Timing of hCG Trigger in IVF Cycles
Administer hCG trigger when at least three follicles reach 16-18 mm mean diameter, then perform oocyte retrieval 36-38 hours later. 1, 2
Standard Protocol for hCG Administration
The American Society for Reproductive Medicine recommends hCG trigger injections primarily for inducing final oocyte maturation in IVF/ICSI cycles when the dominant follicle(s) reach approximately 18 mm mean diameter. 1 The standard approach involves:
- Follicle size threshold: Administer hCG when at least three follicles measure 16 mm or more in diameter with adequate estradiol plasma concentrations. 3
- Timing to retrieval: Perform oocyte retrieval 36-38 hours after hCG administration. 2
- Mean ovulation time: The mean time to ovulation is 40.4 hours after intramuscular hCG injection. 1
Monitoring Parameters
Follicle development is monitored by serial ultrasounds and blood tests during the approximately two weeks of ovarian stimulation with FSH. 4 The decision to trigger should be based on:
- Follicular diameter measurements via ultrasound (target: ≥3 follicles at 16-18 mm) 1, 3
- Estradiol plasma concentrations (adequate levels required, though no specific threshold universally defined) 3
- The percentage of mature oocyte-cumulus-corona radiata complexes collected (77.5%) is typically higher than suggested by the number of leading follicles alone, indicating that heterogeneous follicle size does not exclude a high rate of mature oocytes. 3
Alternative Trigger Options
Dual Trigger (GnRH Agonist + hCG)
For patients at risk of poor response or those seeking optimized outcomes, consider dual trigger with GnRH agonist plus hCG. 5, 6
- Dual trigger (GnRH agonist combined with hCG) is associated with significantly higher live birth rates compared to hCG alone (RR = 1.37,95% CI 1.07-1.76). 6
- This approach increases the number of retrieved oocytes, mature oocytes, fertilized embryos, and usable embryos. 5, 6
- Particularly beneficial for poor responder patients, showing statistically significant increases in positive beta-hCG rate, implantation rate, and newborn/transferred embryo rate. 5
Modified Low-Dose hCG Trigger
For high-risk OHSS patients, use 1500 IU hCG plus 450 IU FSH instead of conventional 3300 IU hCG. 7
- This novel trigger is associated with decreased OHSS symptoms compared to conventional triggers (3300 IU hCG or GnRHa plus 1500 IU hCG) while producing similar IVF and pregnancy outcomes. 7
- Provides a superior alternative in down-regulated cycles and in patients with hypothalamic dysfunction where GnRHa triggers cannot be utilized. 7
GnRH Agonist Alone
For high responders at significant OHSS risk, GnRH agonist trigger alone is an effective alternative. 8
- GnRH agonist trigger yields significantly higher numbers of MII oocytes retrieved and 2PN embryos compared to hCG trigger (p<0.001). 8
- Associated with dramatically lower OHSS rates: 1.9% versus 11.8% with hCG trigger (p=0.004). 8
- Clinical pregnancy and ongoing pregnancy rates are comparable to hCG trigger. 8
Critical OHSS Prevention Considerations
Retrieving significantly more than 13-15 oocytes does not improve pregnancy rates and increases OHSS risk, which can cause capillary leak syndrome, thrombosis, and renal failure. 9
- Underlying thrombophilias increase the risk for severe OHSS. 2
- For patients with antiphospholipid antibodies, prophylactic anticoagulation with low-molecular-weight heparin should begin with ovarian stimulation, be interrupted 24-36 hours before oocyte retrieval, and resumed afterward. 2
Special Populations
Fertility Preservation in Cancer Patients
In cancer patients requiring urgent fertility preservation, priming methods (either hCG or GnRHa) before IVM cycles do not significantly affect oocyte maturation, making both methods viable. 4 Standard ovarian stimulation in this population yields approximately 6.8 ± 4.6 oocytes when vitrified. 9
Hormone-Sensitive Tumors
For women with hormone-sensitive tumors, alternative hormonal stimulation approaches such as letrozole or tamoxifen concurrent with FSH administration have been developed to reduce estrogen exposure, with short-term breast cancer recurrence rates comparable to non-randomized controls. 4