LAUSR

Do serum progesterone (P4) levels ≥ or < 10ng/ml, with or without rescue strategy, influence ongoing pregnancy rates (OPR) in artificial frozen embryo transfer (FET) cycles? OPR was comparable in patients with P4 ≥ or < 10ng/ml, including those with P4 <10ng/ml without MVP increase from 800mg to 1200mg as rescue strategy. Several retrospective studies have proposed varying serum P4 thresholds on the day of transfer below which frozen embryo transfers in artificially prepared FET may negatively impact OPR and/or miscarriage rates. Based on these findings, rescue strategies involving supplemental progesterone administered via different routes have been proposed. One prospective study found improved live birth rates with subcutaneous progesterone rescue when comparing to a historical non-rescued cohort. Prospective randomized studies in which a rescue strategy is compared with an untreated low P4 arm are non-existent. This prospective study was conducted from April 2021 to December 2024 at a tertiary academic fertility center, involving a total of 270 patients. For each patient, one warmed single blastocyst transfer was performed in an artificially prepared endometrium. This study included a randomized controlled trial (RCT) introducing a rescue strategy with MVP 400mg for those cycles with a serum progesterone on day of transfer < 10ng/ml involving 87 of the 270 patients. Patients with serum P4 <10n/ml were randomized to either continue MVP 400mg BID (n = 44) or to increase the MVP to 400mg TID (n = 43) from the day after transfer as rescue strategy. Cycles with P4 ≥10ng/ml (n = 183) continued MVP 400mg BID. The primary outcome was OPR, defined as an ongoing intrauterine pregnancy at 12 weeks. A binary logistic regression model was adjusted for maternal age, blastocyst quality and progesterone levels. ROC analysis evaluated optimal progesterone cut-offs. No significant difference in OPR was observed between patients with P4 ≥10ng/ml (31.1%) and those with P4 <10ng/ml (27.3%) using MPV 400 mg BID (aOR 1.587, 95% CI 0.018-9.52; p = 0.791). Increasing the dose of MPV to TID in the intervention group did not improve OPR (30.2%, aOR 1.04, 95% CI 0.37-2.88; p = 0.943). No alternative serum P4 threshold level for optimal OPR could be identified in this patient population. Early pregnancy loss rates were also similar did not differ between control (11.4%) and intervention group (9.3%, aOR 0.93, 95% CI 0.50-4.91; p = 0.929). The initial RCT design aimed to randomize 242 patients. Recruitment was halted following interim analysis, which showed no discernable cut-off for an optimal serum progesterone level. This finding and the disappointing recruitment resulted in the early cessation of the trial. These findings suggest that progesterone levels on the day of frozen embryo transfer in artificial FET cycles are not associated to ongoing pregnancy rate or early pregnancy loss. Larger prospective studies across broader patient populations are needed to confirm these findings. Yes