What are the effects and mechanism of action of HUCOG (human chorionic gonadotropin) in the treatment of infertility?

HUCOG (Human Chorionic Gonadotropin) for Infertility: Effects and Mechanism of Action

Primary Mechanism of Action

HUCOG (human chorionic gonadotropin) mimics luteinizing hormone (LH) by binding to LH/hCG receptors throughout the reproductive system, stimulating testosterone production in males and triggering final oocyte maturation and ovulation in females. 1

In Males with Hypogonadotropic Hypogonadism

• HCG directly stimulates testicular Leydig cells to produce intratesticular testosterone at concentrations 50-100 times higher than serum levels, which is essential for spermatogenesis 2
• The hormone restores testosterone production while preserving fertility potential, unlike exogenous testosterone which suppresses spermatogenesis through negative feedback 1
• HCG maintains the hypothalamic-pituitary-gonadal axis function by providing LH-like stimulation without suppressing endogenous gonadotropin secretion 3

In Females Undergoing Fertility Treatment

• HCG triggers final follicular maturation and ovulation by mimicking the natural LH surge 4, 5
• The hormone enhances endometrial receptivity by improving endometrial quality and stromal fibroblast function 6
• HCG stimulates endometrial angiogenesis through actions on insulin-like growth factor binding protein-1 and vascular endothelial growth factor, potentially extending the implantation window 6

Clinical Effects and Indications

Male Infertility - Primary Indication

• The American Urological Association recommends HCG as first-line treatment for males with hypogonadotropic hypogonadism who need testosterone restoration while preserving fertility potential 1
• For men with idiopathic hypogonadotropic hypogonadism, HCG initiates spermatogenesis with 75% achieving sperm in ejaculate when combined with FSH if needed 2
• Standard dosing is 500-2500 IU administered 2-3 times weekly via subcutaneous or intramuscular injection 1

Pediatric Application

• A therapeutic trial of HCG is indicated for treatment of undescended testes in boys with Prader-Willi syndrome before surgery, as it increases scrotal size and normalizes phallus length while avoiding general anesthesia risks 7

Female Ovulation Induction

• HCG administration at peak follicular maturation is associated with high pregnancy rates during ovarian stimulation with timed intercourse or intrauterine insemination 5
• The minimum effective dose for oocyte retrieval in IVF programs is 5000 IU, with doses of 2000 IU showing significantly lower success rates (77.3% vs 95.5-98.1%) 4
• The recommended dose for triggering ovulation is 10,000 IU administered when follicles reach 18-24mm diameter with serum estradiol >200 pg/ml 5, 8

Treatment Protocols and Sequencing

Male Hypogonadism Protocol

• Initial treatment with HCG alone normalizes testosterone levels, followed by FSH injections when indicated for optimal sperm production 1
• Response to HCG correlates with baseline testicular size, with better outcomes in men with preserved testicular volume 2
• Recovery of spermatogenesis after prior testosterone therapy may take months or rarely years, making HCG the preferred initial approach 1

Female Stimulation Timing

• Timing of HCG administration in relation to follicular maturity is the most important variable affecting treatment success after patient age 5
• HCG should be given when lead follicles reach appropriate size rather than waiting for spontaneous LH surge, particularly with FSH-based stimulation protocols 5
• With clomiphene citrate stimulation, awaiting natural LH surge may provide better outcomes, but with FSH protocols, HCG administration yields superior results 5

Critical Clinical Considerations

Absolute Contraindications

• Men interested in current or future fertility should never receive exogenous testosterone, as it suppresses spermatogenesis and can cause azoospermia 1, 2
• Exogenous testosterone provides negative feedback to the hypothalamus and pituitary, eliminating intratesticular testosterone production essential for sperm production 2

Monitoring Requirements

• In males, monitor testosterone levels and semen parameters to assess response and determine if FSH supplementation is needed 1
• In females undergoing IVF, doses below 5000 IU result in significantly lower oocyte recovery rates and should be avoided 4

Special Populations

• For non-obstructive azoospermia, HCG may be used off-label to optimize reproductive hormones before surgical sperm retrieval, though evidence is limited 1
• In men with functioning pituitary glands but low testosterone, HCG serves as an alternative to testosterone therapy when fertility preservation is desired 1

Mechanism Beyond Traditional Understanding

• The LH/hCG receptor has nearly ubiquitous distribution in reproductive organs, suggesting HCG actions extend beyond classic pregnancy support functions 6
• Independent of FSH, low-dose HCG can support development and maturation of larger ovarian follicles that have acquired granulosa cell LH/hCG receptors 6
• HCG appears capable of improving uterine receptivity and making pregnancy more likely through multiple pathways affecting endometrial function 6