonists (i.e., long protocol) (Al-Inany, 2002).
In the final stage of IVF protocols, human chorionic gonadotropin (hCG) is administered to prompt final follicle maturation. HCG is available in a urine-derived formula (Pregnyl, Novarel and generic urinary hCG) and a recombinant form (Ovidrel). Similarly, a Cochrane review found no difference in follicular maturation/quality and live birth rates between the urine-derived and recombinant formulations (Al-Inany, 2005). Safety and tolerability of urine-derived and recombinant products appear to be similar.
One recombinant luteinizing hormone (r-LH) formulation is available (Luveris). The labeled indication for Luveris identifies only a very small subset of infertile women, i.e. those hypogonadal women with a profound LH deficiency (Burgues, 2001; European Recombinant Human LH Study Group, 1998). While Luveris is useful for this small population, there is no data to support its use for other more common causes of infertility. For example, purified urine preparation of FSH will contain some LH, while recombinant FSH contains none. Therefore, some physicians may suggest that Luveris has a role in "adding back" LH to those women treated with recombinant FSH. There is inadequate data to support this practice as studies have shown no benefit in improving pregnancy or live birth rates by the addition of Luveris to ART protocols (De Placido, 2005; Fabregues, 2006; Sauer, 2004).
Progesterone intravaginal supplementation has been found in several studies to have benefits in promoting fertility (Ho, 2008; Check, 2009). Crinone 8% and Prochieve 8% are both vaginal progesterone gels and Endometrin is a vaginal progesterone tablet. Crinone 8% and Prochieve 8% are FDA approved for progesterone supplementation or replacement as part of an ART treatment for women with a progesterone deficiency who are undergoing fertility treatment. Crinone 4% and Prochieve 4% are not FDA approved for use as part of an ART treatment. Endometrin is FDA approved to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an ART treatment program for infertile women.
Assisted reproductive technology (ART): Refers to fertility treatments in which embryos, eggs, or both the eggs and sperm are handled. Not included in ART is artificial insemination using sperm from either a woman's partner or a sperm donor.
Fecundity: The ability to produce offspring.
Intrauterine insemination: A procedure for treating infertility in which washed and concentrated sperm are placed directly into the uterus.
In vitro fertilization (IVF): A fertility treatment that involves the transfer of fertilized human eggs into a woman's uterus.
Peer Reviewed Publications:
- Aboulghar M, Mansour RT, Serour G, et al. Controlled ovarian hyperstimulation and intrauterine insemination for the treatment of unexplained infertility should be limited to a maximum of three trials. Fertil Steril. 2001; 75:88-91.
- Badaway A, Abdel AI and Abullata M. Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 2009; 92(3):849-852.
- Bouloux P, Warne D, Loumave E, et al. Efficacy and safety of recombinant human follicle stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril. 2002; 77(2): 270-273.
- Bugues S et al. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence form a multicenter study in Spain. Hum Reprod 2001; 16:2525-2532.
- Check JH. Luteal Phase Support in assisted reproductive technology treatment: focus on Endometrin(R) (progesterone) vaginal insert. Ther Clin Risk Manag. 2009; 5(4):403-407.
- Depenbusch M, vonEckarstein, Simoni M, et al. Maintenance of spermatogenesis in hypogonadotropic men with human chorionic gonadotropin alone. Eur J Endocrinol. 2002; 147:617-624.
- De Placido G, et al. Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotropic women with initial inadequate ovarian response to rFSH. A multicenter, prospective, randomized controlled trial. Hum Reprod 2005; 20:390-396.
- Dickey RP, Taylor SN, Lu PY, et al. Risk factors for high-order multiple pregnancy and multiple after controlled ovarian hyper stimulation: Results of 4,062 intrauterine insemination cycles. Fertil Steril. 2005; 83:671-683.
- Eijkemans MJ, Imani B, Mulders AG, et al. High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility (WHO 2) Human Reprod. 2003; 18: 2357-2362.
- Fabregues F, et al. Effects of recombinant human luteinizing hormone supplementation on ovarian stimulation and the implantation rate in down-regulated women of advanced reproductive age. Fertil Steril 2006; 85:925-931.
- Ho CH, Chen SU, Peng FS, Chang CY, Yang YS. Luteal support for IVF/ICSI cycles with Crinone 8% (90 mg) twice daily results in higher pregnancy rates than with intramuscular progesterone. J Chin Med Assoc. 2008; 71(8):386-391.
- Homburg R. Clomiphene citrate - end of an era? A mini-review. Hum Reprod. 2005; 20(8):2043-2051.
- Hughes E. Why choose OI/IUI for unexplained subfertility. Effective treatment or not a natural choice. Hum Reprod. 2003; 18:912-914.
- Kumar R, Gautam G and Gupta NP. Drug therapy for idiopathic male infertility: rationale versus evidence. J Urol 2006; 176:1307-1312.
- Legro RS, et al. Clomiphene, metformin or both for infertility in polycystic ovary syndrome. NEJM 2007; 356:551-566.
- Moll E, Bossuyt PM, Korevaar JC, et al. Effect of clomiphene citrate plus metformin and clomiphene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomized double-blind clinical trial. BMJ. 2006; 332(7556):1485.
- Sauer M. Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction. Reproductive Biomedicine Online. 2004; 9: 487-493.
- Smith JF, Eisenberg ML, Millstein SG, et al. Katz PP; Infertility Outcomes Program Project Group. Fertility treatments and outcomes among couples seeking fertility care: data from a prospective fertility cohort in the United States. Fertil Steril. 2011; 95(1):79-84.
- The European Recombinant Human LH Study Group. Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH))-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. J Clin Endrocrinol Metab 1998; 83:1507-1514.
- Yang JH, Wu MY, Chao KH, et al. Controlled ovarian hyperstimulation and intrauterine insemination in subfertility. How many treatment cycles are enough? J Reprod Med. 1998; 43:903-908.
- Zain MM, Jamaluddin R, Ibrahim A, Norman RJ. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril. 2009; 91(2):514-521.
Government Agency, Medical Society, and Other Authoritative Publications:
- ACOG Practice Bulletin. Management of infertility caused by ovarian dysfunction. ACOG Practice Bulletin No. 34, Volume 99, February 2002.
- Al-Inany HG, Aboulghar M, Mansour R. Gonadotropin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev. 2006; (3):CD001750.
- Al-Inany HG, Aboulghar M, Mansour R, Proctor M. Recombinant versus urinary human chorionic gonadotropin for ovulation induction in assisted conception. Cochrane Database Syst Rev. 2005; (2):CD003719.
- Al-Inany HG, Abou Setta AM, Aboulghar M. Gonadotropin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev. 2002; (17):CD001750.
- 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: 439-456.
- American Hospital Formulary Service (AHFS). AHFS Drug Information 2013. Bethesda, MD: American Society of Health-System Pharmacists, 2013.
- Attia AM, Al-Inany, HG, Proctor ML. Gonadotropins for idiopathic male factor subfertility. Cochrane Database Syst Rev. 2006; (1):CD005071.
- Beck JI, Boothroyd C, Proctor M, et al. Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev. 2005; (2):CD002249.
- Bravelle [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc.; June 29, 2012. Available at: https://www.ferringfertility.com/bravelle/. Accessed on July 14, 2013.
- Centers for Disease Control and Prevention. Assisted Reproductive Technology (ART). Updated July 2, 2013. Available at: http://www.cdc.gov/art/index.htm. Accessed on July 14, 2013.
- Cetrorelix Acetate (Cetrotide). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated September 13, 2010. Available at: http://www.micromedexsolutions.com/home/dispatch Accessed on July 14, 2013.
- Cetrotide [Product Information], Rockland, MA. Serono Inc.; April 2012. Available at: http://www.emdserono.com/cmg.emdserono_us/en/images/Cetrotide_tcm115_19346.pdf. Accessed on July 14, 2013.
- Chorionic Gonadotropin Alfa, Recombinant (Ovidrel). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated August 23, 2010. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on July 14, 2013.
- Chorionic Gonadotropin (Novarel, Pregnyl). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated March 25, 2013. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on July 14, 2013.
- Clomiphene Citrate [Product Information], Bridgewater, NJ. Sanofi-Aventis U.S. LLC.; October 2012. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016131s026lbl.pdf. Accessed on July 14, 2013.
- Clomiphene Citrate (Clomid, Serophene). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated March 13, 2013. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on July 14, 2013.
- Crinone [Product Information], Livingston, NJ. Columbia Laboratories, Inc.; May 2009. Available at: http://www.columbialabs.com/Collateral/Documents/English-US/Crinone%20PI%20v09.pdf. Accessed on July 14, 2013.
- Endometrin [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc.; April 2012. Available at: https://www.ferringfertility.com/endometrin/. Accessed on July 14, 2013.
- Follicle Stimulating Hormone/Luteinizing Hormone (Repronex, Menopur). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated August 27, 2012. Available at: http://www.micromedexsolutions.com/home/dispatch Accessed on July 14, 2013.
- Follistim AQ cartridge [Product Information], Whitehouse Station, NJ. Merck Sharp & Dohme Corp.; August, 2012. Available at: http://www.spfiles.com/pifollistimaqcartridge.pdf. Accessed on July 14, 2013.
- Follistim AQ vial [Product Information], Whitehouse Station, NJ. Organon; June, 2010. Available at: http://www.spfiles.com/pifollistimaqvial.pdf. Accessed on October 6, 2012.
- Follitropin Beta (Follistim, Follistim AQ, Gonal-f RFF). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated August 27, 2012. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on July 14, 2013.
- Ganirelix Acetate. In: DrugPoints® System [electronic version]. Truven Health Analytics Greenwood Village, CO: Truven Health Analytics. Updated July 17, 2012. Available at: http://www.micromedexsolutions.com/home/dispatch Accessed on July 14, 2013.
- Ganirelix Acetate [Product Information], Whitehouse Station, NJ; May 2012. Available at: http://www.spfiles.com/piganirelix.pdf. Accessed on July 14, 2013.
- Gonal–f® (follitropin alfa for injection) Multi–Dose [Product Information], Rockland, MA. Serono Inc.; December 2012. Available at: http://www.emdserono.com/cmg.emdserono_us/en/images/Gona-f_Multidose_tcm115_19349.pdf?Version=. Accessed on July 14, 2013.
- Gonal–f® RFF (follitropin alfa for injection) 75 IU Vial, Rockland, MA., Serono Inc.; December 2011. Available at: http://www.emdserono.com/cmg.emdserono_us/en/images/Gonal-f_RFF_75IU_tcm115_19348.pdf?Version=. Accessed on July 14, 2013.
- Gonal–f® RFF Pen (follitropin alfa injection), Rockland, MA. Serono Inc.; December 2011. Available at: http://www.emdserono.com/cmg.emdserono_us/en/images/Gonal-f_RFF_Pen_tcm115_19350.pdf?Version=. Accessed on July 14, 2013.
- Hughes E, Collin J, Vandekerckhove P. Clomiphene citrate for unexplained subfertility in women. The Cochrane Library. 2000; (2):CD000057.
- Lutropin Alfa (Luveris). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated August 23, 2012. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on July 14, 2013.
- Luveris [Product Information], Rockland, MA. EMD Serono, Inc.; April 2009. Available at: http://www.emdserono.com/cmg.emdserono_us/en/images/Luveris_tcm115_19351.pdf. Accessed on July 14, 2013.
- Menopur [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc; July 2012. Available at: https://www.ferringfertility.com/menopur/. Accessed on July 14, 2013.
- National Institute for Clinical Evidence. Fertility: Assessment and treatment for people with fertility problems. Clinical Guideline. 2013. Available at: http://publications.nice.org.uk/fertility-cg156. Accessed on June 24, 2013.
- Novarel [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc.; July 2012. Available at: http://www.ferringfertility.com/medications/novarel/. Accessed on July 14, 2013.
- Ovidrel [Product Information], Rockland, MA. Serano Inc.; June 2010. Available at: http://fertilitylifelines.com/hcp/gonal-f-treatment. Accessed on June 21, 2013.
- Pandian Z, Bhattacharya S, Vale L, et al. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev. 2005 (2): CD003357.
- Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril. 2008; 90:S60.
- Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012; 98(3):591-598.
- Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in women. Fertil Steril. 2006; 86(5 Suppl 1):S187-193.
- Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril. 2013 Jun 27. doi:pii: S0015-0282(13)00643-2. 10.1016/j.fertnstert.2013.05.033. [Epub ahead of print]
- Pregnyl [Product Information], Bloomington, IN, Baxter Pharmaceutical; August 2012. Available at: http://www.spfiles.com/pipregnyl.pdf . Accessed on July 14, 2013.
- Prochieve [Product Information], Livingston, NJ. Columbia Laboratories, Inc.; October 2008. Available at: http://www.columbialabs.com/Collateral/Documents/English-US/Prochieve%20PI%20v06.pdf. Accessed on July 14, 2013.
- Progesterone (Crinone, Endometrin, Prochieve). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated July 18, 2012. Available at: http://www.micromedexsolutions.com/home/dispatch Accessed on July 14, 2013.
- Repronex [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc; June 14, 2012. Available at: https://www.ferringfertility.com/repronex/. Accessed on July 14, 2013.
- Urofollitropin (Bravelle). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated September 11, 2012. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on July 14, 2013.
- Van Wely M, Westergaard LG, Bossuyt PM, et al. Human menopausal gonadotropin versus recombinant follicle stimulation hormone for ovarian stimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2003; (1):CD003973.
- Vause TD, Cheung AP, Sierra S; Society of Obstetricians and Gynaecologists of Canada. Ovulation induction in polycystic ovary syndrome: No. 242, 2010. Int J Gynaecol Obstet. 2010; 111(1):95-100.
Assisted Reproductive Technology (ART)
Chorionic Gonadotropin Alfa, Recombinant
Follicle Stimulating Hormone
Follicle Stimulating Hormone/Luteinizing Hormone
Intracytoplasmic sperm injection (ICSI)
Intrauterine insemination (IUI)
In Vitro Fertilization (IVF)
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Revised||08/08/2013||Medical Policy & Technology Assessment Committee (MPTAC) review. Position statement for clomiphene citrate updated to include stage I or II endometriosis as medically necessary. Description, Rationale, and Reference sections updated.|
|Reviewed||11/08/2012||MPTAC review. Reference section updated.|
|Revised||11/17/2011||MPTAC review. Coding, Description, Discussion, Reference, and Index sections updated. Definition section added. Reformatted clinical indications. Clarified clinical indication II by replacing "gonadotropins" with "menotropins". Updated clinical indication III with additional drugs. Minor clarifications made to clinical indications IV and V. Title updated to Infertility Drugs.|
|Revised||11/18/2010||MPTAC review. Title updated to Oral, Injectable and Topical Infertility Drugs. Discussion, References, Coding and Index sections updated. Added a medically necessary statement for progesterone vaginal insert or 8% gel. Added a not medically necessary statement for progesterone vaginal insert or 8% gel and a not medically necessary statement for progesterone 4% gel.|
|Reviewed||11/19/2009||MPTAC review. Discussion, references and note under description updated. Place of service and case management sections removed from document.|
|Reviewed||11/20/2008||MPTAC review. Description, references and index updated. Added the word "induction" after "ovulation" in the not medically necessary statement of clinical indication II for clarification. Position stance was not changed.|
|Revised||11/29/2007||MPTAC review. References, index and coding updated. Added not medical necessary statement to clinical indication IV. Gonadotropins for Male Infertility Associated with Hypogonadotropic Hypogonadism.|
|Revised||12/07/2006||MPTAC review. References updated. Added index. Coding updated; removed HCPCS Q2018 deleted 12/31/05.|
|Revised||12/01/2005||MPTAC review. Removed age limits; added clarification to some clinical indications.|
|New||09/22/2005||MPTAC initial guideline development. |