What are the Human Chorionic Gonadotropin (HCG) treatment recommendations for male infertility?

From the Guidelines

Human chorionic gonadotropin (hCG) therapy is the recommended first-line treatment for male infertility caused by idiopathic hypogonadotropic hypogonadism (IHH), with a typical dosage of 500-2500 IU, 2-3 times weekly, as stated in the 2024 AUA/ASRM guideline 1. The treatment approach for IHH involves initial hCG injections to restore testosterone production and spermatogenesis, with the degree of response correlating with the size of the testis prior to treatment.

• Key points to consider in hCG therapy for IHH include:
  • Initial treatment with hCG injections (500-2500 IU, 2-3 times weekly) to normalize testosterone levels
  • Addition of FSH injections when indicated, after testosterone levels are normalized on hCG
  • Avoidance of exogenous testosterone therapy in males pursuing or planning to pursue family building in the near future, due to its inhibitory effects on spermatogenesis
  • Counseling patients about the potential negative effects of exogenous testosterone therapy on spermatogenesis and the time course required for resumption of spermatogenesis after cessation, as highlighted in the 2024 AUA/ASRM guideline 1. The use of hCG in patients with non-obstructive azoospermia may also be considered to optimize spermatogenesis and improve the chances of sperm recovery at the time of attempted surgical sperm retrieval, as mentioned in the guideline 1.
• Important considerations in the treatment of male infertility with hCG include:
  • Regular monitoring of semen analyses every 3 months and testosterone levels every 1-3 months
  • Treatment duration until pregnancy is achieved or for up to 18-24 months
  • Patient counseling about the potential benefits and risks of hCG therapy, including the success rates of inducing spermatogenesis in true hypogonadotropic hypogonadism cases, as reported in the guideline 1.

From the FDA Drug Label

INDICATIONS AND USAGE Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males.

The HCG treatment is recommended for selected cases of hypogonadotropic hypogonadism in males, which is a cause of male infertility. The treatment is intended for males with hypogonadism secondary to a pituitary deficiency. 2

From the Research

HCG Treatment Recommendations in Male Infertility

• HCG treatment is used in the treatment of male infertility due to its luteinizing hormone (LH)-like action triggering testosterone and sperm production 3.
• The combination of FSH and hCG has been demonstrated to be associated with better outcomes than single compounds in male individuals, regarding the ability to stimulate spermatogenesis and eventually inducing physiological pregnancy 4.
• HCG can be administered either subcutaneously or intramuscularly, and the combination therapy with hCG and FSH for a period of 12-24 months was found to promote testicular growth in almost all patients, spermatogenesis in approximately 80%, and pregnancy rates in the range of 50% 4.
• Key baseline predictors of successful spermatogenesis-induction include prior spontaneous testicular development, serum inhibin B concentration, and no history of maldescended testes (cryptorchidism) 5.
• The therapeutic success is higher in patients with post-pubertal HH, in those without previously undescended testes, in patients with higher baseline testicular volume, who underwent repeated cycles of therapy, and in patients with higher baseline inhibin B serum concentrations 4.

Treatment Modalities

• Testosterone replacement therapy is the classic treatment for hypogonadism, but it can increase the risk of infertility 3, 6.
• GnRH or gonadotropin therapies are the best options for men wishing to have children 6.
• Human chorionic gonadotropin (hCG) is used in combination with different FSH formulations, such as human menopausal gonadotropins (hMG), highly purified urinary FSH preparations (hpFSH), or recombinant FSH (rFSH) 4.
• Assisted reproductive techniques, ranging from intrauterine insemination to in vitro fertilization, can also be used depending on the woman's potential for pregnancy and the quality and quantity of the sperm 6, 7.

Treatment Outcomes

• Pregnancy rates of the spouses of the patients with hypogonadotropic hypogonadism were reported as follows: spontaneous 64.6%, intrauterine insemination 12.3%, in vitro fertilization 15.3%, and microscopic testicular sperm extraction + intracytoplasmic sperm injection 4.6% 7.
• Almost all idiopathic hypogonadotropic hypogonadism patients can be treated with gonadotropins (human chorionic gonadotropin + follicle-stimulating hormone) in order to have children 7.
• The required gonadotropin dose varies according to each patient, and the treatment dose and duration should be increased until patients have children 7.