Short Agonist Protocol for IVF Stimulation
Protocol Overview
The short GnRH agonist protocol involves starting GnRH agonist administration at the beginning of the menstrual cycle (typically day 2-3) and continuing throughout ovarian stimulation, utilizing the initial "flare" effect to enhance follicular recruitment before pituitary suppression occurs. 1
Specific Protocol Details
Timing and Initiation
- Start GnRH agonist on cycle day 2 or 3 of the natural menstrual cycle 1, 2
- Begin recombinant FSH at 150-225 IU daily, with dosing dependent on patient age and ovarian reserve 3
- The agonist is continued throughout the stimulation phase until trigger 1
Stimulation Parameters
- Duration of stimulation averages 10-11 days with the short protocol 4, 1
- Total FSH requirements are typically 37.5 ampoules on average 4
- Monitor for adequate follicular development with serial ultrasound and estradiol measurements 3
Trigger and Retrieval
- Administer hCG 5,000-10,000 IU when adequate follicular maturity is achieved 5, 3
- Perform oocyte retrieval 36-38 hours after hCG administration via transvaginal ultrasound-guided follicle aspiration 5, 3
Clinical Efficacy
Comparative Outcomes
- The short protocol prevents premature LH surges as effectively as the long protocol 1
- Fertilization rates, embryo quality, and pregnancy rates are comparable to long agonist protocols in unselected patients 1
- No significant differences in number of oocytes retrieved compared to long protocols 1
Specific Patient Populations
For patients with elevated baseline FSH (>6.5 IU/L on day 3):
- A low-dose GnRH agonist protocol is superior to long depot protocols 4
- Results in fewer gonadotropin ampoules required (37.5 vs 46.1), shorter stimulation duration (10.7 vs 12.3 days), and higher numbers of mature oocytes (5.9 vs 4.4) 4
- Lower cancellation rates (11% vs 24%) compared to long protocols in this population 4
Critical Safety Considerations
OHSS Risk Management
- The short agonist protocol carries inherent risk of severe OHSS due to the flare effect and inability to use GnRH agonist trigger 6
- If severe OHSS risk develops mid-cycle, attempting to rescue by switching to antagonist protocol is NOT recommended if insufficient time exists between conversion and trigger 6
- Consider alternative protocols (antagonist-based) from the outset in high-risk patients (young age, high AMH, PCOS) 7, 8
Anticoagulation in High-Risk Patients
- For patients with antiphospholipid antibodies undergoing IVF, initiate prophylactic LMWH (enoxaparin 40 mg daily) at the start of ovarian stimulation 5, 3
- Withhold LMWH 24-36 hours prior to oocyte retrieval to minimize bleeding risk 5, 3
- Resume anticoagulation after retrieval and continue until estrogen levels normalize or throughout pregnancy if indicated 5
Practical Advantages
- More cost-effective than long protocols due to reduced medication requirements 1
- Simpler for patients as it avoids the need for mid-luteal phase initiation 1
- Shorter overall treatment duration compared to long protocols 4, 1
Key Pitfalls to Avoid
- Do not use short agonist protocol in patients at high risk for OHSS (consider antagonist protocols with GnRH agonist trigger instead) 7, 6
- Do not attempt mid-cycle protocol conversion from agonist to antagonist if OHSS risk emerges—this approach is ineffective 6
- Ensure adequate time for pituitary suppression before expecting full downregulation (the protocol relies on initial flare, not suppression) 1
- Monitor closely for premature luteinization, though rates are similar to long protocols 1