What is the recommended dosing of Gonal-F (follitropin alfa) for women with low Anti-Mullerian Hormone (AMH) levels undergoing egg retrieval?

Gonal-F Dosing for Women with Low AMH Undergoing Egg Retrieval

For women with low AMH (<1.0 ng/ml or <7 pmol/L) undergoing ovarian stimulation for egg retrieval, use maximal stimulation with either corifollitropin alfa (100-150 mcg based on body weight) or recombinant FSH at 12 mcg/day (approximately 300 IU/day), as individualized AMH-based dosing algorithms demonstrate superior outcomes compared to standard fixed-dose protocols. 1, 2

AMH-Based Dosing Algorithm

The evidence supports a stratified approach based on pretreatment AMH levels:

For Low AMH (<12 pmol/L or <1.0 ng/ml):

• Maximal stimulation is required: Corifollitropin alfa 100 mcg (if body weight <60 kg) or 150 mcg (if body weight ≥60 kg), OR recombinant FSH 12 mcg/day 1
• This approach reduced unintended poor response (retrieval of <5 oocytes) from 47% with standard dosing to 24% with individualized dosing 1
• Standard 150 IU/day dosing is insufficient for this population and results in nearly half of patients having inadequate oocyte yield 1

For Medium AMH (12-24 pmol/L):

• Recombinant FSH 150 IU/day is appropriate 1

For High AMH (>24 pmol/L):

• Recombinant FSH 100 IU/day (though note: this dose proved insufficient in 38% of patients, suggesting 125 IU/day may be more appropriate) 1

Clinical Outcomes with Individualized Dosing

Individualized AMH-based dosing achieves equivalent pregnancy rates while improving safety profiles:

• Live birth rates are similar between individualized and standard protocols (29.8% vs 30.7%) 2
• Ongoing pregnancy rates remain equivalent (30.7% vs 31.6%) 2
• However, individualized dosing significantly increases the proportion of patients achieving optimal oocyte yield (8-14 oocytes): 43.3% vs 38.4% 2

Safety Considerations for Low AMH Patients

Women with low AMH face distinct clinical challenges beyond suboptimal response:

• Miscarriage risk is elevated: Women with AMH <1.0 ng/ml have 28% increased relative risk of miscarriage (OR 1.28,95% CI 1.07-1.53) 3
• Women with severely low AMH (<0.7 ng/ml) face 91% increased odds of miscarriage (OR 1.91) 4, 3
• In women ≥35 years, low AMH confers 85% increased miscarriage risk 5, 3

Optimal Oocyte Yield Targets

The target range of 8-14 oocytes retrieved maximizes live birth rates while minimizing OHSS risk:

• Live birth rate peaks at 34.9% with 11 oocytes retrieved 6
• Patients with 8-14 oocytes achieve 33.6% live birth rate 6
• OHSS incidence remains low (5.2%) in the 8-14 oocyte range 6
• Beyond 15 oocytes, live birth rates decline to 30.9% while OHSS risk increases to 17.0% 6

Critical Pitfalls to Avoid

Underdosing is the primary concern in low AMH patients:

• Standard 150 IU/day protocols result in poor response in 47% of low AMH patients 1
• Using 100 IU/day in presumed "high responders" based on AMH >24 pmol/L leads to inadequate response in 38% of cases 1
• Always use maximal stimulation (corifollitropin or 12 mcg/day rFSH) for AMH <12 pmol/L 1

Counseling Requirements

Women with low AMH require specific counseling before initiating treatment:

• Discuss significantly reduced fertility potential and elevated miscarriage risk 5, 3
• The American Society for Reproductive Medicine recommends women with AMH <1 ng/ml pursue fertility evaluation and attempts promptly 5, 3
• Consider fertility preservation options (oocyte cryopreservation) before any planned surgeries 5
• Set realistic expectations: while pregnancy is possible, likelihood is significantly reduced 3

Monitoring During Stimulation

AMH levels decrease progressively during ovarian stimulation:

• Serum AMH drops significantly from baseline through hCG administration in all ovarian reserve categories 7
• This decline is most pronounced in low ovarian reserve patients, though absolute levels remain consistently lower throughout stimulation 7
• This underscores the importance of accurate baseline AMH measurement before initiating protocols 7