L26/P-693 Laboratory–Clinical KPI alignment in POSEIDON 3 and 4 patients: Implications for counselling, predictability, and time to pregnancy

Abstract

Study question Do laboratory performance indicators align with pregnancy outcomes in POSEIDON 3 and 4 patients, and can they reliably guide counselling? Summary answer Laboratory indicators demonstrate clear differences between POSEIDON 3 and 4 patients, but do not consistently predict pregnancy and live birth outcomes. What is known already POSEIDON Groups 3 and 4 represent poor-prognosis IVF patients primarily limited by low oocyte numbers. Laboratory key performance indicators (KPIs) such as cycle cancellation, blastocyst formation, and embryo utilisation are commonly used to assess prognosis and guide counselling regarding expected success, number of cycles, and embryo pooling strategies. However, whether favourable laboratory performance translates predictably into pregnancy, miscarriage, and live birth outcomes remains unclear. The relationship between laboratory KPIs and reproductive outcomes in poor-prognosis patients has not been well characterised. Study design, size, duration This retrospective cohort study analysed IVF cycles performed between 2014–2024 at a tertiary fertility centre. A total of 1,250 women classified as POSEIDON Groups 3 and 4 were included. POSEIDON Group-3 comprised women aged <35 years with AMH <1.2 ng/mL (n = 547), and Group-4 comprised women aged ≥35 years with AMH <1.2 ng/mL (n = 703). All comparative analyses and outcome assessments were performed exclusively between POSEIDON Groups 3 and 4. Participants/materials, setting, methods All autologous IVF cycles in POSEIDON Groups 3 and 4 with extended embryo culture and without PGT were included. Laboratory KPIs—including cycle cancellation, blastulation rate, and embryo utilisation—were analysed to assess progression to embryo transfer. Pregnancy and live birth outcomes were evaluated only in cycles reaching transfer. All women underwent frozen embryo transfer of two good-quality blastocysts. Comparative assessments between Groups 3 and 4 used unadjusted odds ratios. Main results and the role of chance POSEIDON Group-3 demonstrated consistently more favourable laboratory performance and reproductive efficiency compared with Group-4. Cycle-cancellation prior to embryo transfer was significantly lower in Group-3 than Group-4(6%vs10%), corresponding to a reduced likelihood of cycle-cancellation before transfer in Group-3 (unadjusted OR 0.57, 95% CI 0.40–0.81). Blastocyst-conversion was significantly higher in Group-3(63%) compared with Group-4(43%), translating into more than a two-fold higher likelihood of blastocyst formation (unadjusted OR 2.24, 95%-CI 2.01–2.49), indicating superior upstream laboratory progression despite similarly reduced ovarian reserve. This laboratory advantage increased the probability of reaching embryo transfer; however, its translation into reproductive outcomes was incomplete. Implantation rates per embryo transferred were higher in Group-3 than Group-4 (49% vs 32%), corresponding to a modest but statistically significant increase in implantation likelihood (unadjusted OR 1.31, 95% CI 1.04–1.65). Live-birth rate per blastocyst transferred was also higher in Group-3 (23.4%) compared with Group-4 (15.8%), reflecting greater biological efficiency once transfer occurred (unadjusted OR 1.62, 95% CI 1.22–2.16). Miscarriage rates were comparable between groups (7%vs12%), suggesting that post-implantation loss did not primarily account for differences in live birth outcomes. Overall, laboratory KPIs primarily determined the likelihood of reaching embryo transfer, while age-related biological efficiency appeared to govern implantation and live birth potential once transfer occurred. Limitations, reasons for caution The retrospective design limits causal inference. Analyses were unadjusted, and residual confounding—particularly related to male factor infertility and treatment heterogeneity—cannot be excluded. Embryo genetic competence was not assessed, and cumulative live birth per patient was not evaluated, limiting inference on long-term reproductive efficiency. Wider implications of the findings In POSEIDON 3 and 4 patients, laboratory KPIs should guide expectations of embryo yield and time to transfer, not predict pregnancy success. Counselling should prioritise biological efficiency, blastocysts required per live birth, and rational embryo pooling, while avoiding unnecessary add-on treatments that lack scientific evidence in poor-prognosis patients. Trial registration number No