What are the recommended dosing and benefits of Human Chorionic Gonadotropin (HCG)?

HCG Dosing and Benefits

For ovulation induction in assisted reproductive technology, administer 5,000 IU of hCG intramuscularly when at least three follicles reach >17 mm diameter with appropriately rising estradiol levels. 1

Recommended Dosing Regimens

For Ovulation Induction and ART

• Standard dose: 5,000 IU hCG administered intramuscularly or subcutaneously when follicular maturation criteria are met 1
• Timing: Administer when ≥3 follicles measure >17 mm diameter with appropriately rising serum estradiol 1
• Oocyte retrieval: Perform 36 hours after hCG administration 1
• Route equivalence: Subcutaneous administration of 5,000 IU produces similar serum hCG levels to intramuscular injection and is well-tolerated in lean women (BMI <30) 2, 3

For Male Hypogonadotropic Hypogonadism

• Initial therapy: hCG 500-2,500 IU administered 2-3 times weekly 1
• Mechanism: hCG acts as an LH analogue, stimulating Leydig cells to produce testosterone 1, 4
• Sequential approach: After testosterone normalization on hCG monotherapy, add FSH injections when indicated to optimize spermatogenesis 1
• Monitoring: Track serum testosterone response; testicular size prior to treatment correlates with degree of response 1

Pharmacokinetic Considerations

• Half-life advantage: hCG has a much longer plasma half-life than LH, allowing less frequent dosing 5
• Detection window: After 10,000 IU administration (either route), beta-hCG remains detectable for 7 days; 5,000 IU intramuscular may not be detectable at 7 days 2
• Peak levels: 10,000 IU subcutaneous produces highest serum concentrations compared to equivalent intramuscular dose 2

Clinical Benefits

In Assisted Reproductive Technology

• Pregnancy rates: When used appropriately in IUI with ovarian stimulation, pregnancy rates increase from 8.4% with monofollicular growth to 15% with multifollicular development 1
• Optimal follicular response: Two follicles increase pregnancy rates by 5%, three follicles by 8%, and four follicles by 8% compared to single follicle 1
• Luteal support: Higher doses (10,000 IU) may be needed for adequate luteal phase support versus ovulation triggering alone 2

In Male Infertility with Hypogonadotropic Hypogonadism

• Testosterone restoration: hCG effectively normalizes testosterone levels in men with deficient LH and FSH secretion 1, 4
• Spermatogenesis induction: Initiates and maintains sperm production when combined with FSH after testosterone normalization 1
• Fertility preservation: Unlike exogenous testosterone therapy, hCG does not suppress spermatogenesis and preserves fertility potential 1, 4
• Pregnancy achievement: Many men with idiopathic hypogonadotropic hypogonadism achieve pregnancies when treated with gonadotropins 1

Advantages Over Alternative Therapies

• Versus testosterone replacement: hCG triggers endogenous testosterone and sperm production without causing testicular atrophy or azoospermia seen with exogenous testosterone 1, 4
• Fertility maintenance: Critical advantage for males of reproductive age who require testosterone normalization but wish to preserve fertility 1, 4
• Metabolic effects: Addresses multiple testosterone-dependent systems including metabolism, bone health, cardiovascular function, and muscle mass 4

Critical Safety Considerations

Multiple Pregnancy Prevention

• Withhold hCG administration when >2 dominant follicles >15 mm OR >5 follicles >10 mm are present to prevent high-order multiple gestations 1
• Multiple pregnancy risk: Increases to 6% with two follicles, 14% with three follicles, and 10% with four follicles 1
• Alternative to cancellation: Consider aspiration of excess follicles at time of hCG injection as option for reducing multiple pregnancy risk 1

Contraindications and Warnings

• Avoid in women with hyperandrogenism: Do not use exogenous testosterone or hCG in females with hyperandrogenism as this worsens symptoms 6
• OHSS risk: Monitor for ovarian hyperstimulation syndrome, particularly with multifollicular development 1
• Pregnancy complications: Inform patients about increased risks of preterm birth and low birthweight in IUI-OS pregnancies compared to spontaneous conception 1

Monitoring Requirements

• hCG response monitoring: Measure serum beta-hCG at least every 1-2 weeks during chemotherapy for gestational trophoblastic neoplasia 1
• Testosterone monitoring: In males with hypogonadotropic hypogonadism, monitor serum testosterone response before adding FSH 1
• Clinical pregnancy confirmation: Verify with serial serum beta-hCG starting 16 days after oocyte pickup and gestational sac visualization at 6 weeks 1

Common Pitfalls to Avoid

Do not use hCG in males currently on or planning exogenous testosterone therapy, as testosterone suppresses gonadotropin secretion and negates hCG benefits 1. Recovery from testosterone-induced azoospermia may take months to years 1.

Do not administer hCG when excessive follicular development occurs, as this dramatically increases multiple pregnancy rates with associated maternal and neonatal morbidity including preterm delivery, growth retardation, and pre-eclampsia 1.

Do not use lower doses (5,000 IU) when luteal phase support is the primary goal, as this may provide insufficient duration of action; 10,000 IU doses maintain detectable levels longer 2.