ArticleFrontiers in endocrinology2026
Serum progesterone levels for 'rescue' in hormone replacement FET: a retrospective cohort study of 917 cycles.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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 Results: 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). Conclusions: 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.
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