Injectable Medications in IVF from Cycle Day 2-3 Until Egg Retrieval
In a standard IVF cycle, the primary injectable medications given from cycle day 2-3 until egg retrieval are: (1) gonadotropins (FSH/hMG) for ovarian stimulation, (2) GnRH antagonists (ganirelix/cetrorelix) or GnRH agonists (nafarelin/leuprolide) for ovulation suppression, and (3) hCG trigger injection 36 hours before retrieval.
Core Injectable Medication Protocol
1. Gonadotropins for Ovarian Stimulation
The foundation of controlled ovarian hyperstimulation involves:
- FSH (Follicle-Stimulating Hormone): Starting dose typically 75-150 IU daily, with individually adjusted doses based on ovarian response 1
- hMG (Human Menopausal Gonadotropin): Alternative or combination option, often 150 IU on specific days 2
- Monitoring: Response tracked via serum estradiol (E2) levels and transvaginal ultrasound 1
The evidence shows that lower doses (75 IU or less) are preferred when using gonadotropins in ovarian stimulation protocols, as higher doses increase multiple pregnancy rates without improving pregnancy outcomes 3.
2. GnRH Agonists or Antagonists for Ovulation Suppression
Two main approaches exist:
GnRH Agonist Protocol (Long or Flare):
- Nafarelin acetate: 0.5 mg/day starting either in the luteal phase (long protocol) or on day 2 of the follicular phase (flare/boost protocol) 1
- Continues until hCG trigger
GnRH Antagonist Protocol (More Common Currently):
- Ganirelix or Cetrorelix: Started when the leading follicle reaches 14 mm diameter 2
- Typical dose: 0.25 mg daily subcutaneously
- Cetrorelix: Can use 2.5 mg single dose with additional 0.25 mg injections as needed 2
- Recommended for high responders, especially with freeze-all embryo strategies 4
The antagonist protocol is particularly recommended for PGT cycles and freeze-all strategies due to its flexibility and reduced ovarian hyperstimulation syndrome (OHSS) risk 4.
3. hCG Trigger Injection
- Timing: Administered when at least three follicles reach >17 mm diameter and serum E2 is appropriately rising 1
- Dose: 5,000-10,000 IU intramuscularly 1, 4, 1
- Retrieval: Oocytes retrieved 36-38 hours after hCG administration 1, 4, 1
Alternative and Adjunctive Options
Oral Medications Combined with Injectables
While not injectable, letrozole (aromatase inhibitor) is increasingly used alongside gonadotropins:
- Particularly in poor responders or patients with hormone-sensitive cancers (e.g., BRCA carriers) 4
- Can reduce total gonadotropin dose needed 5
- Typically 2.5-5 mg daily for 5-8 days 5
Emerging Injectable Options
Recent research suggests intradermal FSH administration may allow extended injection intervals (every 5 days instead of daily), reducing injection burden while maintaining efficacy 6. However, this remains investigational and is not standard practice.
Common Pitfalls to Avoid
- Premature LH surge: Ensure GnRH antagonist is started when lead follicle reaches 14 mm, not later 2
- OHSS risk: Use antagonist protocols in high responders; consider freeze-all strategy 4
- Multiple pregnancy risk: Cancel cycle if >2 dominant follicles >15 mm or >5 follicles >10 mm develop (though this applies more to IUI than IVF) 3
- Timing precision: hCG trigger must be given exactly 36-38 hours before scheduled retrieval 1, 4, 1
Protocol Selection Considerations
For normal responders: GnRH antagonist protocol with FSH 75-150 IU daily is standard 4
For poor responders: Consider higher FSH doses, alternative protocols (natural cycle, minimal stimulation, luteal phase stimulation), or letrozole adjunct 4, 5
For high responders/PCOS: GnRH antagonist protocol mandatory to reduce OHSS risk; consider freeze-all strategy 4
For cancer patients: Letrozole + FSH protocols preferred for hormone-sensitive cancers; rapid start protocols available when time-sensitive 4, 7
The total stimulation period typically lasts 8-14 days from gonadotropin start to hCG trigger, with daily or near-daily injections throughout this period 1.