When Are hCG Trigger Injections Indicated?
hCG trigger injections are indicated primarily for timing ovulation in intrauterine insemination (IUI) cycles with ovarian stimulation and for inducing final oocyte maturation in IVF/ICSI cycles when the dominant follicle(s) reach approximately 18 mm mean diameter. 1
Primary Indications in Fertility Treatment
IUI with Ovarian Stimulation
- hCG injections are most commonly used to trigger ovulation in IUI cycles with ovarian stimulation when the dominant follicle reaches a mean diameter of approximately 18 mm. 1
- Providers can determine the method of triggering in IUI stimulated with gonadotropins, as there is no evidence to recommend for or against a specific method over alternatives like LH testing or GnRH agonists. 1
- When hCG injection is used, single IUI can be performed any time between 24 and 40 hours after hCG injection without compromising pregnancy rates. 1
IVF/ICSI Cycles
- hCG is FDA-approved for induction of ovulation and pregnancy in anovulatory, infertile women in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who have been appropriately pretreated with human menotropins. 2, 3
- The standard approach involves administering hCG when follicles reach appropriate size to trigger final oocyte maturation before retrieval. 1
- Ovulation typically occurs over a broad range of time after hCG administration, with mean time to ovulation of 40.4 hours after intramuscular hCG (range ≤36 to ≥48 hours). 4
Dosing Considerations
Minimum Effective Dose
- The recommended minimum dose of hCG should be at least 5,000 IU for adequate oocyte retrieval. 5
- A dose of 2,000 IU resulted in significantly lower successful oocyte recovery (77.3%) compared with 5,000 IU (95.5%) or 10,000 IU (98.1%). 5
- No significant difference exists between 5,000 IU and 10,000 IU doses in terms of oocyte recovery rates. 5
Route of Administration
- Both intramuscular and intravenous routes are effective, with no significant differences in time interval to ovulation or rate of change in circulating estradiol and progesterone levels. 4
- Mean time to ovulation was 40.4 hours after intramuscular hCG versus 38.3 hours after intravenous hCG, a clinically insignificant difference. 4
Alternative Triggering Methods
GnRH Agonist Trigger
- GnRH agonists can trigger ovulation by inducing endogenous LH surge and may reduce risk of ovarian hyperstimulation syndrome (OHSS) compared to hCG. 6, 7
- A single subcutaneous injection of leuprolide acetate (0.5 mg) can trigger ovulation in gonadotropin-stimulated cycles, with 74% ovulatory cycles and 17.4% pregnancy rate per cycle. 7
- However, GnRH agonist triggering has been associated with luteal phase deficiency and may require additional luteal support. 6, 7
Dual Trigger Strategy
- Adding GnRH agonist to hCG trigger (dual trigger) significantly increases the number of MII oocytes (7.82 vs. 5.92) and day-3 grade-1 embryos (4.24 vs. 1.8) compared to hCG alone. 8
- Dual trigger results in more embryos available for cryopreservation (2.68 vs. 0.94), potentially increasing cumulative live birth rates. 8
- Clinical pregnancy rates remain comparable between dual trigger and hCG alone (21% vs. 19.6%). 8
Additional FDA-Approved Indications
Male Hypogonadotropic Hypogonadism
- hCG is indicated for selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to pituitary deficiency) in males. 2, 3
- Clinicians may use hCG, aromatase inhibitors, selective estrogen receptor modulators (SERMs), or combinations for infertile men with low serum testosterone. 1
- For men interested in current or future fertility, testosterone monotherapy should not be prescribed as it suppresses spermatogenesis. 1
Prepubertal Cryptorchidism
- hCG is indicated for prepubertal cryptorchidism not due to anatomical obstruction, typically instituted between ages 4 and 9. 2, 3
- hCG may help predict whether orchiopexy will be needed in the future, though in most cases the response is temporary. 2, 3
Critical Pitfalls to Avoid
OHSS Risk
- The permanent risk for OHSS following hCG administration is a major concern, as hCG shows discrepancies in pharmacokinetics and bioavailability compared to physiologic LH. 6
- In patients at high risk for OHSS (≥4 mature follicles and estradiol >1,000 pg/mL), consider GnRH agonist trigger instead of hCG to reduce OHSS risk. 7
Timing Considerations
- Ovulation occurs over a broad time range (33 to ≥48 hours) after hCG administration, not at a precise time point. 4
- For IUI cycles, the 24-40 hour window after hCG provides flexibility without compromising pregnancy rates. 1