Timing of Blastocyst Transfer After Starting Progesterone
Blastocyst transfer should be performed 5-6 days (117-120 hours) after initiating progesterone supplementation in hormone replacement therapy (HRT) frozen embryo transfer cycles. 1
Standard Protocol for HRT-FET Cycles
The timing calculation begins from the first progesterone dose and is critical to achieving endometrial-embryo synchrony during the window of implantation 1, 2:
- Day 5 blastocysts: Transfer on the 6th day of progesterone (after 5 full days of progesterone exposure) 1, 3
- Day 6 blastocysts: Transfer on the 7th day of progesterone (after 6 full days of progesterone exposure) 4
Evidence Supporting 6-Day Protocol for Day 5 Blastocysts
The 6-day progesterone protocol demonstrates superior outcomes compared to 7-day protocols for day 5 blastocysts, with significantly higher live birth rates (38.43% vs 31.57%, P=0.01) and clinical pregnancy rates (50.43% vs 44.14%, P=0.02) 3. This advantage is particularly pronounced in:
- Patients under age 35 3
- High-quality blastocyst transfers 3
- Standard HRT cycles (non-suppression protocols) 3
Critical Timing Considerations
Transferring day 6 blastocysts on the 6th day of progesterone (rather than the 7th day) results in significantly higher miscarriage rates (50.0% vs 21.4%) and lower live birth rates (21.5% vs 35.5%), indicating the importance of matching embryo developmental stage to endometrial maturation 4.
The European Society of Human Reproduction and Embryology emphasizes that embryo transfer timing must be calculated precisely from the first progesterone dose, with blastocyst transfer occurring 117-120 hours after progesterone initiation 1.
Prerequisites Before Starting Progesterone
Do not initiate progesterone until endometrial preparation is adequate 5, 1:
- Endometrial thickness ≥7-8 mm (target ≥7 mm minimum) 5, 1
- Trilaminar endometrial pattern on ultrasound 1, 6
- Typically requires 12-14 days of estrogen priming (e.g., Progynova 6mg daily) 1
Common Pitfalls to Avoid
Starting progesterone on a fixed cycle day without confirming adequate endometrial preparation risks poor outcomes, as most patients require 12-14 days of estrogen priming before the endometrium is ready for progesterone-induced transformation 1. The American College of Obstetricians and Gynecologists specifically recommends that progesterone supplementation should begin only after achieving adequate endometrial thickness, regardless of how many days of estrogen have been administered 5.
Mismatching embryo developmental stage with progesterone duration (e.g., transferring a day 6 blastocyst after only 5 days of progesterone) leads to endometrial-embryo asynchrony and significantly worse outcomes 4.