What are the ideal progesterone serum levels post Frozen Embryo Transfer (FET) day 15?

Ideal Progesterone Serum Levels Post FET Day 15

There is no established ideal progesterone serum level specifically for day 15 post FET, but serum progesterone levels ≥16.5 ng/mL on pregnancy test day are associated with significantly higher ongoing pregnancy and live birth rates. 1

Progesterone Level Targets and Outcomes

Optimal Progesterone Levels

• Serum progesterone ≥16.5 ng/mL on pregnancy test day (typically day 15 post-FET) is associated with:
  • Higher ongoing pregnancy rates (OR = 12.5,95% CI 3.61-43.33) 1
  • Higher live birth rates (OR = 11.88,95% CI 3.30-42.71) 1
• Women with ongoing pregnancies show significantly higher median progesterone levels compared to those with miscarriages (55.9 ng/mL vs. 18.1 ng/mL) 1
• Levels below 9-11 ng/mL have been shown to negatively impact reproductive outcomes in hormone replacement therapy FET cycles 2

Caution with Excessive Levels

• Progesterone levels >20 ng/mL on transfer day have been associated with:
  • Lower live birth rates (49% vs. 65% when P4 <20 ng/mL) 3
  • Higher pregnancy loss rates (27% vs. 12% when P4 <20 ng/mL) 3
• A trend of decreasing live birth rates has been observed with increasing progesterone levels: 70% (10-15 ng/mL), 62% (15-20 ng/mL), 52% (20-30 ng/mL), 50% (30-40 ng/mL), and 33% (>40 ng/mL) 3

Progesterone Supplementation Protocol

Route of Administration

• Intramuscular progesterone shows superior outcomes compared to vaginal-only progesterone:
  • Higher live birth rates (44% vs. 27%) 4
  • Lower miscarriage rates (50% of pregnancies with vaginal-only progesterone ended in miscarriage) 4
• Combination therapy (vaginal progesterone 200 mg twice daily plus intramuscular progesterone 50 mg every third day) is non-inferior to daily intramuscular progesterone (46% vs. 44% live birth rates) 4

Duration of Supplementation

• For artificial FET cycles, the Chinese experts' consensus guideline recommends:
  • Continue estrogen and progesterone at original doses for 3-4 weeks after pregnancy confirmation by ultrasound 5, 6
  • Gradually reduce doses to complete discontinuation within 2 weeks 5, 6
• For natural or stimulated cycles, continue luteal support for 1-3 weeks after pregnancy confirmation 5, 6

Factors Affecting Progesterone Levels

Product Selection

• Significant differences exist between vaginal progesterone products and dosing regimens 2:
  • Cyclogest (800 mg) produces different serum levels compared to Crinone (180 mg or 270 mg)
  • Cyclogest (800 mg) differs from Utrogestan/Progestan (600 mg or 800 mg)
  • Cyclogest (800 mg) differs from Lutinus (300 mg)
• No significant differences were found between products with equivalent daily doses 2

Administration Considerations

• Oral micronized progesterone results in comparable circulating progesterone levels to intramuscular progesterone but leads to reduced embryo implantation rates 7
• Variable metabolism of progesterone affects therapeutic efficacy, with plasma concentrations varying substantially between individuals receiving identical doses 6

Clinical Monitoring and Adjustment

• Consider measuring serum progesterone on pregnancy test day (day 15 post-FET) to identify women who might benefit from prolonged luteal phase support 1
• If levels are <16.5 ng/mL, patients may be at higher risk for miscarriage 1
• For patients with low progesterone levels, consider adjusting the supplementation protocol (route, dose, or duration)

Key Pitfalls to Avoid

• Discontinuing progesterone too early in patients with low serum levels (<16.5 ng/mL) on pregnancy test day 1
• Relying solely on vaginal progesterone without monitoring serum levels, as this approach is associated with higher miscarriage rates 4
• Assuming all progesterone products with the same administration route produce equivalent serum levels 2
• Overlooking the potential negative impact of excessively high progesterone levels (>20 ng/mL) 3