Clinical UM Guideline

 

Subject: Infertility Drugs
Guideline #:  CG-DRUG-11 Publish Date:    08/29/2018
Status: Reviewed Last Review Date:    07/26/2018

Description

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 document for additional information:

Clinical Indications

I. Clomiphene Citrate

Medically Necessary:

Clomiphene citrate for a maximum of 6 cycles of therapy is considered medically necessary for ovulation induction in an infertile* individual with any of the following:

  1. Normogonadotropin anovulatory dysfunction such as polycystic ovary syndrome; or
  2. Young individual with unexplained infertility of short duration, with normal levels of luteal progesterone and a normal hysterosalpingogram; or
  3. Stage I or II endometriosis.

Not Medically Necessary:

Clomiphene citrate is considered not medically necessary for ovulation induction when the medically necessary criteria are not met or for an individual with ANY of the following:

  1. Primary ovarian failure or tubal occlusion; or
  2. Hypogonadotropic anovulatory disorders or hypopituitarism; or
  3. Received greater than 6 cycles of therapy.

II. Ovulation Stimulation Alone or With Intrauterine Insemination - Injectable Low Dose Follicle Stimulating Hormone (Bravelle, Follistim AQ®, Gonal-f®, Gonal-f®-RFF) or Menotropins (Menopur®)

Medically Necessary:

Ovulation induction with a maximum of 3 cycles of injectable low dose follicle stimulating hormone or menotropins, with or without intrauterine insemination, is considered medically necessary in an infertile* individual with ANY of the following:

  1. Hypogonadotropic anovulatory disorders or hypopituitarism - these individuals will not respond to follicle stimulating hormone alone, but will require additional therapy with luteinizing hormone containing product such as human chorionic gonadotropins or will use a mixed follicle stimulating hormone/luteinizing hormone product like Menopur; or
  2. Normogonadotropin anovulatory disorders (that is, polycystic ovary syndrome) or those with unexplained infertility who have not ovulated or conceived after a prior trial of 3 cycles of clomiphene.

Not Medically Necessary:

Ovulation induction with injectable low dose follicle stimulating hormone or menotropins is considered not medically necessary when the medically necessary criteria are not met and for an individual with either of the following:

  1. Receiving more than 3 ovulatory cycles of therapy; or
  2. Tubal occlusion or primary ovarian failure.

III. Ovarian Stimulation in Conjunction with In Vitro Fertilization or Intracytoplasmic Sperm Injection  (Bravelle, Follistim AQ, Gonal-f, Gonal-f RFF, Menopur, recombinant human chorionic gonadotropin [Ovidrel] or, urinary derived human chorionic gonadotropins [Pregnyl, Novarel and generics]), with gonadotropin releasing hormone agonists (Lupron Depot, generic leuprolide) or antagonists (Cetrotide, Ganirelix)

Medically Necessary:

A maximum of 3 cycles of ovarian stimulation in conjunction with in vitro fertilization or intracytoplasmic sperm injection is considered medically necessary for an infertile* individual or couple with ANY of the following:

  1. Couples with severe male factor infertility; or
  2. Bilateral tubal occlusion; or
  3. Unexplained infertility that has not responded to ovarian induction therapy.

Not Medically Necessary:

Ovarian stimulation in conjunction with in vitro fertilization or intracytoplasmic sperm injection is considered not medically necessary when the medically necessary criteria are not met including for an individual with greater than 3 cycles of therapy.

IV. Gonadotropins for Male Infertility Associated with Hypogonadotropic Hypogonadism (Follistim AQ, Gonal-f)

Medically Necessary:

Follistim AQ or Gonal-f in combination with human chorionic gonadotropins, are considered medically necessary for an infertile* individual with hypogonadotropic hypogonadism with onset prior to completion of pubertal development.

The use of human chorionic gonadotropin alone or in combination with follicle stimulating hormone is considered medically necessary to maintain spermatogenesis for an infertile* individual with post-pubertal acquired hypogonadotropic hypogonadism who have previously had normal sperm production.

The use of human chorionic gonadotropin alone or in combination with follicle stimulating hormone is considered medically necessary to maintain spermatogenesis for an infertile* individual 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 medically necessary criteria are not met.

V. Progesterone Vaginal Supplementation or Replacement for Infertility Treatment (Crinone 8% gel, Endometrin vaginal insert, Prochieve 8% gel)

Medically Necessary:

Progesterone vaginal insert or 8% gel is considered medically necessary as part of an Assisted Reproductive Technology treatment for an infertile* individual who requires progesterone supplementation.

Not Medically Necessary:

The use of progesterone vaginal insert or 8% gel for an individual is considered not medically necessary when the medically necessary criteria above are not met.

The use of progesterone 4% gel is considered not medically necessary as part of an Assisted Reproductive Technology treatment for an infertile individual who requires progesterone supplementation.

*Note: For the purposes of this document, infertility is defined clinically in women and men who cannot achieve a successful pregnancy after 12 months or more of appropriate, timed unprotected intercourse or 6 cycles of therapeutic donor insemination. The diagnosis of male or female infertility requires evaluation of the couple versus a single individual.

Coding

 The following codes for treatments and procedures applicable to this document are included below for informational purposes. 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.

HCPCS

 

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 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]

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-10 Diagnosis

 

 

All diagnoses

Discussion/General Information

Infertility can occur due to either female factors, male factors, a combination of both female and male factors, or for unknown reasons. The diagnosis of male or female infertility requires evaluation of the couple versus a single individual. Common causes of female infertility include, but are not limited to: ovulatory disorders, endometriosis and tubal blockage. Common causes of male infertility include, but are not limited to: a low number of sperm cells in the ejaculate (oligozoospermia), no sperm cells in the ejaculate (azoospermia) and sperm transport disorders.

The American Society for Reproductive Medicine (ASRM) (2013) defines infertility and states:

Infertility is a disease, 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.

Therapeutic donor insemination (TDI) is artificial insemination performed using sperm from a male other than the individual’s partner. An early study by Peek and colleagues (1984) evaluated couples undergoing TDI with fresh semen. The authors reported a fecundity rate (number of pregnancies/number of treatment cycles) of 20% and a six-cycle cumulative pregnancy rate of 74%, which approached the pregnancy rate in women who discontinued oral contraceptive pills to attempt pregnancy.

Drugs used to enhance fertility include the gonadotropin releasing hormones (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 (for example, 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). A product containing both FSH and luteinizing hormone (LH) is also available (Menopur). Another menotropin product, Repronex is no longer being marketed in the United States.

Categories of infertility drugs with pharmacologic actions are summarized in the following table:

Drug

Pharmacologic Actions

Menotropins: FSH and LH
(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.

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.

GnRH antagonists
(Cetrotide, Ganirelix)

  • 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.

Clomiphene citrate
(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 2013, the ASRM reported the following summary and conclusions regarding the use of CC in women:

SUMMARY

CONCLUSIONS

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.

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.

In 2018, Banker and colleagues published a retrospective, observational study conducted from November 2014 to February 2016 with the aim to compare the effectiveness of different controlled ovarian hyperstimulation protocols in IUI. The method for the comparison consisted of two groups: Group A CC (n=115) and Group B CC and gonadotropin or gonadotropin alone (n=886). After IUI was performed, the authors found that clinical pregnancy rates were significantly higher in Group B (14.55%) versus Group A (7.82%) (p=0.05). Some limitations include lack of blinding and retrospective study design. The authors concluded that CC and gonadotropin or gonadotropin alone is an effective controlled ovarian hyperstimulation protocol in combination with IUI.

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 menotropin product (Menopur). All gonadotropin cycles should be carefully monitored with ultrasound to decrease the risk of multiple pregnancies and ovarian hyperstimulation syndrome (Aboulghar, 2001; Dickey, 2005; Eijkemans, 2003; Hughes, 2003). Protocols may include the use of either urine-derived formulations of FSH (Bravelle) or a menotropin product containing FSH and LH (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).

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 acetate (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 (that is, short vs. long protocol); however, some reviews have reported that use of GnRH antagonists (that is, short protocol) is associated with a lower clinical pregnancy rate compared to GnRH agonists (that is, long protocol) (Al-Inany, 2002; Siristatidis, 2015). GnRH antagonists cycles can be supplemented with menotropin, which may be associated with lower pregnancy loss (Yang 2018).

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, several Cochrane reviews found no difference in follicular maturation/quality and live birth rates between the urine-derived and recombinant formulations (Al-Inany, 2005; Weiss, 2015). Safety and tolerability of urine-derived and recombinant products appear to be similar. 

Lutropin alfa (Luveris), a recombinant luteinizing hormone (r-LH) formulation previously available was withdrawn from the U.S. market by EMD Serono, Inc. as of July 16, 2012.

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.

Definitions

Artificial insemination: Introduction of semen into the vagina, uterus, or oviduct by a method other than sexual intercourse.

Assisted reproductive technology (ART): 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.

Male infertility: Inability of a male to impregnate a female after 1 year of trying.

References

Peer Reviewed Publications:

  1. 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.
  2. 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.
  3. Banker M, Patel A, Deshmukh A, et al. Comparison of effectiveness of different protocols used for controlled ovarian hyperstimulation in intrauterine insemination cycle. J Obstet Gynaecol India. 2018; 68(1):65-69.
  4. 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.
  5. 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.
  6. Check JH. Luteal Phase Support in assisted reproductive technology treatment: focus on Endometrin® (progesterone) vaginal insert. Ther Clin Risk Manag. 2009; 5(4):403-407.
  7. 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.
  8. De Placido G, Alviggi C, Perino A, 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.
  9. 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.
  10. 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.
  11. 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.
  12. Ho CH, Chen SU, Peng FS, et al. 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.
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  19. 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.
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Government Agency, Medical Society, and Other Authoritative Publications:

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  2. 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.
  3. Al-Inany HG, Abou Setta AM, Aboulghar M. Gonadotropin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev. 2002;(17):CD001750.
  4. 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.
  5. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014;101(3):633-634.
  6. Attia AM, Al-Inany, HG, Proctor ML. Gonadotropins for idiopathic male factor subfertility. Cochrane Database Syst Rev. 2006;(1):CD005071.
  7. 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.
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  32. Lupron Depot [Product Information], North Chicago, IL. AbbVie Inc.; June 2014. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020517s036_019732s041lbl.pdf. Accessed on June 21, 2018.
  33. Menopur [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc; April 2017. Available at: http://www.ferringusa.com/wp-content/uploads/2017/06/8109000029-Menopur-PI-Revisions-to-PI-PPI-Rev.-04.2017.pdf. Accessed on June 21, 2018.
  34. Novarel [Product Information], Parsippany, NJ. Ferring Pharmaceuticals Inc.; September 2016. Available at: http://www.ferringfertility.com/medications/novarel/. Accessed on June 21, 2018.
  35. Ovidrel [Product Information], Rockland, MA. Serano Inc.; September 2014. Available at: http://www.emdserono.com/ms.country.us/en/images/Ovidrel_Prefilled_Syringe_PI_tcm115_140013.pdf?Version=. Accessed on June 21, 2018.
  36. Pandian Z, Gibreel A, Bhattacharya S. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev. 2015; (11):CD003357.
  37. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013; 99(1):63.
  38. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015; 103(3):e18-25.
  39. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012; 98(3):591-598.
  40. Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril. 2013; 100(2):341-348.
  41. Pregnyl [Product Information], Bloomington, IN, Baxter Pharmaceutical; January 2015. Available at: https://www.merckconnect.com/pregnyl/overview.html. Accessed on June 21, 2018.
  42. Prochieve [Product Information], Livingston, NJ. Columbia Laboratories, Inc.; November 2009. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f8dc923-65d7-42ff-b718-97e7a7e87822. Accessed on June 21, 2018. 
  43. Progesterone (Crinone, Endometrin, Prochieve). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated May 4, 2018. Available at: http://www.micromedexsolutions.com/home/dispatch. Accessed on June 21, 2018.
  44. Progesterone Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised November 2, 2012. Accessed on June 21, 2018.
  45. Siristatidis CS, Gibreel A, Basios G, et al. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. Cochrane Database Syst Rev. 2015;(11):CD006919.
  46. Urofollitropin (Bravelle). In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated November 17, 2017. Available at: http://www.micromedexsolutions.com. Accessed on June 21, 2018. 
  47. 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.
  48. Weiss NS, Nahuis M, Bayram N, et al. Gonadotrophins for ovulation induction in women with polycystic ovarian syndrome. Cochrane Database Syst Rev. 2015;(9):CD010290.
Websites for Additional Information
  1.  American Congress of Obstetricians and Gynecologists. Treating infertility. October 2017. Available at: https://www.acog.org/Patients/FAQs/Treating-Infertility. Accessed on June 21, 2018.
  2. Centers for Disease Control and Prevention. Assisted Reproductive Technology (ART). Updated November 28, 2017. Available at: http://www.cdc.gov/art/index.htm. Accessed on June 21, 2018.
  3. Centers for Disease Control and Prevention. Infertility Facts. Updated April 18, 2018. Available at: https://www.cdc.gov/reproductivehealth/infertility/index.htm. Accessed on June 21, 2018.
  4. National Institute of Health. How common is male infertility, and what are its causes? Available at: https://www.nichd.nih.gov/health/topics/menshealth/conditioninfo/Pages/infertility.aspx. Accessed on June 21, 2018.
Index

Assisted Reproductive Technology (ART)
Bravelle
Cetrotide
Chorionic Gonadotropin
Chorionic Gonadotropin Alfa, Recombinant
Clomid
Clomiphene Citrate
Crinone
Endometrin
Follicle Stimulating Hormone
Follicle Stimulating Hormone/Luteinizing Hormone
Follistim AQ
Follitropin Beta
Ganirelix
Gonadotropin
Gonal-f
Gonal-f-RFF
Infertility
Intracytoplasmic sperm injection (ICSI)
Intrauterine insemination (IUI)
In Vitro Fertilization (IVF)
Leuprolide acetate
Lupron Depot
Lutropin Alfa
Male Infertility
Menopur
Novarel
Ovidrel
Ovulation Induction
Ovulation Stimulation
Pregnyl
Prochieve
Progesterone
Serophene
Urofollitropin

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.

History

Status

Date

Action

Reviewed

07/26/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. The document header wording updated from “Current Effective Date” to “Publish Date.” Discussion, References, and Websites sections updated.

Revised

08/03/2017

MPTAC review. Added a note to Clinical Indications section defining infertility. Clarified Medically Necessary statements to indicate that the individual receiving treatment is infertile. Clarified the Not Medically Necessary statements to include when the Not Medically Necessary criteria are not met. Discussion, Definitions, References, and Index sections updated.

Revised

08/04/2016

MPTAC review. Formatting updated in clinical indication section. Repronex removed from clinical indication statement as product has now been discontinued. Discussion, References and Index sections updated. Removed ICD-9 codes from Coding section.

Revised

08/06/2015

MPTAC review. Medically necessary statement for ovulation stimulation alone or with intrauterine insemination clarified and updated with the removal of recombinant LH (Luveris). Discussion, References and Index sections updated.

Reviewed

08/14/2014

MPTAC review. Discussion and References sections updated.

Revised

08/08/2013

MPTAC review. Position statement for clomiphene citrate updated to include stage I or II endometriosis as medically necessary. Description, Rationale, and References sections updated.

Reviewed

11/08/2012

MPTAC review. References 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.