Pre-treatment serum phosphate as a metabolic correlate of live birth after IVF/ICSI: a retrospective cohort study

Oocyte developmental competence is influenced by the systemic metabolic milieu during folliculogenesis. Inorganic phosphate is essential for ATP synthesis, nucleic acid metabolism, and phosphorylation-dependent signalling, but its relationship with assisted reproductive technology outcomes remains unclear. We investigated whether pre-treatment fasting serum phosphate was associated with live birth after first IVF/ICSI fresh embryo transfer.

This retrospective cohort study included 2, 226 women aged 20-42 years undergoing their first IVF/ICSI cycle with fresh embryo transfer between January 2022 and June 2024. Serum phosphate was measured before ovarian stimulation and analysed as quartiles and per 1-SD increase (0.146 mmol/L). Multivariable logistic regression assessed associations with live birth, adjusting for demographic, ovarian reserve, metabolic, and treatment-related factors. Restricted cubic splines evaluated dose-response relationships. Measurement-window analyses stratified participants by the interval between biochemistry assessment and oocyte retrieval.

The overall live birth rate was 60%, increasing from 56% in the lowest phosphate quartile to 66% in the highest (P for trend = 0.003). Each 1-SD increase in serum phosphate was associated with higher odds of live birth (adjusted OR 1.15, 95% CI 1.06-1.26; P = 0.002), with a linear dose-response (P for non-linearity = 0.305). Serum phosphate was not associated with MII oocyte count or usable embryo count. In measurement-window analyses, the association was consistent in the 60-120 day window (n = 1, 485; adjusted OR 1.18, 95% CI 1.03-1.35) and the 120-180 day window (n = 637; adjusted OR 1.16, 95% CI 1.01-1.34). The 0-60 day stratum was underpowered (n = 104). Additional adjustment for calcium, alkaline phosphatase, fasting glucose, and trigger-day progesterone did not materially alter the results.

Higher pre-treatment serum phosphate was associated with higher odds of live birth after IVF/ICSI, independent of oocyte yield. External validation and mechanistic studies are required before clinical application.