Modified Natural Cycle FET Protocol
Overview and Core Principle
The modified natural cycle (mNC) FET protocol utilizes the patient's spontaneous ovulation with the addition of an ovulation trigger (typically hCG) to facilitate precise embryo transfer timing, combined with luteal phase progesterone supplementation. This approach leverages the natural corpus luteum while providing scheduling flexibility and enhanced luteal support 1, 2.
Protocol Components and Monitoring
Cycle Monitoring Phase
Serial ultrasound monitoring begins in the early follicular phase to track endometrial thickness and dominant follicle development 2, 3.
Endometrial thickness target of ≥7 mm must be achieved before proceeding to trigger 4.
Follicular monitoring continues until the dominant follicle reaches appropriate size (typically 16-18 mm) 2, 3.
Hormonal monitoring includes tracking estradiol, progesterone, and LH levels to confirm appropriate follicular development and exclude premature luteinization 3.
LH surge detection using urinary LH testing kits helps identify spontaneous ovulation timing, though the protocol allows flexibility independent of LH surge timing 2, 3.
Ovulation Trigger Administration
hCG trigger (5000-10,000 IU) is administered when the dominant follicle reaches appropriate size and endometrial thickness is adequate 1, 2.
The trigger serves dual purposes: ensuring final follicular maturation and facilitating precise embryo transfer scheduling 5, 1.
Some protocols incorporate additional hCG injection on the day of transfer to enhance luteal support 1.
Luteal Phase Support
Progesterone supplementation begins 48 hours before embryo transfer for day 2-3 cleavage embryos, or appropriately timed for blastocyst transfer 3.
Vaginal progesterone (400 mg twice daily) is the standard route and dose, continuing from transfer day 2.
Enhanced luteal support protocols may include:
Embryo Transfer Timing
Transfer scheduling is disconnected from the exact LH surge timing when using the modified protocol with progesterone support, providing operational flexibility 3.
For cleavage-stage embryos: transfer occurs 48 hours after progesterone initiation 3.
For blastocyst transfer: timing is adjusted accordingly based on embryo developmental stage 6.
Single embryo transfer (SET) is strongly recommended regardless of embryo quality in vitrified-warmed blastocyst cycles 7.
Post-Transfer Hormonal Support
Continuation Protocol
Progesterone continues until 10 weeks of pregnancy if conception occurs 2.
Estrogen continuation (when used): maintain original doses for 3-4 weeks after positive pregnancy confirmation, then gradually taper over 2 weeks 4.
Luteal support duration in natural cycles: continue for 1-3 weeks after ultrasound confirmation of viable intrauterine pregnancy 8.
Timing Considerations: Immediate vs Postponed Transfer
Immediate FET (in the first menstrual cycle following stimulation) versus postponed FET remains under investigation 6.
Current practice often postpones transfer for at least one cycle after oocyte retrieval, though retrospective data does not strongly support this delay 6.
The modified natural cycle allows flexibility in timing without compromising outcomes 3.
Advantages of Modified Natural Cycle
Higher pregnancy rates compared to unmodified natural cycles when enhanced luteal support is used (51% vs 26% clinical pregnancy rate) 1.
Comparable outcomes to artificial hormone replacement cycles while avoiding exogenous estrogen 1, 2.
Operational flexibility for clinics with limited weekend or daily availability 3.
Utilizes the natural corpus luteum, which may provide superior endocrine environment compared to fully artificial cycles 5.
Reduced medication burden compared to hormone replacement protocols 2.
Clinical Outcomes
Implantation rates: 29.2% with modified natural cycle versus 17.6% with true natural cycle 2.
Clinical pregnancy rates: 51% with enhanced luteal support (hCG + GnRH agonist) versus 22% with artificial hormone replacement 1.
Live birth rates: up to 52.4% reported with progesterone-supported modified natural cycles 3.
Key Protocol Distinctions
The modified natural cycle differs from true natural cycles by incorporating: