What is the recommended protocol for choosing an in vitro fertilization (IVF) treatment?

Selecting the Appropriate IVF Protocol

The most appropriate IVF protocol should be selected based on individual patient characteristics, with GnRH antagonist protocols recommended for most patients due to shorter stimulation duration, lower gonadotropin requirements, and comparable pregnancy outcomes to long GnRH agonist protocols. 1, 2

Patient Assessment Factors for Protocol Selection

• Ovarian Reserve Assessment: Evaluate AMH levels, antral follicle count, and baseline FSH/LH levels to determine expected response to stimulation 1, 2
• Age: Younger patients typically respond better to stimulation; older patients may require more aggressive protocols 3
• Previous IVF Response: Prior poor response indicates need for modified protocols 1, 4
• Cause of Infertility: Male factor infertility with low total motile sperm count suggests ICSI as the preferred fertilization method 1, 3
• Risk Factors for OHSS: High responders should be identified for modified protocols to reduce OHSS risk 2

Protocol Options Based on Expected Response

For Normal Responders:

• GnRH Antagonist Protocol:
  • Start FSH 150-225 IU daily from day 2-3 of cycle 2
  • Add GnRH antagonist from day 8 or when lead follicle reaches 14mm 2, 5
  • Benefits: Shorter duration, lower gonadotropin requirements, reduced OHSS risk 5, 6
  • Recommended for most patients due to comparable pregnancy rates with better patient tolerance 5, 6

For Poor Responders:

• Long GnRH Agonist Protocol:
  • Higher clinical pregnancy rates per initiated cycle (35.8% vs 25.6%) compared to antagonist protocols 4
  • Lower cancellation rates compared to antagonist protocols 4
• Alternative Options:
  • Minimal stimulation with letrozole/antagonist protocol 7
  • Natural cycle IVF 1
  • Luteal phase stimulation 1

For High Responders:

• GnRH Antagonist Protocol with Freeze-All Strategy:
  • Recommended to minimize OHSS risk 1, 2
  • Consider lower starting dose of FSH (150 IU/day) 5
  • Elective cryopreservation of all embryos for later transfer 1

Laboratory Considerations

• Fertilization Method:

  • ICSI is recommended for PGT cycles to minimize contamination from maternal granulosa cells or paternal sperm 1
  • ICSI is preferred when total motile sperm count is below 3 million 1
  • Conventional IVF for normal sperm parameters 3

• Embryo Transfer Strategy:

  • Elective single embryo transfer (eSET) is strongly recommended for most patients to reduce multiple pregnancy risks 1
  • Double embryo transfer (DET) should not be based on previous unsuccessful treatments, duration of infertility, or endometrial characteristics 1
  • Transfer of more than two embryos is not recommended due to risks of higher-order multiple pregnancies 1

Special Populations

• Donor Oocyte/Embryo Recipients: Only single embryo transfer should be practiced 1
• Gestational Carriers: Only single embryo transfer should be practiced 1
• Patients Requiring PGT: Blastocyst biopsy with 5-8 cells is recommended, with subsequent freeze-all approach 1
• Patients with Specific Medical Conditions:
  • BRCA mutation carriers: Consider timing of IVF before potential risk-reducing surgeries 1
  • Patients requiring anticoagulation: Prophylactic anticoagulation with low-molecular-weight heparin should be interrupted 24-36 hours before oocyte retrieval 2

Common Pitfalls to Avoid

• Overestimating Response: Starting with excessive gonadotropin doses increases OHSS risk 2, 5
• Underestimating Poor Response: Failure to adjust protocols for poor responders leads to cycle cancellations 4
• Multiple Embryo Transfer: Increases risks of maternal and fetal complications without significantly improving cumulative pregnancy rates 1
• Ignoring Cost-Effectiveness: GnRH antagonist protocols typically require less medication and monitoring 5, 6

By following this structured approach to IVF protocol selection based on patient characteristics and expected ovarian response, clinicians can optimize outcomes while minimizing risks and costs.