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Research Article: Serum progesterone levels for ‘rescue’ in hormone replacement FET: a retrospective cohort study of 917 cycles

Date Published: 2026-06-01

Abstract:
In hormone replacement frozen embryo transfer (HRT-FET) cycles with low pre-transfer progesterone, evidence on when single-dose rescue is insufficient is limited. Under an institutional protocol using a 10 ng/mL trigger applied at clinician discretion (no cycles deferred), we describe outcomes and explore whether very low pre-ET P4 identifies a poor-prognosis subgroup, without seeking to establish a deferral threshold. Single-center retrospective cohort (2017–2023) of 917 HRT-FET patients grouped by rescue receipt: 650 No-Rescue, 267 Rescue (single 50 mg IM progesterone; all proceeded to transfer). 40 borderline cycles (P4 9.1–9.9 ng/mL) were managed without rescue at clinician discretion. Progesterone was measured by Cobas ® e411 ECLIA. The Rescue group was stratified by pre-ET P4 (<5, 5–7.49, 7.5–9.99 ng/mL). Analyses included Fisher’s exact, multivariable logistic regression, restricted cubic splines, ROC, and 1000-resample bootstrap. Within the Rescue group, LBR was lower when pre-ET P4 was <5 ng/mL: 19.2% (n=78) versus 43.8% (5–7.49, n=112) and 39.0% (7.5–9.99, n=77; trend p=0.010). The <5 vs. ?5 comparison yielded OR 0.33 (95% CI 0.17–0.62; p=0.0004); aOR 0.35 (95% CI 0.18–0.66; p=0.002). Miscarriage among clinical pregnancies was 46.7% below 5 versus 9.9% above. Rescue with P4 ?5 had unadjusted LBR similar to No-Rescue (41.8% vs. 39.2%; p=0.55), without isolating a rescue effect. Among 61 borderline cycles (9.1–9.9 ng/mL), LBR was numerically higher with rescue (57.1%) than without (40.0%; p=0.28), but underpowered. ROC AUC was 0.609 (95% CI 0.54–0.68); Youden cutoff 5.3 ng/mL. In 1000 bootstrap resamples, the median Youden threshold was 5.4 ng/mL (IQR 5.0–5.6). Under a single 50 mg IM rescue protocol, pre-ET P4 <5 ng/mL was associated with poor per-transfer prognosis (LBR ~19%, miscarriage ~47%). This is an exploratory, assay-specific (Cobas e411 ECLIA) signal, not a validated deferral rule, and requires recalibration for other platforms. Because no cycles were deferred and the only rescue-versus-no-rescue contrast was confined to a small 9.1–9.9 ng/mL borderline subset, the rescue effect cannot be formally isolated. Shared decision-making is advised for P4 <5 ng/mL; external validation is required.

Introduction:
In hormone replacement frozen embryo transfer (HRT-FET) cycles with low pre-transfer progesterone, evidence on when single-dose rescue is insufficient is limited. Under an institutional protocol using a 10 ng/mL trigger applied at clinician discretion (no cycles deferred), we describe outcomes and explore whether very low pre-ET P4 identifies a poor-prognosis subgroup, without seeking to establish a deferral threshold.

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