Human Chorionic Gonadotropin (hCG)

Number: 1081

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

---

Policy

Scope of Policy

This Clinical Policy Bulletin addresses human chorionic gonadotropin (hCG) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of Novarel (chorionic gonadotropin), Pregnyl (chorionic gonadotropin), Ovidrel (choriogonadotropin alfa), or chorionic gonadotropin is required of all Aetna participating providers and members in applicable plan designs. For precertification, call (866) 782-2779 or fax (860) 754-2515. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.

Note: Medical/Pharmacy Benefit Alignment of Coverage for Infertility Drugs and Procedures:

Medical necessity review of infertility drugs by Aetna Specialty Pharmacy Guideline Management may be bypassed for infertility assisted reproductive technology (ART) drugs that are for use with infertility medical procedures if the infertility procedure has been approved for coverage under the member’s Aetna medical benefit plan. During precertification, a medical authorization number and confirmation of the approval of the infertility procedures will be required to bypass medical necessity review by Specialty Pharmacy Guideline Management. Note: Some plans may require medical necessity review of all infertility drugs by Aetna Specialty Guideline Management. Members of these plans must undergo Specialty Pharmacy Guideline Management medical necessity review of all infertility drugs regardless of whether the drugs are for use with approved infertility medical procedures. For additional information, see CPB 0327 - Infertility.

1. Criteria for Initial Approval

   Aetna considers human chorionic gonadotropin (hCG) (e.g., Novarel, Pregnyl, Ovidrel, generic) medically necessary for the following indications when criteria are met:

   1. Induction of oocyte maturation and/or release for members undergoing assisted reproductive technology (ART) or ovulation induction; or
   2. Prepubertal cryptorchidism treatment; or
   3. Hypogonadotropic hypogonadism treatment in members who meet both of the following criteria:
      
      
      1. Member has low pretreatment testosterone levels; and
      2. Member has low or low to normal follicle stimulating hormone (FSH) or luteinizing hormone (LH) levels; or

   4. Steroid-refractory acute graft-versus-host-disease when member meets either of the following:

      1. The requested medication will be taken in conjunction with systemic corticosteroids; or
      2. Member has an intolerance or contraindication to systemic corticosteroids.

   Note: Many plans that otherwise cover infertility treatments exclude coverage for infertility injectable medications.  Please check benefit plan descriptions.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of hCG therapy medically necessary for all members (including new members) requesting reauthorization and meet all initial authorization criteria.

3. Related Policies 

   1. CPB 0001 - Transrectal Ultrasound
   2. CPB 0007 - Erectile Dysfunction
   3. CPB 0020 - Injectable Medications
   4. CPB 0327 - Infertility
   5. CPB 0532 - Scrotal Ultrasonography

Dosage and Administration

The dosage regimen for hCG products used in any particular case will depend upon the indication for use, the age and weight of the individual, and the the physician's preference. Refer to the Full Prescribing Information of the requested product for additional information.

Experimental, Investigational, or Unproven 

Aetna considers the following indications experimental, investigational, or unproven because there is insufficient evidence for the use of hCG for these indications (not an all-inclusive list):

• Idiopathic male infertility (except for the medically necessary indications in Section I)
• Idiopathic microphallus 
• Treatment of obesity or weight loss management
• Use solely for endometrium preparation for frozen embryo transfer (FET) (see CPB 0327 - Infertility).

---

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
0167U	Gonadotropin, chorionic (hCG), immunoassay with direct optical observation, blood
58974	Embryo transfer, intrauterine [hCG therapy not covered for use solely for endometrium preparation for frozen embryo transfer (FET)]
84702	Gonadotropin, chorionic (hCG); quantitative
84703	qualitative
89255	Preparation of embryo for transfer (any method) [hCG therapy not covered for use solely for endometrium preparation for frozen embryo transfer (FET)]
HCPCS codes covered if selection criteria are met:
J0725	Injection, chorionic gonadotropin, per 1,000 usp units
ICD-10 codes covered if selection criteria are met (not all-inclusive):
D89.810	Acute graft-versus-host disease
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
E66.01 - E66.9	Overweight and obesity
Z68.1 - Z68.56	Body mass index (BMI)

---

Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Chorionic gonadotropin (Novarel and Pregnyl) are indicated for:

  • Prepubertal cryptorchidism not due to anatomic obstruction
  • Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males.
  • Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately pretreated with human gonadotropins.
    
    

• Choriogonadotropin alfa (Ovidrel) is indicated for:

  • Induction of final follicular maturation and early luteinization in infertile women who have undergone pituitary desensitization and who have been appropriately pretreated with follicle stimulating hormones as part of an assisted reproductive technology (ART) program such as in vitro fertilization and embryo transfer.
  • Induction of ovulation (OI) and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary ovarian failure.

Compendial Uses

• Acute graft-versus-host disease (GVHD)[AR1]  (chorionic gonadotropin, Novarel, and Pregnyl only)
• Infertility, luteal phase support

Human chorionic gonadotropin (HCG), available for injection as Novarel (Ferring Pharmaceuticals, Inc.) and Pregnyl (Merck & Co, Inc.), is a polypeptide hormone produced by the human placenta. It acts primarily as a functional analog of pituitary luteinizing hormone (LH), with minor follicle-stimulating hormone (FSH) activity. HCG stimulates gonadal steroidogenesis by binding to the LH / chorionic gonadotropin (CG) receptor: in males, it acts on Leydig cells to promote androgen production, which drives the development of secondary sex characteristics and can induce testicular descent in the absence of anatomical barriers. This effect is reversible upon discontinuation of hCG. In females, hCG stimulates the corpus luteum to produce progesterone, supporting the luteal phase and early pregnancy. During the menstrual cycle, LH and FSH together support follicular development, and the LH surge triggers ovulation—hCG can substitute for LH in this role, particularly in assisted reproduction protocols.

During pregnancy, hCG secreted by the placenta maintains the corpus luteum after LH secretion decreases, supporting continued secretion of estrogen and progesterone, and preventing menstruation.

Choriogonadotropin alfa (Ovidrel, EMD Serono, Inc.) is a recombinant form of human chorionic gonadotropin (hCG). It's essentially a lab-made version of hCG, which is a naturally occurring hormone produced during pregnancy. The physicochemical, immunological, and biological activities of recombinant hCG are comparable to those of placental and human pregnancy urine-derived hCG. 

Human chorionic gonadotropin is contraindicated in precocious puberty, prostatic carcinoma or other androgen-dependent neoplasm, prior allergic reaction to hCG. hCG may cause fetal harm when administered to a pregnant woman. Combined hCG/PMS (pregnant mare's serum) therapy has been noted to induce high incidences of external congenital anomalies in the offspring of mice, in a dose-dependent manner. The potential extrapolation to humans has not been determined.

Per the label, hCG should be used in conjunction with human menopausal gonadotropins only by physicians experienced with infertility problems who are familiar with the criteria for patient selection, contraindications, warnings, precautions, and adverse reactions described in the package insert for menotropins. The principal serious adverse reactions during this use are: (i) ovarian hyperstimulation, a syndrome of sudden ovarian enlargement, ascites with or without pain, and/or pleural effusion; (ii) enlargement of preexisting ovarian cysts or rupture of ovarian cysts with resultant hemoperitoneum; (iii) multiple births, and (iv) arterial thromboembolism. Anaphylaxis has been reported with urinary-derived hCG products.

Induction of androgen secretion by hCG may induce precocious puberty in patients treated for cryptorchidism. Therapy should be discontinued if signs of precocious puberty occur. Since androgens may cause fluid retention, hCG should be used with caution in patients with cardiac or renal disease, epilepsy, migraine, or asthma.

HCG can cross-react in the radioimmunoassay of gonadotropins, especially luteinizing hormone. Each individual laboratory should establish the degree of cross-reactivity with their gonadotropin assay. Physicians should make the laboratory aware of patients on hCG if gonadotropin levels are requested.

There have been sporadic reports of testicular tumors in otherwise healthy young men receiving hCG for secondary infertility. A causative relationship between hCG and tumor development in these men has not been established. Defects of forelimbs and of the central nervous system, as well as alterations in sex ratio, have been reported in mice on combined gonadotropin and HCG regimens. The dose of gonadotropin used was intended to induce superovulation. No mutagenic effect has been clearly established in humans.

Adverse reactions to hCG injection include headache, irritability, restlessness, depression, fatigue, edema, precocious puberty, gynecomastia, and pain at the site of injection. Hypersensitivity reactions both localized and systemic in nature, including erythema, urticaria, rash, angioedema, dyspnea and shortness of breath, have been reported. The relationship of these allergic-like events to the polypeptide hormone or the diluent containing benzyl alcohol is not clear. 

Human chorionic gonadotropin has not been demonstrated to be effective adjunctive therapy in the treatment of obesity. There is no substantial evidence that it increases weight loss beyond that resulting from caloric restriction, that it causes a more attractive or “normal” distribution of fat, or that it decreases the hunger and discomfort associated with calorie‐restricted diets.

Safety and effectiveness in children below the age of 4 have not been established.

Endometrium Preparation for Frozen Embryo Transfer

Human chorionic gonadotropin (hCG) is given to women to trigger ovulation once a naturally developing follicle is observed via ultrasound and hormone monitoring. This mimics the body's natural luteinizing hormone (LH) surge, helping to synchronize the timing of the endometrial lining (under the influence of the corpus luteum) with the embryo transfer. 

In the context of frozen embryo transfer (FET), hCG medications like Pregnyl and Novarel are typically timed when the lead follicle reaches about 18-20 mm in diameter (Baksh et al, 2021). However, hCG is not used to directly enhance endometrial development, but to ensure timely ovulation and synchronization of the luteal phase for embryo transfer. 

In a 2025 Cochrane review, Ghobara et al systematically evaluated 18 randomized controlled trials comparing various endometrial preparation regimens for frozen embryo transfer (FET) in ovulatory women. The review found no significant differences in live birth or ongoing pregnancy rates between natural cycles, modified natural cycles with hCG triggering, or hormone therapy (HRT) cycles, with or without GnRH-agonist suppression. All key outcomes (live birth, ongoing pregnancy, miscarriage, and multiple pregnancy) were statistically similar, with most evidence categorized as low or moderate certainty. 

There is no strong consensus or guideline recommending routine use of hCG for endometrial preparation in FET cycles without follicle stimulation, and the optimal protocol remains uncertain due to low-certainty evidence and variability in clinical practice. Thus, while hCG (Pregnyl or Novarel) may be used in specific artificial FET protocols, its use is not standard of care across all FET regimens (Ghobara et al, 2025; Zhang et al, 2023).

---

References