L26/O-271 The clinical impact of the progesterone-to-estradiol ratio on blastocyst development is confined to low-estradiol IVF cycles

Abstract Study question Does the progesterone-to-estradiol ratio predict good-quality blastocyst formation, and is its impact modified by pre-ovulatory estradiol levels in IVF/ICSI cycles? Summary answer A higher P/E2 ratio was associated with reduced good-quality blastocyst formation, mainly in cycles with low pre-ovulatory estradiol levels. What is known already Premature luteinization, reflected by elevated progesterone on the day of trigger, has been linked to poorer IVF outcomes. The progesterone-to-estradiol ratio (P/E2) has been proposed as a marker to normalize progesterone elevation for ovarian response. However, whether the clinical relevance of P/E2 varies according to estradiol levels and ovarian response remains unclear, and clinically actionable thresholds have not been consistently defined. Study design, size, duration Retrospective cohort study including 20,778 IVF/ICSI cycles with available pre-ovulatory progesterone and estradiol measurements and blastocyst culture outcomes. Cycles were analysed according to estradiol level on the day of trigger and P/E2 ratio. The study covered consecutive cycles performed at a single tertiary fertility centre over the study period. Participants/materials, setting, methods We retrospectively analysed 20,778 IVF/ICSI cycles from a single tertiary fertility centre with serum progesterone and estradiol measured on the day of trigger. The primary outcome was obtaining ≥1 good-quality blastocyst. Associations between P/E2 ratio and outcomes were evaluated overall and stratified by estradiol level (<500 vs ≥ 500 pg/mL), including interaction testing. Multivariable logistic regression was performed in the E2 <500 pg/mL subgroup adjusting for age and AMH. Main results and the role of chance In the overall cohort, increasing P/E2 ratio was associated with a reduced likelihood of good-quality blastocyst formation. This association was strongly modified by pre-ovulatory estradiol level, with a significant interaction between P/E2 ratio and estradiol category. In cycles with E2 <500 pg/mL, good-quality blastocyst formation decreased as P/E2 ratio increased, suggesting a clinically relevant threshold around P/E2 = 1.0. In contrast, in cycles with E2 ≥500 pg/mL, the negative impact of increasing P/E2 ratio appeared attenuated.In multivariable logistic regression restricted to E2 <500 pg/mL (n = 7,641), P/E2 ratio ≥1.0 was independently associated with a lower likelihood of obtaining at least one good-quality blastocyst after adjustment for age and AMH (odds ratio 0.77, 95% confidence interval 0.61–0.97; p = 0.025). These findings indicate that the clinical relevance of P/E2 ratio is most pronounced in low-estradiol cycles. Limitations, reasons for caution This retrospective single-centre study is subject to residual confounding and selection bias. Protocol heterogeneity and unmeasured factors may influence outcomes. Results require external validation and prospective confirmation before generalisation. Wider implications of the findings The progesterone-to-estradiol (P/E2) ratio may be most clinically useful in low-response IVF/ICSI cycles with low pre-ovulatory estradiol levels. In such cycles (E2 <500 pg/mL), maintaining P/E2 below 1.0 may help optimise trigger timing and improve good-quality blastocyst formation. Trial registration number No