What is the management of poor ovarian reserve?

Management of Poor Ovarian Reserve

For women with poor ovarian reserve, double stimulation protocols combined with letrozole are the most effective management strategy to maximize oocyte yield and improve pregnancy outcomes. 1

Diagnosis and Assessment

Poor ovarian reserve is characterized by:

• Low Anti-Müllerian Hormone (AMH) levels
• Elevated Follicle Stimulating Hormone (FSH) levels
• Low antral follicle count (AFC) on ultrasound
• Poor response to previous ovarian stimulation (≤3 oocytes retrieved)

Management Strategies

Ovarian Stimulation Protocols

1. Double Stimulation Protocol

   • Recommended for women with low ovarian reserve without urgent need for treatment
   • Requires approximately 4 weeks
   • Approximately doubles the number of oocytes retrieved 1
   • Sequential stimulations in the same menstrual cycle

2. Minimal Stimulation Protocol with Letrozole

   • Letrozole 2.5mg daily for 5 days starting from day 2 of cycle
   • Add low-dose gonadotropins (150 IU daily) starting from day 3 of letrozole
   • GnRH antagonist when follicles reach 14mm
   • Significantly higher clinical pregnancy and live birth rates compared to high-dose protocols 2
   • Lower total gonadotropin usage and cost-effective 2

3. Clomiphene Citrate + Estradiol Protocol

   • Particularly effective for Bologna-criteria poor responders
   • Combined administration results in lower cancellation rates and higher oocyte yield 3
   • Clomiphene 100mg/day + estradiol 1.0mg/day continuously until ovulation induction

4. Random Start Stimulation

   • Can be initiated at any point in menstrual cycle
   • Particularly useful when time is limited 1

Adjuvant Treatments

1. DHEA Supplementation

   • Not consistently shown to enhance IVF outcomes in poor responders
   • Studies have failed to demonstrate significant improvement in pregnancy rates 4

2. Aromatase Inhibitors (Letrozole)

   • Reduces peak estradiol levels
   • Creates more favorable follicular environment with higher testosterone, androstenedione, FSH, and AMH levels 5
   • Associated with lower miscarriage rates when used sequentially with gonadotropins 5

Fertility Preservation Options

1. Oocyte Cryopreservation

   • Success rates depend on number of mature oocytes retrieved
   • Age-dependent outcomes: cumulative live birth rate of 61.9% with 12 oocytes in women ≤35 years vs. 43.4% with 10 oocytes in women >35 years 1

2. Embryo Cryopreservation

   • Requires a partner or sperm donor
   • Generally higher success rates than oocyte freezing

3. Ovarian Tissue Cryopreservation

   • Experimental option
   • Not recommended for women >40 years due to insufficient primordial follicles 1
   • Should only be performed in centers with necessary expertise under IRB-approved protocols 1

Special Considerations

• Cancer Patients: Letrozole or tamoxifen can be used during stimulation to reduce estrogen exposure in hormone-sensitive cancers 1
• Monitoring: Regular transvaginal ultrasound and serum estradiol measurements are essential during stimulation
• Ovarian Hyperstimulation Syndrome (OHSS): Risk is lower in poor responders but should still be monitored 6

Pitfalls and Caveats

1. Realistic Expectations: Poor ovarian reserve is associated with lower success rates; counseling should address this reality
2. Age Factor: Advanced age compounds the challenges of poor ovarian reserve
3. Overstimulation Risk: Aggressive protocols may not improve outcomes and could increase side effects
4. Premature Ovarian Insufficiency (POI): This is distinct from poor ovarian reserve and requires different management approaches 1
5. Medication Interactions: Be aware of potential interactions between fertility medications and other treatments

Algorithm for Management

1. Assessment: Determine AMH, FSH, and AFC
2. Protocol Selection:
   • For severely diminished reserve: Minimal stimulation with letrozole + low-dose gonadotropins
   • For moderately diminished reserve: Double stimulation protocol
   • For time-sensitive cases: Random start protocol
3. Monitoring: Frequent ultrasound and hormone assessments
4. Trigger: When lead follicles reach appropriate size (17-20mm)
5. Retrieval: 34-36 hours after trigger
6. Fertilization and Cryopreservation: Consider all viable embryos/oocytes precious

By implementing these evidence-based strategies, clinicians can optimize outcomes for patients with poor ovarian reserve while minimizing unnecessary medication exposure and costs.