A Frozen Embryo Transfer (FET) involves thawing a previously frozen embryo and placing it into the uterus. For a successful FET, the uterine lining (endometrium) must be prepared and synchronized with the embryo’s developmental stage. This preparation relies on the precisely timed administration of the hormone progesterone, which signals the uterus to become receptive. The exact timing of when to start this hormone is critical, often calculated down to the hour.
Progesterone’s Role in Endometrial Receptivity
Progesterone acts as the hormonal switch that transforms the uterine environment from a state of growth to a state of receptivity. Before its introduction, estrogen influences the endometrium, causing it to thicken during the proliferative phase. This phase builds the lining suitable for implantation.
Once the lining reaches adequate thickness, progesterone administration begins, shifting the endometrium into the secretory phase. This hormonal change causes uterine glands to mature, secrete specialized nutrients, and calms muscular contractions. This transformation creates the “Window of Implantation” (WOI), the brief period when the endometrium can accept an embryo.
In a natural cycle, the embryo arrives when the endometrium is already in the secretory phase. If the embryo is transferred too early or too late relative to this hormonal shift, asynchrony occurs, reducing the chance of implantation. Low progesterone levels can prevent the full secretory transformation, leaving the uterine lining unaccepting.
Calculating the Progesterone Window for Transfer
The timing of progesterone aims to synchronize the age of the transferred embryo with the maturity of the uterine lining, mimicking a natural cycle. The countdown begins precisely with the first dose of progesterone, marking the artificial start of the post-ovulation phase. This timing is calculated down to the hour to ensure the embryo arrives at a receptive endometrium.
For the most common transfer, a Day 5 blastocyst, the standard protocol involves five full days of progesterone exposure before the transfer. This translates to approximately 120 hours from the initial progesterone dose to the moment of transfer.
If transferring a Day 3 cleavage-stage embryo, the required progesterone exposure is shorter, typically three days, or roughly 72 hours. These precise time frames are important because the endometrium’s optimal receptivity window is narrow. Patients must adhere strictly to the clinic’s schedule, as the exact hour of the first dose dictates the hour of the transfer several days later.
Administration Routes and Cycle-Specific Timing Adjustments
The precise calculation of the progesterone window is consistent, but the method of administration introduces practical variables. Progesterone can be administered through intramuscular injections (Progesterone in Oil or PIO) or via vaginal suppositories and gels. PIO injections tend to result in higher, more consistent blood serum levels, which some clinics prefer in programmed cycles.
Vaginal suppositories deliver the hormone more directly to the uterine tissue. The choice of route may influence monitoring, but the timing of the transfer window is based on the start of the drug, not the blood level.
Cycle-Specific Timing Adjustments
Timing adjustments vary between programmed (medicated) and modified natural cycles. In a programmed cycle, the patient’s natural hormone production is suppressed, and the start of progesterone is artificially controlled by the clinic. This allows for maximum scheduling flexibility.
In a modified natural cycle, the patient’s own follicular development is tracked. The progesterone countdown begins with the documentation of the Luteinizing Hormone (LH) surge or a trigger shot that induces ovulation. While the required 72 or 120 hours of progesterone exposure remains the same, the marker used to start the clock changes from an external medication dose to a natural physiological event.