When to Hold the Trigger Shot for IUI
Hold the hCG or GnRH-agonist trigger and cancel the IUI cycle when more than 2 dominant follicles >15 mm OR more than 5 follicles >10 mm are present at the time of planned trigger, to prevent life-threatening multiple pregnancies and ovarian hyperstimulation syndrome. 1
Primary Cancellation Criteria Based on Follicular Development
The most critical decision point is follicle count at trigger time:
- Cancel the cycle if >2 follicles are ≥15 mm at the time of planned hCG injection or LH surge 1, 2
- Cancel the cycle if >5 follicles are ≥10 mm at the time of planned hCG injection or LH surge 1, 2
These thresholds are based on moderate-quality evidence showing that multiple pregnancy risk escalates dramatically with multifollicular development: 6% with 2 dominant follicles, 14% with 3 follicles, and 10% with 4 follicles. 2
Additional Absolute Contraindications to Trigger
Beyond follicle count, withhold the trigger in these clinical scenarios:
Medical Contraindications
- Positive pregnancy test (endogenous hCG present) 3
- Uncontrolled thyroid disease (must be euthyroid before proceeding) 3
- Severe hypertension (pregnancy contraindicated) 3
- Active pelvic infection (risk of ascending infection with instrumentation) 3
- Hypersensitivity to hCG or GnRH agonist (documented allergy) 3
- Significant cardiac disease where pregnancy poses unacceptable risk 3
- Anticoagulation therapy (increased bleeding risk with procedure) 3
Ovarian-Specific Contraindications
- Polycystic ovary syndrome with excessive response (highest OHSS risk population) 4, 5
- Estradiol >3500 pg/mL (markedly elevated OHSS risk) 4
- Recent ovarian surgery (structural integrity concerns) 3
- Severe endometriosis with significant anatomical distortion 3
Why GnRH Agonist Trigger Is NOT the Solution for IUI
A critical pitfall: GnRH agonist triggers should NOT be used in IUI cycles as an alternative to cycle cancellation. 2 The international fertility guidelines explicitly recommend against GnRH agonists in IUI with ovarian stimulation because they provide no increase in pregnancy rates despite increasing multiple pregnancy rates and costs. 1, 2
GnRH agonist triggers are reserved for IVF cycles with GnRH antagonist protocols, not IUI. 2, 3
Alternative Risk-Reduction Strategies (When Cancellation Is Undesirable)
If the patient strongly objects to cycle cancellation and follicle counts are borderline:
- Aspiration of excess follicles at the time of planned trigger may reduce multiple pregnancy risk, though this is supported by low-quality evidence 1
- Conversion to IVF with single embryo transfer eliminates multiple pregnancy risk while salvaging the cycle 4
- Freeze-all approach if proceeding with retrieval, avoiding fresh transfer 4, 6
However, these alternatives require IVF capabilities and do not apply to standard IUI programs.
Prevention Strategies for Future Cycles
To avoid repeated cancellations in high-risk patients:
- Use low-dose gonadotropins (≤75 IU/day) rather than higher doses, which have similar pregnancy rates but lower multiple pregnancy rates 1, 2
- Consider clomiphene citrate or tamoxifen as alternatives with lower multiple pregnancy rates, though at slightly lower live birth rates than gonadotropins 1, 2
- Add metformin in patients with PCOS undergoing ovarian stimulation, as it may reduce OHSS incidence 4
- Avoid GnRH agonist addition to gonadotropins in IUI, as this increases multiple pregnancy rates without improving outcomes 1
Common Pitfalls to Avoid
- Do not substitute GnRH agonist trigger for hCG in IUI cycles thinking it will prevent OHSS—this is only appropriate in IVF protocols 2, 7
- Do not proceed with trigger hoping for selective reduction later—primary prevention through cycle cancellation is the evidence-based approach 2, 4
- Do not use higher gonadotropin doses (>75 IU/day) thinking more stimulation improves outcomes—it only increases complications 1
- Do not rely on estradiol levels alone—follicle count is the primary determinant of cancellation 1, 2