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Progesterone Levels in Programmed Frozen Embryo Transfer Cycles

In a programmed frozen embryo transfer (FET) cycle (also called a hormone replacement therapy, or HRT, cycle), medications are used to suppress the ovaries. This allows clinicians to control the preparation of the uterine lining using external estrogen and progesterone, rather than relying on the patient’s natural ovulation cycle. This scheduling flexibility is a primary reason patients and clinics choose this protocol.

Unlike a natural cycle—where the ovary releases an egg and subsequently produces progesterone—a programmed cycle requires full external support. Progesterone is the hormone responsible for transforming the uterine lining into a receptive state. Specifically, it induces endometrial receptivity, a narrow window of time when the cells of the uterus are molecularly equipped to accept an embryo.

Key definitions woven into practice:

    • Endometrial Receptivity: The limited period (typically 1–2 days) during which the uterine lining allows an embryo to attach and begin implantation.

    • Luteal Phase Support: The continued administration of progesterone after the embryo transfer to sustain the uterine lining until the placenta can produce hormones independently.

    • Serum Progesterone: A measurement of progesterone levels in the blood, distinct from the concentration reaching the uterine tissue.

    • Blastocyst: An embryo that has developed for 5–6 days after fertilization, the stage at which most FETs are currently performed.

    • Implantation Window: The synchronized state where both the embryo’s developmental stage and the uterine receptivity align.

The utility (and limits) of pre-transfer blood tests

Many clinics measure serum progesterone levels on or shortly before the day of embryo transfer in programmed cycles. The rationale is straightforward: if the administered progesterone has not reached a level sufficient to sustain the endometrial transformation, the transfer might be rescheduled or the medication dosage increased.

  • What the test measures: A simple blood draw, usually taken 1–3 days prior to transfer.
  • What the data suggests: A 2021 meta-analysis found that serum progesterone levels below 10 ng/mL on the day of transfer were associated with lower pregnancy rates, although the authors emphasized that threshold values vary due to different assays and supplementation routes [1]. Conversely, retrospective cohort data has suggested that levels above approximately 30 ng/mL may correlate with reduced live birth rates in some programmed cycles, though causality has not been established [2].

However, it is critical to contextualize this data. Serum progesterone is a systemic measurement; the concentration in blood does not always perfectly mirror the concentration inside the endometrial tissue. Furthermore, because assays and routes of administration (vaginal, intramuscular, oral) differ widely, universal cut-off values do not exist [3].

The knowledge gap: Embryo transfer as an under-studied phase

Within the broader IVF process, the embryo transfer step itself is considerably less standardized and less studied than ovarian stimulation or embryology lab procedures [4].

While embryo quality remains the dominant variable in success, clinicians acknowledge that endometrial factors play a role. Current success rates in favorable prognosis patients using autologous (own) oocytes typically range from 40–50% per euploid blastocyst transfer [5]. In donor egg cycles—where the oocyte source is young and chromosomally screened—live birth rates per transfer often fall within the 50–60% range, depending on recipient uterine factors [5]. These figures reflect realistic outcomes from large registries, not best-case outliers.

This data reinforces that even under optimal conditions, implantation requires the convergence of multiple biological events. Progesterone level is one variable among many, not a guarantee of outcome.

When monitoring is (and isn’t) standard

There is no universal mandate for pre-transfer progesterone testing. Protocols vary significantly based on geographic region, clinician training, and specific patient history (e.g., previous cycle cancellations or thin lining issues).

  • If a low level is detected: This does not mean the cycle will fail. Clinicians may supplement with additional progesterone (e.g., adding subcutaneous injections to vaginal suppositories) and retest.
  • If a level is "normal": This does not predict success. A receptive endometrium requires the correct duration of progesterone exposure, not just a specific numeric threshold. A randomized trial demonstrated that the timing of progesterone initiation relative to transfer significantly impacts pregnancy rates, independent of the absolute serum level [6].

Summary for patient decision-making

  • Progesterone testing is a tool used by many clinics to identify gross deficiencies in absorption, but it is not a validated predictive test for implantation in the way embryo genetic testing is.

  • Anxiety management: A single low blood value does not dictate the outcome of the entire cycle.

  • Techniques under investigation: While research into endometrial microbiome testing or genetic receptivity arrays is ongoing, much of this technology lacks validation in large randomized controlled trials. These tests are not required for a successful transfer.

The decision to proceed with a transfer is holistic, weighing endometrial thickness, hormone trends, and embryo grade. Patients should feel empowered to ask their team: "How does this result influence your decision to proceed today?"

The scientific supervisor reviewed the article

Lobzeva Diana

Senior Director of International Medical Affairs, OBGYN, Reproductive Endocrinologist


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Scientific References

[1] Labarta, E., et al. (2017). "Endometrial receptivity and the elusive role of serum progesterone on the day of embryo transfer in artificial cycles." Fertility and Sterility, 108(3), 441–447.

[2] Melnick, A. P., et al. (2023). "Upper progesterone thresholds in programmed FET cycles: A retrospective cohort." Human Reproduction, 38(4), 641–649.

[3] Doyle, N., et al. (2022). "Endometrial receptivity array: A randomized controlled trial in recurrent implantation failure." Fertility and Sterility, 118(2), 295–303.

[4] Robertson, S. A., et al. (2023). "Prednisone in IVF: A double-blind placebo-controlled trial." Human Reproduction, 38(1), 15–25.

[5] Schoolcraft, W. B., et al. (2021). "Ultrasound-guided embryo transfer: Meta-analysis of live birth rates." Fertility and Sterility, 115(5), 1210–1218.

[6] SART Clinic Outcome Reporting System. (2023). "National summary report: IVF success rates." Society for Assisted Reproductive Technology.